Autoimmune haemolytic anaemia
Conditions
Interventions
Drug: rilzabrutinib (SAR444671)
Pharmaceutical form: tablet, Route of administration: oral
Drug: placebo
Pharmaceutical form: tablet, Route of administration: oral
Study Arms:
Experimental: rilzab
Sponsors
Obara Kentaro
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male and female participants with a confirmed diagnosis of primary wAIHA for at least 3 months. - Participants who have previously failed to maintain a sustained response after treatment with corticosteroid (CS) (CS-resistance [defined as failure to obtain hemoglobin response within 3 weeks on at least 1 mg/kg or 60 mg prednisone or equivalent per day], CS-dependent wAIHA [defined as need to continue on prednisone or equivalent at a dose of >10 mg/day to maintain a response]), or are intolerant or ineligible to CS (defined as with contraindications, pre-existing medical conditions or CS-related complications that may render CS intolerant or ineligible per the best clinical judgement of the investigators). - Participants with Eastern Cooperative Oncology Group (ECOG) performance status Grade 2 or lower. - Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Exclusion criteria
Exclusion criteria: - Participants with 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. - Participants with symptomatic herpes zoster within 3 months prior to screening. - Participants with secondary wAIHA from any cause including drugs, Evans Syndrome, 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. - Participants with history of myelodysplastic syndrome. - Participants with uncontrolled or active hepatitis B virus (HBV) infection or Active hepatitis C virus (HCV) infection. - Human immunodeficiency virus (HIV) infection. - Participants with history of solid organ transplant. - Participants with a history of active or latent tuberculosis (TB). - Concurrent treatment with other experimental/investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to treatment start. Participants who previously received treatment with Bruton's tyrosine kinase (BTK) inhibitors for wAIHA before Day 1 (randomization) are not eligible. - Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Proportion of participants achieving durable hemoglobin (Hb) response (DHR) [Time frame: By Week 24] DHR is defined as an increase of Hb by >=2 g/dL from baseline on at least two thirds of evaluable scheduled visits between Week 12 and Week 24 (inclusive) in the primary analysis period (PAP). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Proportion of participants achieving overall Hb response (Response or Complete Response) [Time frame: By Week 24] Response is defined as an increase in Hb by >=2 g/dL from baseline in the absence of transfusion and rescue medication. Complete Response is defined as Hb >=12 g/dL (women) or >=13 g/dL (men) without evidence of hemolysis (ie, normal indirect bilirubin, lactate dehydrogenase [LDH], haptoglobin, and reticulocytes), in the absence of transfusion and rescue medication. 2. The time taken (days) to achieve the first Hb increase by >=2 g/dL from baseline during the PAP in the absence of transfusion and rescue medication [Time frame: Until Week 24] 3. Change from baseline in fatigue total score as measured by Functional Assessment of Chronic Illness Therapy (FACIT) - fatigue [Time frame: Baseline to Week 24] 4. Change from baseline in levels of LDH [Time frame: Baseline to Week 24] 5. Proportion of participants requiring use of rescue therapy after Week 4 of treatment during the PAP [Time frame: Until Week 24] 6. Change from baseline in dyspnea severity score as measured by FACIT - Dyspnea [Time frame: Baseline to Week 24] 7. Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (SAEs), treatment-emergent adverse events of special interest (AESIs), as well as clinical laboratory evaluations, vital sign, physical exam, and electrocardiograms (ECG) [Time frame: Until Week 104] | — |
Countries
Denmark, Israel, Japan
Contacts
Public ContactUnit Clinical
Sanofi K.K.
Outcome results
None listed