Brief Summary
The main aim of this study is to evaluate the PK, safety, tolerability and immunogenicity of subcutaneous (SC) administration of TAK-881 in adult and pediatric participants with PIDD and compare them to HYQVIA in participants 16 years old and older.
The participants will be treated with TAK-881/HYQVIA or HYQVIA/TAK-881 with the same dose and dosing interval of immunoglobulin for up to 51 weeks (for participants greater than or equal to \[\>=\]16 years) and only with TAK-881 for up to 27 weeks (for participants aged 2 to less than \[\<\]16 years) as they were treated with another immunoglobulin before enrollment. Participants will need to visit the clinic every 3 or 4 weeks during the duration of the study.
The participants will be treated with TAK-881/HYQVIA or HYQVIA/TAK-881 with the same dose and dosing interval of immunoglobulin for up to 51 weeks (for participants greater than or equal to \[\>=\]16 years) and only with TAK-881 for up to 27 weeks (for participants aged 2 to less than \[\<\]16 years) as they were treated with another immunoglobulin before enrollment. Participants will need to visit the clinic every 3 or 4 weeks during the duration of the study.
Brief Title
A Study About How TAK-881 is Processed by the Body and Side Effects in People With Primary Immunodeficiency Diseases
Detailed Description
The study consists of a screening epoch, a ramp-up epoch (if needed) and treatment epochs. Participants who have been receiving conventional subcutaneous intravenous immunoglobin G (cIGSC) or intravenous immunoglobulin G (IGIV) before the study, will enter a ramp-up epoch which will start 1, 2, 3 or 4 weeks after the last cIGSC or IGIV pre study dose before screening. Participants who have already been receiving HYQVIA treatment before the study, will directly enter the treatment epochs after screening. Participants aged greater than or equal to \[\>=\]16 years will be randomized at a 1:1 ratio to one of the following treatment sequences: either TAK-881 followed by HYQVIA or HYQVIA followed by TAK-881. Each participant aged \>=16 years will complete both crossover epochs. Pediatric participants aged 2 to less than \[\<\]16 years will complete a single arm treatment with the study drug (TAK-881 only).
Categories
Completion Date
Completion Date Type
Actual
Conditions
PRIMARY IMMUNODEFICIENCY DISEASES (PID)
Eligibility Criteria
Inclusion Criteria
* Participant must have a documented diagnosis of a form of primary humoral immunodeficiency involving a defect in antibody formation and requiring IgG replacement, as defined according to the International Union of Immunological Societies (IUIS) Committee.
* Participant is 2 years to \<16 years at the time of signing the informed consent form (ICF) for the single arm treatment part of the study OR 16 years or older at the time of signing the ICF for the crossover part of the study.
* Participant has received a stable dose of regular treatment with any IGIV OR HYQVIA with a treatment interval of every 21 or 28 days OR any cIGSC with a treatment interval of every 7 or 14 days over a period of at least 12 weeks prior to screening at a minimum prestudy IgG dose equivalent to 0.3 grams per kilograms per body weight per 4 weeks (g/kg BW/4 weeks) and a maximum dose equivalent to 1 g/kg BW/4 weeks. Over that period, the participant should have been on the same product of IGIV, HYQVIA, or cIGSC. A stable dose is defined as one that deviates less than +-25 percentage (%) from the mean dose for all IgG infusions within this 12-week period prior to screening. Variations in the treatment interval of up to +-5 days for participant with a 28-day treatment interval and of up to +-3 days for participant with a 7, 14, or 21-day treatment interval are acceptable up to the first IP infusion.
* Participant has a serum trough level of IgG greater than (\>) 5 grams per liter (g/L) at the following time points:
1. At screening (sample taken prior to prestudy IgG infusion after signing the ICF) and
2. Within 12 weeks prior to screening.
* If female of childbearing potential, participant presents with a negative pregnancy test and agrees to employ highly effective form of contraception for the duration of the study.
* Participant, or in the case of minors, legally designated representative(s) is/are willing and able to comply with the requirements of the protocol, including PK blood sampling, for the duration of the study.
Informed Consent
* The participant or, in the case of minors, legally designated representative(s) is/are willing and able to understand and fully comply with study procedures and requirements, in the opinion of the investigator.
* The participant or, in the case of minors, legally designated representative(s) has/have provided informed consent/assent, if applicable, (that is, in writing, documented via a signed and dated ICF and/or eConsent, if available), and any required privacy authorization prior to the initiation of any study procedures.
Exclusion Criteria
* Participant has a known history of a positive result or is positive at screening for one or more of the following: hepatitis B surface antigen (HBsAg), polymerase chain reaction (PCR) for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1/2. Cured participants with a history of hepatitis C infection who have a negative PCR test at screening is eligible.
* Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent):
1. Persistent alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \>2.5\* the upper limit of normal (ULN) for the testing laboratory.
2. Persistent severe neutropenia (defined as an absolute neutrophil count \[ANC\] less than and equal to (\<=) 500 per cubic millimeter (/mm\^3).
* Known history of chronic kidney disease or estimated glomerular filtration rate (eGFR) of \<60 milliliter per minute per 1.73 square meter (mL/min/1.73m\^2) at screening.
* Participant has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site, at the discretion of the investigator.
* Participant has a known history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IV immunoglobulin, SC immunoglobulin, and/or immune serum globulin infusions.
* Participants with a known systemic hypersensitivity to any of the excipients of TAK-881/HYQVIA in accordance with the Investigator's Brochure (IB)/package insert/Summary of Product Characteristics (SmPC).
* Known substance or prescription drug abuse within 12 months of screening.
* Participant has immunoglobulin A (IgA) deficiency (IgA less than 0.07 g/L) associated with known anti-IgA antibodies and a history of hypersensitivity.
* Participant has a known systemic hypersensitivity to hyaluronidase or rHuPH20.
* Participant has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening.
* Participant has a bleeding disorder, or a platelet count less than 20,000 per microliter (mcL), or in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of immune globulin subcutaneous (IGSC) therapy.
* Treatment with immunosuppressants including chemotherapeutic agents, immunomodulators, and long-term systemic corticosteroid (defined as a daily dose of \>1 mg of prednisone equivalent/kg/day for \>30 days) within 12 weeks prior to screening. Short or intermittent courses (\<=10 days) of corticosteroids are allowed.
* Live-attenuated viral vaccination within 12 weeks prior to screening.
* History or current diagnosis of thrombotic episodes; venous thrombus that occurred in association with a medical device \>2 years prior to screening are allowed.
* Participant has severe dermatitis that would preclude adequate sites for safe product administration in the opinion of the investigator.
* Participant has a medical condition, laboratory finding, or physical examination finding that precludes participation, or with clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may interfere with successful completion of the study or place the participant at undue medical risk.
* Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to screening.
* Participant is scheduled to participate in another clinical study involving an IP (except for participants scheduled to enroll in a long-term follow-up study with TAK-881) or investigational device during the course of this study.
* Participant is a family member or employee of the investigator or the investigator's site staff.
* If female, participant is pregnant or lactating at the time of screening.
* Participant must have a documented diagnosis of a form of primary humoral immunodeficiency involving a defect in antibody formation and requiring IgG replacement, as defined according to the International Union of Immunological Societies (IUIS) Committee.
* Participant is 2 years to \<16 years at the time of signing the informed consent form (ICF) for the single arm treatment part of the study OR 16 years or older at the time of signing the ICF for the crossover part of the study.
* Participant has received a stable dose of regular treatment with any IGIV OR HYQVIA with a treatment interval of every 21 or 28 days OR any cIGSC with a treatment interval of every 7 or 14 days over a period of at least 12 weeks prior to screening at a minimum prestudy IgG dose equivalent to 0.3 grams per kilograms per body weight per 4 weeks (g/kg BW/4 weeks) and a maximum dose equivalent to 1 g/kg BW/4 weeks. Over that period, the participant should have been on the same product of IGIV, HYQVIA, or cIGSC. A stable dose is defined as one that deviates less than +-25 percentage (%) from the mean dose for all IgG infusions within this 12-week period prior to screening. Variations in the treatment interval of up to +-5 days for participant with a 28-day treatment interval and of up to +-3 days for participant with a 7, 14, or 21-day treatment interval are acceptable up to the first IP infusion.
* Participant has a serum trough level of IgG greater than (\>) 5 grams per liter (g/L) at the following time points:
1. At screening (sample taken prior to prestudy IgG infusion after signing the ICF) and
2. Within 12 weeks prior to screening.
* If female of childbearing potential, participant presents with a negative pregnancy test and agrees to employ highly effective form of contraception for the duration of the study.
* Participant, or in the case of minors, legally designated representative(s) is/are willing and able to comply with the requirements of the protocol, including PK blood sampling, for the duration of the study.
Informed Consent
* The participant or, in the case of minors, legally designated representative(s) is/are willing and able to understand and fully comply with study procedures and requirements, in the opinion of the investigator.
* The participant or, in the case of minors, legally designated representative(s) has/have provided informed consent/assent, if applicable, (that is, in writing, documented via a signed and dated ICF and/or eConsent, if available), and any required privacy authorization prior to the initiation of any study procedures.
