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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04163991
Recruitment Status : Completed
First Posted : November 15, 2019
Results First Posted : February 14, 2023
Last Update Posted : February 14, 2023
Sponsor:
Information provided by (Responsible Party):
Viela Bio (acquired by Horizon Therapeutics)

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-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.

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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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: VIB4920 1500 mg 4 Times
Participants receive intravenous (IV) infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57
Drug: VIB4920
liquid for IV infusion following dilution in normal saline
Other Names:
  • MEDI4920
  • dazodalibep

Experimental: VIB4920 1500 mg Twice
Participants receive IV infusion of VIB4920 1500 mg on Days 1 and 57, placebo on Days 15 and 29.
Drug: VIB4920
liquid for IV infusion following dilution in normal saline
Other Names:
  • MEDI4920
  • dazodalibep

Drug: Placebo
0.9% saline for IV infusion

Experimental: VIB4920 3000 mg Twice
Participants receive IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29.
Drug: VIB4920
liquid for IV infusion following dilution in normal saline
Other Names:
  • MEDI4920
  • dazodalibep

Drug: Placebo
0.9% saline for IV infusion

Experimental: VIB4920 3000 mg Once
Participants receive IV infusion of VIB4920 3000 mg on Day 1 and placebo on Days 15, 29, and 57.
Drug: VIB4920
liquid for IV infusion following dilution in normal saline
Other Names:
  • MEDI4920
  • dazodalibep

Drug: Placebo
0.9% saline for IV infusion

Placebo Comparator: Placebo
Participants receive IV infusion of placebo matched to VIB4920 on Days 1, 15, 29, and 57.
Drug: Placebo
0.9% saline for IV infusion




Primary Outcome Measures :
  1. Change From Baseline to Day 113 in DAS28-CRP [ Time Frame: Day 1 (Baseline), Day 113 ]
    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.

  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: From first dose of study drug through Day 309 ± 7 days ]
    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.)


Secondary Outcome Measures :
  1. Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax) [ Time Frame: 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 ]
  2. PK of VIB4920: Time to Cmax (Tmax) [ Time Frame: 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 ]
  3. PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) [ Time Frame: 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 ]
  4. PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to Day 56 (AUC0-56D) [ Time Frame: 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 ]
  5. PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4 [ Time Frame: 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 ]
  6. PK of VIB4920: Terminal Elimination Half-Life (t1/2) [ Time Frame: 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 ]
  7. PK of VIB4920: Volume of Distribution at Steady State (Vss) [ Time Frame: 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 ]
  8. Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time [ Time Frame: Day 1 (Baseline), Days 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309 ]
    Total sCD40L (free sCD40L and sCD40L bound to VIB4920) was measured in plasma samples using a modified commercially available kit.

  9. Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 [ Time Frame: Day 1 (Baseline) to Day 309 Day 1 (Baseline) up to Day 309 (± 7 days) ]

    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.


  10. Change From Baseline to Day 113 in Anti-Citrullinated Protein Antibodies (ACPAs) [ Time Frame: Day 1 (Baseline), Day 113 ]
    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.

  11. Change From Baseline to Day 113 in Rheumatoid Factor (RF) [ Time Frame: Day 1 (Baseline), Day 113 ]
    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.

  12. Percentage of Participants With Clinical Remission at Day 113 [ Time Frame: 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.

  13. Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication) [ Time Frame: Day 1 (Baseline) up to Day 309 (± 7 days) ]
    Based on Kaplan-Meier method.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 (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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04163991


Locations
Layout table for location information
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 (acquired by Horizon Therapeutics)
Investigators
Layout table for investigator information
Study Director: Ilias Alevizos, PhD, DMD Horizon Therapeutics
  Study Documents (Full-Text)

Documents provided by Viela Bio (acquired by Horizon Therapeutics):
Study Protocol  [PDF] October 2, 2020
Statistical Analysis Plan  [PDF] June 7, 2021

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Responsible Party: Viela Bio (acquired by Horizon Therapeutics)
ClinicalTrials.gov Identifier: NCT04163991    
Other Study ID Numbers: VIB4920.P2.S3
2019-003697-70 ( EudraCT Number )
First Posted: November 15, 2019    Key Record Dates
Results First Posted: February 14, 2023
Last Update Posted: February 14, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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):
Rheumatoid Arthritis
RA
VIB4920
MEDI4920
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases