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

• ClinicalTrials.gov Identifier: NCT04163991
• Recruitment Status: Completed
• First Posted: November 15, 2019
• Last Update Posted: February 16, 2022
• Sponsor: Viela Bio
• Information provided by (Responsible Party): Viela Bio (acquired by Horizon Therapeutics) ( Viela Bio )

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: VIB4920; Drug: Placebo	Phase 2

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-rheumatoid arthritis (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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 78 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: December 9, 2019
• Actual Primary Completion Date: December 28, 2021
• Actual Study Completion Date: December 28, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: VIB4920 Dose1 (dosing interval 1); Participants will receive intravenous (IV) infusion of VIB4920 Dose1 in dosing interval 1.	Drug: VIB4920; VIB4920 Dose 1 or 2 will be administered intravenously per dosing interval of 1 or 2 or 4.; Other Name: MEDI4920
Experimental: VIB4920 Dose1 (dosing interval 2)+Placebo (dosing interval 3); Participants will receive IV infusion of VIB4920 Dose1 in dosing interval 2 and placebo matched to VIB4920 in dosing interval 3.	Drug: VIB4920; VIB4920 Dose 1 or 2 will be administered intravenously per dosing interval of 1 or 2 or 4.; Other Name: MEDI4920; Drug: Placebo; Placebo will be administered intravenously per dosing interval of 1 or 3 or 5.
Experimental: VIB4920 Dose2 (dosing interval 2)+Placebo (dosing interval 3); Participants will receive IV infusion of VIB4920 Dose2 in dosing interval 2 and placebo matched to VIB4920 in dosing interval 3.	Drug: VIB4920; VIB4920 Dose 1 or 2 will be administered intravenously per dosing interval of 1 or 2 or 4.; Other Name: MEDI4920; Drug: Placebo; Placebo will be administered intravenously per dosing interval of 1 or 3 or 5.
Experimental: VIB4920 Dose2 (dosing interval 4)+Placebo (dosing interval 5); Participants will receive IV infusion of VIB4920 Dose2 in dosing interval 4 and placebo matched to VIB4920 in dosing interval 5.	Drug: VIB4920; VIB4920 Dose 1 or 2 will be administered intravenously per dosing interval of 1 or 2 or 4.; Other Name: MEDI4920; Drug: Placebo; Placebo will be administered intravenously per dosing interval of 1 or 3 or 5.
Placebo Comparator: Placebo (dosing interval 1); Participants will receive IV infusion of placebo matched to VIB4920 in dosing interval 1.	Drug: Placebo; Placebo will be administered intravenously per dosing interval of 1 or 3 or 5.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline to Day 113 in Disease Activity Score in 28 Joints Using C-reactive Protein (DAS28-CRP) (range: 1-10; higher score is worse outcome) [ Time Frame: Day 1 (Baseline) through Day 113 ]
2. Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) [ Time Frame: Day 1 (Baseline) through Day 309 ]

Secondary Outcome Measures :

1. Plasma Concentration of VIB4920 [ Time Frame: Day 1 to Day 225 ]
2. Total Soluble Cluster of Differentiation 40 (sCD40L) Plasma Concentration [ Time Frame: Day 1 (Baseline) through Day 309 ]
3. Percentage of Participants With Positive Anti-drug Antibodies (ADA) Titre to VIB4920 [ Time Frame: Day 1 (Baseline) to Day 309 ]
4. Change in Rheumatoid Factor (RF) From Baseline to Day 113 [ Time Frame: Day 1 (Baseline) through Day 113 ]
5. Change in Anti-citrullinated Protein Antibodies (ACPAs) From Baseline to Day 113 [ Time Frame: Day 1 (Baseline) through Day 113 ]
6. Percentage of Participants With Clinical Remission at Day 113 [ Time Frame: Day 113 ]
7. Time to Start of New Treatment for RA [ Time Frame: Day 1 (Baseline) through Day 309 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 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 RF and/or 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-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.

Contacts and Locations

Locations

United States, Alabama

Research Site

Anniston, Alabama, United States, 36207

United States, Arizona

Research Site

Sun City, Arizona, United States, 85704

United States, California

Research Site

Upland, California, United States, 91786

United States, Florida

Research Site

Clearwater, Florida, United States, 33765

Research Site

Margate, Florida, United States, 33063

Research Site

Miami Lakes, Florida, United States, 33014

Research Site

Zephyrhills, Florida, United States, 33542

United States, Georgia

Research Site

Atlanta, Georgia, United States, 30342

United States, Kentucky

Research Site

Lexington, Kentucky, United States, 40504

United States, Maryland

Research Site

Wheaton, Maryland, United States, 20902

United States, North Carolina

Research Site

Charlotte, North Carolina, United States, 28210

Research Site

Rocky Mount, North Carolina, United States, 27804

Research Site

Salisbury, North Carolina, United States, 28144

United States, Ohio

Research Site

Vandalia, Ohio, United States, 45377

United States, Oklahoma

Research Site

Norman, Oklahoma, United States, 73069

United States, Pennsylvania

Research Site

Duncansville, Pennsylvania, United States, 16635

United States, Texas

Research Site

Baytown, Texas, United States, 77477

Research Site

Dallas, Texas, United States, 75231

Poland

Research Site

Nadarzyn, Mazowieckie, Poland

Research Site

Siedlce, Mazowieckie, Poland

Research Site

Krakow, Małopolskie, Poland

Research Site

Bialystok, Podlaskie, Poland

Research Site

Elblag, Warmińsko-mazurskie, Poland

Research Site

Poznan, Wielkopolskie, Poland

Research Site

Warszawa, Poland

Sponsors and Collaborators

Viela Bio

Investigators

• Study Director: Gabor Illei, PhD, MD, MHS; Viela Bio

More Information

• Responsible Party: Viela Bio
• ClinicalTrials.gov Identifier: NCT04163991
• Other Study ID Numbers: VIB4920.P2.S3; 2019-003697-70 ( EudraCT Number )
• First Posted: November 15, 2019
• Last Update Posted: February 16, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Viela Bio (acquired by Horizon Therapeutics) ( Viela Bio ):

Rheumatoid Arthritis; RA; VIB4920; MEDI4920

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases