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

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.

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.