A Study to Evaluate the Efficacy and Safety of VIB4920 in Participants With Sjögren's Syndrome

Sponsor: Amgen

Sommario: The purpose of the study is to evaluate the efficacy, safety, and tolerability of VIB4920 (formerly MEDI4920) in adult participants with Sjögren's Syndrome (SS).

TIPOLOGIA STUDIO

Interventistico

FASE

Fase 2

TRATTAMENTO

• VIB4920
• Placebo

OBIETTIVO PRIMARIO

• Misura: Population 1: Change From Baseline in ESSDAI at Day 169
• Tempo: Baseline and Day 169
• Descrizione: The ESSDAI is a systemic disease activity index for SS, assessing 12 domains (Constitutional, Salivary Glands, Lungs, Kidneys, Musculoskeletal, Peripheral Nervous System, Central Nervous System, Vascular, Gastrointestinal, Hematological, Ocular, and Extraglandular Manifestations). Each domain is graded for activity (0 = no activity to 3 = high activity) and weighted (1 for Biological to 6 for Muscular) based on its clinical significance, with the final score calculated as the sum of all weighted domain scores. The theoretical range is 0 to 123, with disease activity categorized as low (<5), moderate (5-13), and high (≥14). A positive change form baseline represents an increase in symptoms.

• Misura: Population 2: Change From Baseline in ESSPRI at Day 169
• Tempo: Baseline and Day 169
• Descrizione: The ESSPRI is a self-assessment tool for evaluating symptoms of dryness, fatigue, and pain (articular and/or muscular) in SS. Participants rate each of the three domains on a 0-10 numerical scale (0 = no; 10 maximal imaginable severity). All domains are equally weighted, and the total score is the mean of the three domain scores. The maximum total score for the ESSPRI assessment is 10. A positive change form baseline represents an increase in symptoms.

OBIETTIVO SECONDARIO

• Misura: Population 1: Change From Baseline in ESSPRI at Day 169
• Tempo: Baseline and Day 169
• Descrizione: The ESSPRI is a self-assessment tool for evaluating symptoms of dryness, fatigue, and pain (articular and/or muscular) in SS. Participants rate each of the three domains on a 0-10 numerical scale (0 = no; 10 maximal imaginable severity). All domains are equally weighted, and the total score is the mean of the three domain scores. The maximum total score for the ESSPRI assessment is 10. A positive change from baseline represents an increase in symptoms.

• Misura: Population 1: Number of Participants Who Achieved ESSDAI[3] and ESSDAI[4] Response at Day 169
• Tempo: Day 169
• Descrizione: The ESSDAI is a systemic disease activity index for primary Sjögren's syndrome, assessing 12 domains (e.g., cutaneous, renal, CNS, and biological). Each domain is graded for activity (0 = no activity to 3 = high activity) and weighted (1 for Biological to 6 for Muscular) based on its clinical significance, with the final score calculated as the sum of all weighted domain scores. The theoretical range is 0 to 123, with disease activity categorized as low (<5), moderate (5-13), and high (≥14). A positive change from baseline represents an increase in symptoms. ESSEDAI[3] and [4] responses were defined as a decrease of at least 3 or 4 points respectively in the ESSDAI score from the baseline value, measured at Day 169.

• Misura: Change From Baseline in The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Day 169
• Tempo: Baseline and Day 169
• Descrizione: The FACIT-Fatigue is a 13-item patient-reported questionnaire designed to assess the impact of fatigue on quality of life (QoL). Responses are scored from 0 (Not at all) to 4 (Very Much). The total score is the sum of all responses, ranging from 0 to 52, with higher scores indicating better QoL. A positive change from baseline represents an increase in QoL.

• Misura: Change From Baseline in Ocular Surface Disease Index (OSDI) at Day 169
• Tempo: Baseline and Day 169
• Descrizione: The OSDI is a validated tool for assessing vision-related function and dry eye disease severity (normal, mild, moderate, severe). It consists of 12 questions, with responses ranging from 0 (None of the time) to 4 (All of the time). Scores range from 0 to 100, as it is calculated by transforming the raw responses from the 12 questions into a standardized 0-100 scale, with higher scores indicating greater disability. A positive change from baseline indicates a worsening vision-related function.

• Misura: Patient Global Impression of Severity (PGIS) Score at Day 169
• Tempo: Baseline and Day 169
• Descrizione: The PGIS is a single-item measure that captures a patient's perception of overall symptom severity over the past week, using a 5-point categorical response scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe), with higher scores indicating greater symptom severity. Positive change from baseline values indicate worsening of symptoms severity.

