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Rheumatoid ArthritisPhase 2MIDORANCT04163991

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

A Phase 2 study testing VIB4920 in people with Rheumatoid Arthritis, run by Amgen at 25 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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). Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
VIB4920
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
78 participants
Where
25 sitesin 2 countries
Study dates
9 Dec 2019to 28 Dec 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Trial locations and contacts

25 sites in 2 countries.

25 sites in 2 countries

United States18 sites

  • Research Site

    Anniston, Alabama, 36207

  • Research Site

    Atlanta, Georgia, 30342

  • Research Site

    Baytown, Texas, 77477

  • Research Site

    Charlotte, North Carolina, 28210

  • Research Site

    Clearwater, Florida, 33765

  • Research Site

    Dallas, Texas, 75231

  • Research Site

    Duncansville, Pennsylvania, 16635

  • Research Site

    Lexington, Kentucky, 40504

  • Research Site

    Margate, Florida, 33063

  • Research Site

    Miami Lakes, Florida, 33014

  • Research Site

    Norman, Oklahoma, 73069

  • Research Site

    Rocky Mount, North Carolina, 27804

  • Research Site

    Salisbury, North Carolina, 28144

  • Research Site

    Sun City, Arizona, 85704

  • Research Site

    Upland, California, 91786

  • Research Site

    Vandalia, Ohio, 45377

  • Research Site

    Wheaton, Maryland, 20902

  • Research Site

    Zephyrhills, Florida, 33542

Other trials in United States

Poland7 sites

  • Research Site

    Bialystok, Podlaskie Voivodeship

  • Research Site

    Elblag, Warmian-Masurian Voivodeship

  • Research Site

    Krakow, Lesser Poland Voivodeship

  • Research Site

    Nadarzyn, Masovian Voivodeship

  • Research Site

    Poznan, Greater Poland Voivodeship

  • Research Site

    Siedlce, Masovian Voivodeship

  • Research Site

    Warsaw

Other trials in Poland

About this study

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)

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).

Read the 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.

Being tested
VIB4920, Placebo
Keywords
Rheumatoid Arthritis, RA, VIB4920, MEDI4920
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VIB4920Drug

    Also called MEDI4920, dazodalibep

    liquid for IV infusion following dilution in normal saline

  • PlaceboDrug

    0.9% saline for IV infusion

Study groups in NCT04163991
Study groupRoleWhat they receive
VIB4920 1500 mg 4 TimesExperimentalParticipants receive intravenous (IV) infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57
Receives: Drug: VIB4920
VIB4920 1500 mg TwiceExperimentalParticipants receive IV infusion of VIB4920 1500 mg on Days 1 and 57, placebo on Days 15 and 29.
Receives: Drug: VIB4920; Drug: Placebo
VIB4920 3000 mg TwiceExperimentalParticipants receive IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29.
Receives: Drug: VIB4920; Drug: Placebo
VIB4920 3000 mg OnceExperimentalParticipants receive IV infusion of VIB4920 3000 mg on Day 1 and placebo on Days 15, 29, and 57.
Receives: Drug: VIB4920; Drug: Placebo
PlaceboPlacebo comparatorParticipants receive IV infusion of placebo matched to VIB4920 on Days 1, 15, 29, and 57.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Day 1 (Baseline), 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)

    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.)

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

Secondary outcomes (13)

  1. Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax)

    Measured: 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)

    Measured: 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)

    Measured: 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)

    Measured: 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

    Measured: 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)

    Measured: 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)

    Measured: 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

    Total sCD40L (free sCD40L and sCD40L bound to VIB4920) was measured in plasma samples using a modified commercially available kit.

    Measured: Day 1 (Baseline), Days 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309

  9. 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.

    Measured: Day 1 (Baseline) to Day 309 Day 1 (Baseline) up to Day 309 (± 7 days)

  10. 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.

    Measured: Day 1 (Baseline), Day 113

  11. 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.

    Measured: Day 1 (Baseline), Day 113

  12. 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.

    Measured: Day 113

  13. Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication)

    Based on Kaplan-Meier method.

    Measured: Day 1 (Baseline) up to Day 309 (± 7 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Nov 2019
  2. Study start9 Dec 2019
  3. Primary completion28 Dec 2021
  4. Study completion28 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04163991
Sponsor's protocol ID
VIB4920.P2.S3
Other IDs
2019-003697-70, 2019
Acronym
MIDORA
Status last verified
Dec 2024
First submitted
12 Nov 2019
Last updated
17 Dec 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 37541743

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing VIB4920 in people with Rheumatoid Arthritis, run by Amgen at 25 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to Day 113 in DAS28-CRP (time frame: Day 1 (Baseline), Day 113). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04163991, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2024.

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