Sjögren's Syndrome
Conditions
Keywords
Sjögren's Syndrome, SS, VIB4920, MEDI4920
Brief summary
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).
Detailed description
The study will enrol 2 SS populations: Population 1 will include participants with moderate to high systemic disease activity defined by European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) \>= 5; Population 2 will include participants with moderate to severe subjective symptoms defined by EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score \>= 5 and residual stimulated salivary flow but with mild systemic disease activity defined by ESSDAI score \< 5. This study will include 3 periods: screening (4 weeks), treatment period (40 Weeks) and follow-up period (12 weeks). In the treatment period, participants from each of the populations will be randomized at 1:1 ratio to receive intravenous (IV) dose of VIB4920 or placebo (Stage I). After completion of Stage I, participants randomized to VIB4920 in Stage I will receive placebo and participants randomized to placebo in Stage I will receive VIB4920 (Stage II). Participants who had study drug discontinuation will not be eligible for treatment during Stage II. All participants will be followed for at least 12 weeks after their last dose of study drug administration. Study acquired from Horizon in 2024.
Interventions
DRUGVIB4920
Intravenous Dose 1.
DRUGPlacebo
Intravenous dose matched to VIB4920.
Sponsors
Amgen
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 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Population 1: Change From Baseline in ESSDAI at Day 169 | Baseline and Day 169 | 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. |
| Population 2: Change From Baseline in ESSPRI at Day 169 | Baseline and Day 169 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Day 169 | Baseline and Day 169 | 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. |
| Change From Baseline in Ocular Surface Disease Index (OSDI) at Day 169 | Baseline and Day 169 | 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. |
| Patient Global Impression of Severity (PGIS) Score at Day 169 | Baseline and Day 169 | 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. |
| Population 1: Change From Baseline in ESSPRI at Day 169 | Baseline and Day 169 | 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. |
| Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Up to approximately 365 days | 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). |
| Serum Concentration of VIB4920 | 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 | Blood samples were collected at the specified time points. |
| Population 2: Number of Participants Who Achieved ESSPRI Response at Day 169 | Day 169 | 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. |
| Population 1: Number of Participants Who Achieved ESSDAI[3] and ESSDAI[4] Response at Day 169 | Day 169 | 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. |
Countries
Argentina, France, Hungary, India, Italy, Mexico, Peru, Poland, South Korea, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Participants were recruited across 70 international sites between November 2019 and March 2023.
Pre-assignment details
Eligibility for Sjögren's syndrome (SS) was assessed using the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria. Participants were then randomized into a double-blind treatment period and categorized into two populations based on the severity of systemic disease activity and symptoms.
Participants by arm
| Arm | Count |
|---|---|
| Population 1: Placebo/VIB4920 Participants with SS characterized by moderate to severe systemic disease activity (defined by an ESSDAI score of ≥ 5), were randomized to receive a placebo in Stage I, followed by VIB4920 in Stage II. | 38 |
| Population 1: VIB4920/Placebo Participants with SS characterized by moderate to severe systemic disease activity (defined by a ESSDAI score of ≥ 5), were randomized to receive multiple doses of VIB4920 in Stage I, followed by a placebo in Stage II. | 36 |
| Population 2: Placebo/VIB4920 Participants with SS characterized by moderate to severe subjective symptoms (defined by an ESSPRI score of ≥ 5), and low systemic disease activity (ESSDAI score \< 5), were randomized to receive a placebo in Stage I, followed by VIB4920 in Stage II. | 55 |
| Population 2: VIB4920/Placebo Participants with SS, characterized by moderate to severe subjective symptoms (defined by an ESSPRI score of ≥ 5), and low systemic disease activity (ESSDAI score \< 5), were randomized to receive multiple doses of VIB4920 in Stage I, followed by a placebo in Stage II. | 54 |
| Total | 183 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 | 0 |
| Overall Study | Death | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Non-compliance with procedures | 0 | 0 | 2 | 0 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 4 | 6 |
Baseline characteristics
| Characteristic | Population 1: Placebo/VIB4920 | Population 1: VIB4920/Placebo | Population 2: Placebo/VIB4920 | Population 2: VIB4920/Placebo | Total |
|---|---|---|---|---|---|
| Age, Customized 18-85 years | 38 participants | 36 participants | 55 participants | 54 participants | 183 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 8 Participants | 23 Participants | 22 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 28 Participants | 32 Participants | 32 Participants | 122 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Population 1: Baseline ESSDAI Total Score | 10.1 score on scale STANDARD_DEVIATION 4.1 | 11.4 score on scale STANDARD_DEVIATION 4.5 | — | — | 10.7 score on scale STANDARD_DEVIATION 4.3 |
| Population 2: Baseline ESSPRI Total Score | — | — | 6.8 score on a scale STANDARD_DEVIATION 1.2 | 7.1 score on a scale STANDARD_DEVIATION 1.6 | 6.9 score on a scale STANDARD_DEVIATION 1.4 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 4 Participants | 11 Participants | 9 Participants | 25 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 5 Participants | 11 Participants | 18 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 3 Participants | 3 Participants | 4 Participants | 11 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 1 Participants | 5 Participants | 7 Participants | 15 Participants |
| Race/Ethnicity, Customized White | 34 Participants | 26 Participants | 31 Participants | 23 Participants | 114 Participants |
| Sex: Female, Male Female | 38 Participants | 35 Participants | 50 Participants | 53 Participants | 176 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 5 Participants | 1 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 1 / 36 | 0 / 37 | 0 / 34 | 0 / 55 | 0 / 54 | 0 / 52 | 0 / 49 |
| other Total, other adverse events | 18 / 38 | 20 / 36 | 24 / 37 | 22 / 34 | 21 / 55 | 21 / 54 | 20 / 52 | 21 / 49 |
| serious Total, serious adverse events | 0 / 38 | 1 / 36 | 1 / 37 | 3 / 34 | 1 / 55 | 3 / 54 | 1 / 52 | 2 / 49 |
Outcome results
Primary
Population 1: Change From Baseline in ESSDAI at Day 169
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.
Time frame: Baseline and Day 169
Population: FAS: included all randomized participants who received any dose of investigational product, analyzed according to the randomized treatment, and had available data at the specified time points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Population 1: Placebo | Population 1: Change From Baseline in ESSDAI at Day 169 | -4.1 Score on scale | Standard Error 0.6 |
| Population 1: VIB4920 | Population 1: Change From Baseline in ESSDAI at Day 169 | -6.3 Score on scale | Standard Error 0.6 |
Primary
Population 2: Change From Baseline in ESSPRI at Day 169
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.
Time frame: Baseline and Day 169
Population: FAS: included all randomized participants who received any dose of investigational product, analyzed according to the randomized treatment, and had available data at the specified time points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Population 1: Placebo | Population 2: Change From Baseline in ESSPRI at Day 169 | -0.53 Score on scale | Standard Error 0.23 |
| Population 1: VIB4920 | Population 2: Change From Baseline in ESSPRI at Day 169 | -1.80 Score on scale | Standard Error 0.23 |
Secondary
Change From Baseline in Ocular Surface Disease Index (OSDI) at Day 169
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.
Time frame: Baseline and Day 169
Population: FAS: included all randomized participants who received any dose of investigational product, analyzed according to the randomized treatment, and had available data at the specified time points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Population 1: Placebo | Change From Baseline in Ocular Surface Disease Index (OSDI) at Day 169 | -14.02 Score on scale | Standard Error 3.06 |
| Population 1: VIB4920 | Change From Baseline in Ocular Surface Disease Index (OSDI) at Day 169 | -16.00 Score on scale | Standard Error 3.22 |
| Population 2: Placebo | Change From Baseline in Ocular Surface Disease Index (OSDI) at Day 169 | -8.52 Score on scale | Standard Error 2.94 |
| Population 2: VIB4920 | Change From Baseline in Ocular Surface Disease Index (OSDI) at Day 169 | -13.95 Score on scale | Standard Error 2.95 |
Secondary
Change From Baseline in The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Day 169
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.
