An Efficacy and Safety Study of Injectable Ravagalimab to Assess Change in EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) in Adult Participants With Moderately to Severely Active Primary Sjogren's Syndrome (pSS)

Study Overview
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Brief Summary
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Sjogren's syndrome (SS) is a chronic, multisystem autoimmune disease characterized by lacrimal and salivary gland inflammation, with resultant dryness of the eyes and mouth and occasional glandular enlargement. In addition, a variety of systemic manifestations may occur; including fatigue, musculoskeletal symptoms, rashes, and internal organ (e.g., pulmonary, renal, hepatic, and neurologic) disease. Sjogren's syndrome may occur in isolation, primary Sjogren's syndrome (pSS), or in a secondary form, often associated with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or systemic sclerosis. Ravagalimab is an investigational drug being developed to help treat patients with inflammatory diseases like SS. This study will evaluate how well ravagalimab works within the body and how safe it is in patients with primary SS (pSS). Ravagalimab, a potent CD40 antagonist is an investigational drug being developed for the treatment of Sjogren's syndrome (SS). This study is double-blinded, which means that neither the trial participants nor the study doctors will know who will be given which study drug. Study doctors put the participants in 1 of 2 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to placebo. Participants 18-75 years of age with Sjogren's syndrome (SS) will be enrolled. Around 45 participants will be enrolled in the study in multiple sites within Netherlands. Participants will receive ravagalimab intravenous (IV) loading dose or IV placebo at baseline followed by subcutaneous (SC) ravagalimab or matching placebo for 22 weeks. There will be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, labial gland (lip) biopsy, and checking for side effects and completing questionnaires.

Official Title
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A Phase 2a, Double-Blind, Randomized, Placebo-Controlled Study of Ravagalimab in Subjects With Moderately to Severely Active Primary Sjogren's Syndrome

Conditions
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Sjogren's Syndrome (SS)

