Abatacept for Treating Adults With Giant Cell Arteritis and Takayasu's Arteritis

NCT00556439 | Completed Phase 2 Results DMC

• 3 other identifiers: N01 AR070018268200700036C-5-0-1HHSN2682007000036C
• Study Type: interventional
• Target: 97
• Locations: 2 countries
• Sites: 10

Brief Summary

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are diseases that cause swelling of the arteries in the head, neck, upper body, and arms. TAK specifically affects the aorta, the largest blood vessel in the body, and its branches. Therapies are available to improve the symptoms of GCA and TAK, but relapse often occurs, and better treatments are needed. Abatacept is a drug that interacts with certain cells in the body that are involved with GCA and TAK. This study will evaluate the effectiveness of abatacept in treating GCA and TAK and preventing disease relapse.

Conditions

Takayasu's Arteritis; Giant Cell Arteritis

Keywords

Vasculitis; Arteritis; Takayasu's; Temporal Arteritis; Abatacept

Outcome Measures

Primary Outcomes (1)

• Primary Outcome - Relapse-free Survival (RFS)

  Relapse: presence of active disease occurring after a period of remission Remission: absence of active disease Active disease defined by clinical features or imaging or both: Clinical features: 1 or more of the following attributed to GCA/TAK: * Sustained fever of \>38 C for \> 1 week * Vascular pain/tenderness \> 1 day, non-fleeting * Headache a) present \> 1 day b) non-fleeting c) not relieved with analgesics d) not typical for pre-existing headaches * Ischemic retinopathy, optic neuropathy, or visual loss * Tongue/jaw pain and/or claudication * TIA or stroke * Extremity claudication * Musculoskeletal symptoms + ESR of \> 40 mm/hr or CRP above the normal limit * Malaise/fatigue + ESR of \> 40 mm/hr or CRP above the normal limit * Other symptoms/signs due to GCA/TAK requiring reinstitution/increase in GC Imaging features • Development of new vascular stenosis or aneurysm in new vascular territories as seen by MRI/MRA or arteriogram

  Weeks 0 to 64

Study Arms (2)

A and C

EXPERIMENTAL

This is a randomized withdrawal design protocol. All participants will receive abatacept and prednisone (a glucocorticoid) for the first 3 months. Abatacept will be given intravenously on selected days. Prednisone will be started at a dose of 40 to 60mg, then tapered to 20mg by Month 3, and finally further tapered until discontinuation is reached. At Month 3, participants who have achieved remission will be randomly assigned under double-blind conditions to receive monthly infusions of either abatacept or placebo. Participants who are assigned to abatacept at this point will be in Group A for giant cell arteritis and Group C for Takayasu arteritis.

Drug: Abatacept

B and D

PLACEBO COMPARATOR

This is a randomized withdrawal design protocol. All participants will receive abatacept and prednisone (a glucocorticoid) for the first 3 months. Abatacept will be given intravenously on selected days. Prednisone will be started at a dose of 40 to 60mg, then tapered to 20mg by Month 3, and finally further tapered until discontinuation is reached. At Month 3, participants who have achieved remission will be randomly assigned under double-blind conditions to receive monthly infusions of either abatacept or placebo. Participants who are assigned to placebo at this point will be in Group B for giant cell arteritis and Group D for Takayasu arteritis.

Drug: Abatacept; Drug: Placebo

Interventions

Abatacept DRUG

Participants will receive a fixed dose of abatacept, approximating 10mg per kilogram of body weight. The following dosing rules will be followed: * Participants weighing less than 60kg will receive 500mg of abatacept. * Participants weighing 60 to 100kg will receive 750mg of abatacept. * Participants weighing more than 100kg will receive 1000mg of abatacept. Abatacept will be administered in a 30-minute intravenous infusion on Days 1, 15, 29 (Month 1) and at Month 2. In the absence of toxicity or relapse, participants will remain on abatacept at the same dosage until randomization at Month 3. After randomization, only Group A (giant cell arteritis) and Group C (Takayasu arteritis) participants will continue on abatacept.

Also known as: Orencia

A and C; B and D

Placebo DRUG

Placebo abatacept infusions will be given monthly after random assignment at Month 3.