Time frame: Baseline and Day 169
Population: FAS: included all randomized participants who received any dose of investigational product, analyzed according to the randomized treatment, and had available data at the specified time points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Population 1: Placebo | Change From Baseline in The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Day 169 | 5.8 Score on scale | Standard Error 1.6 |
| Population 1: VIB4920 | Change From Baseline in The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Day 169 | 8.1 Score on scale | Standard Error 1.6 |
| Population 2: Placebo | Change From Baseline in The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Day 169 | 2.8 Score on scale | Standard Error 1.4 |
| Population 2: VIB4920 | Change From Baseline in The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Day 169 | 8.1 Score on scale | Standard Error 1.4 |
Secondary
Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs)
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).
Time frame: Up to approximately 365 days
Population: Safety Analysis Set: included all participants who received any dose of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Population 1: Placebo | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 1 TEAEs | 23 Participants |
| Population 1: Placebo | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 1 SAEs | 0 Participants |
| Population 1: Placebo | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 1 Grade ≥ 3 | 0 Participants |
| Population 1: Placebo | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 1 Fatal AEs | 0 Participants |
| Population 1: Placebo | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 2 TEAEs | 28 Participants |
| Population 1: Placebo | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 2 SAEs | 1 Participants |
| Population 1: Placebo | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 2 Grade ≥ 3 | 0 Participants |
| Population 1: Placebo | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 2 Fatal AEs | 0 Participants |
| Population 1: VIB4920 | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 2 SAEs | 3 Participants |
| Population 1: VIB4920 | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 2 TEAEs | 25 Participants |
| Population 1: VIB4920 | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 1 SAEs | 1 Participants |
| Population 1: VIB4920 | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 2 Fatal AEs | 0 Participants |
| Population 1: VIB4920 | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 2 Grade ≥ 3 | 2 Participants |
| Population 1: VIB4920 | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 1 Fatal AEs | 1 Participants |
| Population 1: VIB4920 | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 1 Grade ≥ 3 | 2 Participants |
| Population 1: VIB4920 | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 1 TEAEs | 28 Participants |
| Population 2: Placebo | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 2 Grade ≥ 3 | 0 Participants |
| Population 2: Placebo | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 1 Grade ≥ 3 | 1 Participants |
| Population 2: Placebo | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 1 Fatal AEs | 0 Participants |
| Population 2: Placebo | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 2 TEAEs | 34 Participants |
| Population 2: Placebo | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 2 SAEs | 1 Participants |
| Population 2: Placebo | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 2 Fatal AEs | 0 Participants |
| Population 2: Placebo | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 1 TEAEs | 38 Participants |
| Population 2: Placebo | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 1 SAEs | 1 Participants |
| Population 2: VIB4920 | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 1 Grade ≥ 3 | 2 Participants |
| Population 2: VIB4920 | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 1 Fatal AEs | 0 Participants |
| Population 2: VIB4920 | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 1 SAEs | 3 Participants |
| Population 2: VIB4920 | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 1 TEAEs | 37 Participants |
| Population 2: VIB4920 | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 2 TEAEs | 32 Participants |
| Population 2: VIB4920 | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 2 Fatal AEs | 0 Participants |
| Population 2: VIB4920 | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 2 Grade ≥ 3 | 3 Participants |
| Population 2: VIB4920 | Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Stage 2 SAEs | 2 Participants |
Secondary
Patient Global Impression of Severity (PGIS) Score at Day 169
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.
Time frame: Baseline and Day 169
Population: FAS: included all randomized participants who received any dose of investigational product, analyzed according to the randomized treatment, and had available data at the specified time points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Population 1: Placebo | Patient Global Impression of Severity (PGIS) Score at Day 169 | -0.5 Score on scale | Standard Error 0.1 |
| Population 1: VIB4920 | Patient Global Impression of Severity (PGIS) Score at Day 169 | -0.6 Score on scale | Standard Error 0.1 |
| Population 2: Placebo | Patient Global Impression of Severity (PGIS) Score at Day 169 | -0.4 Score on scale | Standard Error 0.1 |
| Population 2: VIB4920 | Patient Global Impression of Severity (PGIS) Score at Day 169 | -0.6 Score on scale | Standard Error 0.1 |
Secondary
Population 1: Change From Baseline in ESSPRI at Day 169
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.
Time frame: Baseline and Day 169
Population: FAS: included all randomized participants who received any dose of investigational product, analyzed according to the randomized treatment, and had available data at the specified time points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Population 1: Placebo | Population 1: Change From Baseline in ESSPRI at Day 169 | -1.12 Score on scale | Standard Error 0.29 |
| Population 1: VIB4920 | Population 1: Change From Baseline in ESSPRI at Day 169 | -1.80 Score on scale | Standard Error 0.31 |
Secondary
Population 1: Number of Participants Who Achieved ESSDAI[3] and ESSDAI[4] Response at Day 169
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.
Time frame: Day 169
Population: FAS: included all randomized participants who received any dose of investigational product, analyzed according to the randomized treatment, and had available data at the specified time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Population 1: Placebo | Population 1: Number of Participants Who Achieved ESSDAI[3] and ESSDAI[4] Response at Day 169 | ESSDAI[3] Day 169 | 22 Participants |
| Population 1: Placebo | Population 1: Number of Participants Who Achieved ESSDAI[3] and ESSDAI[4] Response at Day 169 | ESSDAI[4] Day 169 | 18 Participants |
| Population 1: VIB4920 | Population 1: Number of Participants Who Achieved ESSDAI[3] and ESSDAI[4] Response at Day 169 | ESSDAI[3] Day 169 | 26 Participants |
| Population 1: VIB4920 | Population 1: Number of Participants Who Achieved ESSDAI[3] and ESSDAI[4] Response at Day 169 | ESSDAI[4] Day 169 | 24 Participants |
Secondary
Population 2: Number of Participants Who Achieved ESSPRI Response at Day 169
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.
Time frame: Day 169
Population: FAS: included all randomized participants who received any dose of investigational product, analyzed according to the randomized treatment, and had available data at the specified time points.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Population 1: Placebo | Population 2: Number of Participants Who Achieved ESSPRI Response at Day 169 | 18 Participants |
| Population 1: VIB4920 | Population 2: Number of Participants Who Achieved ESSPRI Response at Day 169 | 36 Participants |
Secondary
Serum Concentration of VIB4920
Blood samples were collected at the specified time points.
