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

A Phase 2 Randomized, Double-blind, Placebo-controlled, Proof of Concept Study to Evaluate the Efficacy and Safety of VIB4920 in Subjects With Sjögren's Syndrome (SS)

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).

Study Overview

• Status: Completed
• Conditions: Sjögren's Syndrome
• Intervention / Treatment: Drug: VIB4920; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 183
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1114AAH
      • Research Site
• France
  • Bordeaux, France
    • Research Site
  • Brest, France
    • Research Site
  • Grenoble, France
    • Research Site
  • Paris, France
    • Research Site
  • Paris Cedex 13, France
    • Research Site
  • Strasbourg, France
    • Research Site
• Hungary
  • Budapest, Hungary, 1097
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
  • Gyula, Hungary, 5700
    • Research Site
• India
  • Andhra Pradesh
    • Secunderabad, Andhra Pradesh, India, 5000003
      • Research Site
  • Gujarat
    • Ahmedabad, Gujarat, India, 380015
      • Research Site
  • Karnataka
    • Bangalore, Karnataka, India, 560010
      • Research Site
  • Maharshtra
    • Pune, Maharshtra, India, 411001
      • Research Site
    • Pune, Maharshtra, India, 411013
      • Research Site
  • Odisha
    • Bhubaneswar, Odisha, India, 751005
      • Research Site
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600004
      • Research Site
• Italy
  • Pisa, Italy, 56126
    • Research Site
  • Udine, Italy, 33100
    • Research Site
  • Lambardia
    • Milano, Lambardia, Italy, 20122
      • Research Site
  • Lazio
    • Rome, Lazio, Italy, 00161
      • Research Site
  • Province Of Brescia
    • Brescia, Province Of Brescia, Italy, 25123
      • Research Site
  • Umbria
    • Perugia, Umbria, Italy, 06129
      • Research Site
• Korea, Republic of
  • Gyeonggi
    • Suwon si, Gyeonggi, Korea, Republic of, 16499
      • Research Site
  • Republic Of Korea
    • Incheon, Republic Of Korea, Korea, Republic of, 21565
      • Research Site
    • Incheon, Republic Of Korea, Korea, Republic of, 22332
      • Research Site
    • Seoul, Republic Of Korea, Korea, Republic of, 06591
      • Research Site
• Mexico
  • Ciudad de mexico, Mexico, 06700
    • Research Site
  • Coahuila
    • Saltillo, Coahuila, Mexico, 25000
      • Research Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44650
      • Research Site
    • Guadalajara, Jalisco, Mexico, 44690
      • Research Site
• Peru
  • Lima, Peru, 1
    • Research Site
  • Lima, Peru, 33
    • Research Site
  • San Martin De Porres
    • Lima, San Martin De Porres, Peru, 31
      • Research Site
• Poland
  • Krakow, Poland, 30-363
    • Research Site
  • Lublin, Poland, 20-412
    • Research Site
  • Poznan, Poland, 60-693
    • Research Site
  • Siedlce, Poland, 08-110
    • Research Site
  • Szczecin, Poland, 71-252
    • Research Site
  • Warszawa, Poland, 02-637
    • Research Site
  • Warszawa, Poland, 02-691
    • Research Site
  • Wrocław, Poland, 02-637
    • Research Site
  • Elblag
    • Elbląg, Elblag, Poland, 82-300
      • Research Site
• Taiwan
  • Kaohsiung, Taiwan, 81362
    • Research Site
  • Taichung City, Taiwan, 40705
    • Research Site
• United Kingdom
  • Newcastle Upon Tyne, United Kingdom, NE1 4LP
    • Research Site
  • Truro, United Kingdom, TR13LJ
    • Research Site
• United States
  • California
    • Fullerton, California, United States, 92835
      • Research Site
    • Upland, California, United States, 91786
      • Research Site
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Research Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Research Site
    • Wheaton, Maryland, United States, 20902
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Research Site
    • Durham, North Carolina, United States, 27710
      • Research Site
    • Salisbury, North Carolina, United States, 28144
      • Research Site
    • Wilmington, North Carolina, United States, 28401
      • Research Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75231
      • Research Site
    • Houston, Texas, United States, 77084
      • Research Site
    • Houston, Texas, United States, 77089
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VIB4920 Dose 1 in Population 1; Participants in population 1 will receive IV VIB4920 Dose 1 in Stage I and placebo matched to VIB4920 in Stage II.	Drug: VIB4920; Intravenous Dose 1.; Other Names: Dazodalibep; Drug: Placebo; Intravenous dose matched to VIB4920.
Placebo Comparator: Placebo in Population 1; Participants in population 1 will receive IV placebo matched to VIB4920 in Stage I and IV VIB4920 Dose 1 in Stage II.	Drug: VIB4920; Intravenous Dose 1.; Other Names: Dazodalibep; Drug: Placebo; Intravenous dose matched to VIB4920.
Experimental: VIB4920 Dose 1 in Population 2; Participants in population 2 will receive IV VIB4920 Dose 1 in Stage I and placebo matched to VIB4920 in Stage II.	Drug: VIB4920; Intravenous Dose 1.; Other Names: Dazodalibep; Drug: Placebo; Intravenous dose matched to VIB4920.
Placebo Comparator: Placebo in Population 2; Participants in population 2 will receive IV placebo matched to VIB4920 in Stage I and IV VIB4920 Dose 1 in Stage II.	Drug: VIB4920; Intravenous Dose 1.; Other Names: Dazodalibep; Drug: Placebo; Intravenous dose matched to VIB4920.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and Day 169
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.	Baseline and Day 169

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and Day 169
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.	Day 169
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.	Baseline and Day 169
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.	Baseline and Day 169
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.	Baseline and Day 169
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.	Day 169
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).	Up to approximately 365 days
Serum Concentration of VIB4920	Blood samples were collected at the specified time points.	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

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• St Clair EW, Baer AN, Ng WF, Noaiseh G, Baldini C, Tarrant TK, Papas A, Devauchelle-Pensec V, Wang L, Xu W, Pham TH, Sikora K, Rees WA, Alevizos I. CD40 ligand antagonist dazodalibep in Sjogren's disease: a randomized, double-blinded, placebo-controlled, phase 2 trial. Nat Med. 2024 Jun;30(6):1583-1592. doi: 10.1038/s41591-024-03009-3. Epub 2024 Jun 5.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2019
• Primary Completion (Actual): September 1, 2022
• Study Completion (Actual): March 10, 2023

Study Registration Dates

• First Submitted: October 2, 2019
• First Submitted That Met QC Criteria: October 14, 2019
• First Posted (Actual): October 16, 2019

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 10, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: VIB4920; MEDI4920; Sjögren's Syndrome; SS
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Mouth Diseases; Stomatognathic Diseases; Pathologic Processes; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Disease; Eye Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Syndrome; Sjogren's Syndrome
• Other Study ID Numbers: VIB4920.P2.S2; 2019-002713-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No