Clinical trial NCT04129164: A Study to Evaluate the Efficacy and Safety of VIB4920 in Participants With Sjögren's Syndrome
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sjögren's Syndrome
Keywords: Sjögren's Syndrome
SS
VIB4920
MEDI4920
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2019-10-16
Enrollment: 183
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Population 1: Change From Baseline in ESSDAI at Day 169
timeFrame: Baseline and Day 169
measure: Population 2: Change From Baseline in ESSPRI at Day 169
timeFrame: Baseline and Day 169
Secondary outcomes:
measure: Population 1: Change From Baseline in ESSPRI at Day 169
timeFrame: Baseline and Day 169
measure: Population 1: Number of Participants Who Achieved ESSDAI[3] and ESSDAI[4] Response at Day 169
timeFrame: Day 169
measure: Change From Baseline in The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Day 169
timeFrame: Baseline and Day 169
measure: Change From Baseline in Ocular Surface Disease Index (OSDI) at Day 169
timeFrame: Baseline and Day 169
measure: Patient Global Impression of Severity (PGIS) Score at Day 169
timeFrame: Baseline and Day 169
measure: Population 2: Number of Participants Who Achieved ESSPRI Response at Day 169
timeFrame: Day 169
measure: Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 365 days
measure: Serum Concentration of VIB4920
timeFrame: 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
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: Research Site
state: California
city: Upland
country: United States
facility: Research site
state: California
city: Lawrenceville
country: United States
facility: Research Site
state: Georgia
city: Kansas City
country: United States
facility: Research Site
state: Kansas
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Wheaton
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Salisbury
country: United States
facility: Research Site
state: North Carolina
city: Wilmington
country: United States
facility: Research Site
state: North Carolina
city: Duncansville
country: United States
facility: Research site
state: Pennsylvania
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Research Site
state: Buenos Aires
city: Bordeaux
country: France
facility: Research Site
city: Brest
country: France
facility: Research Site
city: Grenoble
country: France
facility: Research Site
city: Paris Cedex 13
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Gyula
country: Hungary
facility: Research Site
city: Secunderabad
country: India
facility: Research Site
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Research Site
state: Gujarat
city: Bangalore
country: India
facility: Research Site
state: Karnataka
city: Pune
country: India
facility: Research Site
state: Maharshtra
city: Pune
country: India
facility: Research Site
state: Maharshtra
city: Bhubaneswar
country: India
facility: Research Site
state: Odisha
city: Chennai
country: India
facility: Research Site
state: Tamil Nadu
city: Milano
country: Italy
facility: Research Site
state: Lambardia
city: Rome
country: Italy
facility: Research Site
state: Lazio
city: Brescia
country: Italy
facility: Research Site
state: Province Of Brescia
city: Perugia
country: Italy
facility: Research Site
state: Umbria
city: Pisa
country: Italy
facility: Research Site
city: Udine
country: Italy
facility: Research Site
city: Suwon si
country: Korea, Republic of
facility: Research Site
state: Gyeonggi
city: Incheon
country: Korea, Republic of
facility: Research Site
state: Republic Of Korea
city: Incheon
country: Korea, Republic of
facility: Research Site
state: Republic Of Korea
city: Seoul
country: Korea, Republic of
facility: Research Site
state: Republic Of Korea
city: Saltillo
country: Mexico
facility: Research Site
state: Coahuila
city: Guadalajara
country: Mexico
facility: Research Site
state: Jalisco
city: Guadalajara
country: Mexico
facility: Research Site
state: Jalisco
city: Ciudad de mexico
country: Mexico
facility: Research Site
city: Lima
country: Peru
facility: Research Site
state: San Martin De Porres
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Elbląg
country: Poland
facility: Research Site
state: Elblag
city: Krakow
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Siedlce
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung City
country: Taiwan
facility: Research Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: Research Site
city: Truro
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.