Brief Summary
The purpose of this study is to evaluate the efficacy and safety of parsaclisib compared with placebo in participants with Primary Warm Autoimmune Hemolytic Anemia (wAIHA),
Brief Title
Study of the Efficacy and Safety of Parsaclisib in Participants With Primary Warm Autoimmune Hemolytic Anemia
Detailed Description
Prospective participants must have primary wAIHA as well as other protocol-defined criteria. After participants have been determined to be eligible for the study, they will be randomized to 2:1, with stratification factor of corticosteroid dose and hemoglobin (Hgb \<9 g/dL or ≥ 9 g/dL). Once a participant has completed the week 24 assessments in the double-blind period, the participant will have the opportunity to receive parsaclisib in the open-label treatment which will last up to another 24 weeks. Participants may then continue to receive parsaclisib in a long-term extension period.
Completion Date
Completion Date Type
Actual
Conditions
Warm Autoimmune Hemolytic Anemia (wAIHA)
Eligibility Criteria
Inclusion Criteria:
* Diagnosis of primary warm AIHA.
* Participants who have at least 1 unsuccessful prior therapy for warm AIHA or unable to receive or tolerate other therapies.
* Hemoglobin ≥ 6.5 to \< 10 g/dL with symptoms of anemia at screening.
* FACIT-F score ≤ 43 at screening.
* Willingness to avoid pregnancy or fathering children.
* Willingness to receive PJP prophylaxis.
* Further inclusion criteria apply.
Exclusion Criteria:
* Women who are pregnant, breastfeeding or who are planning a pregnancy.
* Diagnosis of other types of AIHA (CAD, cold agglutinin syndrome, mixed-type AIHA or paroxysmal cold hemoglobinuria).
* Secondary warm AIHA from any cause or diagnosis of Evans syndrome.
* Splenectomy less than 3 months before randomization.
* Participants with a history or ongoing significant illness as assessed by the investigator.
* Participants with a current of medical history of a malignancy within the past 5 years except basal or squamous cell skin cancer that has been removed and considered cured, or superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy.
* Participants know to be infected with HIV, Hepatitis B, or hepatitis C.
* Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment or exposure to a live vaccine.
* Participants with laboratory values outside of the protocol defined ranges.
* Further exclusion criteria apply.
* Diagnosis of primary warm AIHA.
* Participants who have at least 1 unsuccessful prior therapy for warm AIHA or unable to receive or tolerate other therapies.
* Hemoglobin ≥ 6.5 to \< 10 g/dL with symptoms of anemia at screening.
* FACIT-F score ≤ 43 at screening.
* Willingness to avoid pregnancy or fathering children.
* Willingness to receive PJP prophylaxis.
* Further inclusion criteria apply.
Exclusion Criteria:
* Women who are pregnant, breastfeeding or who are planning a pregnancy.
* Diagnosis of other types of AIHA (CAD, cold agglutinin syndrome, mixed-type AIHA or paroxysmal cold hemoglobinuria).
* Secondary warm AIHA from any cause or diagnosis of Evans syndrome.
* Splenectomy less than 3 months before randomization.
* Participants with a history or ongoing significant illness as assessed by the investigator.
* Participants with a current of medical history of a malignancy within the past 5 years except basal or squamous cell skin cancer that has been removed and considered cured, or superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy.
* Participants know to be infected with HIV, Hepatitis B, or hepatitis C.
* Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment or exposure to a live vaccine.
* Participants with laboratory values outside of the protocol defined ranges.
* Further exclusion criteria apply.
Inclusion Criteria
Inclusion Criteria:
* Diagnosis of primary warm AIHA.
* Participants who have at least 1 unsuccessful prior therapy for warm AIHA or unable to receive or tolerate other therapies.
* Hemoglobin ≥ 6.5 to \< 10 g/dL with symptoms of anemia at screening.
* FACIT-F score ≤ 43 at screening.
* Willingness to avoid pregnancy or fathering children.
* Willingness to receive PJP prophylaxis.
* Further inclusion criteria apply.