Intervention / Treatment
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* Drug: Ravaglimab
* Drug: Ravagalimab
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary Sjogren's syndrome (pSS) diagnosed according to the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2016 Criteria. Lymphocyte focus score (local lymphocytic infiltrates) >= 1 in sublabial salivary gland specimen. Subjects with sublabial salivary gland biopsy obtained 3 months prior to Screening and meeting this criterion will be eligible without a biopsy at Screening. Subjects without a sublabial salivary gland biopsy within 3 months of Screening will obtain a biopsy for a lymphocyte focus score at Screening. EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) >= 5 at Screening. EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) >= 6 at Screening. Exclusion Criteria: History of clinically significant drug or alcohol abuse within the last 6 months. History of an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients), the ingredients of Chinese hamster ovary cells and/or other products in the same class.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ravagalimab<br>Participants will receive a loading dose of intravenous (IV) ravagalimab dose A at Week 0 followed by subcutaneous (SC) ravagalimab dose A every other week (eow) | Drug: Ravaglimab<br>* Intravenous Injection<br>* Other names: ABBV-323;Drug: Ravagalimab<br>* Subcutaneous Injection<br>* Other names: ABBV-323;|
| Placebo Comparator: Placebo<br>Participants will receive a loading dose of intravenous (IV) placebo at Week 0 followed by subcutaneous (SC) placebo every other week (eow) | Drug: Placebo<br>* Intravenous Injection<br>Drug: Placebo<br>* Subcutaneous Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) | ESSDAI is a systemic disease activity index including 12 domains (i.e., organ systems: cutaneous, respiratory, renal, articular, muscular, peripheral nervous system, central nervous system, haematological, glandular, constitutional, lymphadenopathic and biological). | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) | ESSDAI is a systemic disease activity index including 12 domains (i.e., organ systems: cutaneous, respiratory, renal, articular, muscular, peripheral nervous system, central nervous system, haematological, glandular, constitutional, lymphadenopathic and biological). | Up to Week 16 | 
| Change From Baseline in EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) | ESSPRI is designed to evaluate the patient symptoms with 3 questions related to the dryness, pain and fatigue a participant has experienced in the prior 2 weeks. It is a numeric rating scale from 0 - 10, with a final score the mean of the 3 questions | Up to Week 24 | 
| Change From Baseline in Tender Joint Count | An assessment of 68 joints will be done for tenderness by pressure manipulation on physical examination. Joint pain/tenderness will be classified as: present, absent, replaced or no assessment. | Up to Week 24 | 
| Change From Baseline in Swollen Joint Count | An assessment of 66 joints will be done by directed physical examination. The joints to be examined for swelling are the same as those examined for tenderness, except the hip joints are excluded. Joint swelling will be classified as present, absent, replaced or no assessment. | Up to Week 24 | 
| Change From Baseline in Salivary Flow (Unstimulated) | Patients will be asked to collect their saliva in a cup every 30 seconds for a total period of 5 minutes. The saliva production is expressed in ml/minute. | Up to Week 24 | 
| Change From Baseline in Salivary Flow (Stimulated) | Saliva production is stimulated by parafilm and collected in a cup every 30 seconds for a total period of 5 minutes.. The saliva production is expressed in ml/minute. | Up to Week 24 | 
| Change From Baseline in Lacrimal Flow (Schirmer's Test of Ocular Function) | Lachrymal flow will be assessed by Schirmer's test of ocular function. A small filter paper will be placed in the conjunctival sac for 5 minutes. After that, the degree of wetting is evaluated | Up to Week 24 | 
| Change From Baseline in Van Bijsterveld Score | The van Bijsterveld score is an ocular score for dryness. The Bijsterveld score is determined by adding up the combined score (from 0 to 3; 0 is normal and 3 is the highest level of staining) in the central and two outer sections of the eye. | Up to Week 24 | 
| Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) | FACIT-Fatigue is a 13-item questionnaire that evaluates fatigue/tiredness and its impact on daily activities and functioning in chronic diseases. This instrument includes items such as tiredness, weakness, listlessness, lack of energy, and the impact of these feelings on daily functioning (e.g., sleeping, and social activities). A lower score indicates less negative impact on daily activities. | Up to Week 24 | 
| Change From Baseline in Patient's Global Assessment of Disease Activity Numeric Rating Scales | Patient's Global Assessment of Disease Activity Numeric Rating Scale allows a patient to score 0 - 10 to assess the patient's overall functionality assessment considering the disease activity within the past week | Up to Week 24 | 
| Change From Baseline in Physician's Global Assessment of Disease Activity Numeric Rating Scales | Physician's Global Assessment of Disease Activity Numeric Rating Scale allows a physician to score 0 - 10 to assess the patient's overall functionality assessment considering the disease activity within the past week. | Up to Week 24 | 
| Change from Baseline in anti-Sjogrens-syndrome-related antigen A (anti-SSA) | Change from baseline in anti-SSA s assessed. | Up to Week 24 | 
| Change from Baseline in anti-Sjogrens-syndrome-related antigen B (anti-SSB) | Change from baseline in anti-SSB is assessed. | Up to Week 24 | 
| Change from Baseline in antinuclear antibody (ANA) | Change from baseline in antinuclear antibody (ANA) is assessed. | Up to Week 24 | 
| Change from Baseline in rheumatoid factor (RF) | Change from baseline in rheumatoid factor (RF) is assessed. | Up to Week 24 | 
| Change from Baseline in high-sensitivity C-reactive protein (hsCRP) | Change from baseline in high-sensitivity C-reactive protein (hsCRP) is assessed. | Up to Week 24 | 
| Change from Baseline in immunoglobulin M (IgM) | Change from baseline in immunoglobulin M (IgM) is assessed | Up to Week 24 | 
| Change from Baseline in immunoglobulin M (IgG) | Change from baseline in immunoglobulin M (IgG) is assessed. | Up to Week 24 | 
| Change from Baseline in immunoglobulin A (IgA) | Change from baseline in immunoglobulin A (IgA) is assessed. | Up to Week 24 | 
| Change from Baseline in Serum-Free Light Chains | Change from baseline in serum-free light chains is assessed. | Up to Week 24 | 
| Change from Baseline in Serum C3 | Change from baseline in Serum C3 is assessed. | Up to Week 24 | 
| Change from Baseline in Serum C4 | Change from baseline in Serum C4 is assessed. | Up to Week 24 | 
| Change from Baseline in Haemolytic Complement CH50 | Change from baseline in CH50 is assessed. | Up to Week 24 | 
| Change From Baseline in Focus Score of Sublabial Salivary Gland Biopsy (In Participants With a Screening and Week 24 Biopsy) | Change from baseline in focus score of sublabial salivary gland biopsy is assessed. | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sjogren's Syndrome (SS), Primary Sjogren's Syndrome (pSS), Ravagalimab, ABBV-323