Abatacept for Giant Cell Arteritis

Recruiting at 8 trial locations

Overseen By Carol McAlear, MA

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Pennsylvania

Must not be taking: Immunosuppressants, Alkylating agents

Disqualifiers: Infections, Immunodeficiency, Malignancy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

78 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether abatacept, a type of immunotherapy, can treat giant cell arteritis (GCA), a condition causing inflammation of the blood vessels and often leading to headaches or jaw pain. Participants will receive either abatacept or a placebo through weekly injections to determine if abatacept helps achieve and maintain remission (no active symptoms) over 12 months. Individuals diagnosed with GCA in the last eight weeks and experiencing active symptoms may be suitable for this study. Participants who don't achieve remission by the third month or experience a relapse can choose to receive abatacept openly for another 12 months. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially bringing a new treatment to market.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before joining. Specifically, you must discontinue non-biologic immunosuppressants and certain biologic treatments like etanercept, adalimumab, and others within specified time frames before randomization.

Is there any evidence suggesting that abatacept is likely to be safe for humans?

Research has shown that abatacept is generally safe for people with giant cell arteritis (GCA). In past studies, patients who took abatacept with prednisone (a type of steroid) did not experience more side effects than those who did not take abatacept. This suggests that abatacept does not add extra risk when used to treat GCA.

The FDA has already approved abatacept for other conditions, indicating its safety for those uses. However, like any medication, it can have side effects. Participants in the trial will be closely monitored to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for GCA?

Unlike the standard treatments for Giant Cell Arteritis, which often rely on corticosteroids, abatacept is unique because it targets a different pathway in the immune system. Abatacept works by interfering with the communication between certain immune cells, potentially reducing inflammation with fewer side effects than current options. Researchers are excited about abatacept because it offers a new mechanism of action that could provide a more effective and safer alternative for patients with this condition.

What evidence suggests that abatacept might be an effective treatment for giant cell arteritis?

In this trial, participants will receive either abatacept or a placebo to manage giant cell arteritis (GCA), a condition that causes swelling in the arteries. Research has shown that abatacept can help manage GCA. Specifically, patients who took abatacept had a 48% chance of avoiding a return of symptoms after 12 months, compared to 31% for those who took a placebo. This suggests that abatacept may help people with GCA stay symptom-free for longer. The treatment targets specific parts of the immune system to reduce swelling. These findings provide promising evidence for abatacept's effectiveness in treating GCA. ^{1 2 3 6 7}

Who Is on the Research Team?

Peter Merkel, MD, MPH

Principal Investigator

University of Pennsylvania

Jeffrey P Krischer, PhD

Principal Investigator

University of South Florida

Carol A Langford, MD, MHS

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed or relapsing Giant Cell Arteritis (GCA) who meet specific diagnostic criteria. Participants must be able to follow the study plan and use effective birth control. Those with severe diseases, recent infections, certain drug treatments, kidney issues, blood disorders, cancer history within 5 years, or allergy to abatacept can't join.

Inclusion Criteria

I am willing to use effective birth control.

My giant cell arteritis has been active in the last 8 weeks.

I have been newly diagnosed or have a relapse of Giant Cell Arteritis (GCA).

Exclusion Criteria

I haven't taken certain medications recently.

I have not received a live vaccine in the last 3 months.

I have stopped taking non-biologic immunosuppressants.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous abatacept 125mg/week or placebo for 12 months

12 months

Weekly visits for subcutaneous injections

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants who do not achieve remission by Month 3 or relapse within the first 12 months may receive open-label abatacept for up to 12 months

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Abatacept
• Placebo

Trial Overview The trial tests if Abatacept is better than a placebo in treating GCA. Patients are randomly assigned to get either Abatacept or a placebo once a week for up to 12 months. If they don't improve by Month 3 or have a relapse within the first year, they may receive open-label Abatacept.

How Is the Trial Designed?

Group I: Blinded Abatacept Experimental Treatment 1 Intervention

Participants will receive blinded abatacept 125 mg administered by subcutaneous injection once a week for at least 12 months. Subjects may be removed from treatment earlier due to a disease relapse, disease worsening, or if they have not achieved remission.

Group II: Blinded Placebo Placebo Group 1 Intervention

Participants will receive blinded placebo. Placebo will be administered by subcutaneous injection once a week for at least 12 months. Subjects may be removed from treatment earlier due to a disease relapse, disease worsening, or if they have not achieved remission.

Abatacept is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Psoriatic arthritis

Approved in United States as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Psoriatic arthritis

Approved in Canada as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis

Approved in Japan as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

In a multicenter trial involving 49 patients with giant cell arteritis (GCA), the addition of abatacept to a prednisone regimen significantly improved relapse-free survival rates at 12 months (48% for abatacept vs. 31% for placebo).

Patients receiving abatacept also experienced a longer median duration of remission (9.9 months) compared to those on placebo (3.9 months), with no increase in adverse events, indicating that abatacept is both effective and safe for treating GCA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Giant Cell Arteritis. Langford, CA., Cuthbertson, D., Ytterberg, SR., et al.[2022]

In a multicenter trial involving 34 patients with Takayasu arteritis, the addition of abatacept to prednisone treatment did not significantly improve relapse-free survival compared to placebo, with rates of 22% for abatacept and 40% for placebo at 12 months.

There were no significant differences in the frequency or severity of adverse events, including infections, between the abatacept and placebo groups, indicating that abatacept is safe but ineffective in prolonging remission in Takayasu arteritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Takayasu Arteritis. Langford, CA., Cuthbertson, D., Ytterberg, SR., et al.[2018]

In a study of 33 patients with giant cell arteritis, both abatacept (ABA) and tocilizumab (TCZ) were found to be effective treatments, with TCZ showing a higher overall response rate (100% in IV and SC groups) compared to ABA (62%).

Abatacept can be a suitable alternative for patients who cannot tolerate tocilizumab, as it still provided significant clinical responses and allowed 43% of patients to reduce their prednisone dosage to below 7.5 mg/day after 12 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An agent-to-agent real life comparison study of tocilizumab versus abatacept in giant cell arteritis. Rossi, D., Cecchi, I., Sciascia, S., et al.[2022]

Abatacept (Orencia) significantly improves symptoms of active rheumatoid arthritis and slows joint damage progression in patients who have previously been treated with other therapies, based on results from two phase III trials involving multiple centers over 6 to 12 months.

The treatment is generally well tolerated, with similar rates of serious adverse events between abatacept and placebo, although it may be less well tolerated when combined with other biologic DMARDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abatacept. Hervey, PS., Keam, SJ.[2018]

In a study of 70 patients with newly diagnosed giant cell arteritis, adding a 10-week treatment of adalimumab to a standard prednisone regimen did not significantly increase the percentage of patients achieving remission on less than 0.1 mg/kg of prednisone at 6 months.

However, the treatment with adalimumab was associated with a lower rate of serious adverse events (14.7%) compared to the placebo group (47.2%), suggesting a potential safety benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab for steroid sparing in patients with giant-cell arteritis: results of a multicentre randomised controlled trial. Seror, R., Baron, G., Hachulla, E., et al.[2022]

Abatacept significantly improves health outcomes in patients with rheumatoid arthritis, showing higher likelihoods of achieving American College of Rheumatology (ACR) response rates compared to placebo and other treatments, based on a meta-analysis of 13 randomized control trials involving 5978 patients.

Patients treated with abatacept experienced fewer adverse events compared to those receiving other biologic disease-modifying anti-rheumatic drugs, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of efficacy and safety of abatacept for rheumatoid arthritis: systematic review and meta-analysis. Mohamed Ahamada, M., Wu, X.[2023]

Patients with giant cell arteritis (GCA) receiving tocilizumab in combination with glucocorticoids (prednisone) had a significantly lower likelihood of treatment failure compared to those receiving only glucocorticoids, with an odds ratio of 0.2, indicating that tocilizumab is more effective in achieving and maintaining remission.

Female patients receiving only glucocorticoids had a higher risk of treatment failure compared to males, while predictors of failure in the tocilizumab group included lower baseline doses of prednisone and worse patient-reported outcomes, suggesting that these factors should be monitored for better treatment management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment failure in giant cell arteritis. Unizony, SH., Bao, M., Han, J., et al.[2022]

Patients with giant cell arteritis (GCA) are at a significantly higher risk for several adverse outcomes associated with corticosteroid (CS) use, including diabetes (1.4 times higher), osteoporosis (2.4 times higher), and glaucoma (2.0 times higher), compared to matched non-GCA patients.

The study, which included 5011 GCA patients and 5011 matched controls, found that GCA patients also had an increased risk of serious infections requiring hospitalization (1.5 times higher) and a marginally increased risk of death (1.2 times higher), highlighting the need for careful monitoring in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of outcomes potentially associated with corticosteroid therapy in patients with giant cell arteritis. Wilson, JC., Sarsour, K., Collinson, N., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5378642/

A RANDOMIZED, DOUBLE-BLIND TRIAL OF ABATACEPT ... In conclusion, this study demonstrated that treatment of GCA with abatacept combined with glucocorticoids results in a longer duration of relapse-free survival ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04474847

Abatacept for the Treatment of Giant Cell Arteritis This randomized, double-blind, placebo-controlled trial will seek to determine the efficacy of abatacept in GCA.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28133925/

A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for ... The relapse-free survival rate at 12 months was 48% for those receiving abatacept and 31% for those receiving placebo (P = 0.049). A longer ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0049017225000575

Giant cell arteritis – New treatment targets at the horizon In a Phase 2 study in giant cell arteritis, abatacept narrowly met the primary endpoint of superiority to standard of care in relapse-free survival[6]. A Phase ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20522384

A Study to Evaluate Abatacept to Treat Giant Cell Arteritis The purpose of this study is to determine the effectiveness of abatacept in Giant Cell Arteritis (GCA). Patients who have newly diagnosed or relapsing GCA ...

6. go.drugbank.com go.drugbank.com/drugs/DB01281/clinical_trials?conditions=DBCOND0115353&phase=3&purpose=treatment&status=withdrawn

Abatacept Withdrawn Phase 3 Trials for Giant Cell Arteritis ... A Study to Evaluate Efficacy and Safety of Subcutaneous Abatacept With Steroid Treatment Compared to Steroid Treatment Alone in Adults With Giant Cell Arteritis ...

7. explorationpub.com explorationpub.com/Journals/eaa/Article/100954

Pharmacological advances in giant cell arteritis treatment The cornerstone of treatment for GCA is glucocorticoids, but using them for an extended period has numerous, often severe, side effects.