Exclusion Criteria
* Participant has a known history of a positive result or is positive at screening for one or more of the following: hepatitis B surface antigen (HBsAg), polymerase chain reaction (PCR) for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1/2. Cured participants with a history of hepatitis C infection who have a negative PCR test at screening is eligible.
* Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent):
1. Persistent alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \>2.5\* the upper limit of normal (ULN) for the testing laboratory.
2. Persistent severe neutropenia (defined as an absolute neutrophil count \[ANC\] less than and equal to (\<=) 500 per cubic millimeter (/mm\^3).
* Known history of chronic kidney disease or estimated glomerular filtration rate (eGFR) of \<60 milliliter per minute per 1.73 square meter (mL/min/1.73m\^2) at screening.
* Participant has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site, at the discretion of the investigator.
* Participant has a known history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IV immunoglobulin, SC immunoglobulin, and/or immune serum globulin infusions.
* Participants with a known systemic hypersensitivity to any of the excipients of TAK-881/HYQVIA in accordance with the Investigator's Brochure (IB)/package insert/Summary of Product Characteristics (SmPC).
* Known substance or prescription drug abuse within 12 months of screening.
* Participant has immunoglobulin A (IgA) deficiency (IgA less than 0.07 g/L) associated with known anti-IgA antibodies and a history of hypersensitivity.
* Participant has a known systemic hypersensitivity to hyaluronidase or rHuPH20.
* Participant has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening.
* Participant has a bleeding disorder, or a platelet count less than 20,000 per microliter (mcL), or in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of immune globulin subcutaneous (IGSC) therapy.
* Treatment with immunosuppressants including chemotherapeutic agents, immunomodulators, and long-term systemic corticosteroid (defined as a daily dose of \>1 mg of prednisone equivalent/kg/day for \>30 days) within 12 weeks prior to screening. Short or intermittent courses (\<=10 days) of corticosteroids are allowed.
* Live-attenuated viral vaccination within 12 weeks prior to screening.
* History or current diagnosis of thrombotic episodes; venous thrombus that occurred in association with a medical device \>2 years prior to screening are allowed.
* Participant has severe dermatitis that would preclude adequate sites for safe product administration in the opinion of the investigator.
* Participant has a medical condition, laboratory finding, or physical examination finding that precludes participation, or with clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may interfere with successful completion of the study or place the participant at undue medical risk.
* Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to screening.
* Participant is scheduled to participate in another clinical study involving an IP (except for participants scheduled to enroll in a long-term follow-up study with TAK-881) or investigational device during the course of this study.
* Participant is a family member or employee of the investigator or the investigator's site staff.
* If female, participant is pregnant or lactating at the time of screening.
Inclusion Criteria
Inclusion Criteria
* Participant must have a documented diagnosis of a form of primary humoral immunodeficiency involving a defect in antibody formation and requiring IgG replacement, as defined according to the International Union of Immunological Societies (IUIS) Committee.
* Participant is 2 years to \<16 years at the time of signing the informed consent form (ICF) for the single arm treatment part of the study OR 16 years or older at the time of signing the ICF for the crossover part of the study.
* Participant has received a stable dose of regular treatment with any IGIV OR HYQVIA with a treatment interval of every 21 or 28 days OR any cIGSC with a treatment interval of every 7 or 14 days over a period of at least 12 weeks prior to screening at a minimum prestudy IgG dose equivalent to 0.3 grams per kilograms per body weight per 4 weeks (g/kg BW/4 weeks) and a maximum dose equivalent to 1 g/kg BW/4 weeks. Over that period, the participant should have been on the same product of IGIV, HYQVIA, or cIGSC. A stable dose is defined as one that deviates less than +-25 percentage (%) from the mean dose for all IgG infusions within this 12-week period prior to screening. Variations in the treatment interval of up to +-5 days for participant with a 28-day treatment interval and of up to +-3 days for participant with a 7, 14, or 21-day treatment interval are acceptable up to the first IP infusion.
* Participant has a serum trough level of IgG greater than (\>) 5 grams per liter (g/L) at the following time points:
1. At screening (sample taken prior to prestudy IgG infusion after signing the ICF) and
2. Within 12 weeks prior to screening.
* If female of childbearing potential, participant presents with a negative pregnancy test and agrees to employ highly effective form of contraception for the duration of the study.
* Participant, or in the case of minors, legally designated representative(s) is/are willing and able to comply with the requirements of the protocol, including PK blood sampling, for the duration of the study.
Informed Consent
* The participant or, in the case of minors, legally designated representative(s) is/are willing and able to understand and fully comply with study procedures and requirements, in the opinion of the investigator.
