Brief Summary
The purpose of the study is to find out if iptacopan is effective and safe in adult patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) who switch from their current standard of care treatment (eculizumab or ravulizumab) to study treatment, iptacopan/LNP023.
Brief Title
Single Arm, Open Label Trial With Iptacopan Treatment for 24 Weeks, in Patients on Stable Regimen of Anti-C5 Who Switch to Iptacopan.
Detailed Description
This is a multicenter, single-arm, open label trial, with iptacopan treatment for 24 weeks in adult PNH patients.
This study is comprised of two periods:
* A Screening period lasting up to 8 weeks.
* A 24-week open-label, iptacopan Treatment period.
After completion of the treatment period, participants who continue to benefit from the iptacopan treatment based on the study doctor's evaluation will be able to join the Roll-over extension study.
This study is comprised of two periods:
* A Screening period lasting up to 8 weeks.
* A 24-week open-label, iptacopan Treatment period.
After completion of the treatment period, participants who continue to benefit from the iptacopan treatment based on the study doctor's evaluation will be able to join the Roll-over extension study.
Completion Date
Completion Date Type
Actual
Conditions
Paroxysmal Nocturnal Hemoglobinuria
Eligibility Criteria
Inclusion Criteria:
* Signed informed consent must be obtained prior to participation in the study.
* Male and female participants ≥ 18 years of age, at the time of ICF signatures and with a diagnosis of PNH confirmed by treating physician.
* Stable regimen (dose and intervals) of anti-C5 antibody treatment (either eculizumab or ravulizumab) for at least 6 months prior to screening
* Mean hemoglobin level ≥10 g/dL
* Vaccination against Neisseria meningitidis and S. pneumoniae infection are required prior to the start of iptacopan treatment.
* If not received previously, vaccination against Haemophilus influenzae infections is recommended, if available and according to local regulations.
* Ability to communicate well with the investigator, to understand and comply with the requirements of the study
* Other protocol -defined inclusion criteria may apply at the end.
Exclusion Criteria:
* Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment
* Patients requiring red blood cell transfusion in the 6 months prior to screening or during screening
* History of stem cell transplantation or any solid organ transplantation
* Active systemic bacterial, viral (incl. COVID-19) or fungal infection within 14 days prior to study drug administration
* Presence of fever ≥ 38.0 °C (100.4 °F) within 7 days prior to study drug administration
* Human immunodeficiency virus (HIV) infection (known history of HIV or test positive for HIV antibody at Screening)
* A history of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus
* Unstable medical condition including, but not limited to, myocardial ischemia, active gastrointestinal bleeding, coexisting chronic anemia unrelated to PNH, or unstable thrombotic event not amenable to active treatment as judged by the investigator at Screening.
* History of cancer of any part of the body within the past 5 years,
* Ongoing drug or alcohol abuse that could interfere with patient's participation in the trial.
* Any medical condition deemed likely to interfere with the patient's participation in the study
* Female patients who are pregnant or breastfeeding, or intending to conceive during the course of the study
* Signed informed consent must be obtained prior to participation in the study.
* Male and female participants ≥ 18 years of age, at the time of ICF signatures and with a diagnosis of PNH confirmed by treating physician.
* Stable regimen (dose and intervals) of anti-C5 antibody treatment (either eculizumab or ravulizumab) for at least 6 months prior to screening
* Mean hemoglobin level ≥10 g/dL
* Vaccination against Neisseria meningitidis and S. pneumoniae infection are required prior to the start of iptacopan treatment.
* If not received previously, vaccination against Haemophilus influenzae infections is recommended, if available and according to local regulations.
* Ability to communicate well with the investigator, to understand and comply with the requirements of the study
* Other protocol -defined inclusion criteria may apply at the end.
Exclusion Criteria:
* Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment
* Patients requiring red blood cell transfusion in the 6 months prior to screening or during screening
* History of stem cell transplantation or any solid organ transplantation
* Active systemic bacterial, viral (incl. COVID-19) or fungal infection within 14 days prior to study drug administration
* Presence of fever ≥ 38.0 °C (100.4 °F) within 7 days prior to study drug administration
* Human immunodeficiency virus (HIV) infection (known history of HIV or test positive for HIV antibody at Screening)
* A history of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus
* Unstable medical condition including, but not limited to, myocardial ischemia, active gastrointestinal bleeding, coexisting chronic anemia unrelated to PNH, or unstable thrombotic event not amenable to active treatment as judged by the investigator at Screening.
* History of cancer of any part of the body within the past 5 years,
* Ongoing drug or alcohol abuse that could interfere with patient's participation in the trial.
