Immunoglobulin G4 Related Disease
Conditions
Brief summary
This is a Phase 3, parallel group, 2-arm, randomized, double blind, placebo-controlled, 52-week treatment study to assess the efficacy and safety of rilzabrutinib as a treatment for adult patients with active IgG4-RD. The purpose of this study is to measure time to adjudicated IgG4-RD clinical disease flare, and other relevant efficacy endpoints including flare-free rate, control of IgG4-RD disease activity, use of GC rescue and safety parameters such as treatment-emergent adverse events, clinical laboratory values and electrocardiograms (ECG) in participants aged 18 years and above, diagnosed with IgG4-RD and treated with rilzabrutinib tablets over a 52-week placebo-controlled period. Study details include: The study duration will be up to 60 weeks, including a Screening period of 4 to 6 weeks, a 52-week double blind treatment period, and 2 weeks of follow up (plus an optional OLE of 108 weeks). The number of visits will be 16 (plus an optional 9 visits during the OLE).
Interventions
DRUGRilzabrutinib
Pharmaceutical form:Tablet-Route of administration:Oral
DRUGPlacebo
Pharmaceutical form:Tablet-Route of administration:Oral
DRUGGlucocorticoid
Pharmaceutical form:Tablet, solution, suspension formulations according to local standard practices-Route of administration:Oral
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have a clinical diagnosis of IgG4-RD confirmed by the Adjudication Committee. * Participants meeting Step 1 Entry criteria of 2019 ACR/EULAR classification criteria for IgG4-RD and Total inclusion points are ≥20 * Participants with active disease in at least 1 organ system, excluding lymph nodes, with active disease defined by an IgG4-RD Responder Index organ/site activity score ≥2 based on the manifestations of disease activity in the last 28 days. * Participants with history or current involvement of at least 1 organ/site (excluding lymph nodes) affected with IgG4-RD. * Participants with active IgG4-RD controlled for at least 2 weeks while on a stable dose of GC. * Participants willing to taper off GC after starting IMP. * Participants willing and able to participate in repeated study protocol mandated or clinically indicated imaging procedures to assess IgG4-RD such as computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), or ultrasound. * Participants who have an up-to-date vaccination status as per local guidelines. The last dose of live vaccines should be received at least 30 days before Day 1. * 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
* Meet any Step 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to first adjudicated clinical disease flare treated by the investigator during the Blinded Treatment period | Until Week 52 | The Adjudication Committee will include internationally recognized independent experts in diagnosis and management of patients with IgG4-RD, blinded to participant, investigator, and site identifiers |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants without IgG4-RD adjudicated clinical disease flare and off glucocorticoids and immunomodulators | At Week 52 | — |
| Proportion of participants without IgG4-RD adjudicated clinical disease flare and off glucocorticoids | At Week 52 | — |
| Annualized rate of clinical disease flares | At Week 52 | — |
| Change in IgG4-RD RI total activity scores from baseline to Week 52 | From baseline to Week 52 | — |
| Proportion of participants in complete remission at Week 52 | At Week 52 | Defined by an IgG4-RD RI total activity score = 0 or absence of evident disease activity assessed by the Investigator |
| Percent change in IgG4-RD RI total activity scores from baseline to Week 52 | From baseline to Week 52 | — |
| Change in IgG4-RD RI total activity scores from baseline to Week 12 | From baseline to Week 12 | — |
| Percent change in IgG4-RD RI total activity scores from baseline at Week 12 | From baseline to Week 12 | — |
| Proportion of participants with reduction of ≥2 points from the baseline IgG4-RD RI total activity score | At Week 12, Week 24, and Week 52 | — |
| Cumulative glucocorticoid dose for treatment of IgG4-RD | At Week 52 | — |
| Proportion of participants with potentially clinically significant abnormalities in laboratory tests, vital signs, and electrocardiograms in the Safety Population | Until Week 160 | — |
| Proportion of participants with TEAEs, AESIs, SAEs in the Safety Population | Until Week 160 | — |
Countries
Argentina, Belgium, Canada, Chile, China, France, Germany, Israel, Italy, Japan, Netherlands, Poland, Saudi Arabia, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
CONTACTTrial Transparency email recommended (Toll free for US & Canada)
Outcome results
None listed