* Diagnosis of primary warm AIHA.
* Participants who have at least 1 unsuccessful prior therapy for warm AIHA or unable to receive or tolerate other therapies.
* Hemoglobin ≥ 6.5 to \< 10 g/dL with symptoms of anemia at screening.
* FACIT-F score ≤ 43 at screening.
* Willingness to avoid pregnancy or fathering children.
* Willingness to receive PJP prophylaxis.
* Further inclusion criteria apply.
Gender
All
Gender Based
false
Keywords
Warm Autoimmune Hemolytic Anemia (wAIHA)
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
99 Years
Minimum Age
18 Years
NCT Id
NCT05073458
Org Class
Industry
Org Full Name
Incyte Corporation
Org Study Id
INCB 50465-309
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Parsaclisib in Participants With Primary Warm Autoimmune Hemolytic Anemia
Primary Outcomes
Outcome Description
A durable hemoglobin response was defined as hemoglobin ≥10 grams per deciliter (g/dL) with an increase from Baseline of ≥2 g/dL not attributed to rescue therapy at ≥3 of the 4 available visits at Week 12 and/or later during the 24-week double-blind treatment period.
Outcome Measure
Percentage of Participants Attaining a Durable Hemoglobin Response
Outcome Time Frame
up to Week 24
Secondary Outcomes
Outcome Description
The FACIT-F scale was developed to assess anemia-related fatigue. The FACIT-F is a 13-item measure that assesses self-reported fatigue and its impact upon daily activities and function over the past 7 days. A clinically meaningful change in the FACIT-F score was defined as ≥3-point increase from Baseline. Item scores range from 0 ("not at all") to 4 ("very much"), and the total score ranges from 0 to 52; lower scores indicate greater fatigue. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Outcome Time Frame
Baseline; Week 24
Outcome Measure
Percentage of Participants With a ≥3-point Increase From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Week 24
Outcome Description
The 6MWT is used to evaluate submaximal exercise capacity. It is a self-paced measurement of the distance that a participant can quickly walk on a flat, hard surface in a period of 6 minutes.
Outcome Time Frame
Baseline; Week 24
Outcome Measure
Percentage of Participants With a 50 Meter Increase From Baseline to Week 24 in a 6-minute Walk Test (6MWT)
Outcome Description
The FACIT-F scale was developed to assess anemia-related fatigue. The FACIT-F is a 13-item measure that assesses self-reported fatigue and its impact upon daily activities and function over the past 7 days. A clinically meaningful change in the FACIT-F score was defined as ≥3-point increase from Baseline. Item scores range from 0 ("not at all") to 4 ("very much"), and the total score ranges from 0 to 52; lower scores indicate greater fatigue. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. End of Treatment, Double-blind Period: assessment performed for participants who discontinued treatment before Week 24. End of Treatment, Open-label Period: assessment performed for participants who discontinued treatment after Week 24 and before Week 56. Follow-up Visit 3 occurred 12 weeks after the end of treatment visit.
Outcome Time Frame
Baseline; Day 1; Weeks 8, 12, 16, 20, 24, 28, 32, 40, 48, 56, and every 16 weeks post-Week 56
Outcome Measure
Change From Baseline in the FACIT-F Score at Each Post-Baseline Visit
Outcome Description
The FACIT-F scale was developed to assess anemia-related fatigue. The FACIT-F is a 13-item measure that assesses self-reported fatigue and its impact upon daily activities and function over the past 7 days. A clinically meaningful change in the FACIT-F score was defined as ≥3-point increase from Baseline. Item scores range from 0 ("not at all") to 4 ("very much"), and the total score ranges from 0 to 52; lower scores indicate greater fatigue. Percentage change from Baseline was calculated as (\[the post-Baseline value minus the Baseline value\]/Baseline value) x 100. End of Treatment, Double-blind Period: assessment performed for participants who discontinued treatment before Week 24. End of Treatment, Open-label Period: assessment performed for participants who discontinued treatment after Week 24 and before Week 56. Follow-up Visit 3 occurred 12 weeks after the end of treatment visit.
