A study to investigate the efficacy, safety, and pharmacokinetics of oral rilzabrutinib compared with placebo in participants 18 years of age and older 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

19 Aug 2025 → ongoing

Decision date (initial)

2025-07-14

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2024-517972-39-00

WHO UTN

U1111-1314-5112

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Therapy, Efficacy, Safety

To evaluate the effect of rilzabrutinib on durable Hb response (DHR) in participants with wAIHA in the PAP

Secondary objectives 7

1. To evaluate the hemoglobin overall response (OR) in the PAP
2. To evaluate the effect of rilzabrutinib on fatigue as measured by the FACIT-Fatigue scale
3. To assess time to response (TTR)
4. To evaluate the effect of rilzabrutinib on LDH, a marker of hemolysis
5. To assess the effect of rilzabrutinib treatment on rescue therapy requirement
6. To evaluate the effect of rilzabrutinib on dyspnea as measured by the FACIT-Dyspnea scale
7. To evaluate the safety and tolerability of rilzabrutinib in primary wAIHA participants

Conditions and MedDRA coding

Autoimmune haemolytic anaemia

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002438-PIP04-23

Plan to share IPD

Yes

IPD 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://vivli.org

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Male and female participants with a documented (confirmed) diagnosis of primary wAIHA for at least 6 months.
2. Participants who have previously failed to maintain a sustained response after treatment with 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).
3. Participants with Eastern Cooperative Oncology Group (ECOG) performance status Grade 2 or lower.
4. 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 12

1. 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.
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. Participants with symptomatic herpes zoster within 3 months prior to screening.
4. Participants with mixed wAIHA, or 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.
5. Participants with history of myelodysplastic syndrome.
6. Participants with uncontrolled or active HBV infection or Active HCV infection.
7. HIV infection.
8. Participants with history of solid organ transplant.
9. Participants with a history of active or latent tuberculosis (TB).
10. Splenectomy within 12 weeks before screening and planned surgery during the PAP.
11. 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 BTK inhibitors for wAIHA before Day 1 (randomization) are not eligible.
12. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants achieving DHR. 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 PAP

Secondary endpoints 7

1. Proportion of participants achieving overall Hb response (response [R] or complete response [CR]) by Week 24 of treatment in the PAP
2. Change from baseline in fatigue total score as measured by Functional Assessment of Chronic Illness Therapy (FACIT) – fatigue at Week 24
3. The time taken (days) to achieve the first Hb increase by ≥2 g/dL from baseline during the PAP in the absence of transfusion in the previous 14 days and in the absence of rescue medication in the previous 6 weeks
4. Change from baseline in levels of LDH at Week 24
5. Proportion of participants requiring use of rescue therapy after Week 4 of treatment during the PAP
6. Change from baseline in dyspnea severity score as measured by FACIT-Dyspnea at 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)

Investigational products

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

Test 1

Placebo 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 14

Locations

11 EU/EEA countries · 41 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 130 files

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

Application history

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