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.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Studientyp
Einschreibung (Geschätzt)
Phase
- Phase 2
- Phase 3
Kontakte und Standorte
Studienkontakt
- Name: Trial Transparency email recommended (Toll free for US & Canada)
- Telefonnummer: option 6 800-633-1610
- E-Mail: Contact-US@sanofi.com
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Vervierfachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Placebo-Komparator: placebo
placebo |
Oral tablet |
|
Experimental: rilzabrutinib
rilzabrutinib |
Oral tablet |
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Proportion of participants with iCVID who meet any responder definitions
Zeitfenster: At Week 32
|
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
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Change from baseline in FACIT-Fatigue total score at Week 24 in Part A and Week 32 in Part B
Zeitfenster: 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
Zeitfenster: At Week 32
|
At Week 32
|
|
|
Percent change from baseline in diffusing capacity of the lung for carbon monoxide at Week 32
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: At Week 32
|
At Week 32
|
|
|
Incidence of treatment-emergent adverse events (TEAE), serious AEs (SAE), TEAE leading to permanent discontinuation, adverse events of special interest (AESI)
Zeitfenster: Until Week 116 of LPI for Part D
|
including clinical laboratory evaluations, vital sign measurements, and electrocardiograms |
Until Week 116 of LPI for Part D
|
Mitarbeiter und Ermittler
Sponsor
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Geschätzt)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- EFC20516
- 2026-525354-10 (Registrierungskennung: CTIS)
- U1111-1325-2663 (Registrierungskennung: WHO UTN)
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Beschreibung des IPD-Plans
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
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
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