Study of the Efficacy and Safety of Parsaclisib in Participants With Primary Warm Autoimmune Hemolytic Anemia

Study Overview
=================
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),

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.

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

Conditions
-----------------
Warm Autoimmune Hemolytic Anemia (wAIHA)

Intervention / Treatment
-----------------
* Drug: parsaclisinib
* Drug: placebo


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A: Parsaclisib<br>Participants will receive parsaclisib for 24 weeks (double-blind period). Participant who completed the double-blind period and tolerating the study treatment upon investigator's opinion will continue into open-label period for an additional 24 weeks. Participants may then continue to receive parsaclisib in a long-term extension period. | Drug: parsaclisinib<br>* parsaclisib will be administered QD orally<br>* Other names: INCB050465;|
| Placebo Comparator: Group B: Placebo followed by Parsaclisib<br>Participants will receive placebo for 24 weeks (double-blind period). Participants who completed the double-blind period will receive parsaclisib in the 24 week open-label period. Participants may then continue to receive parsaclisib in a long-term extension period. | Drug: placebo<br>* placebo will be administered QD orally follwed by Parsaclisinib in the open label period<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants attaining a durable hemoglobin response | Proportion of participants attaining a durable hemoglobin response, defined as hemoglobin ≥ 10 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. | Up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with a ≥ 3-point increase in FACIT-F score | Increase is measured by Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire. 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. | Up to Week 24 | 
| Proportion of participants with a 50 m increase in a 6MWT | Defined as an increase of 50 m using the Six-minute walk test, a self-paced measurement of the distance that a participant can quickly walk on a flat, hard surface in a period of 6 minutes. | Up to Week 24 | 
| Change in FACIT-F score | Change will be measured by Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire. 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. | Up to 3 years | 
| Percent Change in FACIT-F | will be measured by Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire. 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. | Up to 3 years | 
| Change in hemoglobin | Changes will be measured and compared in the hematology panel. | Up to 3 years | 
| Percentage change in hemoglobin | Percentage change will be measured and compared in the hematology panel. | Up to 3 years | 
| Proportion of participants who received transfusions | Proportion of participants who received transfusions. | Up to 48 weeks | 
| Change in corticosteroid dose from baseline | Change from baseline of daily corticosteroids dose | Up to Week 24 | 
| Percentage change from baseline in daily corticosteroid dose | Percentage change from baseline of daily corticosteroids dose | Up to Week 24 | 
| Proportion of participants who required rescue therapy at any visit | Rescue therapy will include new/increased dose of corticosteroids, transfusions, intravenous immunoglobulin (IVIG), and Erythropoietin. | Up to 48 weeks | 
| Number of Participants with Treatment Emergent Adverse Events (TEAE) | Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug. | Up to 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Warm Autoimmune Hemolytic Anemia (wAIHA)