Efficacy, safety and pharmacokinetics of rilzabrutinib in patients with warm autoimmune hemolytic anemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

31 Jan 2022 → ongoing

Decision date (initial)

2024-02-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi Aventis Recherche et Developpement

External identifiers

EU CT number

2023-509441-13-00

EudraCT number

2021-001671-16

WHO UTN

U1111-1262-2929

ClinicalTrials.gov

NCT05002777

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Therapy, Pharmacodynamic, Safety

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

Secondary objectives 5

1. Part A: To evaluate the durable hemoglobin response in adult patients with wAIHA
2. Part A: To assess time to response (TTR)
3. Parts A and B: To assess the effect of treatment with rilzabrutinib on rescue medication requirement in patients with wAIHA
4. Parts A and B: To evaluate the impact of rilzabrutinib treatment on fatigue
5. Parts A and B: To evaluate the safety and tolerability of rilzabrutinib in patients with wAIHA

Conditions and MedDRA coding

Warm autoimmune hemolytic anemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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)
2. Participants who have previously failed to maintain a sustained response after treatment with corticosteroids
3. Eastern Cooperative Oncology Group (ECOG) performance status grade 2 or lower
4. Up-to-date vaccination status as per local guideline
5. Body mass index (BMI) >17.5 and <40 kg/m2
6. All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
7. Core Part B: Evidence of treatment efficacy to rilzabrutinib as defined by achieving overall response during Part A
8. Core Part B: - Completion of Part A treatment period (24 weeks)
9. Extended Part B: Completion of Core Part B period.

Exclusion criteria 10

1. 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
2. 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
3. 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
4. Myelodysplastic syndrome
5. Uncontrolled or active HBV infection: Patients with positive HBsAg and/or HBV DNA
6. HIV infection
7. 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
8. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
9. Part B only: Participants who receive any therapy during Part A known to be active in wAIHA
10. Part B only: 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Proportion of participants with overall hemoglobin response
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

Secondary endpoints 5

1. Proportion of participants with durable hemoglobin response
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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 5

Locations

3 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications