VIB4920 for Rheumatoid Arthritis

(CONTROL-RA Trial)

No longer recruiting at 12 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: TNFi therapy

Must not be taking: B cell depleting, JAK inhibitors

Disqualifiers: Autoimmune diseases, Infections, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called VIB4920 for individuals with rheumatoid arthritis (RA) who haven't found success with their current TNFi (tumor necrosis factor inhibitor) medications. The researchers aim to determine if adding VIB4920 can better control RA symptoms. Participants will receive either VIB4920 with their current TNFi, VIB4920 without TNFi, or a placebo (a harmless, inactive substance) alongside their TNFi. Individuals with RA who have been on TNFi treatment for at least 12 weeks but still experience symptoms may be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for this trial?

The trial does not require you to stop your current medications, but you must be on a stable dose of certain medications like methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine for at least 12 weeks. You may need to continue or discontinue your current TNFi treatment depending on your study group.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that VIB4920 is safe and well-tolerated in past studies. For instance, one study involved patients with rheumatoid arthritis who didn't respond well to other treatments. This study found that most participants handled VIB4920 well. While some side effects might occur, they were usually not serious. Several studies have tested this treatment, and the results suggest it is safe for humans. However, individual reactions can differ with any treatment. Discuss potential risks and benefits with the study team or your doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about VIB4920 for rheumatoid arthritis because it targets the CD40-CD40L pathway, a novel mechanism compared to standard treatments like TNF inhibitors. Unlike typical therapies that often suppress broad immune functions, VIB4920 aims to modulate a specific immune response, potentially offering a more precise treatment with fewer side effects. Additionally, VIB4920 is administered intravenously at designated intervals, which might improve adherence and convenience for patients compared to daily oral medications. This targeted approach could lead to more effective disease control and improved quality of life for those suffering from rheumatoid arthritis.

What evidence suggests that VIB4920 might be an effective treatment for rheumatoid arthritis?

Research has shown that VIB4920 may help treat rheumatoid arthritis (RA). In earlier studies, VIB4920 effectively reduced joint pain and swelling in people with RA. Another study successfully met its main goal of improving RA symptoms over time. These results suggest that VIB4920 could be a good option for those who haven't had success with other RA treatments. In this trial, participants will receive VIB4920 either with or without TNFi, or a placebo with TNFi, to evaluate its potential to better manage the disease, especially when used with current therapies. ^{2 3 5 6 7}

Who Is on the Research Team?

Eugene William St. Clair

Principal Investigator

Duke University Medical Center: Division of Rheumatology and Immunology

Are You a Good Fit for This Trial?

Adults aged 18-70 with Rheumatoid Arthritis (RA) who haven't responded well to TNFi treatments can join. They must have been diagnosed at least 6 months ago, show certain levels of disease activity and joint tenderness/swelling, and be on stable doses of specific RA medications. Participants need to be vaccinated against COVID-19 as per CDC guidelines for immunocompromised individuals.

Inclusion Criteria

I have been on a stable TNFi treatment for at least 12 weeks and am open to adjusting it for the study.

I can understand and agree to the study's requirements.

SDAI ≥ 17

Exclusion Criteria

Platelet count < 100 x 103/μl

Use of glucocorticoid and/or disease-modifying therapies as specified including prior treatment with any B cell depleting therapy, history of treatment with more than two different TNFi, treatment with other biologic therapy not targeting TNF-α, treatment with a JAK inhibitor, concurrent use of methotrexate and leflunomide in combination, prednisone > 10 mg a day or equivalent glucocorticoid use within the previous 4 weeks, intramuscular, intra-articular, or intravenous glucocorticoids within the previous 4 weeks, other immunomodulatory medications within the previous 12 weeks except for methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine, lack of any subjective or objective clinical response to current TNFi use, use of an investigational agent including VIB4920 in the past 30 days or 5 half-lives, history of severe allergy, hypersensitivity reaction, or infusion reaction to any component of the VIB4920 formulation, history of Felty's syndrome, history of interstitial lung disease, deep venous thrombosis or thromboembolism in the prior two years

