Clinical trial NCT04163991: A Study to Evaluate the Safety and Efficacy of VIB4920 in Participants With Rheumatoid Arthritis
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Mechanistic Insight and Dosage Optimization Study of the Efficacy and Safety of VIB4920 in Patients With Rheumatoid Arthritis (RA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
RA
VIB4920
MEDI4920
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2019-11-15
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
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 pharmacokinetics (PK) of VIB4920 (formerly MEDI4920) in adult participants with rheumatoid arthritis (RA).

Detailed description: The overall study period will be approximately 337 days. After a screening period of up to 28 days, the participants will be randomized in a 1:1:1:1:1 ratio to receive intravenous dose of VIB4920 and/or placebo in 5 cohorts. Participants are to be followed on their stable background anti-RA therapy at least through 12 weeks (Day 85), at which time rescue therapy may be instituted. All participants will be followed at least through the primary (interim) analysis (Day 113), and those who have not instituted rescue therapy will be followed through Day 309 to determine the duration of clinical response. The primary analysis will be after all participants have completed Day 113, and the final analysis will be after all participants have completed follow-up.

Study with completed results acquired from Horizon in 2024.

Eligibility criteria: Principal Inclusion Criteria:

1. Male or female adults, \>= 18 years of age at time of informed consent.
2. Diagnosed with RA according to the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2010 criteria \>= 6 months prior to screening.
3. Disease Activity Score in 28 Joints (DAS 28) using C-reactive Protein (DAS28-CRP) \> 3.2 at screening with \>= 4 tender joint count (TJC) and \>= 4 swollen joint count (SJC) out of the 28 joints assessed for DAS28 present at screening and confirmed present at visit 2 prior to randomization.
4. Positive for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA) at screening, in accordance with criteria at the central laboratory.
5. Treated with methotrexate (MTX), with or without a concomitant conventional disease-modifying anti-rheumatic drug (cDMARD).
6. Agreeing to use of protocol defined contraception methods.

Principal Exclusion Criteria:

1. Prior or current inflammatory joint disease other than RA.
2. Severe interstitial lung disease.
3. Prior receipt of any biologic B-cell-depleting therapy.
4. Receipt of any anti - tumor necrosis factor alpha (TNF-α) biologic agent \< 8 weeks prior to screening.
5. Receipt of any biologic disease-modifying anti-rheumatic drug (bDMARD) with a mechanism of action other than direct TNF-α blockade, \< 12 weeks or \< 5 half-lives of the drug prior to screening.
6. Injectable corticosteroids or treatment with \> 10 mg/day dose of oral prednisolone or equivalent within 4 weeks prior to screening.
7. Previous treatment with anti-cluster of differentiation 40 ligand (CD40L) compounds at any time before randomization.
8. Hepatitis B, hepatitis C, or human immunodeficiency virus infection.
9. Pregnant or lactating or planning to get pregnant during the duration of the study.
10. Evidence of active tuberculosis (TB) or being at high risk for TB.
11. History of more than one episode of herpes zoster in the 12 months prior to screening or any opportunistic infection in the 12 months prior to screening, excluding localized mucocutaneous candidiasis.
12. Receipt of live vaccine or live therapeutic infectious agent within the 4 weeks prior to screening.

Primary outcomes:
measure: Change From Baseline to Day 113 in DAS28-CRP
timeFrame: Day 1 (Baseline), Day 113
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs)
timeFrame: From first dose of study drug through Day 309 ± 7 days
Secondary outcomes:
measure: Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax)
timeFrame: Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d
measure: PK of VIB4920: Time to Cmax (Tmax)
timeFrame: Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d
measure: PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast)
timeFrame: Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d
measure: PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to Day 56 (AUC0-56D)
timeFrame: Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), Day 56
measure: PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4
timeFrame: Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d
measure: PK of VIB4920: Terminal Elimination Half-Life (t1/2)
timeFrame: Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d
measure: PK of VIB4920: Volume of Distribution at Steady State (Vss)
timeFrame: Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d
measure: Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time
timeFrame: Day 1 (Baseline), Days 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309
measure: Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920
timeFrame: Day 1 (Baseline) to Day 309 Day 1 (Baseline) up to Day 309 (± 7 days)
measure: Change From Baseline to Day 113 in Anti-Citrullinated Protein Antibodies (ACPAs)
timeFrame: Day 1 (Baseline), Day 113
measure: Change From Baseline to Day 113 in Rheumatoid Factor (RF)
timeFrame: Day 1 (Baseline), Day 113
measure: Percentage of Participants With Clinical Remission at Day 113
timeFrame: Day 113
measure: Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication)
timeFrame: Day 1 (Baseline) up to Day 309 (± 7 days)
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Research Site
state: Alabama
city: Sun City
country: United States
facility: Research Site
state: Arizona
city: Upland
country: United States
facility: Research Site
state: California
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: Margate
country: United States
facility: Research Site
state: Florida
city: Miami Lakes
country: United States
facility: Research Site
state: Florida
city: Zephyrhills
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Wheaton
country: United States
facility: Research Site
state: Maryland
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Rocky Mount
country: United States
facility: Research Site
state: North Carolina
city: Salisbury
country: United States
facility: Research Site
state: North Carolina
city: Vandalia
country: United States
facility: Research Site
state: Ohio
city: Norman
country: United States
facility: Research Site
state: Oklahoma
city: Duncansville
country: United States
facility: Research Site
state: Pennsylvania
city: Baytown
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Nadarzyn
country: Poland
facility: Research Site
state: Mazowieckie
city: Siedlce
country: Poland
facility: Research Site
state: Mazowieckie
city: Krakow
country: Poland
facility: Research Site
state: Małopolskie
city: Bialystok
country: Poland
facility: Research Site
state: Podlaskie
city: Elblag
country: Poland
facility: Research Site
state: Warmińsko-mazurskie
city: Poznan
country: Poland
facility: Research Site
state: Wielkopolskie
city: Warszawa
country: Poland
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: