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

NCT05002777 | Active Not Recruiting Phase 2 FDA Drug

• 4 other identifiers: ACT17209U1111-1262-29292023-509441-132021-001671-16
• Study Type: interventional
• Target: 22
• Locations: 9 countries
• Sites: 27

Brief Summary

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 can continue in the Core Part B period followed by an Extended Part B period for up to 253 weeks. There will be a 7-day safety follow-up period after receiving the last dose of study medication either in Part A (for those not eligible for Part B or early terminated) or Part B. In addition, each participant will be asked to attend an EOT-Core Part B visit when the last participant completes 52 weeks in Core Part B. The Extended Part B period will last for up to 253 weeks.

Conditions

Warm Autoimmune Hemolytic Anemia (wAIHA)

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (5)

• Proportion of participants with durable hemoglobin response

  By Week 24 in Part A

• Median time from baseline to first hemoglobin response

  From Day 1 to Week 24 in Part A

• 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 305 in Part B

• Change from baseline in FACIT-Fatigue scale score

  Until Week 24 in Part A and Week 305 in Part B

• Incidence of treatment emergent adverse events (TEAEs), serious TEAEs, adverse events of special interest (AESIs)

  Until Week 24 in Part A and Week 305 in Part B

Study Arms (1)

Rilzabrutinib

EXPERIMENTAL

Oral rilzabrutinib 400 mg BID

Drug: rilzabrutinib

Interventions

rilzabrutinib DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Also known as: PRN1008/SAR444671

Rilzabrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Core Part B
• Evidence of treatment efficacy to rilzabrutinib as defined by achieving overall response during Part A.
• Completion of Part A treatment period (24 weeks). Extended Part B
• Completion of Core Part B period.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (27)

The Oncology Institute of Hope & Innovation Site Number : 8400006

Cerritos, California, 90703, United States

Location

TOI Clinical Research LLC_ Cerritos_Investigational Site Number: 8400006

Cerritos, California, 90703, United States

Location

TOI Clinical Research LLC_Glendale_Investigational Site Number: 8400006

Glendale, California, 91204, United States

Location

TOI Clinical Research LLC_Long Beach_Investigational Site Number: 8400006

Long Beach, California, 90805, United States

Location

University of Southern California_Investigational Site Number: 8400009

Los Angeles, California, 90033, United States

Location

TOI Clinical Research LLC_Santa Ana_Investigational Site Number: 8400006

Santa Ana, California, 92705, United States

Location

The Lundquist Institute_Investigational Site Number: 8400005

Torrance, California, 90502, United States

Location

TOI Clinical Research LLC_ Whittier_Investigational Site Number: 8400006

Whittier, California, 90602, United States

Location

Georgetown University Hospital_Investigational Site Number: 8400003

Washington D.C., District of Columbia, 20007, United States

Location

Oncology & Hematology Associates of West Broward_Investigational Site Number: 8400002

Tamarac, Florida, 33321, United States

Location

Massachusetts General Hospital_Investigational Site Number: 8400001

Boston, Massachusetts, 02114, United States

Location

Hanush-Krankenhaus_Investigational Site Number: 0400001

Vienna, 1140, Austria

Location

Peking Union Medical College Hospital_Investigational Site Number: 1560002

Beijing, 100005, China

Location

Institute of hematology&blood diseases hospital_Investigational Site Number: 1560003

Tianjin, 300020, China

Location

Odense Universitetshospital Hæmatologisk Forskningsenhed_Investigational Site Number: 2080001

Odense, 5000, Denmark

Location

Klinik für Hämatologie und Stammzellentransplantation_Investigational Site Number: 2760001

Essen, 45147, Germany

Location

Fejer Varmegyei Szent Gyorgy Egyetemi Oktato Korhaz_Investigational Site Number: 3480001

Székesfehérvár, 8000, Hungary

Location

Ospedale Giuseppe Moscati_Investigational Site Number: 3800002

Avellino, 83100, Italy

Location

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"_Investigational Site Number: 3800003

Meldola, 47014, Italy

Location

Ospedale Maggiore Policlinico_Investigational Site Number: 3800001

Milan, 20149, Italy

Location

Hospital Universitario de Cruces_Investigational Site Number: 7240004

Barakaldo, 48093, Spain

Location

Hospital Clinic de Barcelona_Investigational Site Number: 7240001

Barcelona, 08036, Spain

Location

Hospital Universitario La Paz_Investigational Site Number: 7240003

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocío_Investigational Site Number: 7240002

Seville, 41013, Spain

Location

Leeds Teaching Hospitals NHS Trust_Investigational Site Number: 8260001

Leeds, LS9 7TF, United Kingdom

Location

Barts Health NHS Trust_Investigational Site Number: 8260005

London, E1 2ES, United Kingdom

Location

Imperial College Healthcare NHS Trust_Investigational Site Number: 8260002

London, W2 1NY, United Kingdom

Location

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2021
• First Posted: August 12, 2021
• Study Start: December 7, 2021
• Primary Completion: May 23, 2024
• Study Completion (Estimated): December 31, 2029
• Last Updated: May 21, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

GB (3); AU (1); ES (4); DK (1); US (11); HU (1); CN (2); DE (1); IT (3)