E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Warm autoimmune hemolytic anemia |
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E.1.1.1 | Medical condition in easily understood language |
Warm autoimmune hemolytic anemia |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10073785 |
E.1.2 | Term | Autoimmune haemolytic anaemia |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part A: To evaluate the efficacy of rilzabrutinib in adult patients with wAIHA Part B: To evaluate the long-term efficacy of rilzabrutinib in patients with wAIHA
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E.2.2 | Secondary objectives of the trial |
Part A: • To evaluate the durable hemoglobin response in adult patients with wAIHA • To assess time to response (TTR)
Parts A and B: • To assess the effect of treatment with rilzabrutinib on rescue medication requirement in patients with wAIHA • To evaluate the impact of rilzabrutinib treatment on fatigue • To evaluate the safety and tolerability of rilzabrutinib in patients with wAIHA
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male and female patients with a confirmed diagnosis of primary wAIHA or systemic lupus erythematosus (SLE)-associated wAIHA (without other SLE-related manifestations apart from cutaneous and musculoskeletal manifestations) - Participants who have previously failed to maintain a sustained response after treatment with corticosteroids. - Eastern Cooperative Oncology Group (ECOG) performance status grade 2 or lower. - Up-to-date vaccination status as per local guidelines. - Body mass index (BMI) >17.5 and <40 kg/m2 - All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Part B only - Evidence of treatment efficacy to rilzabrutinib as defined by achieving overall response during Part A. - Completion of Part A treatment period (24 weeks). |
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E.4 | Principal exclusion criteria |
- Clinically significant medical history or ongoing chronic illness that would jeopardize the safety of the participant or compromise the quality of the data derived from his or her participation in the study as determined by the Investigator. - Participants with medical history of lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for the past 3 years. - Secondary wAIHA from any cause including drugs, lymphoproliferative disorders (low-count monoclonal B-cell lymphocytosis is allowed), infectious or autoimmune disease, or active hematologic malignancies. Participants with positive antinuclear antibodies but without a definitive diagnosis of an autoimmune disease are allowed. - Myelodysplastic syndrome. - Uncontrolled or active HBV infection: Patients with positive HBsAg and/or HBV DNA. - HIV infection. - Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days or 5 half-lives, whichever is greater, prior to treatment start. - Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
Part B only - Participants who receive any therapy during Part A known to be active in wAIHA. - Presence of unacceptable side effect(s) or toxicity associated with rilzabrutinib such that there is an unfavorable risk-benefit assessment for continued treatment with rilzabrutinib in the opinion of the Investigator and/or Sponsor. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1 - Proportion of participants with overall hemoglobin response ; Response is defined as an increase in hemoglobin (Hb) by ≥2 g/dL from baseline and an absence of transfusion in the last 7 days, without biochemical resolution of hemolysis at the time response is achieved and an absence of rescue medications during the last 4 weeks. Complete Response is defined as hemoglobin ≥11 g/dL (women) or ≥12 g/dL (men), no evidence of hemolysis (normal bilirubin, LDH, haptoglobin, and reticulocytes), and absence of transfusion in the last 7 days and an absence of rescue medications during the last 4 weeks. 2 - Proportion of participants who maintain durable response achieved during Part A or achieve a durable response during Part B and have a hemoglobin response ; Durable response (Part B) is defined as Hb level ≥10 g/dL with an increase from baseline (Part A) of ≥2 g/dL on three consecutive scheduled visits during Week 24 to Week 50; with absence of transfusion and no rescue medication during the period of 3 consecutive visits and for at least 7 days (transfusions) and 4 weeks (rescue medication) prior to the first consecutive visit. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 - By Week 24 in Part A 2 - By Week 50 in Part B |
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E.5.2 | Secondary end point(s) |
1 - Proportion of participants with durable hemoglobin response ; Durable response (Part A) is defined as Hb level ≥10 g/dL with an increase from baseline of ≥2 g/dL on three consecutive evaluable visits during the 24-week treatment period; with absence of transfusion and no rescue medication during the period of 3 consecutive visits and for at least 7 days (transfusions) and 4 weeks (rescue medication) prior to the first consecutive visit. 2 - Median time from baseline to first hemoglobin response 3 - Frequency of rescue therapy (any wAIHA-directed therapy other than predniso[lo]ne or transfusion) received 4 - Change from baseline in FACIT-Fatigue scale score 5 - Safety assessments |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 - By Week 24 in Part A 2 - From Day 1 to Week 24 in Part A 3 - After Week 1 of treatment to Week 24 in Part A and Week 75 in Part B 4, 5 - Until Week 24 in Part A and Week 75 in Part B |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
China |
United Kingdom |
United States |
Austria |
Denmark |
France |
Germany |
Hungary |
Italy |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 17 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |