A Randomized Double-Blind, Placebo Controlled Trial of Abatacept (CTLA4-Ig) in Giant Cell Arteritis (ABAGART)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Trustees Of The University Of Pennsylvania

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2025-07-11

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Trustees of the University of Pennsylvania

External identifiers

EU CT number

2024-515287-31-00

ClinicalTrials.gov

NCT04474847

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

This protocol seeks to determine the efficacy of abatacept (CTLA4-Ig) in patients with GCA through the conduct of a randomized, double-blind, placebo-controlled trial. The studies primary endpoint will be the proportion of individuals in remission at Month 12 of those randomized to abatacept as compared to placebo.

Secondary objectives 3

1. Assess safety (adverse events/serious adverse events)
2. Assess patient reported outcomes: Mean change from Baseline (Month 0) over time to Month 12 in SF-36, PROMIS.
3. Median duration of glucocorticoid-free remission from Month 6 to Month 12.

Conditions and MedDRA coding

Giant Cell Arteritis

Study design 2 periods

Regulatory references

Plan to share IPD

Yes

IPD plan description

The ABAGART trial study team intends to share deidentified individual participant data (IPD) from this clinical trial. De-identified data sets including demographic information, clinical outcomes, and adverse events will be shared. IPD will be available starting 6 months after the publication of the primary results. IPD will be shared through a secure data repository accessible to qualified researchers upon request via the Vasculitis Clinical Research Consortium (VCRC). IPD will be shared with researchers affiliated with academic institutions, healthcare organizations, and other entities conducting legitimate scientific research whose requests are approved by the VCRC. IPD will be shared for meta-analyses, secondary research, and other analyses aimed at advancing scientific knowledge and improving patient care.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. A diagnosis of newly diagnosed or relapsing GCA
2. GCA with evidence of active disease (defined below) present within the past 8 weeks prior to trial entry
3. Participant must be willing and able to comply with treatment and follow-up procedures.
4. Both women and men who are of child-bearing potential must be willing to use an effective means of birth control while receiving treatment through this study. Effective contraception methods include abstinence, surgical sterilization of either partner, barrier methods such as diaphragm, condom, cap or sponge, or hormonal contraception.
5. They must be willing and able to provide written informed consent.

Exclusion criteria 25

1. Evidence of a recent acute infection defined as: any acute infection within 60 days prior to randomization that required hospitalization or treatment with parenteral antibiotics, or any acute infection within 30 days prior to randomization that required oral antimicrobial or antiviral therapy.
2. Patients with history of chronic or recurrent bacterial infection (such as chronic pyelonephritis, osteomyelitis, and bronchiectasis etc.).
3. Patients with a history of recurrent herpes zoster (more than 1 episode) or disseminated (more than 1 dermatome) herpes zoster or disseminated herpes simplex, or ophthalmic zoster. Symptoms of herpes zoster or herpes simplex must have resolved more than 60 days prior to screening.
4. Patients with a history of systemic fungal infections (such as histoplasmosis, blastomycosis, or coccidiomycosis).
5. Patients with a history of primary immunodeficiency.
6. Patients at risk for tuberculosis (TB) defined as follows: 1) Current clinical, radiographic or laboratory evidence of active TB, even if currently being treated. Chest x-rays (posterior/anterior and lateral) obtained within the 6 months prior to screening and TB testing (IFN-gamma release assay or PPD) performed in the past month prior to screening will be accepted. 2) A history of active TB unless there is documentation that the patient had received prior anti-TB treatment that was appropriate in duration and type according to local health authority guidelines. 3) Patients with a positive TB screening test indicative of latent TB will not be eligible for the study unless they: i. Have no evidence of current TB based on chest x-ray performed during the screening period and by history and physical exam, and ii. They are currently being treated for latent TB or the site has documentation of successful prior treatment of latent TB. Treatment regimens should be dictated by local guidelines as long as the treatment dose and duration meet or exceed local health authority guidelines. If permitted by local guidelines regarding treatment with biologic medications, patients with latent TB may be randomized prior to completion of treatment as long as they have completed at least 4 weeks of treatment and they have no evidence of current TB on chest x-ray at screening.
7. Patients who are pregnant or who are nursing infants.
8. Inability to comply with study guidelines.
9. Cytopenia: platelet count <80,000/mm3, total White Blood Count (WBC) < 3,000/mm3 (3 x 109/L) absolute neutrophil <1500/mm3, hematocrit < 20%.
10. Renal insufficiency defined by a creatinine clearance of less than or equal to 20 ml/min.
11. AST or ALT > 3 times above normal laboratory range.
12. Other severe, progressive, or uncontrolled disease that in the investigator’s opinion could prevent a patient from fulfilling the study requirements or that would increase the risk of study participation.
13. Patients who have a present malignancy or previous malignancy within the last 5 years prior to screening (except documented history of cured non-metastatic squamous or basal cell skin carcinoma or cervical carcinoma in situ). Patients who had a screening procedure that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations.
14. Receipt of an investigational agent or device within 30 days prior to enrollment.
15. A live vaccination within 3 months before randomization.
16. Patients on non-biologic immunosuppressants must discontinue these medications before randomization (azathioprine, mycophenolate mofetil, mycophenolic acid, leflunomide, hydroxychloroquine, cyclosporin, tacrolimus, or other conventional immunosuppressive agent).
17. Patients who had received an alkylating agent such as cyclophosphamide must discontinue these medications at least 8 weeks before randomization.
18. Patients who have been treated within 4 weeks of randomization with etanercept or within 8 weeks with adalimumab, certolizumab, golimumab, or infliximab.
19. Patients who have been treated within 4 weeks of randomization with anti-IL-6 agents (e.g., tocilizumab, sirukumab) or a janus kinase inhibitor.
20. Patients who have been treated within 4 weeks of randomization with anakinra.
21. Patients who have received prior treatment with rituximab within the past 6 months prior to randomization.
22. Patients who have received prior treatment with abatacept or CTLA4-Ig.
23. Patients who will require oral or IV glucocorticoid treatment during the trial for conditions other than GCA.
24. Hypersensitivity to abatacept and/or its excipients.
25. Presence of any of the following disease processes: Takayasu arteritis, Granulomatosis with polyangiitis, Microscopic polyangiitis, Eosinophilic granulomatosis with polyangiitis (Churg-Strauss), Polyarteritis nodosa, Cogan’s syndrome, Behçet’s disease, Sarcoidosis, Lymphoma, lymphomatoid granulomatosis, or other type of malignancy that mimics vasculitis, Cryoglobulinemic vasculitis, Systemic lupus erythematosus, Rheumatoid arthritis, Mixed connective tissue disease or any overlap autoimmune syndrome.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary study endpoint will be the proportion of individuals in remission at Month 12 of those randomized to abatacept as compared to placebo.

Secondary endpoints 3

1. Safety (adverse events/serious adverse events/SUSARs) in patients with GCA taking abatacept compared with placebo
2. Patient reported outcomes (Mean change from Baseline/Month 0 over time to Month 12 in SF-36, PROMIS) in patients with GCA taking abatacept compared with placebo
3. Median duration of glucocorticoid-free remission from Month 6 to Month 12 in patients with GCA taking abatacept compared with placebo

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Trustees Of The University Of Pennsylvania

Sponsor organisation

Trustees Of The University Of Pennsylvania

Address

3400 Spruce Street

City

Philadelphia

Postcode

19104-4238

Country

United States

Scientific contact point

Organisation

Trustees Of The University Of Pennsylvania

Contact name

Carol McAlear

Public contact point

Organisation

Trustees Of The University Of Pennsylvania

Contact name

Carol McAlear

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications