Abstract
BACKGROUND: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) insufficiency and lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency are both complex immune dysregulation syndromes with an underlying regulatory T cell dysfunction due to the lack of CTLA-4 protein. As anticipated, the clinical phenotypes of CTLA-4 insufficiency and LRBA deficiency are similar. Main manifestations include hypogammaglobulinemia, lymphoproliferation, autoimmune cytopenia, immune-mediated respiratory, gastrointestinal, neurological, and skin involvement, which can be severe and disabling. The rationale of this clinical trial is to improve clinical outcomes of affected patients by substituting the deficient CTLA-4 by administration of CTLA4-Ig (abatacept) as a causative personalized treatment. OBJECTIVES: Our objective is to assess the safety and efficacy of abatacept for patients with CTLA-4 insufficiency or LRBA deficiency. The study will also investigate how treatment with abatacept affects the patients' quality of life. METHODS: /Design: ABACHAI is a phase IIa prospective, non-randomized, open-label, single arm multi-center trial. Altogether 20 adult patients will be treated with abatacept 125 mg s.c. on a weekly basis for 12 months, including (1) patients already pretreated with abatacept, and (2) patients not pretreated, starting with abatacept therapy at the baseline study visit. For the evaluation of drug safety infection control during the trial, for efficacy, the CHAI-Morbidity Score will be used. TRIAL REGISTRATION: The trial is registered in the German Clinical Trials Register (Deutsches Register Klinischer Studien, DRKS) with the identity number DRKS00017736, registered: 6 July 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017736.