Abatacept for the Treatment of Giant Cell Arteritis

Study Purpose

This randomized, double-blind, placebo-controlled trial will seek to determine the efficacy of abatacept in GCA. To examine this objective, 62 eligible patients who have newly diagnosed or relapsing GCA within 8 weeks prior to screening will be randomized at a 1:1 ratio to receive subcutaneous abatacept 125mg/week or placebo. Patients who achieve remission will remain on their blinded assignment for 12 months at which time abatacept/placebo will be stopped. Patients who do not achieve remission by Month 3, who experience a relapse within the first 12 months will have the option of receiving open-label abatacept for a maximum of 12 months.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 50 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. A diagnosis of newly diagnosed or relapsing GCA. Diagnostic criteria for GCA A patient will be said to have GCA by meeting 3 of 5 of the following modified ACR criteria for the classification of GCA in which 1 of the 3 must consist of criteria 4 or 5: 1. Age at disease onset ≥ 50 years. 2. New onset or new type of localized pain in the head. 3. ESR of > 40 mm in the first hour by the Westergren method or CRP measurement above the laboratory normal limit. 4. Temporal artery abnormality (i.e., temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries). 5. Temporal artery or large vessel biopsy showing vasculitis characterized by a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cell or an abnormal temporal artery ultrasound showing features consistent with active giant cell arteritis ("halo sign") or characteristic changes of large vessel stenosis or aneurysm by arteriography. 2. GCA with evidence of active disease (defined below) present within the past 8 weeks. 3. They 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:

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.
  • - 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:
  • - 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; however, a copy of the reports must be placed in the participant binder.
  • - 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.
  • - 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 8 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04474847
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 3
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Pennsylvania
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Peter A Merkel, MD, MPHCarol A Langford, MD, MHSJeffrey P Krischer, PhD
Principal Investigator Affiliation University of PennsylvaniaThe Cleveland ClinicUniversity of South Florida
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Not yet recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Giant Cell Arteritis
Arms & Interventions

Arms

Experimental: Blinded Abatacept

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.

Placebo Comparator: Blinded Placebo

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.

Interventions

Drug: - Abatacept

Participants randomized to abatacept will receive abatacept 125 mg administered by subcutaneous injection once a week. Participants randomized to either the abatacept or the placebo arm who experience a non-severe disease relapse, non-severe disease worsening, or who have not achieved remission by month 3 will have the option of entering an open-label trial period whereby they would receive open-label abatacept for up to 12 months.

Drug: - Placebo

Participants randomized to placebo will receive a sterile placebo solution administered by subcutaneous injection once a week. Participants randomized to either the abatacept or the placebo arm who experience a non-severe disease relapse, non-severe disease worsening, or who have not achieved remission by month 3 will have the option of entering an open-label trial period whereby they would receive open-label abatacept for up to 12 months.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of Pennsylvania, Philadelphia, Pennsylvania

Status

Address

University of Pennsylvania

Philadelphia, Pennsylvania, 19104

Site Contact

Alison Keenan

[email protected]

7813214567