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

JRCT ID: jRCT2071220079

Registered date:08/12/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Warm Autoimmune Hemolytic Anemia
• Date of first enrollment: 22/06/2023
• Target sample size: 111
• Countries of recruitment: Brazil,Japan,China,Japan,Czech Republic,Japan,France,Japan,Germany,Japan,Greece,Japan,Hungary,Japan,Israel,Japan,Italy,Japan,Korea, Republic Of,Japan,Malaysia,Japan,Netherlands,Japan,Poland,Japan,Spain,Japan,United Kingdom Of Great BritainAnd Northern Irelan,Japan,United States Of America,Japan,Mexico,Japan,Egypt,Japan
• Study type: Interventional

Intervention(s)

M281 : M281 injection administered as intravenous infusion :
Participants will receive M281 administered every 4weeks alternating with placebo every 4 weeks during the 24 weeks double-blind period.
Participants will receive M281 administered every 2 weeks during the 24 weeks double-blind period.

Participants will receive M281 administered every 4 weeks during the 144 weeks open-label extension period.
Participants will receive M281 administered every 2 weeks during the 144 weeks open-label extension period.

Placebo : Placebo administered as intravenous infusion :
Participants will receive M281 administered every 4 weeks alternating with placebo every 4 weeks during the 24 weeks double-blind period.
Participants will receive M281 matching placebo administered every 2 weeks during the 24 weeks double-blind period.

Outcome(s)

• Primary Outcome: Percentage of Participants Achieving Durable Response of Improvement in Hemoglobin (Hgb) : Up to Week 20 of the double-blind period

Secondary Outcome

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 : 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) : 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 : 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 : 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 : 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 : 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 : 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 : 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 : 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) : 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 : 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 : 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 : 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 : 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.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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

Exclude 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

Related Information

• Primary Sponsor: Nishikawa Kazuko
• Secondary ID(s): NCT04119050