Phase 2 and 3 Placebo Controlled & Long-term Extension Study of Rilzabrutinib in Adults With iCVID to Evaluate Efficacy, Safety, and Tolerability

Phase 2, Randomized, Double-blind, Placebo-controlled Study (Part A) Followed by a Phase 3, Randomized, Double-blind, Placebo Controlled Study (Part B) With an Open Label Extension (Part C) and Long-term Extension (Part D) to Evaluate the Efficacy, Safety and Tolerability of Rilzabrutinib in Adult Participants With Inflammatory Common Variable Immunodeficiency (iCVID)

This is a 4-part study where both Part A and Part B, which starts after the completion of Part A, are randomized (2:1), double-blinded, placebo-controlled studies, followed by an open label (Part C) and long-term extension period (Part D), phase 2 and 3 study, designed to evaluate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of rilzabrutinib in adult patients with iCVID.

In Part A, all participants will have iCVID associated ILD and at least one additional inflammatory/ autoimmune complication (cytopenia [thrombocytopenia, anemia] and/or lymphoproliferative disease [splenomegaly, lymphoid hyperplasia]). At the completion of 24 weeks in Part A, participants will be assessed to the predefined No Response Citeria and may elect to discontinue the DB period (Part A) and enter the OL period (Part C).

Alternatively, for Part B, all participants will have CVID associated with at least one of the following: ILD, other inflammatory/ autoimmune complications (cytopenia, lymphoproliferative disease).

Part A: 32-week DB treatment of rilzabrutinib or placebo. Part B: 32-week DB treatment of rilzabrutinib or placebo. Part C: 32-week OL treatment of rilzabrutinib. Part D: OL treatment of rilzabrutinib until the last-patient-in (LPI- Part D) completes 52 weeks of treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Immunodeficiency Common Variable
• Intervention / Treatment: Drug: rilzabrutinib; Drug: placebo

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: Contact-US@sanofi.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

• Participants who have previously been diagnosed with CVID based on the following criteria A) Documented low serum IgG compared to age-adjusted reference ranges B) Documented low IgA and/or IgM compared to age-adjusted reference range C) Immunophenotypic findings consistent with CVID D) Absence of any other defined immunodeficiency state
• Receiving immunoglobulin IV or SC replacement therapy
• Participants who have been diagnosed with one or more of the following inflammatory complications (iCVID) A) Interstitial lung disease (ILD) B) CVID-related cytopenia for >3 months since diagnosis - thrombocytopenia or anemia C) Lymphoproliferative disease on historical CT imaging - splenomegaly or lymphoid hyperplasia
• Eastern Cooperative Oncology Group performance status Grade 2 or lower, at screening
• 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

• Active pulmonary infection at screening that could account for the HRCT abnormalities
• 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 (e.g. hepatobiliary conditions causing hepatic impairment)
• Refractory nausea or vomiting
• Chronic uncontrolled infectious diseases as determined by the Investigator
• Laboratory abnormalities at the screening visit (e.g. elevated liver enzymes)
• Recent history of substance, alcohol abuse or mental illness
• Malabsorption syndromes, active moderate-to-severe enteropathy
• Concurrent treatment with immunosuppressive or immunomodulatory drugs other than corticosteroids The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; placebo	Drug: placebo; Oral tablet
Experimental: rilzabrutinib; rilzabrutinib	Drug: rilzabrutinib; Oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with iCVID who meet any responder definitions	In participants with ILD at baseline, a responder is defined as achieving a clinically meaningful response at Week 32. In participants with cytopenia (thrombocytopenia, anemia) at baseline, a responder is defined as achieving therapeutic efficacy at Week 32, defined as Durable platelet response or Durable hemoglobin response (DHR) between W16 and W32, and no rescue medication for thrombocytopenia is taken at any time. In participants with lymphoproliferative disease (splenomegaly or lymphoid hyperplasia) at baseline, a responder is defined as achieving therapeutic efficacy by Week 32.	At Week 32

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in FACIT-Fatigue total score at Week 24 in Part A and Week 32 in Part B		At Week 24 in Part A and Week 32 in Part B
Percent change from baseline in FVC% predicted at Week 32		At Week 32
Percent change from baseline in diffusing capacity of the lung for carbon monoxide at Week 32		At Week 32
Change from baseline in FACIT-dyspnea severity score at Week 24 in Part A and Week 32 in Part B		At Week 24 in Part A and Week 32 in Part B
Change from baseline in time spend in moderate to vigorous physical activity measured with a wearable device		At Week 32
Incidence of treatment-emergent adverse events (TEAE), serious AEs (SAE), TEAE leading to permanent discontinuation, adverse events of special interest (AESI)	including clinical laboratory evaluations, vital sign measurements, and electrocardiograms	Until Week 116 of LPI for Part D

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Estimated): November 9, 2026
• Primary Completion (Estimated): May 10, 2035
• Study Completion (Estimated): January 8, 2036

Study Registration Dates

• First Submitted: October 28, 2026
• First Submitted That Met QC Criteria: November 2, 2026
• First Posted (Actual): November 6, 2026

Study Record Updates

• Last Update Posted (Actual): November 6, 2026
• Last Update Submitted That Met QC Criteria: November 2, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Immunologic Deficiency Syndromes; Common Variable Immunodeficiency
• Other Study ID Numbers: EFC20516; 2026-525354-10 (Registry Identifier: CTIS); U1111-1325-2663 (Registry Identifier: WHO UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No