Sjogren Disease
Conditions
Keywords
Sibeprenlimab, Autoimmune Diseases, Immune System Diseases, Dry Mouth, Dry Eyes, Salivary Gland Disorders, Lacrimal Gland Disorders, Immunoglobulin G, EnVISage
Brief summary
This is a phase 2 study to evaluate the effects of sibeprenlimab 400 mg administered subcutaneously (SC) every 4 (Q4) weeks as an add-on to background treatment in participants with Sjögren's disease.
Detailed description
This is a multicenter, randomized, double-blind, placebo-controlled, proof-of-concept study followed by an optional open-label extension to evaluate the efficacy and safety of sibeprenlimab 400 mg administered SC Q4 weeks as an add-on to background treatment in participants with Sjögren's disease. The primary objective is to compare the effect of sibeprenlimab versus placebo added to background treatment on European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) scores at 28 weeks. The key secondary objective is to compare the effect of sibeprenlimab versus placebo added to background treatment on European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index (ESSPRI) at 28 weeks. Approximately 80 participants who have a diagnosis of Sjögren's disease according to the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria will be randomized with approximately 40 participants in the sibeprenlimab group and 40 participants in the placebo group.
Interventions
BIOLOGICALSibeprenlimab
400 mg administered SC Q4 weeks
OTHERPlacebo
Administered SC Q4 weeks
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosed with Sjögren's disease. * ESSDAI score (which measures disease activity) must be 5 or higher. * Salivary flow rate must be at least 0.05 mL/min. * Serum IgG level must be higher than 900 mg/dL. * Must be able to communicate well with the investigator and agree to follow the trial requirements. * Participants can continue certain medications (hydroxychloroquine, methotrexate, leflunomide, or azathioprine) if they have been on a stable dose for at least 30 days. * Corticosteroid dose must be stable and no more than 10 mg/day for at least 30 days. * Test positive for anti-Ro52 and/or anti-Ro60 antibodies. Key
Exclusion criteria
* Another active autoimmune rheumatic disease. * Prior use of B-cell depleting therapy or prohibited immunosuppressants. * Significant comorbidities including uncontrolled type 2 diabetes, malignancy, and chronic and/or acute infections. * Suicidal ideation or behavior based on the Patient Health Questionnaire-9 (PHQ-9).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) score | 28 weeks | Higher scores on the ESSDAI indicate a worse outcome, as they reflect higher disease activity. Minimum value is 0 and the maximum value is 123. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index (ESSPRI) score | 28 weeks | Higher scores on the ESSPRI indicate a worse outcome, as they reflect higher levels of patient-reported symptoms. Minimum value is 0, maximum value is 10. |
| Incidence of treatment-emergent adverse events (TEAEs) | 28 weeks | — |
| Incidence of treatment-emergent adverse events (TEAEs) by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade | 28 weeks | — |
| Incidence of treatment-emergent adverse events (TEAEs) with an outcome of death | 28 weeks | — |
| Incidence of serious treatment-emergent adverse events (TEAEs) | 28 weeks | — |
| Incidence of treatment-emergent adverse events (TEAEs) leading to discontinuation of the investigational medicinal product (IMP) | 28 weeks | — |
| Proportion of participants with minimal clinical improvement defined as European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) reduction ≥ 3 points from baseline | At 28 weeks | Higher scores on the ESSDAI indicate a worse outcome, as they reflect higher disease activity. Minimum value is 0 and the maximum value is 123. |
| Proportion of participants with minimal clinical improvement defined as European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index (ESSPRI) reduction ≥ 1 point from baseline | At 28 weeks | Higher scores on the ESSPRI indicate a worse outcome, as they reflect higher levels of patient-reported symptoms. Minimum value is 0, maximum value is 10. |
| Change from baseline in individual European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) domains | At 28 weeks | Higher scores on the ESSDAI indicate a worse outcome, as they reflect higher disease activity. Minimum value is 0 and the maximum value is 123. |
| Change from baseline in salivary flow rate | At 28 weeks | — |
| Change from baseline in tear flow rate | At 28 weeks | — |
| Change from baseline in Clinical European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ClinESSDAI) score | At 28 weeks | Higher scores on the ClinESSDAI indicate a worse outcome, as they reflect higher disease activity. Minimum value is 0 and the maximum value is 123. |
| Change from baseline in Physician Global Assessment (PhGA) score | At 28 weeks | Higher scores on the PhGA indicate a worse outcome, as they reflect a higher assessment of disease activity or severity by the physician. Minimum value is 0 and the maximum value is 10. |
| Change from baseline in Patient Global Assessment (PaGA) score of participant outcomes | At 28 weeks | Higher scores on the PaGA indicate a worse outcome, as they reflect a higher assessment of disease severity or impact by the patient. Minimum value is 0 and the maximum value is 10. |
| Change from baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) score | At 28 weeks | Higher FACIT-Fatigue scores indicate a better outcome, as they reflect less fatigue. Minimum value is 0 and the maximum value is 52. |
| Change from baseline in 36 Item Short-Form Survey Version 2 (SF-36v2) Physical Component Summary Scale score and Mental Component Summary Scale score | At 28 weeks | Higher scores on the SF-36v2 indicate a better outcome, as they reflect better health status and quality of life. Minimum value is 0 and the maximum value is 100. |
| Change from baseline in patient-reported Sjögren's disease diary score | At 28 weeks | Higher diary score indicates more severe symptoms and greater impact on the patient's daily life. Minimum value is 0 and the maximum value is 10. |
| Proportion of participants with minimal clinical improvement, defined as Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) score increase of ≥ 4 from baseline | At 28 weeks | Higher FACIT-Fatigue scores indicate a better outcome, as they reflect less fatigue. Minimum value is 0 and the maximum value is 52. |
| Time to the first occurrence of minimal clinical improvement in ESSDAI | Week 28 | — |
| Time to the first occurrence of minimal clinical improvement in ESSPRI | Week 28 | — |
| Percent change from baseline in total serum IgA | Week 28 | — |
| Percent change from baseline in total serum IgG | Week 28 | — |
| Percent change from baseline in total serum IgM | Week 28 | — |
| Percent change from baseline in total serum free APRIL (a proliferation-inducing ligand) concentrations | Week 28 | — |
| Cmax of sibeprenlimab | 28 weeks | — |
| Tmax of sibeprenlimab | 28 weeks | — |
| Area Under the Curve (AUC) of sibeprenlimab | 28 weeks | — |
| Serum concentration of sibeprenlimab | 28 weeks | — |
| Presence or absence of serum antidrug antibody (ADA) to sibeprenlimiab | 28 weeks | — |
Countries
Argentina, Bulgaria, Germany, Greece, Poland, Romania, Spain, United States
Outcome results
None listed