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

• ClinicalTrials.gov Identifier: NCT05002777
• Recruitment Status: Not yet recruiting
• First Posted: August 12, 2021
• Last Update Posted: September 29, 2021
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Warm Autoimmune Hemolytic Anemia (wAIHA)	Drug: rilzabrutinib	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: October 4, 2021
• Estimated Primary Completion Date: July 20, 2023
• Estimated Study Completion Date: June 10, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Rilzabrutinib; Oral rilzabrutinib 400 mg BID	Drug: rilzabrutinib; Pharmaceutical form: Tablet Route of administration: Oral; Other Name: PRN1008/SAR444671

Outcome Measures

Primary Outcome Measures :

1. Part A: Proportion of participants with overall hemoglobin response [ Time Frame: By Week 24 in Part A ]

   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.

2. 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 [ Time Frame: At Week 50 in Part B ]
   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.

Secondary Outcome Measures :

1. Proportion of participants with durable hemoglobin response [ Time Frame: By Week 24 in Part A ]
   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 [ Time Frame: From Day 1 to Week 24 in Part A ]
3. Frequency of rescue therapy (any wAIHA-directed therapy other than predniso[lo]ne or transfusion) received [ Time Frame: After Week 1 of treatment to Week 24 in Part A and Week 75 in Part B ]
4. Change from baseline in FACIT-Fatigue scale score [ Time Frame: Until Week 24 in Part A and Week 75 in Part B ]
   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.
5. Incidence of treatment emergent adverse events (TEAEs), serious TEAEs, adverse events of special interest (AESIs) [ Time Frame: Until Week 24 in Part A and Week 75 in Part B ]
   Safety assessment including clinical laboratory evaluations, vital sign measurements and ECG

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Trial Transparency email recommended (Toll free number for US & Canada); 800-633-1610 ext ext option 6; Contact-US@sanofi.com

Locations

United States, District of Columbia

Investigational Site Number 8400003

Washington, District of Columbia, United States, 20007

Contact: Jennifer Steffen 202-687-0116 js4936@georgetown.edu

Principal Investigator: Catherine Broome

United States, Florida

Investigational Site Number 8400002

Tamarac, Florida, United States, 33321

Contact: Nima Nagarajan 954-302-3163 nnagarajan@advancedresearchfl.com

Principal Investigator: Sumit Sawhney

United States, Massachusetts

Investigational Site Number 8400001

Boston, Massachusetts, United States, 02114

Contact 617-724-4000

Principal Investigator: David Kuter

China

Investigational Site Number 1560002

Beijing, China, 100005

Contact: Dr. Bing Han 13601059938 hanbing_li@sina.com.cn

Principal Investigator: Dr. Bing Han

Spain

Investigational Site Number 7240001

Barcelona, Spain, 08036

Contact: Dr. Joan Cid 0034932275400 jcid@clinic.cat

Principal Investigator: Dr. Joan Cid

Investigational Site Number 7240003

Madrid, Spain, 28046

Contact: Dr. Marta Morado 0034917277000 marta.morado@gmail.com

Principal Investigator: Dr. Marta Morado

Investigational Site Number 7240002

Sevilla, Spain, 41013

Contact: Dr. Maria Eva Mingot 0034955012000 memingot@gmail.com

Principal Investigator: Dr. Maria Eva Mingot

Sponsors and Collaborators

Sanofi

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT05002777
• Other Study ID Numbers: ACT17209; 2021-001671-16 ( EudraCT Number ); U1111-1262-2929 ( Registry Identifier: ICTRP )
• First Posted: August 12, 2021
• Last Update Posted: September 29, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Anemia; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Hemolysis; Hematologic Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases