Abatacept for the Treatment of Giant Cell Arteritis
- Conditions
- Giant Cell Arteritis
- Registration Number
- NCT04474847
- Lead Sponsor
- University of Pennsylvania
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria:<br><br> 1. A diagnosis of newly diagnosed or relapsing GCA. Diagnostic criteria for GCA<br><br> A patient will be said to have GCA by meeting 3 of 5 of the following modified ACR<br> criteria for the classification of GCA in which 1 of the 3 must consist of criteria<br> 4 or 5:<br><br> 1. Age at disease onset = 50 years.<br><br> 2. New onset or new type of localized pain in the head.<br><br> 3. ESR of > 40 mm in the first hour by the Westergren method or CRP measurement<br> above the laboratory normal limit.<br><br> 4. Temporal artery abnormality (i.e., temporal artery tenderness to palpation or<br> decreased pulsation, unrelated to arteriosclerosis of cervical arteries).<br><br> 5. Temporal artery or large vessel biopsy showing vasculitis characterized by a<br> predominance of mononuclear cell infiltration or granulomatous inflammation,<br> usually with multinucleated giant cell or an abnormal temporal artery<br> ultrasound showing features consistent with active giant cell arteritis (halo<br> sign) or characteristic changes of large vessel stenosis or aneurysm by<br> arteriography.<br><br> 2. GCA with evidence of active disease (defined below) present within the past 8 weeks.<br><br> 3. They must be willing and able to comply with treatment and follow-up procedures.<br><br> 4. Both women and men who are of child-bearing potential must be willing to use an<br> effective means of birth control while receiving treatment through this study.<br> Effective contraception methods include abstinence, surgical sterilization of either<br> partner, barrier methods such as diaphragm, condom, cap or sponge, or hormonal<br> contraception.<br><br> 5. They must be willing and able to provide written informed consent.<br><br>Exclusion Criteria:<br><br> 1. Evidence of a recent acute infection defined as:<br><br> - Any acute infection within 60 days prior to randomization that required<br> hospitalization or treatment with parenteral antibiotics.<br><br> - Any acute infection within 30 days prior to randomization that required oral<br> antimicrobial or antiviral therapy.<br><br> 2. Patients with history of chronic or recurrent bacterial infection (such as chronic<br> pyelonephritis, osteomyelitis, and bronchiectasis etc.).<br><br> 3. Patients with a history of recurrent herpes zoster (more than 1 episode) or<br> disseminated (more than 1 dermatome) herpes zoster or disseminated herpes simplex,<br> or ophthalmic zoster. Symptoms of herpes zoster or herpes simplex must have resolved<br> more than 60 days prior to screening.<br><br> 4. Patients with a history of systemic fungal infections (such as histoplasmosis,<br> blastomycosis, or coccidiomycosis).<br><br> 5. Patients with a history of primary immunodeficiency.<br><br> 6. Patients at risk for tuberculosis (TB) defined as follows:<br><br> - Current clinical, radiographic or laboratory evidence of active TB, even if<br> currently being treated. Chest x-rays (posterior/anterior and lateral) obtained<br> within the 6 months prior to screening and TB testing (IFN-gamma release assay<br> or PPD) performed in the past month prior to screening will be accepted;<br> however, a copy of the reports must be placed in the participant binder.<br><br> - A history of active TB unless there is documentation that the patient had<br> received prior anti-TB treatment that was appropriate in duration and type<br> according to local health authority guidelines.<br><br> - Patients with a positive TB screening test indicative of latent TB will not be<br> eligible for the study unless they:<br><br> i. Have no evidence of current TB based on chest x-ray performed during the<br> screening period and by history and physical exam, and ii. They are currently<br> being treated for latent TB or the site has documentation of successful prior<br> treatment of latent TB. Treatment regimens should be dictated by local<br> guidelines as long as the treatment dose and duration meet or exceed local<br> health authority guidelines. If permitted by local guidelines regarding<br> treatment with biologic medications, patients with latent TB may be randomized<br> prior to completion of treatment as long as they have completed at least 4<br> weeks of treatment and they have no evidence of current TB on chest x-ray at<br> screening.<br><br> 7. Patients who are pregnant or who are nursing infants.<br><br> 8. Inability to comply with study guidelines.<br><br> 9. Cytopenia: platelet count <80,000/mm3, total White Blood Count (WBC) < 3,000/mm3 (3<br> x 109/L) absolute neutrophil <1500/mm3, hematocrit < 20%.<br><br> 10. Renal insufficiency defined by a creatinine clearance of less than or equal to 20<br> ml/min.<br><br> 11. AST or ALT > 3 times above normal laboratory range.<br><br> 12. Other severe, progressive, or uncontrolled disease that in the investigator's<br> opinion could prevent a patient from fulfilling the study requirements or that would<br> increase the risk of study participation.<br><br> 13. Patients who have a present malignancy or previous malignancy within the last 5<br> years prior to screening (except documented history of cured non-metastatic squamous<br> or basal cell skin carcinoma or cervical carcinoma in situ). Patients who had a<br> screening procedure that is suspicious for malignancy, and in whom the possibility<br> of malignancy cannot be reasonably excluded following additional clinical,<br> laboratory or other diagnostic evaluations.<br><br> 14. Receipt of an investigational agent or device within 30 days prior to enrollment.<br><br> 15. A live vaccination within 3 months before randomization.<br><br> 16. Patients on non-biologic immunosuppressants must discontinue these medications<br> before randomization (azathioprine, mycophenolate mofetil, mycophenolic acid,<br> leflunomide, hydroxychloroquine, cyclosporin, tacrolimus, or other conventional<br> immunosuppressive agent).<br><br> 17. Patients who had received an alkylating agent such as cyclophosphamide must<br> discontinue these medications at least 8 weeks before randomization.<br><br> 18. Patients who have been treated within 4 weeks of randomization with etanercept or<br> within 8 weeks with adalimumab, certolizumab, golimumab, or infliximab.<br><br> 19. Patients who have been treated within 8 weeks of randomization with anti-IL-6 agents<br> (e.g., tocilizumab, sirukumab) or a janus kinase inhibitor.<br><br> 20. Patients who have been treated within 4 weeks of randomization with anakinra.<br><br> 21. Patients who have received prior treatment with rituximab within the past 6 months<br> prior to randomization.<br><br> 22. Patients who have received prior treatment with abatacept or CTLA4-Ig.<br><br> 23. Patients who will require oral or IV glucocorticoid treatment during the trial for<br> conditions other than GCA.<br><br> 24. Hypersensitivity to abatacept and/or its excipients.<br><br> 25. Presence of any of the following disease processes:<br><br> - Takayasu arteritis<br><br> - Granulomatosis with polyangiitis<br><br> - Microscopic polyangiitis<br><br> - Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)<br><br> - Polyarteritis nodosa<br><br> - Cogan's syndrome<br><br> - Behçet's disease<br><br> - Sarcoidosis<br><br> - Lymphoma, lymphomatoid granulomatosis, or other type of malignancy that mimics<br>
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The proportion of participants in remission of those randomized to abatacept as compared to placebo.
- Secondary Outcome Measures
Name Time Method Safety of abatacept in GCA;Health-related quality of life in those treated with abatacept versus placebo: SF-36;Health-related quality of life in those treated with abatacept versus placebo: PROMIS questionnaire;Duration of glucocorticoid-free remission from Month 6 to Month 12