Efficacy, Safety and Pharmacokinetics of Rilzabrutinib in Patients With Warm Autoimmune Hemolytic Anemia (wAIHA)

Warm Autoimmune Hemolytic Anemia (wAIHA) Clinical Trial

Official title:

A Multicenter, Open-label, Phase IIb Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Rilzabrutinib in Patients With Warm Autoimmune Hemolytic Anemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05002777
• Other study ID #: ACT17209
• Secondary ID: U1111-1262-29292
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 7, 2021
• Est. completion date: May 28, 2025

Study information

• Verified date: February 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single group treatment, Phase 2, open-label, study to evaluate the efficacy, safety and pharmacokinetics of rilzabrutinib in adult patients with wAIHA. All participants will receive rilzabrutinib orally. The screening period is up to 28 days, followed by a treatment period of 24 weeks for Part A. Participants who complete Part A and are deemed eligible for Part B will continue to receive the study medication for 52 weeks following the Last Patient In (LPI-Part B). There will be a 7-day safety follow-up period after receiving the last dose of study drug either in Part A (for those not eligible for Part B or early terminated) or Part B. The estimated total duration of the study is approximately 137 weeks (Parts A and B), including the follow-up period. For participants deemed ineligible for Part B, the total length of the study will be 29 weeks (Part A only), including screening and the follow-up period. In Part B, participants who temporarily stop rilzabrutinib treatment and maintain a durable response from W50 to W74, will have their EOS visit at Week 75. In this case, participation will be for 79 weeks including the screening period.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 22
• Est. completion date: May 28, 2025
• Est. primary completion date: May 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

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. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Anemia
• Anemia, Hemolytic
• Anemia, Hemolytic, Autoimmune
• Hemolysis
• Warm Autoimmune Hemolytic Anemia (wAIHA)

Intervention

Drug:
• rilzabrutinib
Pharmaceutical form: Tablet Route of administration: Oral

Locations

Country	Name	City	State
Austria	Hanush-Krankenhaus_Investigational Site Number: 0400001	Vienna
China	Peking Union Medical College Hospital_Investigational Site Number: 1560002	Beijing
China	Institute of hematology&blood diseases hospital_Investigational Site Number: 1560003	Tianjin
Denmark	Odense Universitetshospital Hæmatologisk Forskningsenhed_Investigational Site Number: 2080001	Odense
Germany	Klinik für Hämatologie und Stammzellentransplantation_Investigational Site Number: 2760001	Essen
Hungary	Fejer Varmegyei Szent Gyorgy Egyetemi Oktato Korhaz_Investigational Site Number: 3480001	Szekesfehervar
Italy	Ospedale Giuseppe Moscati_Investigational Site Number: 3800002	Avellino
Italy	Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"_Investigational Site Number: 3800003	Meldola
Italy	Ospedale Maggiore Policlinico_Investigational Site Number: 3800001	Milan
Spain	Hospital Universitario de Cruces_Investigational Site Number: 7240004	Barakaldo
Spain	Hospital Clinic de Barcelona_Investigational Site Number: 7240001	Barcelona
Spain	Hospital Universitario La Paz_Investigational Site Number: 7240003	Madrid
Spain	Hospital Universitario Virgen del Rocío_Investigational Site Number: 7240002	Sevilla
United Kingdom	Leeds Teaching Hospitals NHS Trust_Investigational Site Number: 8260001	Leeds
United Kingdom	Barts Health NHS Trust_Investigational Site Number: 8260005	London
United Kingdom	Imperial College Healthcare NHS Trust_Investigational Site Number: 8260002	London
United States	Massachusetts General Hospital_Investigational Site Number: 8400001	Boston	Massachusetts
United States	The Oncology Institute of Hope & Innovation Site Number : 8400006	Cerritos	California
United States	TOI Clinical Research LLC_ Cerritos_Investigational Site Number: 8400006	Cerritos	California
United States	TOI Clinical Research LLC_Glendale_Investigational Site Number: 8400006	Glendale	California
United States	TOI Clinical Research LLC_Long Beach_Investigational Site Number: 8400006	Long Beach	California
United States	University of Southern California_Investigational Site Number: 8400009	Los Angeles	California
United States	TOI Clinical Research LLC_Santa Ana_Investigational Site Number: 8400006	Santa Ana	California
United States	Oncology & Hematology Associates of West Broward_Investigational Site Number: 8400002	Tamarac	Florida
United States	The Lundquist Institute_Investigational Site Number: 8400005	Torrance	California
United States	Georgetown University Hospital_Investigational Site Number: 8400003	Washington	District of Columbia
United States	TOI Clinical Research LLC_ Whittier_Investigational Site Number: 8400006	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Austria,  China,  Denmark,  Germany,  Hungary,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: 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, lactate dehydrogenase (LDH) , haptoglobin, and reticulocytes), and absence of transfusion in the last 7 days and an absence of rescue medications during the last 4 weeks.	By Week 24 in Part A
Primary	Part B: 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.	By Week 50 in Part B
Secondary	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.	By Week 24 in Part A
Secondary	Median time from baseline to first hemoglobin response		From Day 1 to Week 24 in Part A
Secondary	Frequency of rescue therapy (any wAIHA-directed therapy other than predniso[lo]ne or transfusion) received		After Week 1 of treatment to Week 24 in Part A and Week 75 in Part B
Secondary	Change from baseline in FACIT-Fatigue scale score	The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale is a 13-item questionnaire used to assesses self-reported fatigue and its impact on daily activities and function.	Until Week 24 in Part A and Week 75 in Part B
Secondary	Incidence of treatment emergent adverse events (TEAEs), serious TEAEs, adverse events of special interest (AESIs)	Safety assessment including clinical laboratory evaluations, vital sign measurements and ECG	Until Week 24 in Part A and Week 75 in Part B