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

Phase 2
Recruiting
Conditions
Warm Autoimmune Hemolytic Anemia
Interventions
Drug: Placebo
Registration Number
NCT04119050
Lead Sponsor
Janssen Research & Development, LLC
Brief Summary

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

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
111
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
M281 administered every 4 weeks (double-blind period)M281Participants will receive M281 administered every 4 weeks alternating with placebo every 4 weeks during the 24 weeks double-blind period.
M281 administered every 4 weeks (double-blind period)PlaceboParticipants will receive M281 administered every 4 weeks alternating with placebo every 4 weeks during the 24 weeks double-blind period.
M281 administered every 2 weeks (double-blind period)M281Participants will receive M281 administered every 2 weeks during the 24 weeks double-blind period.
Placebo administered every 2 weeks (double-blind period)PlaceboParticipants will receive M281 matching placebo administered every 2 weeks during the 24 weeks double-blind period.
M281 administered every 4 weeks (open-label extension period)M281Participants will receive M281 administered every 4 weeks during the 144 weeks open-label extension period.
M281 administered every 2 weeks (open-label extension period)M281Participants will receive M281 administered every 2 weeks during the 144 weeks open-label extension period.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Achieving Durable Response of Improvement in Hemoglobin (Hgb)Up to Week 20 of the double-blind period
Secondary Outcome Measures
NameTimeMethod
Change From Baseline in the Total Score From the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale at the Time of Durable ResponseBaseline (Day 1, Week 0) through 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.

Number of Participants That Simultaneously Attain Normal Lactate Dehydrogenase, Haptoglobin, and Indirect Bilirubin Levels at a Minimum of 3 Consecutive Visits After BaselineBaseline (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)Baseline (Day 1, Week 0) through Week 24 of the double-blind period

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.

Time to Hgb ResponseBaseline (Day 1, Week 0) through Week 24
Change from Baseline in Average Daily Dose of Prednisone or EquivalentBaseline (Day 1, Week 0) and at Week 24

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.

Change From Baseline in Reticulocyte CountBaseline (Day 1, Week 0) through Week 24
Change From Baseline in Hemolytic Marker - HaptoglobinBaseline (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 StudyBaseline (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 VisitsBaseline (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 TherapyUp to 24 weeks

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.

Change From Baseline in Hemolytic Marker - Lactate DehydrogenaseBaseline (Day 1, Week 0) through Week 24
Mean Time During Which the Primary Endpoint is MaintainedBaseline (Day 1, Week 0) through Week 24
Change From Baseline in Hgb ConcentrationBaseline (Day 1, Week 0) through Week 24
Change From Baseline in Hemolytic Marker - Indirect BilirubinBaseline (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 ScaleBaseline (Day 1, Week 0) through Week 24 of the double-blind period

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.

Absolute Change from Baseline in Average Daily Dose of Prednisone or EquivalentBaseline (Day 1, Week 0) and at Week 24

Absolute change from baseline in average daily dose of prednisone or equivalent at Week 24 among all participants will be reported.

Change From Baseline in EuroQol 5-dimension 5-level ( EQ-5D-5L) Scale ScoreBaseline (Day 1, Week 0) through Week 24

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).

Hgb Range at Steady StateBaseline (Day 1, Week 0) through Week 24

It will be estimated using a model-based longitudinal analysis of Hgb/hemolysis parameters in relationship to IgG level and dose regimen.

Change From Baseline in Medical Outcomes Study Short Form 36 Item Health Survey Version 2 Acute (SF-36v2) ScoreBaseline (Day 1, Week 0) through Week 24

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.

Patient-reported Status As Assessed by Patient Global Impression of Change (PGIC) Scale ScoreAt Week 24

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.

Change From Baseline in Patient Global Impression of Severity (PGIS)Baseline (Day 1, Week 0) through Week 24

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.

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 BaselineAt Week 24

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.

Trial Locations

Locations (171)

MemorialCare Medical Group

🇺🇸

Fountain Valley, California, United States

University of Southern California

🇺🇸

Los Angeles, California, United States

Compassionate Cancer Care

🇺🇸

Riverside, California, United States

American Institute of Research

🇺🇸

Whittier, California, United States

University of Colorado Anschutz Medical Campus

🇺🇸

Aurora, Colorado, United States

GNP Research

🇺🇸

Cooper City, Florida, United States

University of Florida College of Medicine

🇺🇸

Gainesville, Florida, United States

21st Century Oncology

🇺🇸

Jacksonville, Florida, United States

Lakes Research

🇺🇸

Miami Lakes, Florida, United States

AdventHealth Cancer Institute

🇺🇸

Orlando, Florida, United States

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MemorialCare Medical Group
🇺🇸Fountain Valley, California, United States

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