* The participant or, in the case of minors, legally designated representative(s) has/have provided informed consent/assent, if applicable, (that is, in writing, documented via a signed and dated ICF and/or eConsent, if available), and any required privacy authorization prior to the initiation of any study procedures.
* Participant must have a documented diagnosis of a form of primary humoral immunodeficiency involving a defect in antibody formation and requiring IgG replacement, as defined according to the International Union of Immunological Societies (IUIS) Committee.
* Participant is 2 years to \<16 years at the time of signing the informed consent form (ICF) for the single arm treatment part of the study OR 16 years or older at the time of signing the ICF for the crossover part of the study.
* Participant has received a stable dose of regular treatment with any IGIV OR HYQVIA with a treatment interval of every 21 or 28 days OR any cIGSC with a treatment interval of every 7 or 14 days over a period of at least 12 weeks prior to screening at a minimum prestudy IgG dose equivalent to 0.3 grams per kilograms per body weight per 4 weeks (g/kg BW/4 weeks) and a maximum dose equivalent to 1 g/kg BW/4 weeks. Over that period, the participant should have been on the same product of IGIV, HYQVIA, or cIGSC. A stable dose is defined as one that deviates less than +-25 percentage (%) from the mean dose for all IgG infusions within this 12-week period prior to screening. Variations in the treatment interval of up to +-5 days for participant with a 28-day treatment interval and of up to +-3 days for participant with a 7, 14, or 21-day treatment interval are acceptable up to the first IP infusion.
* Participant has a serum trough level of IgG greater than (\>) 5 grams per liter (g/L) at the following time points:
1. At screening (sample taken prior to prestudy IgG infusion after signing the ICF) and
2. Within 12 weeks prior to screening.
* If female of childbearing potential, participant presents with a negative pregnancy test and agrees to employ highly effective form of contraception for the duration of the study.
* Participant, or in the case of minors, legally designated representative(s) is/are willing and able to comply with the requirements of the protocol, including PK blood sampling, for the duration of the study.
Informed Consent
* The participant or, in the case of minors, legally designated representative(s) is/are willing and able to understand and fully comply with study procedures and requirements, in the opinion of the investigator.
* The participant or, in the case of minors, legally designated representative(s) has/have provided informed consent/assent, if applicable, (that is, in writing, documented via a signed and dated ICF and/or eConsent, if available), and any required privacy authorization prior to the initiation of any study procedures.
Gender
All
Gender Based
false
Keywords
Immunoglobulin replacement therapy; facilitated subcutaneous
Immunoglobulin; primary immunodeficiency disease
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
2 Years
NCT Id
NCT05755035
Org Class
Industry
Org Full Name
Takeda
Org Study Id
TAK-881-3001
Overall Status
Completed
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Multicenter, Prospective, Open-label, Randomized, Crossover Study to Evaluate Pharmacokinetics (PK), Safety, and Tolerability of TAK-881 in Primary Immunodeficiency Diseases (PIDD)
Primary Outcomes
Outcome Description
AUC0-tau;ss was defined as the area under the curve over one dosing interval at steady-state. The AUC0-tau;ss was calculated during the dosing interval after the last dose in each crossover epoch by the non-compartmental analysis (NCA) based on total IgG levels for TAK-881 and HYQVIA.
Outcome Measure
Area Under the Curve Over One Dosing Interval at Steady-State (AUC0-tau;ss) of Total IgG Levels With TAK-881 and HYQVIA Treatment in Participants >= 16 Years
Outcome Time Frame
During the dosing interval of 8th dose (3-week) or 6th dose (4-week): 3-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21 days (post-infusion); 4-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21,28 days (post-infusion)
Secondary Ids
Secondary Id
2022-502095-23-01
Secondary Outcomes
Outcome Description
Mean annualized rates and corresponding two-sided 95% CIs were reported for TAK-881 and HYQVIA and were analyzed using a generalized linear model. The response distribution was assumed to be Poisson with a logarithmic link function. The model included the natural logarithm of the length of the observational period in years as an offset to account for potential differences in lengths of the observational periods per participant. Results were back transformed from the logarithmic scale.
Outcome Time Frame
Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks
Outcome Measure
Mean Annualized Rate of All Infections
Outcome Description
Mean annualized rates of ASBIs and corresponding two-sided 95% CIs were reported for TAK-881 and HYQVIA and were analyzed using a generalized linear model. The response distribution was assumed to be Poisson with a logarithmic link function. The model included the natural logarithm of the length of the observational period in years as an offset to account for potential differences in lengths of the observational periods per participant. Results were back transformed from the logarithmic scale.
