Abatacept for the Treatment of Giant Cell Arteritis

NCT04474847 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: VCRC5528
• Study Type: interventional
• Target: 78
• Locations: 2 countries
• Sites: 9

Brief Summary

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.

Conditions

Giant Cell Arteritis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• The proportion of participants in remission of those randomized to abatacept as compared to placebo.

  Remission is defined as the absence of clinical or imaging features of active disease

  12 months

Secondary Outcomes (4)

• Safety of abatacept in GCA

  12 months

• Health-related quality of life in those treated with abatacept versus placebo: SF-36

  12 months

• Health-related quality of life in those treated with abatacept versus placebo: PROMIS questionnaire

  12 months

• Duration of glucocorticoid-free remission from Month 6 to Month 12

  6 months

Study Arms (2)

Blinded Abatacept

EXPERIMENTAL

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.

Drug: Abatacept

Blinded Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Abatacept DRUG

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.

Also known as: CTLA4-Ig, Orencia

Blinded Abatacept

Placebo DRUG

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.

Blinded Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Age at disease onset ≥ 50 years.
• New onset or new type of localized pain in the head.
• ESR of \> 40 mm in the first hour by the Westergren method or CRP measurement above the laboratory normal limit.
• Temporal artery abnormality (i.e., temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries).
• 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.
• GCA with evidence of active disease (defined below) present within the past 8 weeks.
• They must be willing and able to comply with treatment and follow-up procedures.
• 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.
• They must be willing and able to provide written informed consent.

You may not qualify if:

• 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.
• Patients with history of chronic or recurrent bacterial infection (such as chronic pyelonephritis, osteomyelitis, and bronchiectasis etc.).
• 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.
• Patients with a history of systemic fungal infections (such as histoplasmosis, blastomycosis, or coccidiomycosis).
• Patients with a history of primary immunodeficiency.
• 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.
• Patients who are pregnant or who are nursing infants.
• Inability to comply with study guidelines.
• Cytopenia: platelet count \<80,000/mm3, total White Blood Count (WBC) \< 3,000/mm3 (3 x 109/L) absolute neutrophil \<1500/mm3, hematocrit \< 20%.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (9)

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Hospital for Special Surgery

New York, New York, 10021, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Vanderbilt University

Nashville, Tennessee, 37240, United States

RECRUITING

University of British Columbia

Vancouver, British Columbia, V6Z 2C7, Canada

RECRUITING

St. Joseph's Healthcare

Hamilton, Ontario, Canada

RECRUITING

Mount Sinai Hospital

Toronto, Ontario, Canada

RECRUITING

Hôpital du Sacré-Coeur de Montréal Université de Montréal

Montreal, Quebec, H4J 1C5, Canada

RECRUITING

MeSH Terms

Conditions

Giant Cell Arteritis; Vasculitis; Arteritis; Autoimmune Diseases; Immune System Diseases

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• Peter A Merkel, MD, MPH

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Carol A Langford, MD, MHS

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

• Jeffrey P Krischer, PhD

  University of South Florida

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carol McAlear, MA

CONTACT

7813214567; cmcalear@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2020
• First Posted: July 17, 2020
• Study Start: March 29, 2021
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); CA (4)