Safety and efficacy of abatacept in patients with treatment-resistant SARCoidosis (ABASARC) - protocol for a multi-center, single-arm phase IIa trial

Björn C Frye; Ina Caroline Rump; Annette Uhlmann; Fabian Schubach; Gabriele Ihorst; Bodo Grimbacher; Gernot Zissel; Joachim Müller Quernheim

doi:10.1016/j.conctc.2020.100575

Safety and efficacy of abatacept in patients with treatment-resistant SARCoidosis (ABASARC) - protocol for a multi-center, single-arm phase IIa trial

Contemp Clin Trials Commun. 2020 May 29:19:100575. doi: 10.1016/j.conctc.2020.100575. eCollection 2020 Sep.

Authors

Björn C Frye¹, Ina Caroline Rump^{1

2}, Annette Uhlmann^{2

3}, Fabian Schubach³, Gabriele Ihorst³, Bodo Grimbacher^{2

4

5

6}, Gernot Zissel¹, Joachim Müller Quernheim¹

Affiliations

¹ Department of Pneumology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
² Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
³ Clinical Trials Unit, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
⁴ DZIF - German Center for Infection Research, Satellite Center Freiburg, Germany.
⁵ CIBSS - Centre for Integrative Biological Signalling Studies, University of Freiburg, Germany.
⁶ RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Germany.

Abstract

Introduction: Sarcoidosis is a granulomatous systemic disease that becomes chronic in approximately one third of affected patients resulting in quality of life and functional impairment. Immunosuppressive drugs other than steroids represent alternative therapeutic options, but side effects like liver and bone marrow toxicity or increased susceptibility to infections limit their use. Pathophysiological studies in sarcoidosis patients demonstrate altered regulatory T-cell functions with a reduced expression of CTLA-4 (CD152) and prolonged inflammation. Therefore, interfering with CTLA-4 using abatacept might be a therapeutic option in sarcoidosis similar to rheumatoid arthritis therapy.

Methods/design: This is a multicenter prospective open-labeled single arm phase II study addressing the safety of abatacept in sarcoidosis patients. 30 patients with chronic sarcoidosis requiring immunosuppressive therapy beyond 5 mg prednisolone equivalent will be treated with abatacept in combination with corticosteroids for one year in two centers.The primary endpoint is the number and characterization of severe infectious complications under treatment with abatacept.Secondary endpoints are the rate of all infections, patient-related outcomes (assessed by questionnaires), lung function and immunological parameters including alveolar inflammation assessed by bronchoaveolar lavage.

Discussion: This is the first trial of abatacept in patients with sarcoidosis. It is hypothesized that administration of abatacept is safe in patients with chronic sarcoidosis and can limit ongoing inflammation. Patients' wellbeing is assessed by established questionnaires. Immunological work-up will highlight the effect of abatacept on inflammatory pathways in sarcoidosis.

Trial registration: The trial has been registered at the German Clinical Trial Registry (Deutsches Register Klinischer Studien, DRKS) with the identity number DRKS00011660.

Keywords: 18FDG-PET-CT, 18Fluor-Desoxy-Glucose positron-emission tomography combined with computer tomography; Abatacept; BAL, bronchoalveolar lavage; CMV, cytomegaly-virus; Chronic sarcoidosis; EBV, Epstein-Barr-Virus; FVC, forced vital capacity; GHS, general health score; IFN-γ, Interferon-γ; IL, interleukin; KSQ, King's sarcoidosis questionnaire; King's sarcoidosis questionnaire; Patient-reported outcome; Regulatory T-cells; TLC, total lung capacity; TNF, tumor-necrosis factor; TReg, regulatory T-cells; Therapy.