I have had infections or symptoms related to hepatitis, HIV, tuberculosis, COVID-19, herpes zoster, opportunistic infections, or recurrent lung infections in the past year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VIB4920 or placebo intravenously at weeks 0, 2, 4, 8, and 12, with continued background RA therapy

12 weeks

5 visits (in-person)

Post-administration observation

Participants are monitored for safety and efficacy after the treatment phase

28 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VIB4920

Trial Overview The trial is testing VIB4920, a new potential treatment for RA. Some patients will add VIB4920 to their current TNFi therapy for 12 weeks, while others will take it without TNFi or receive a placebo. The goal is to see if VIB4920 improves symptoms in those not helped by TNFi alone.

How Is the Trial Designed?

Group I: VIB4920 without TNFi Experimental Treatment 1 Intervention

Participants will stop TNFi after randomization to this arm, and receive VIB4920 in an evaluator-blinded fashion intravenously at a dose of 1500 mg at weeks 0, 2, 4, 8, and 12 while maintaining all other background disease-modifying RA therapy (e.g., methotrexate, hydroxychloroquine, etc.) through the study period. This arm is evaluator blinded (not aware of treatment status), with the participant aware of treatment status but evaluator is not, due to not using a TNFi placebo for this study

Group II: VIB4920 with TNFi Experimental Treatment 1 Intervention

Participants will receive VIB4920 in a blinded fashion intravenously at a dose of 1500 mg at weeks 0, 2, 4, 8, and 12 and continue all background disease-modifying RA therapy, including the TNFi, through the study period

Group III: VIB4920 Placebo with TNFi Placebo Group 1 Intervention

Participants will receive VIB4920 placebo in a blinded fashion intravenously at weeks 0, 2, 4, 8, and 12 and continue all background disease-modifying RA therapy, including the TNFi, through the study period VIB4920 placebo consists of 0.9% normal saline in 250mL bags.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Immune Tolerance Network (ITN)

Collaborator

Trials

68

Recruited

7,900+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10407378/

The MIDORA trial: a phase II, randomised, double-blind ... These study results support the continued evaluation of DAZ for the treatment of RA and other autoimmune disorders. DAZ dosing with more widely ...

2. control-ra.org control-ra.org/about-control-ra

About CONTROL-RA In a previous study, VIB4920 was found to be safe, tolerable, and effective in reducing joint pain and swelling in patients with rheumatoid arthritis. VIB4920 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04163991

NCT04163991 | A Study to Evaluate the Safety and ... The purpose of the study is to evaluate the efficacy, safety, and pharmacokinetics (PK) of VIB4920 (formerly MEDI4920) in adult participants with rheumatoid ...

4. acrabstracts.org acrabstracts.org/abstract/a-phase-2-randomized-double-blind-placebo-controlled-mechanistic-insight-and-dosage-optimization-study-of-the-efficacy-and-safety-of-dazodalibep-vib4920-hzn4920-in-patients-with-rheumatoid-arthr/

A Phase 2, Randomized, Double-Blind, Placebo ... ... Study of the Efficacy and Safety of Dazodalibep (VIB4920/HZN4920) in Patients with Rheumatoid Arthritis Having Inadequate Response to Conventional/Biological ...

5. firstwordpharma.com firstwordpharma.com/story/5562249

Topline Data for Dazodalibep (HZN-4920) Meets Primary ... The study met its primary endpoint of change from baseline in DAS28-CRP at Day 113 in all four dazodalibep dosing arms. This endpoint is a ...

6. ard.bmj.com ard.bmj.com/content/82/Suppl_1/95.1

OP0143 EFFICACY AND SAFETY OF DAZODALIBEP ... The objective of this study was to evaluate the efficacy and safety of DAZ therapy in adult SS subjects with moderate-to-high systemic disease activity.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003496724635983

OP0143 EFFICACY AND SAFETY OF DAZODALIBEP ... The objective of this study was to evaluate the efficacy and safety of DAZ therapy in adult SS subjects with moderate-to-high systemic disease activity.