Efficacy and Safety of M281 in Adults With Warm Autoimmune Hemolytic Anemia

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the efficacy and safety of M281 in participants with warm autoimmune hemolytic anemia (wAIHA).

Detailed Description
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The study consists of a 24-week double-blind, placebo control period, a 144-week open-label extension period and follow-up period of 8 weeks after last study drug administration. Eligible participants will be randomized to placebo or nipocalimab (2 dose levels) during the double-blind period and nipocalimab (2 dose levels) during the open-label extension period.

Official Title
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Efficacy and Safety of M281 in Adults With Warm Autoimmune Hemolytic Anemia: A Multicenter, Randomized, Double-blind, Placebo-controlled Study With a Long-term Open-label Extension

Conditions
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Warm Autoimmune Hemolytic Anemia

Intervention / Treatment
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* Drug: M281
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Participants greater than or equal to (>=)18 years of age Have been diagnosed with warm autoimmune hemolytic anemia (wAIHA) for at least 3 months, and are currently receiving treatment for wAIHA or have previously received treatment for wAIHA (treatment-naive participants are not eligible) Participants must be able to understand and voluntarily provide written informed consent to participate in the study and comply with all study procedures Exclusion criteria: Participants must not be pregnant or breastfeeding Participants must not have other clinically relevant abnormalities currently or in their history that the Investigator would deem them ineligible to participate Have been diagnosed with cold antibody autoimmune hemolytic anemia (AIHA), cold agglutinin syndrome, mixed type (that is, warm and cold) AIHA, or paroxysmal cold hemoglobinuria

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M281 administered every 4 weeks (double-blind period)<br>Participants will receive M281 administered every 4 weeks alternating with placebo every 4 weeks during the 24 weeks double-blind period. | Drug: M281<br>* M281 injection administered as intravenous infusion<br>* Other names: Nipocalimab, JNJ-80202135;Drug: Placebo<br>* Placebo administered as intravenous infusion<br>|
| Experimental: M281 administered every 2 weeks (double-blind period)<br>Participants will receive M281 administered every 2 weeks during the 24 weeks double-blind period. | Drug: M281<br>* M281 injection administered as intravenous infusion<br>* Other names: Nipocalimab, JNJ-80202135;|
| Experimental: Placebo administered every 2 weeks (double-blind period)<br>Participants will receive M281 matching placebo administered every 2 weeks during the 24 weeks double-blind period. | Drug: Placebo<br>* Placebo administered as intravenous infusion<br>|
| Experimental: M281 administered every 4 weeks (open-label extension period)<br>Participants will receive M281 administered every 4 weeks during the 144 weeks open-label extension period. | Drug: M281<br>* M281 injection administered as intravenous infusion<br>* Other names: Nipocalimab, JNJ-80202135;|
| Experimental: M281 administered every 2 weeks (open-label extension period)<br>Participants will receive M281 administered every 2 weeks during the 144 weeks open-label extension period. | Drug: M281<br>* M281 injection administered as intravenous infusion<br>* Other names: Nipocalimab, JNJ-80202135;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Durable Response of Improvement in Hemoglobin (Hgb) |  | Up to Week 20 of the double-blind period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Total Score From the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale at the Time of Durable Response | The FACIT-Fatigue is a self-administered 13-item questionnaire that assess patient-reported fatigue associated with chronic illness therapy. It assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement. | Baseline (Day 1, Week 0) through Week 24 | 
| Change From Baseline in the Total Score From the FACIT-Fatigue Scale at the end of the Double-blind Period (Week 24) | The FACIT-Fatigue is a self-administered 13-item questionnaire that assess patient-reported fatigue associated with chronic illness therapy. It assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement. | Baseline (Day 1, Week 0) through Week 24 of the double-blind period | 
| Change from Baseline in Average Daily Dose of Prednisone or Equivalent | Change from baseline in average daily dose of prednisone or equivalent at week 24 among participants on prednisone or equivalent at baseline will be reported. | Baseline (Day 1, Week 0) and at Week 24 | 
| Number of Participants That Simultaneously Attain Normal Lactate Dehydrogenase, Haptoglobin, and Indirect Bilirubin Levels at a Minimum of 3 Consecutive Visits After Baseline |  | Baseline (Day 1, Week 0) through Week 24 | 
| Percentage of Participants who Experience at Least a 2 g/dL Increase in Hgb From Baseline and Normalization of Lactate Dehydrogenase, Haptoglobin, and Indirect Bilirubin at any Time During the Study |  | Baseline (Day 1, Week 0) through Week 24 | 
| Percentage of Participants who Experience at Least a 2 g/dL Increase in Hgb From Baseline and Normalization of Lactate Dehydrogenase, Haptoglobin, and Indirect Bilirubin at 3 Consecutive Visits |  | Baseline (Day 1, Week 0) through Week 24 | 
| Percentage of Participants who Achieve the Durable Response in Improvement of Hgb During the Double-blind Period and Maintain that Response for Up to 24 Weeks, Without the Need of Rescue Therapy | Percentage of participants who achieve the durable response in improvement of Hgb during the double-blind period and maintain that response for up to 24 weeks, without the need of rescue therapy will be reported. | Up to 24 weeks | 
| Change From Baseline in Hgb Concentration |  | Baseline (Day 1, Week 0) through Week 24 | 
| Change From Baseline in Reticulocyte Count |  | Baseline (Day 1, Week 0) through Week 24 | 
| Change From Baseline in Hemolytic Marker - Lactate Dehydrogenase |  | Baseline (Day 1, Week 0) through Week 24 | 
| Change From Baseline in Hemolytic Marker - Haptoglobin |  | Baseline (Day 1, Week 0) through Week 24 | 
| Change From Baseline in Hemolytic Marker - Indirect Bilirubin |  | Baseline (Day 1, Week 0) through Week 24 | 
| Time to Hgb Response |  | Baseline (Day 1, Week 0) through Week 24 | 
| Mean Time During Which the Primary Endpoint is Maintained |  | Baseline (Day 1, Week 0) through Week 24 | 
| Change From Baseline in the Total Score, Item Scores, and Impact and Experience Domains From the FACIT-Fatigue Scale | The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement. | Baseline (Day 1, Week 0) through Week 24 of the double-blind period | 
| Change From Baseline in EuroQol 5-dimension 5-level ( EQ-5D-5L) Scale Score | The EQ-5D-5L quality of life questionnaire will be used to assess health related quality of life status. The 5 dimensions are mobility, self-care, usual activities, pain/discomfort, and anxiety/depression; each dimension is rated by the patient on a 5 level scale (no problems, slight problems, moderate problems, severe problems, extreme problems). | Baseline (Day 1, Week 0) through Week 24 | 
| Change From Baseline in Medical Outcomes Study Short Form 36 Item Health Survey Version 2 Acute (SF-36v2) Score | The SF-36v2 will be used to assess general quality of life. The 36 items on the SF-36 health survey encompass the following 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The 8 domains can be aggregated into 2 summary scales that reflect physical and mental health: a physical component summary (PCS) and a mental component summary (MCS). Responses to all items are rated on a 3-, 5- or 6-point Likert scale. Higher scores indicate a higher level of functioning. A positive change from baseline score indicates an improvement. | Baseline (Day 1, Week 0) through Week 24 | 
| Change From Baseline in Patient Global Impression of Severity (PGIS) | The PGIS will be used to assess the severity of warm autoimmune hemolytic anemia (wAIHA) fatigue symptoms. The PGIS is a 5-point response scale. Participant will be asked to rate their fatigue over the past 7 days using the following 5-point scale: 1 = None, 2 = Mild, 3 = Moderate, 4 = Severe, and 5 = Very severe. | Baseline (Day 1, Week 0) through Week 24 | 
| Patient-reported Status As Assessed by Patient Global Impression of Change (PGIC) Scale Score | The PGIC will assess if there has been an improvement or decline in patient-reported status since the beginning of the treatment. The PGIC is a 7-point response scale. Participants will be asked to rate their current fatigue as compared to when they started the study, using the following 7-point scale: 1 = Much better, 2 = Moderately better, 3 = A little better, 4 = No change, 5 = A little worse, 6 = Moderately worse, and 7 = Much worse. | At Week 24 | 
| Hgb Range at Steady State | It will be estimated using a model-based longitudinal analysis of Hgb/hemolysis parameters in relationship to IgG level and dose regimen. | Baseline (Day 1, Week 0) through Week 24 | 
| Absolute Change from Baseline in Average Daily Dose of Prednisone or Equivalent | Absolute change from baseline in average daily dose of prednisone or equivalent at Week 24 among all participants will be reported. | Baseline (Day 1, Week 0) and at Week 24 | 
| Percentage of participants who Achieve Corticosteroid Reduction to less than or equal to (<=) 7.5 milligrams per day (mg/day) of Oral Prednisone (or Equivalent), Among Participants with Prednisone or Equivalent greater than (>) 7.5 mg/day at Baseline | Percentage of participants who achieve corticosteroid reduction to <= 7.5 mg/day of oral prednisone (or equivalent) at Week 24 of the double-blind period, among participants with prednisone or equivalent >7.5 mg/day at baseline will be reported. | At Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Warm Autoimmune Hemolytic Anemia, M281 (Nipocalimab), wAIHA, JNJ-80202135