A Study to Evaluate the Safety and Efficacy of VIB4920 in Participants With Rheumatoid Arthritis

NCT04163991 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: VIB4920.P2.S32019-003697-70
• Study Type: interventional
• Target: 78
• Locations: 2 countries
• Sites: 25

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).

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; RA; VIB4920; MEDI4920

Outcome Measures

Primary Outcomes (2)

• Change From Baseline to Day 113 in DAS28-CRP

  The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from baseline indicates improvement in disease activity. Results are from a mixed-effect model for repeated measures (MMRM) analysis with treatment, visit, visit by treatment interaction, and baseline DAS28-CRP score included in the model.

  Day 1 (Baseline), Day 113

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs)

  Adverse event (AE): any untoward medical occurrence associated with the use of an intervention in humans, whether or not it is considered intervention-related. Serious adverse event (SAE): an AE that results in any of the following outcomes: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity; congenital anomaly/birth defect; other important medical event jeopardizing the participant's well-being. AEs of special interest (AESIs) include: thrombotic and embolic events; anaphylaxis and clinically significant (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 3 or higher) hypersensitivity reactions; severe infusion-related reactions (CTCAE Grade 3 or higher); immune complex disease; severe (CTCAE Grade 3 or higher) and/or opportunistic infections; hepatic function abnormality meeting the definition of Hy's Law; malignant neoplasm. (CTCAE Grade 3=Severe; Grade 4=Life-threatening; Grade 5=Fatal.)

  From first dose of study drug through Day 309 ± 7 days

Secondary Outcomes (13)

• Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax)

  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

• PK of VIB4920: Time to Cmax (Tmax)

  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

• PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast)

  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

• PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to Day 56 (AUC0-56D)

  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

• PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4

  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

Study Arms (5)

VIB4920 1500 mg 4 Times

EXPERIMENTAL

Participants receive intravenous (IV) infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57

Drug: VIB4920

VIB4920 1500 mg Twice

EXPERIMENTAL

Participants receive IV infusion of VIB4920 1500 mg on Days 1 and 57, placebo on Days 15 and 29.

Drug: VIB4920; Drug: Placebo

VIB4920 3000 mg Twice

EXPERIMENTAL

Participants receive IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29.

Drug: VIB4920; Drug: Placebo

VIB4920 3000 mg Once

EXPERIMENTAL

Participants receive IV infusion of VIB4920 3000 mg on Day 1 and placebo on Days 15, 29, and 57.

Drug: VIB4920; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Participants receive IV infusion of placebo matched to VIB4920 on Days 1, 15, 29, and 57.

Drug: Placebo

Interventions

VIB4920 DRUG

liquid for IV infusion following dilution in normal saline

Also known as: MEDI4920, dazodalibep

VIB4920 1500 mg 4 Times; VIB4920 1500 mg Twice; VIB4920 3000 mg Once; VIB4920 3000 mg Twice

Placebo DRUG

0.9% saline for IV infusion

Placebo; VIB4920 1500 mg Twice; VIB4920 3000 mg Once; VIB4920 3000 mg Twice

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female adults, \>= 18 years of age at time of informed consent.
• Diagnosed with RA according to the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2010 criteria \>= 6 months prior to screening.
• 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.
• Positive for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA) at screening, in accordance with criteria at the central laboratory.
• Treated with methotrexate (MTX), with or without a concomitant conventional disease-modifying anti-rheumatic drug (cDMARD).
• Agreeing to use of protocol defined contraception methods.

You may not qualify if:

• Prior or current inflammatory joint disease other than RA.
• Severe interstitial lung disease.
• Prior receipt of any biologic B-cell-depleting therapy.
• Receipt of any anti - tumor necrosis factor alpha (TNF-α) biologic agent \< 8 weeks prior to screening.
• 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.
• Injectable corticosteroids or treatment with \> 10 mg/day dose of oral prednisolone or equivalent within 4 weeks prior to screening.
• Previous treatment with anti-cluster of differentiation 40 ligand (CD40L) compounds at any time before randomization.
• Hepatitis B, hepatitis C, or human immunodeficiency virus infection.
• Pregnant or lactating or planning to get pregnant during the duration of the study.
• Evidence of active tuberculosis (TB) or being at high risk for TB.
• 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.
• Receipt of live vaccine or live therapeutic infectious agent within the 4 weeks prior to screening.

Sponsors & Collaborators

• Amgen: lead

Study Sites (25)

Research Site

Anniston, Alabama, 36207, United States

Location

Research Site

Sun City, Arizona, 85704, United States

Location

Research Site

Upland, California, 91786, United States

Location

Research Site

Clearwater, Florida, 33765, United States

Location

Research Site

Margate, Florida, 33063, United States

Location

Research Site

Miami Lakes, Florida, 33014, United States

Location

Research Site

Zephyrhills, Florida, 33542, United States

Location

Research Site

Atlanta, Georgia, 30342, United States

Location

Research Site

Lexington, Kentucky, 40504, United States

Location

Research Site

Wheaton, Maryland, 20902, United States

Location

Research Site

Charlotte, North Carolina, 28210, United States

Location

Research Site

Rocky Mount, North Carolina, 27804, United States

Location

Research Site

Salisbury, North Carolina, 28144, United States

Location

Research Site

Vandalia, Ohio, 45377, United States

Location

Research Site

Norman, Oklahoma, 73069, United States

Location

Research Site

Duncansville, Pennsylvania, 16635, United States

Location

Research Site

Baytown, Texas, 77477, United States

Location

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Dallas, Texas, 75231, United States

Location

Research Site

Poznan, Greater Poland Voivodeship, Poland

Location

Research Site

Krakow, Lesser Poland Voivodeship, Poland

Location

Research Site

Nadarzyn, Masovian Voivodeship, Poland

Location

Research Site

Siedlce, Masovian Voivodeship, Poland

Location

Research Site

Bialystok, Podlaskie Voivodeship, Poland

Location

Research Site

Elblag, Warmian-Masurian Voivodeship, Poland

Location

Research Site

Warsaw, Poland

Location

Related Publications (1)

• Kivitz A, Wang L, Alevizos I, Gunsior M, Falloon J, Illei G, St Clair EW. The MIDORA trial: a phase II, randomised, double-blind, placebo-controlled, mechanistic insight and dosage optimisation study of the efficacy and safety of dazodalibep in patients with rheumatoid arthritis. RMD Open. 2023 Aug;9(3):e003317. doi: 10.1136/rmdopen-2023-003317.

  PMID: 37541743 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Ilias Alevizos, PhD, DMD
• Organization: Horizon Therapeutics USA, Inc.

clinicaltrials@horizontherapeutics.com

866-479-6742

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2019
• First Posted: November 15, 2019
• Study Start: December 9, 2019
• Primary Completion: December 28, 2021
• Study Completion: December 28, 2021
• Last Updated: December 17, 2024
• Results First Posted: February 14, 2023

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (18); PL (7)