Outcome Time Frame
Baseline; Day 1; Weeks 8, 12, 16, 20, 24, 28, 32, 40, 48, 56, and every 16 weeks post-Week 56
Outcome Measure
Percentage Change From Baseline in the FACIT-F Score at Each Post-Baseline Visit
Outcome Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. End of Treatment, Double-blind Period: assessment performed for participants who discontinued treatment before Week 24. End of Treatment, Open-label Period: assessment performed for participants who discontinued treatment after Week 24 and before Week 56. Follow-up Visits 1, 2, and 3 occurred 4, 8, and 12 weeks, respectively, after the end of treatment visit.
Outcome Time Frame
Baseline; Day 1; Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, and every 8 weeks post-Week 56
Outcome Measure
Change From Baseline in Hemoglobin at Each Post-Baseline Visit
Outcome Description
Percentage change from Baseline was calculated as (\[the post-Baseline value minus the Baseline value\]/Baseline value) x 100. End of Treatment, Double-blind Period: assessment performed for participants who discontinued treatment before Week 24. End of Treatment, Open-label Period: assessment performed for participants who discontinued treatment after Week 24 and before Week 56. Follow-up Visits 1, 2, and 3 occurred 4, 8, and 12 weeks, respectively, after the end of treatment visit.
Outcome Time Frame
Baseline; Day 1; Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, and every 8 weeks post-Week 56
Outcome Measure
Percentage Change From Baseline in Hemoglobin at Each Post-Baseline Visit
Outcome Description
Transfusion was permitted as a rescue treatment. Rescue medication was to be considered if the absolute hemoglobin level continued to decline, there was a \> 1 g/dL decrease in hemoglobin from the prior assessment, or the participant developed new or worsening symptoms of warm autoimmune hemolytic anemia (wAIHA).
Outcome Time Frame
Week 6 to Week 24; Week 24 to Week 48
Outcome Measure
Percentage of Participants Who Received Transfusions From Week 6 to Week 24 and From Week 24 to Week 48
Outcome Description
A new or increased dose of corticosteroids (prednisone or equivalent) from the Day 1 dose was permitted as rescue treatment. Rescue medication was to be considered if the absolute hemoglobin level continued to decline, there was a \> 1 g/dL decrease in hemoglobin from the prior assessment, or the participant developed new or worsening symptoms of wAIHA. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Outcome Time Frame
Baseline; Week 24
Outcome Measure
Change From Baseline in Daily Corticosteroid Dose at Week 24
Outcome Description
A new or increased dose of corticosteroids (prednisone or equivalent) from the Day 1 dose was permitted as rescue treatment. Rescue medication was to be considered if the absolute hemoglobin level continued to decline, there was a \> 1 g/dL decrease in hemoglobin from the prior assessment, or the participant developed new or worsening symptoms of wAIHA. Percentage change from Baseline was calculated as (\[the post-Baseline value minus the Baseline value\]/Baseline value) x 100.
Outcome Time Frame
Baseline; Week 24
Outcome Measure
Percentage Change From Baseline in Daily Corticosteroid Dose at Week 24
Outcome Description
Rescue medication was to be considered if the absolute hemoglobin level continued to decline, there was a \> 1 g/dL decrease in hemoglobin from the prior assessment, or the participant developed new or worsening symptoms of wAIHA.
Outcome Time Frame
Week 6 to Week 24; Week 24 to Week 48
Outcome Measure
Percentage of Participants Who Required Rescue Therapy at Any Visit From Week 6 Through Week 24, and From Week 24 to Week 48
Outcome Description
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. An AE could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. TEAEs were defined as AEs reported for the first time or the worsening of pre-existing events after the first dose of study drug.
Outcome Time Frame
up to 446 days
Outcome Measure
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Outcome Description
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. TEAEs were defined as AEs reported for the first time or the worsening of pre-existing events after the first dose of study drug. The severity of AEs were assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grades 1 through 5. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.
Outcome Time Frame
up to 446 days
Outcome Measure
Number of Participants With Any ≥Grade 3 TEAE
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)
99
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