Outcome Time Frame
Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks
Outcome Measure
Mean Annualized Rate of Acute Serious Bacterial Infections (ASBIs)
Outcome Description
Mean annualized rates of fever episodes and corresponding two-sided 95% CIs were reported for TAK-881 and HYQVIA and were analyzed using a generalized linear model. The response distribution was assumed to be Poisson with a logarithmic link function. The model included the natural logarithm of the length of the observational period in years as an offset to account for potential differences in lengths of the observational periods per participant. Results were back transformed from the logarithmic scale.
Outcome Time Frame
Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks
Outcome Measure
Mean Annualized Rate of Fever Episodes
Outcome Description
The time to first ASBI was defined as the time between the first investigational product (IP) administration (referring to the first ramp-up dose, if ramp-up is applicable, or to the first full dose at Week 1, if ramp-up is not applicable) and the first occurrence of the ASBI. The median time to first ASBI was reported.
Outcome Time Frame
Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks
Outcome Measure
Time to First ASBI
Outcome Description
The median duration of infections was reported. Only participants with an infection are included here.
Outcome Time Frame
Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks
Outcome Measure
Duration of Infections
Outcome Description
The mean number of days with daily activity impairment per participant-year was reported.
Outcome Time Frame
Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks
Outcome Measure
Number of Days Not Able to go to School, Work, Daycare, or to Perform Normal Daily Activities Due to Infections and/or Their Treatment, or Other Illnesses
Outcome Description
Days on antibiotics were calculated as the total number of calendar days during which at least one respective antibiotic was administered due to treatment of infection. Data was collected for administration via oral or parenteral and all routes. The mean number of days on antibiotics per participant-year was reported.
Outcome Time Frame
Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks
Outcome Measure
Number of Days on Antibiotics Due to Treatment of Infection
Outcome Description
Number of participants hospitalized due to infection or other illnesses were reported.
Outcome Time Frame
Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks
Outcome Measure
Number of Participants Hospitalized Due to Infection or Other Illnesses
Outcome Description
The number of days of hospitalization due to infection per participant-year was reported.
Outcome Time Frame
Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks
Outcome Measure
Number of Days of Hospitalization Due to Infections or Other Illnesses
Outcome Description
Number of participants with acute physician visits due to infection or other illnesses was reported.
Outcome Time Frame
Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks
Outcome Measure
Number of Participants With Acute Physician Visits Due to Infection or Other Illnesses
Outcome Description
Cmax of total IgG with TAK-881 and HYQVIA at steady-state was reported.
Outcome Time Frame
During the dosing interval of 8th dose (3-week) or 6th dose (4-week): 3-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21 days (post-infusion); 4-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21,28 days (post-infusion)
Outcome Measure
Maximum Concentration (Cmax) of Total IgG With TAK-881 and HYQVIA at Steady-State in Participants >=16 Years
Outcome Description
Tmax of total IgG with TAK-881 and HYQVIA at steady-state was reported.
Outcome Time Frame
During the dosing interval of 8th dose (3-week) or 6th dose (4-week): 3-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21 days (post-infusion); 4-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21,28 days (post-infusion)
Outcome Measure
Time to Maximum Concentration (Tmax) of Total IgG With TAK-881 and HYQVIA at Steady-State in Participants >=16 Years
Outcome Description
t1/2 of total IgG with TAK-881 and HYQVIA at steady-state was reported. t1/2 was estimated by noncompartmental analysis from the terminal elimination-rate constant derived from the slope of the log-linear decline in total IgG concentrations during the terminal phase of the concentration-time profile. The estimated t1/2 may exceed the 21- or 28-day PK sampling interval. The PK assessment period did not extend beyond the protocol-defined 21-day or 28-day interval.
Outcome Time Frame
During the dosing interval of 8th dose (3-week) or 6th dose (4-week): 3-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21 days (post-infusion); 4-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21,28 days (post-infusion)
Outcome Measure
Terminal Half-life (t1/2) of Total IgG With TAK-881 and HYQVIA at Steady-State in Participants >=16 Years
Outcome Description
CL/F of total IgG with TAK-881 and HYQVIA at steady-state was reported.
Outcome Time Frame
During the dosing interval of 8th dose (3-week) or 6th dose (4-week): 3-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21 days (post-infusion); 4-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21,28 days (post-infusion)
Outcome Measure
Apparent Clearance (CL/F) of Total IgG With TAK-881 and HYQVIA at Steady-State in Participants >=16 Years
Outcome Description
Vz/F of total IgG with TAK-881 and HYQVIA at steady-state was reported.