* Any medical condition deemed likely to interfere with the patient's participation in the study
* Female patients who are pregnant or breastfeeding, or intending to conceive during the course of the study
Inclusion Criteria
Inclusion Criteria:
* Signed informed consent must be obtained prior to participation in the study.
* Male and female participants ≥ 18 years of age, at the time of ICF signatures and with a diagnosis of PNH confirmed by treating physician.
* Stable regimen (dose and intervals) of anti-C5 antibody treatment (either eculizumab or ravulizumab) for at least 6 months prior to screening
* Mean hemoglobin level ≥10 g/dL
* Vaccination against Neisseria meningitidis and S. pneumoniae infection are required prior to the start of iptacopan treatment.
* If not received previously, vaccination against Haemophilus influenzae infections is recommended, if available and according to local regulations.
* Ability to communicate well with the investigator, to understand and comply with the requirements of the study
* Other protocol -defined inclusion criteria may apply at the end.
* Signed informed consent must be obtained prior to participation in the study.
* Male and female participants ≥ 18 years of age, at the time of ICF signatures and with a diagnosis of PNH confirmed by treating physician.
* Stable regimen (dose and intervals) of anti-C5 antibody treatment (either eculizumab or ravulizumab) for at least 6 months prior to screening
* Mean hemoglobin level ≥10 g/dL
* Vaccination against Neisseria meningitidis and S. pneumoniae infection are required prior to the start of iptacopan treatment.
* If not received previously, vaccination against Haemophilus influenzae infections is recommended, if available and according to local regulations.
* Ability to communicate well with the investigator, to understand and comply with the requirements of the study
* Other protocol -defined inclusion criteria may apply at the end.
Gender
All
Gender Based
false
Keywords
Paroxysmal Nocturnal Hemoglobinuria
iptacopan
single arm open-label
Hb≥10 g/dL in response to anti-C5 antibody
switch to iptacopan
PNH
LNP023
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
100 Years
Minimum Age
18 Years
NCT Id
NCT05630001
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CLNP023C12303
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Multicenter, Single Arm, Open-label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily Iptacopan in Adult PNH Patients Who Have Hb≥10 g/dL in Response to Anti-C5 Antibody and Switch to Iptacopan
Primary Outcomes
Outcome Description
To assess the efficacy of iptacopan after 24 weeks of treatment in PNH patients who switch to iptacopan from prior SoC
Outcome Measure
Change from baseline in Hb levels to demonstrate non-inferiority of iptacopan
Outcome Time Frame
Up to 168 days
Secondary Ids
Secondary Id
2022-502148-10-00
Secondary Outcomes
Outcome Description
To assess efficacy of iptacopan after 24 weeks of treatment in PNH patients who switch to iptacopan from prior SoC
Outcome Time Frame
Up to 168 days
Outcome Measure
Change in Hb levels to demonstrate superiority of iptacopan
Outcome Description
Percentage of hematological responders to iptacopan treatment will be collected
Outcome Time Frame
Up to 168 days
Outcome Measure
Percentage of hematological responders to iptacopan treatment
Outcome Description
To assess the effect of iptacopan on markers of Extravascular Hemolysis (EVH) and Intravascular Hemolysis (IVH).
Outcome Time Frame
Up to 168 days
Outcome Measure
Change from baseline in Absolute Reticulocytes count (ARC) levels
Outcome Description
To assess the effect of iptacopan on markers of EVH and IVH.
Outcome Time Frame
Up to 168 days
Outcome Measure
Percentage change from baseline in lactate dehydrogenase (LDH) levels
Outcome Description
TSQM-9 is a patient reported outcomes measure that was designed to assess patients' satisfaction with medication across three domains of effectiveness, convenience and global satisfaction. The TSQM-9 contains 3 questions in each domain. Domain scores range from 0 - 100 with higher representing better scores for the domain.
Outcome Time Frame
Up to 168 days
Outcome Measure
Change in treatment satisfaction score using TSQM-9 questionnaire
Outcome Description
The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. All FACIT scales are scored so that a high score is better. As each of the 13 items of the FACIT-Fatigue scale ranges from 0-4, the range of possible scores is 0-52, with 0 being the worst possible score and 52 the best.
Outcome Time Frame
Up to 168 days
Outcome Measure
Change in fatigue score using FACIT-F questionnaire
Outcome Description
Occurrence of BTH reported from D1 to D168
Outcome Time Frame
24 weeks
Outcome Measure
Rate of Breakthrough hemolysis (BTH)
Outcome Description
Occurrence of MAVEs reported from D1 to D168
Outcome Time Frame
24 weeks
Outcome Measure
Rate of Major Adverse Vascular Events (MAVEs)
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
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
100
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Irina Murakhovskaya
Investigator Email
imurakho@montefiore.org
Investigator Phone
IMURAKHO