RECRUITING

Abatacept for the Treatment of Giant Cell Arteritis

Conditions

Giant Cell Arteritis Vasculitis Arteritis Temporal Arteritis Abatacept CTLA4-Ig Autoimmune Diseases Immune System Diseases Immunosuppressive agent Prednisone Glucocorticoids Corticosteroids Treatment Pharmacologic Actions Therapeutic Uses Anti Inflammatory Agents Antirheumatic Agents

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2021-03-15

Study Completion:2026-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04474847

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:50 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. A diagnosis of newly diagnosed or relapsing GCA. Diagnostic criteria for GCA 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.	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: 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

Inclusion Criteria

Exclusion Criteria

1. A diagnosis of newly diagnosed or relapsing GCA. Diagnostic criteria for GCA
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.

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:
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

Contacts and Locations

Study Contact

Carol McAlear, MA

CONTACT

7813214567

cmcalear@pennmedicine.upenn.edu

Principal Investigator

Peter A Merkel, MD, MPH

PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Carol A Langford, MD, MHS

PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Jeffrey P Krischer, PhD

PRINCIPAL_INVESTIGATOR

University of South Florida

Study Locations (Sites)

Mayo Clinic

Rochester, Minnesota, 55905

United States

Hospital for Special Surgery

New York, New York, 10021

United States

Cleveland Clinic

Cleveland, Ohio, 44195

United States

University of Pennsylvania

Philadelphia, Pennsylvania, 19104

United States

Vanderbilt University

Nashville, Tennessee, 37240

United States

Collaborators and Investigators

Sponsor: University of Pennsylvania

Peter A Merkel, MD, MPH, PRINCIPAL_INVESTIGATOR, University of Pennsylvania
Carol A Langford, MD, MHS, PRINCIPAL_INVESTIGATOR, The Cleveland Clinic
Jeffrey P Krischer, PhD, PRINCIPAL_INVESTIGATOR, University of South Florida

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-03-15

Study Completion Date2026-12

Study Record Updates

Study Start Date2021-03-15

Study Completion Date2026-12

Terms related to this study

Keywords Provided by Researchers

Vasculitis
Arteritis
Temporal Arteritis
Abatacept
CTLA4-Ig
Autoimmune Diseases
Immune System Diseases
Immunosuppressive agent
Prednisone
Glucocorticoids
Corticosteroids
Treatment
Pharmacologic Actions
Therapeutic Uses
Anti Inflammatory Agents
Antirheumatic Agents

Additional Relevant MeSH Terms

Giant Cell Arteritis