Outcome Time Frame
During the dosing interval of 8th dose (3-week) or 6th dose (4-week): 3-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21 days (post-infusion); 4-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21,28 days (post-infusion)
Outcome Measure
Apparent Volume of Distribution (Vz/F) of Total IgG With TAK-881 and HYQVIA at Steady-State in Participants >=16 Years
Outcome Description
AUC0-tau;ss/week of total IgG with TAK-881 and HYQVIA at steady-state was reported.
Outcome Time Frame
During the dosing interval of 8th dose (3-week) or 6th dose (4-week): 3-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21 days (post-infusion); 4-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21,28 days (post-infusion)
Outcome Measure
AUC0-tau;ss Per Week (AUC0-tau;ss/Week) of Total IgG With TAK-881 and HYQVIA at Steady-State in Participants >=16 Years
Outcome Description
The trough level of total IgG was reported. Total IgG trough levels were analyzed using the last trough level per participants (at the end of the last dosing interval).
Outcome Time Frame
Single arm treatment: pre-infusion at Week 25 during the 4-week dosing; Crossover treatment: pre-infusion at Weeks 25, 49, corresponding to 21 days after the last dose for 3-week dosing and 28 days after the last dose for 4-week regimen
Outcome Measure
Trough Level of Total IgG
Outcome Description
The trough level of IgG subclasses was reported. Trough levels of IgG subclasses were analyzed using the last trough level per participants (at the end of the last dosing interval).
Outcome Time Frame
Single arm treatment: pre-infusion at Week 21 during the 4-week dosing; Crossover treatment: pre-infusion at Weeks 25, 49, corresponding to 21 days after the last dose for 3-week dosing and 28 days after the last dose for 4-week regimen
Outcome Measure
Trough Level of IgG Subclasses
Outcome Description
The trough level of antigen specific IgG antibodies (Clostridium tetani toxoid, Haemophilus influenzae, and hepatitis B) was reported. Antigen-specific IgG antibodies were analyzed using the last trough level per participant in each crossover epoch (at the end of the last dosing interval).
Outcome Time Frame
Crossover treatment: pre-infusion at Weeks 25, 49, corresponding to 21 days after the last dose for 3-week dosing and 28 days after the last dose for 4-week regimen
Outcome Measure
Trough Level of Antigen Specific IgG Antibodies in Participants >=16 Years
Outcome Description
Sparse PK sampling was conducted for participants aged 2 to \<16 years. A population PK model integrating PK data from participants aged 2 to \<16 years and participants aged \>=16 years was developed. Population PK simulations were performed using virtual pediatric and adult populations constructed from age- and sex-specific body weight distributions, ensuring that the simulations were representative of the target PIDD population. AUC0-tau;ss was estimated for the simulated PK profiles and summarized by age group. Geometric mean and 90% predicted interval (PI) derived from the simulation (N = 3000 per age group) at the observed median of average body weight adjusted TAK-881 full-dose per participant for every-4-week dosing frequency were reported.
Outcome Time Frame
During the dosing interval of 6th dose (4-week): From Day 1 (pre and post infusion) every day up to 4 weeks
Outcome Measure
Simulated AUC0-tau;ss of TAK-881 at Steady-State
Outcome Description
Sparse PK sampling was conducted for participants aged 2 to \<16 years. A population PK model integrating PK data from participants aged 2 to \<16 years and participants aged \>=16 years was developed. Population PK simulations were performed using virtual pediatric and adult populations constructed from age- and sex-specific body weight distributions, ensuring that the simulations were representative of the target PIDD population. Cmax was estimated for the simulated PK profiles and summarized by age group. Geometric mean and 90% PI derived from the simulation (N = 3000 per age group) at the observed median of average body weight adjusted TAK-881 full-dose per participant for every-4-week dosing frequency were reported.
Outcome Time Frame
During the dosing interval of 6th dose (4-week): From Day 1 (pre and post infusion) every day up to 4 weeks
Outcome Measure
Simulated Cmax of TAK-881 at Steady-State
Outcome Description
Sparse PK sampling was conducted for participants aged 2 to \<16 years. A population PK model integrating PK data from participants aged 2 to \<16 years and participants aged \>=16 years was developed. Population PK simulations were performed using virtual pediatric and adult populations constructed from age- and sex-specific body weight distributions, ensuring that the simulations were representative of the target PIDD population. Tmax was estimated for the simulated PK profiles and summarized by age group. Median and full range derived from the simulation (N = 3000 per age group) at the observed median of average body weight adjusted TAK-881 full-dose per participant for every-4-week dosing frequency were reported.
