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

Rheumatoid Arthritis Clinical Trial

— MIDORA  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04163991
• Other study ID #: VIB4920.P2.S3
• Secondary ID: 2019-003697-70
• Status: Completed
• Phase: Phase 2
• Start date: December 9, 2019
• Est. completion date: December 28, 2021

Study information

• Verified date: January 2023
• Source: Viela Bio (acquired by Horizon Therapeutics)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: December 28, 2021
• Est. primary completion date: December 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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-a) 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-a 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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• VIB4920
liquid for IV infusion following dilution in normal saline
• Placebo
0.9% saline for IV infusion

Locations

Country	Name	City	State
Poland	Research Site	Bialystok	Podlaskie
Poland	Research Site	Elblag	Warminsko-mazurskie
Poland	Research Site	Krakow	Malopolskie
Poland	Research Site	Nadarzyn	Mazowieckie
Poland	Research Site	Poznan	Wielkopolskie
Poland	Research Site	Siedlce	Mazowieckie
Poland	Research Site	Warszawa
United States	Research Site	Anniston	Alabama
United States	Research Site	Atlanta	Georgia
United States	Research Site	Baytown	Texas
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Clearwater	Florida
United States	Research Site	Dallas	Texas
United States	Research Site	Duncansville	Pennsylvania
United States	Research Site	Lexington	Kentucky
United States	Research Site	Margate	Florida
United States	Research Site	Miami Lakes	Florida
United States	Research Site	Norman	Oklahoma
United States	Research Site	Rocky Mount	North Carolina
United States	Research Site	Salisbury	North Carolina
United States	Research Site	Sun City	Arizona
United States	Research Site	Upland	California
United States	Research Site	Vandalia	Ohio
United States	Research Site	Wheaton	Maryland
United States	Research Site	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Viela Bio (acquired by Horizon Therapeutics)

Countries where clinical trial is conducted

United States,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	PK of VIB4920: Terminal Elimination Half-Life (t1/2)		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
Secondary	PK of VIB4920: Volume of Distribution at Steady State (Vss)		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
Secondary	Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time	Total sCD40L (free sCD40L and sCD40L bound to VIB4920) was measured in plasma samples using a modified commercially available kit.	Day 1 (Baseline), Days 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309
Secondary	Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920	ADA positive at any time: observed at least once during the study (baseline included).; Treatment-emergent ADA: ADA positive post-baseline only or boosted pre-existing ADA during the study period.; Persistent positive: treatment-induced ADA positive at = 2 post-baseline assessments (with = 16 weeks between first and last positive) or positive at last post-baseline assessment.; Transient positive: treatment-induced ADA post-baseline positive but does not fulfill the criteria of persistent positive.	Day 1 (Baseline) to Day 309 Day 1 (Baseline) up to Day 309 (± 7 days)
Secondary	Change From Baseline to Day 113 in Anti-Citrullinated Protein Antibodies (ACPAs)	Excluding data after rescue. Adjusted geometric mean ratio to baseline (90% CI) results are from MMRM analysis on log(ratio to baseline) with treatment, visit, visit by treatment interaction, and log(baseline) included in the model. Ratios less than 1 indicate a decrease.	Day 1 (Baseline), Day 113
Secondary	Change From Baseline to Day 113 in Rheumatoid Factor (RF)	Excluding data after rescue. Adjusted geometric mean ratio to baseline (90% CI) results are from MMRM analysis on log(ratio to baseline) with treatment, visit, visit by treatment interaction, and log(baseline) included in the model. Ratios less than 1 indicate a decrease.	Day 1 (Baseline), Day 113
Secondary	Percentage of Participants With Clinical Remission at Day 113	Clinical remission is defined as DAS28-CRP < 2.6. 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.	Day 113
Secondary	Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication)	Based on Kaplan-Meier method.	Day 1 (Baseline) up to Day 309 (± 7 days)