The ABACHAI clinical trial protocol: Safety and efficacy of abatacept (s.c.) in patients with CTLA-4 insufficiency or LRBA deficiency: A non controlled phase 2 clinical trial

Máté Krausz; Annette Uhlmann; Ina Caroline Rump; Gabriele Ihorst; Sigune Goldacker; Georgios Sogkas; Sara Posadas-Cantera; Reinhold Schmidt; Manuel Feißt; Laia Alsina; Ingunn Dybedal; Mike Recher; Klaus Warnatz; Bodo Grimbacher

doi:10.1016/j.conctc.2022.101008

The ABACHAI clinical trial protocol: Safety and efficacy of abatacept (s.c.) in patients with CTLA-4 insufficiency or LRBA deficiency: A non controlled phase 2 clinical trial

Contemp Clin Trials Commun. 2022 Sep 24:30:101008. doi: 10.1016/j.conctc.2022.101008. eCollection 2022 Dec.

Authors

Máté Krausz^{1

2

3}, Annette Uhlmann^{2

4}, Ina Caroline Rump^{1

2}, Gabriele Ihorst⁴, Sigune Goldacker¹, Georgios Sogkas⁵, Sara Posadas-Cantera¹, Reinhold Schmidt⁵, Manuel Feißt⁶, Laia Alsina⁷, Ingunn Dybedal⁸, Mike Recher⁹, Klaus Warnatz^{1

2}, Bodo Grimbacher^{1

2

10

11

12}

Affiliations

¹ Department of Rheumatology and Clinical Immunology, Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany.
² Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Breisacher Straße 115, 79106 Freiburg, Germany.
³ Faculty of Biology, Albert-Ludwigs-University of Freiburg, Schaenzlestraße 1, 79104, Freiburg, Germany.
⁴ Clinical Trials Unit, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Elsaesser Straße 2, 79110 Freiburg, Germany.
⁵ Hannover Medical School, Klinik für Rheumatologie und Immunologie, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
⁶ Medical Center - University of Heidelberg, Institut für Medizinische Biometrie und Informatik, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany.
⁷ Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Barcelona, Germany.
⁸ Oslo University Hospital, Rikshospitalet, Oslo, Norway.
⁹ Outpatient Internal Medicine Clinic, University Hospital, Basel, Switzerland.
¹⁰ DZIF - German Center for Infection Research, Satellite Center Freiburg, Germany.
¹¹ CIBSS - Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University, Schaenzlestraße 18, 79104, Freiburg, Germany.
¹² RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Germany.

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.

Keywords: CTLA-4 insufficiency; Clinical trial protocol; Disease severity score; Immunodeficiency; LRBA deficiency; abatacept.