Outcome Time Frame
During the dosing interval of 6th dose (4-week): From Day 1 (pre and post infusion) every day up to 4 weeks
Outcome Measure
Simulated Tmax of TAK-881 at Steady-State
Outcome Description
Sparse PK sampling was conducted for participants aged 2 to \<16 years. A population PK model integrating PK data from participants aged 2 to \<16 years and participants aged \>=16 years was developed. Population PK simulations were performed using virtual pediatric and adult populations constructed from age- and sex-specific body weight distributions, ensuring that the simulations were representative of the target PIDD population. t1/2 was estimated for the simulated PK profiles and summarized by age group. Geometric mean and 90% PI derived from the simulation (N = 3000 per age group) at the observed median of average body weight adjusted TAK-881 full-dose per participant for every-4-week dosing frequency were reported.
Outcome Time Frame
During the dosing interval of 6th dose (4-week): From Day 1 (pre and post infusion) every day up to 4 weeks
Outcome Measure
Simulated t1/2 of TAK-881 at Steady-State
Outcome Description
Sparse PK sampling was conducted for participants aged 2 to \<16 years. A population PK model integrating PK data from participants aged 2 to \<16 years and participants aged \>=16 years was developed. Population PK simulations were performed using virtual pediatric and adult populations constructed from age- and sex-specific body weight distributions, ensuring that the simulations were representative of the target PIDD population. CL/F was estimated for the simulated PK profiles and summarized by age group. Geometric mean and 90% PI derived from the simulation (N = 3000 per age group) at the observed median of average body weight adjusted TAK-881 full-dose per participant for every-4-week dosing frequency were reported.
Outcome Time Frame
During the dosing interval of 6th dose (4-week): From Day 1 (pre and post infusion) every day up to 4 weeks
Outcome Measure
Simulated CL/F of TAK-881 at Steady-State
Outcome Description
Sparse PK sampling was conducted for participants aged 2 to \<16 years. A population PK model integrating PK data from participants aged 2 to \<16 years and participants aged \>=16 years was developed. Population PK simulations were performed using virtual pediatric and adult populations constructed from age- and sex-specific body weight distributions, ensuring that the simulations were representative of the target PIDD population. Vz/F was estimated for the simulated PK profiles and summarized by age group. Geometric mean and 90% PI derived from the simulation (N = 3000 per age group) at the observed median of average body weight adjusted TAK-881 full-dose per participant for every-4-week dosing frequency were reported.
Outcome Time Frame
During the dosing interval of 6th dose (4-week): From Day 1 (pre and post infusion) every day up to 4 weeks
Outcome Measure
Simulated Vz/F of TAK-881 at Steady-State
Outcome Description
Sparse PK sampling was conducted for participants aged 2 to \<16 years. A population PK model integrating PK data from participants aged 2 to \<16 years and participants aged \>=16 years was developed. Population PK simulations were performed using virtual pediatric and adult populations constructed from age- and sex-specific body weight distributions, ensuring that the simulations were representative of the target PIDD population. AUC0-tau;ss/week was estimated for the simulated PK profiles and summarized by age group. Geometric mean and 90% PI derived from the simulation (N = 3000 per age group) at the observed median of average body weight adjusted TAK-881 full-dose per participant for every-4-week dosing frequency were reported.
Outcome Time Frame
During the dosing interval of 6th dose (4-week): From Day 1 (pre and post infusion) every day up to 4 weeks
Outcome Measure
Simulated AUC0-tau;ss/Week of TAK-881 at Steady-State
Outcome Description
An adverse event (AE) was any untoward medical occurrence in a clinical study subject, temporally associated with the use of the study intervention, whether or not the occurrence is considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study intervention. A TEAE was defined as any event emerging or manifesting at or after the initiation of treatment with a study intervention or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the study intervention or medicinal product.
Outcome Time Frame
From the start of study drug administration, up to 27 weeks (Single arm treatment) and up to 51 weeks (Crossover treatment)
Outcome Measure
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Outcome Description
Number of participants with infusion withdrawals, interruptions, or infusion rate reductions due to TAK-881-related TEAEs were reported.
Outcome Time Frame
From the start of study drug administration, up to 23 weeks (Single arm treatment) and up to 48 weeks (Crossover treatment)
Outcome Measure
Number of Participants With Infusion Withdrawals, Interruptions, or Infusion Rate Reductions Due to TAK-881-related TEAEs
Outcome Description
Participants were considered "Positive" if corresponding titer is \>=1:160 and were considered "Negative" if no anti-drug antibodies (ADA) is quantified (negative assay result) or the corresponding titer is \<1:160.