Time frame: 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
Population: Pharmacokinetic (PK) Analysis Set: included all participants who received investigational product and had at least one quantifiable plasma PK observation post-first dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Population 1: Placebo | Serum Concentration of VIB4920 | Day 141 post-dose | 0.577 mg/L | — |
| Population 1: Placebo | Serum Concentration of VIB4920 | Day 281 | 46.368 mg/L | Standard Deviation 23.349 |
| Population 1: Placebo | Serum Concentration of VIB4920 | Day 365 | 2.446 mg/L | Standard Deviation 2.536 |
| Population 1: Placebo | Serum Concentration of VIB4920 | Day 197 | 39.535 mg/L | Standard Deviation 16.655 |
| Population 1: Placebo | Serum Concentration of VIB4920 | Day 309 | 52.409 mg/L | Standard Deviation 23.754 |
| Population 1: Placebo | Serum Concentration of VIB4920 | Day 225 | 46.885 mg/L | Standard Deviation 21.633 |
| Population 1: Placebo | Serum Concentration of VIB4920 | Day 169 post-dose | 469.366 mg/L | Standard Deviation 92.413 |
| Population 1: Placebo | Serum Concentration of VIB4920 | Day 253 | 45.069 mg/L | Standard Deviation 23.143 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 85 | 53.716 mg/L | Standard Deviation 21.3 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 113 | 52.796 mg/L | Standard Deviation 29.229 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 253 | 0.360 mg/L | Standard Deviation 0.343 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 141 pre-dose | 49.318 mg/L | Standard Deviation 27.952 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 141 post-dose | 525.702 mg/L | Standard Deviation 155.286 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 1 pre-dose | 0.002 mg/L | Standard Deviation 0.013 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 225 | 1.903 mg/L | Standard Deviation 1.594 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 169 pre-dose | 50.390 mg/L | Standard Deviation 18.717 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 365 | 0 mg/L | Standard Deviation 0 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 169 post-dose | 65.459 mg/L | Standard Deviation 113.805 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 197 | 10.808 mg/L | Standard Deviation 9.982 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 1 post-dose | 470.370 mg/L | Standard Deviation 111.047 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 15 | 97.058 mg/L | Standard Deviation 26.48 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 309 | 0.008 mg/L | Standard Deviation 0.026 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 29 | 128.228 mg/L | Standard Deviation 31.805 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 57 | 62.363 mg/L | Standard Deviation 25.562 |
| Population 1: VIB4920 | Serum Concentration of VIB4920 | Day 281 | 0.086 mg/L | Standard Deviation 0.16 |
| Population 2: Placebo | Serum Concentration of VIB4920 | Day 365 | 1.531 mg/L | Standard Deviation 1.017 |
| Population 2: Placebo | Serum Concentration of VIB4920 | Day 141 post-dose | 25.004 mg/L | — |
| Population 2: Placebo | Serum Concentration of VIB4920 | Day 169 post-dose | 572.071 mg/L | Standard Deviation 200.235 |
| Population 2: Placebo | Serum Concentration of VIB4920 | Day 197 | 39.399 mg/L | Standard Deviation 15.325 |
| Population 2: Placebo | Serum Concentration of VIB4920 | Day 225 | 73.173 mg/L | Standard Deviation 194.836 |
| Population 2: Placebo | Serum Concentration of VIB4920 | Day 253 | 63.950 mg/L | Standard Deviation 77.006 |
| Population 2: Placebo | Serum Concentration of VIB4920 | Day 281 | 54.050 mg/L | Standard Deviation 50.595 |
| Population 2: Placebo | Serum Concentration of VIB4920 | Day 309 | 44.732 mg/L | Standard Deviation 24.888 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 309 | 0.018 mg/L | Standard Deviation 0.044 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 225 | 1.979 mg/L | Standard Deviation 1.624 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 141 pre-dose | 80.912 mg/L | Standard Deviation 125.684 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 113 | 66.778 mg/L | Standard Deviation 59.558 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 1 post-dose | 496.984 mg/L | Standard Deviation 182.915 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 253 | 0.427 mg/L | Standard Deviation 0.485 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 85 | 68.812 mg/L | Standard Deviation 60.349 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 57 | 80.093 mg/L | Standard Deviation 64.358 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 1 pre-dose | 0.002 mg/L | Standard Deviation 0.013 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 281 | 0.139 mg/L | Standard Deviation 0.34 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 29 | 141.365 mg/L | Standard Deviation 100.163 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 15 | 111.636 mg/L | Standard Deviation 56.244 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 169 post-dose | 57.018 mg/L | Standard Deviation 31.592 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 365 | 0.003 mg/L | Standard Deviation 0.014 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 197 | 14.958 mg/L | Standard Deviation 28.728 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 169 pre-dose | 54.031 mg/L | Standard Deviation 30.161 |
| Population 2: VIB4920 | Serum Concentration of VIB4920 | Day 141 post-dose | 532.216 mg/L | Standard Deviation 241.67 |