B and D

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of GCA or TAK (defined below)
• History of active GCA or TAK within the past 2 months
• Age of 15 years or older
• Willing to use an effective means of birth control throughout the study
• Participants must meet three of the following five criteria, including either Criterion 4 or 5:
• Age at disease onset was equal to or greater than 50 years
• Disease onset was recent or experiencing a new type of localized pain in the head
• Erythrocyte sedimentation rate greater than 40mm in the first hour, as determined using the Westergren method
• 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 characteristic changes of large vessel stenosis or aneurysm by arteriography
• Presence of abnormalities that are consistent with TAK identified using arteriography, plus at least one of the following criteria:
• Age at disease onset was less than 50 years
• Pain in the legs or arms
• Decreased brachial artery pulse (one or both arteries)
• Difference of more than 10mm Hg in blood pressure between the arms

You may not qualify if:

• Evidence of active infection (including chronic infection)
• Pregnant or breastfeeding
• HIV infected, hepatitis C infected, or a positive hepatitis B surface antigen
• Inability to comply with study guidelines
• Inability to provide informed consent
• Cytopenia, as defined by a platelet count of less than 80,000/mm3, an absolute neutrophil count of less than 1,500/mm3, and hematocrit less than 20%
• Insufficient kidney function, as defined by a serum creatinine of more than 3 mg/dL or creatinine clearance of 20 ml/min or less
• Other uncontrolled disease that could prevent safe study completion
• History of any malignant neoplasm except adequately treated basal or squamous cell carcinoma of the skin or solid tumors treated with curative therapy and disease-free for at least 5 years
• Receipt of an investigational agent or device within 30 days prior to study entry
• A live vaccination within 4 weeks prior to study entry
• Presence of a positive tuberculin skin test with induration of at least 5mm
• Radiographic evidence suggestive of tuberculosis
• Poor tolerability of blood draws or lack of adequate access to veins for medication administration and blood draws
• History of treatment with rituximab within 12 months prior to study entry or history of treatment with rituximab more than 12 months prior to study entry, where the B lymphocyte count has not returned to normal

Sponsors & Collaborators

• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): lead
• The Cleveland Clinic: collaborator
• Office of Rare Diseases (ORD): collaborator
• Rare Diseases Clinical Research Network: collaborator

Study Sites (10)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Johns Hopkins Medical Center

Baltimore, Maryland, 21224, United States

Location

Boston University

Boston, Massachusetts, 02118, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

St. Joseph's Hospital

Hamilton, Ontario, L8P 3B3, Canada

Location

Mt. Sinai Hospital Toronto

Toronto, Ontario, M5T 3L9, Canada

Location

Related Publications (3)

• Langford CA, Cuthbertson D, Ytterberg SR, Khalidi N, Monach PA, Carette S, Seo P, Moreland LW, Weisman M, Koening CL, Sreih AG, Spiera R, McAlear CA, Warrington KJ, Pagnoux C, McKinnon K, Forbess LJ, Hoffman GS, Borchin R, Krischer JP, Merkel PA; Vasculitis Clinical Research Consortium. A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Takayasu Arteritis. Arthritis Rheumatol. 2017 Apr;69(4):846-853. doi: 10.1002/art.40037. Epub 2017 Mar 8.

  PMID: 28133931 DERIVED

• Langford CA, Cuthbertson D, Ytterberg SR, Khalidi N, Monach PA, Carette S, Seo P, Moreland LW, Weisman M, Koening CL, Sreih AG, Spiera R, McAlear CA, Warrington KJ, Pagnoux C, McKinnon K, Forbess LJ, Hoffman GS, Borchin R, Krischer JP, Merkel PA; Vasculitis Clinical Research Consortium. A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Giant Cell Arteritis. Arthritis Rheumatol. 2017 Apr;69(4):837-845. doi: 10.1002/art.40044. Epub 2017 Mar 3.

  PMID: 28133925 DERIVED

• Goldstein BL, Gedmintas L, Todd DJ. Drug-associated polymyalgia rheumatica/giant cell arteritis occurring in two patients after treatment with ipilimumab, an antagonist of ctla-4. Arthritis Rheumatol. 2014 Mar;66(3):768-9. doi: 10.1002/art.38282. No abstract available.

  PMID: 24574239 DERIVED

Related Links

• Click here for the Cleveland Clinic Center for Vasculitis Care and Research Web site

MeSH Terms

Conditions

Takayasu Arteritis; Giant Cell Arteritis; Vasculitis; Arteritis

Interventions

Abatacept

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Small sample size, challenges in assessing disease activity in giant cell arteritis and Takayasu arteritis, 84.6% of patients with Takayasu arteritis were enrolled for the treatment of a disease relapse.

Results Point of Contact

• Title: Carol A Langford, MD MHS
• Organization: Cleveland Clinic

langfoc@ccf.org

216-445-6056

Study Officials

• Carol A. Langford, MD, MHS

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2007
• First Posted: November 12, 2007
• Study Start: December 1, 2008
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: February 26, 2018
• Results First Posted: February 26, 2018

Record last verified: 2018-01

Locations

CA (2); US (8)