Outcome Time Frame
From the start of study drug administration, up to 23 weeks (Single arm treatment) and up to 51 weeks (Crossover treatment)
Outcome Measure
Number of Participants With Positive Binding Antibodies (Titer Greater Than and Equal to [>=] 1:160) and Positive Neutralizing Antibodies to Recombinant Human Hyaluronidase PH20 (rHuPH20)
Outcome Description
Number of infusion per month at full dose was calculated as the total number of full dose infusions divided by the total time in months on treatment. A single aggregate value was therefore presented; a measure of dispersion was not applicable.
Outcome Time Frame
Single arm treatment: Up to 20 weeks; Crossover treatment: Up to 45 weeks
Outcome Measure
Number of Infusions Per Month at Full Dose With Both TAK-881 and HYQVIA
Outcome Description
The sum of the following: 1) Stop time of rHuPH20 - start time of rHuPH20; 2) Sum of all individual IgG duration steps; 3) Start time of IgG - Stop time of rHuPH20, 4) Duration of all IgG interruptions independent of the reason for interruption. For each participant, the average infusion duration was calculated; participant-level averages were then summarized using median and full range.
Outcome Time Frame
Single arm treatment: Up to 20 weeks; Crossover treatment: Up to 45 weeks
Outcome Measure
Duration of Infusions Per Participant at Full Dose With Both TAK-881 and HYQVIA
Outcome Description
Monthly infusion time per participant at full dose was calculated as the total duration of full dose infusions per treatment divided by the total time in months on the respective treatment. For each participant, the average monthly infusion time was calculated; participant-level averages were then summarized using median and full range.
Outcome Time Frame
Single arm treatment: Up to 20 weeks; Crossover treatment: Up to 45 weeks
Outcome Measure
Monthly Infusion Time Per Participant at Full Dose With Both TAK-881 and HYQVIA
Outcome Description
Number of infusion sites per infusion at full dose was calculated as the total number of full dose infusion sites divided by the total number of full dose infusions with an available infusion site. A single aggregate value was therefore presented; a measure of dispersion was not applicable.
Outcome Time Frame
Single arm treatment: Up to 20 weeks; Crossover treatment: Up to 45 weeks
Outcome Measure
Number of Infusion Sites (Needle Sticks) Per Infusion at Full Dose With Both TAK-881 and HYQVIA
Outcome Description
Number of infusion sites per month at full dose was calculated as the total number of full dose infusion sites divided by the total time in months on treatment. A single aggregate value was therefore presented; a measure of dispersion was not applicable.
Outcome Time Frame
Single arm treatment: Up to 20 weeks; Crossover treatment: Up to 45 weeks
Outcome Measure
Number of Infusion Sites (Needle Sticks) Per Month at Full Dose With Both TAK-881 and HYQVIA in All Participant
Outcome Description
The maximum tolerated infusion rate at full dose was reported for rHuPH20 and IgG.
Outcome Time Frame
Single arm treatment: Up to 20 weeks; Crossover treatment: Up to 45 weeks
Outcome Measure
Maximum Tolerated Infusion Rate Per Site at Full Dose With Both TAK-881 and HYQVIA
Outcome Description
Infusion volume per site at full dose was reported for rHuPH20 and IgG. Infusion volume was measured in milliliters (mL), and infusion volume per site was reported in terms of mL per site per participant. For each participant, the average infusion volume per site was calculated; participant-level averages were then summarized using median and full range.
Outcome Time Frame
Single arm treatment: Up to 20 weeks; Crossover treatment: Up to 45 weeks
Outcome Measure
Infusion Volume Per Site Per Participant at Full Dose With Both TAK-881 and HYQVIA
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
2
Investigators
Investigator Type
Principal Investigator
Investigator Name
Arye Rubinstein
Investigator Email
arye.rubinstein@einsteinmed.edu
Investigator Department
Pediatrics
Investigator Division
Pediatric Allergy & Immunology
Investigator Sponsor Organization
External
Study Department
Pediatrics
Study Division
Pediatrics Allergy & Immunology
Categories Mesh Debug
Immune System --- IMMUNE SYSTEM DISEASES
MeSH Terms
PRIMARY IMMUNODEFICIENCY DISEASES
GENETIC DISEASES, INBORN
CONGENITAL, HEREDITARY, AND NEONATAL DISEASES AND ABNORMALITIES
IMMUNOLOGIC DEFICIENCY SYNDROMES
IMMUNE SYSTEM DISEASES
GAMMA-GLOBULINS
SOLUTIONS
IMMUNOGLOBULINS
IMMUNOPROTEINS
BLOOD PROTEINS
PROTEINS
AMINO ACIDS, PEPTIDES, AND PROTEINS
SERUM GLOBULINS
GLOBULINS
PHARMACEUTICAL PREPARATIONS