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

• ClinicalTrials.gov Identifier: NCT04119050
• Recruitment Status: Recruiting
• First Posted: October 8, 2019
• Last Update Posted: May 6, 2023
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: September 18, 2019
• First Posted Date: October 8, 2019
• Last Update Posted Date: May 6, 2023
• Actual Study Start Date: October 24, 2019
• Estimated Primary Completion Date: March 20, 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 20, 2022): Percentage of Participants Achieving Durable Response of Improvement in Hemoglobin (Hgb) [ Time Frame: Up to Week 20 of the double-blind period ]
• Original Primary Outcome Measures (submitted: October 4, 2019): Number of Participants That Attain Hemoglobin (Hgb) Response [ Time Frame: Up to Week 20 ]

Current Secondary Outcome Measures (submitted: September 16, 2022)

• 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 [ Time Frame: Baseline (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.
• Change From Baseline in the Total Score From the FACIT-Fatigue Scale at the end of the Double-blind Period (Week 24) [ Time Frame: 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.
• Change from Baseline in Average Daily Dose of Prednisone or Equivalent [ Time Frame: Baseline (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.
• Number of Participants That Simultaneously Attain Normal Lactate Dehydrogenase, Haptoglobin, and Indirect Bilirubin Levels at a Minimum of 3 Consecutive Visits After Baseline [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up 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 Hgb Concentration [ Time Frame: Baseline (Day 1, Week 0) through Week 24 ]
• Change From Baseline in Reticulocyte Count [ Time Frame: Baseline (Day 1, Week 0) through Week 24 ]
• Change From Baseline in Hemolytic Marker - Lactate Dehydrogenase [ Time Frame: Baseline (Day 1, Week 0) through Week 24 ]
• Change From Baseline in Hemolytic Marker - Haptoglobin [ Time Frame: Baseline (Day 1, Week 0) through Week 24 ]
• Change From Baseline in Hemolytic Marker - Indirect Bilirubin [ Time Frame: Baseline (Day 1, Week 0) through Week 24 ]
• Time to Hgb Response [ Time Frame: Baseline (Day 1, Week 0) through Week 24 ]
• Mean Time During Which the Primary Endpoint is Maintained [ Time Frame: 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 [ Time Frame: Baseline (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.
• Change From Baseline in EuroQol 5-dimension 5-level ( EQ-5D-5L) Scale Score [ Time Frame: Baseline (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).
• Change From Baseline in Medical Outcomes Study Short Form 36 Item Health Survey Version 2 Acute (SF-36v2) Score [ Time Frame: Baseline (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.
• Change From Baseline in Patient Global Impression of Severity (PGIS) [ Time Frame: 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.
• Patient-reported Status As Assessed by Patient Global Impression of Change (PGIC) Scale Score [ Time Frame: At 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.
• Hgb Range at Steady State [ Time Frame: Baseline (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.
• Absolute Change from Baseline in Average Daily Dose of Prednisone or Equivalent [ Time Frame: Baseline (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.
• 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 [ Time Frame: At 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.

Original Secondary Outcome Measures (submitted: October 4, 2019)

• Percentage of Participants That Achieve any Reduction in the Daily Dose of Corticosteroids While Maintaining Hgb Response [ Time Frame: Baseline (Day 1, Week 0) through 24 weeks ]
• Percent Reduction in Daily Corticosteroid Dose [ Time Frame: Baseline (Day 1, Week 0) through 24 weeks ]
• Hgb Range at Steady State [ Time Frame: Baseline (Day 1, Week 0) through 24 weeks ]
  It will be estimated using a model-based longitudinal analysis of Hgb/hemolysis parameters in relationship to IgG level and dose regimen.
• Percentage of Participants With Hgb Within the Normal Range for Their Gender [ Time Frame: Baseline (Day 1, Week 0) through Week 16 and Week 24 ]
• Change From Baseline in Hgb [ Time Frame: Baseline (Day 1, Week 0) through Week 16 and Week 24 ]
• Percentage of Participants who Experience at Least a 2 g/dL Increase in Hgb From Baseline and Normalization of Lactate Dehydrogenase and Haptoglobin [ Time Frame: Baseline (Day 1, Week 0) through Week 24 ]
• Mean Time During Which the Primary Endpoint is Maintained [ Time Frame: Baseline (Day 1, Week 0) through Week 24 ]
• Change From Baseline in the Total Score From the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale [ Time Frame: Baseline (Day 1, Week 0) through Week 24 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of M281 in Adults With Warm Autoimmune Hemolytic Anemia
• Official Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Warm Autoimmune Hemolytic Anemia

Intervention

• Drug: M281
  M281 injection administered as intravenous infusion
  Other Name: Nipocalimab, JNJ-80202135
• Drug: Placebo
  Placebo administered as intravenous infusion

Study Arms

• Experimental: M281 administered every 4 weeks (double-blind period)
  Participants will receive M281 administered every 4 weeks alternating with placebo every 4 weeks during the 24 weeks double-blind period.
  Interventions:

  • Drug: M281
  • Drug: Placebo
• Experimental: M281 administered every 2 weeks (double-blind period)
  Participants will receive M281 administered every 2 weeks during the 24 weeks double-blind period.
  Intervention: Drug: M281
• Experimental: Placebo administered every 2 weeks (double-blind period)
  Participants will receive M281 matching placebo administered every 2 weeks during the 24 weeks double-blind period.
  Intervention: Drug: Placebo
• Experimental: M281 administered every 4 weeks (open-label extension period)
  Participants will receive M281 administered every 4 weeks during the 144 weeks open-label extension period.
  Intervention: Drug: M281
• Experimental: M281 administered every 2 weeks (open-label extension period)
  Participants will receive M281 administered every 2 weeks during the 144 weeks open-label extension period.
  Intervention: Drug: M281

• Publications *: Liu AP, Cheuk DK. Disease-modifying treatments for primary autoimmune haemolytic anaemia. Cochrane Database Syst Rev. 2021 Mar 26;3(3):CD012493. doi: 10.1002/14651858.CD012493.pub2.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 4, 2021): 111
• Original Estimated Enrollment (submitted: October 4, 2019): 90
• Estimated Study Completion Date: December 27, 2027
• Estimated Primary Completion Date: March 20, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

• Listed Location Countries: China, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Spain, Ukraine, United Kingdom, United States
• Removed Location Countries: Brazil, Canada, Malaysia, Mexico

Administrative Information

• NCT Number: NCT04119050
• Other Study ID Numbers: CR108987; 2019-000720-17 ( EudraCT Number ); MOM-M281-006 ( Other Identifier: Janssen Research & Development, LLC )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Momenta Pharmaceuticals, Inc.
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Momenta Pharmaceuticals, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: May 2023