• Misura: Population 2: Number of Participants Who Achieved ESSPRI Response at Day 169
• Tempo: Day 169
• Descrizione: The ESSPRI is a self-assessment tool for evaluating symptoms of dryness, fatigue, and pain (articular and/or muscular) in SS. Participants rate each of the three domains on a 0-10 numerical scale (0 = no; 10 maximal imaginable severity). All domains are equally weighted, and the total score is the mean of the three domain scores. The maximum total score for the ESSPRI assessment is 10. A positive change form baseline represents an increase in symptoms. Participants achieving an ESSPRI response were defined as at least a 1 point or 15% reduction from baseline in ESSPRI score at Day 169 without premature discontinuation from the study and without receiving rescue medications.

• Misura: Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs)
• Tempo: Up to approximately 365 days
• Descrizione: An adverse event (AE) referred to any untoward medical occurrence in a clinical study participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received the study treatment. Clinically significant changes in vital signs, electrocardiograms, and laboratory tests recorded after treatment administration were documented as TEAEs. Serious TEAEs (SAEs) were untoward medical occurrences after the first dose, irrespective of a causal link to the study treatment, that led to death, were life-threatening, required hospitalization or its prolongation, caused significant disability, resulted in congenital anomalies, or were considered other medically important events. AEs were graded (Grade 3: severe; Grade 4: life-threatening; Grade 5: death) using the Common Terminology Criteria for Adverse Events (CTCAE).

• Misura: Serum Concentration of VIB4920
• Tempo: Day 1 pre-dose, Day 1 post-dose, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141 pre-dose, Day 141 post-dose, Day 169 pre-dose, Day 169 post-dose, Day 197, Day 225, Day 253, Day 281, Day 309, Day 365
• Descrizione: Blood samples were collected at the specified time points.

CRITERI DI ELIGIBILITA'

• Criteri di inclusione e esclusione

  Inclusion Criteria: - Diagnosed with SS by meeting the 2016 American College of Rheumatology (ACR)/EULAR Classification Criteria. - Residual salivary gland function as defined by whole stimulated salivary flow > 0.1 mL/min (only for Population 2). - Have an ESSDAI score of >= 5 at screening; (not including the peripheral nervous system, central nervous system, and pulmonary domains) (only for Population 1). - Have an ESSPRI score of >= 5 at screening (only for Population 2). - Have an ESSDAI score of < 5 at screening (only for Population 2). - Positive for either anti-Ro autoantibodies or rheumatoid factor, or both at screening. - Male and female participants who agree to follow protocol defined contraceptive methods. - No active or untreated latent tuberculosis (TB). Exclusion Criteria: - Medical history of confirmed deep venous thrombosis or arterial thromboembolism within 2 years of signing the informed consent form (ICF). - Risk factors for venous thromboembolism or arterial thrombosis, prothrombotic status. - Concomitant polymyositis or dermatomyositis or systemic sclerosis. - Active malignancy or history of malignancy, except in situ carcinoma of the cervix and cutaneous basal cell carcinoma. - Hepatitis B, hepatitis C, or human immunodeficiency virus infection. - More than one episode of herpes zoster and/or an opportunistic infection in the last 12 months. - Active viral, bacterial, or other infections or history of more than 2 infections requiring intravenous antibiotics within 12 months prior to signing the ICF. - Participants with corona virus disease 2019 (COVID-19) infection or who, in the judgment of the investigator, are at unacceptable risk of COVID-19 or its complications. - A documented positive severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) test within 2 weeks prior to randomization. - Received live (attenuated) vaccine within the 4 weeks prior to ICF signature. - Treated with any biologic B-cell-depleting therapy within 12 months or other B-cell targeting therapy < 3 months before randomization. - Injectable corticosteroids (including intraarticular) or treatment with > 10 mg/day dose oral prednisone or equivalent within 6 weeks prior to randomization (only for Population 1). - Treated with systemic corticosteroids for indications other than SS, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) for more than a total of 2 weeks within 24 weeks prior to screening visit (only for Population 1). - Received previous treatment with anti-CD40L compounds at any time before screening. - Pregnant or lactating or planning to get pregnant during the duration of the study.

SESSO

Tutti

ETA' MINIMA

Età Minima: 18 Years
Età Massima: 75 Years

LUOGO

Research Site
Milano, 20122

Research Site
Rome, 00161

Research Site
Brescia, 25123

Research Site
Perugia, 06129

Research Site
Pisa, 56126

Research Site
Udine, 33100