Safety and Efficacy of abatacept (s.c.) in patients with CTLA4 insufficiency or LRBA deficiency

Phase 2

• Conditions: CTLA4 insufficiency or LRBA deficiency; D84.9; Immunodeficiency, unspecified

• Registration Number: DRKS00017736
• Lead Sponsor: niversitätsklinikum Freiburg vertreten durch den Leitenden Ärztlichen Direktor und die Kaufmännische Direktorin

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-07-06
• Study Completion: 2023-06-28
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Molecular diagnosis of CTLA4 (haplo)-insufficiency or LRBA deficiency with either published mutations or mutations with proven functional effect (impaired CTLA4 staining or CTLA4-dependent transendocytosis).
2. Age =18 years.
3. IgG serum trough level = 4 g/l (+/- IRT): last test result within 3 months at baseline visit.
4. Signed written informed consent.
5. Need for intervention on clinical grounds or continued need of therapy with abatacept as evaluated by the treating physician.
6. One organ system has to be involved: lung involvement, gut involvement (enteropathy), cytopenias, CNS involvement, lymphoproliferation, immune system, skin involvement. In case of pretreatment with abatacept, organ involvement should be defined using retrospective data from the period before first application of abatacept.

Exclusion Criteria

1. Patient without legal capacity who is unable to understand the nature,
significance and consequences of the trial
2. Other current immunosuppressive treatments with biologicals or diseasemodifying
antirheumatic drugs (DMARDs) other than corticosteroids
= 20 mg or abatacept. Between treatment with other biologicals or DMARDs
and start of abatacept trial treatment the wash out period of the pretreatment
must be kept. In case of pretreatment with rituximab, therapy must be
stopped at least 6 month before inclusion to trial.
3. Treatment with systemic steroids (prednisolone) in daily dose > 20 mg
4. Active or chronic Hepatitis B or tuberculosis infection.
5. Active infection or any major episode of infection requiring hospitalization or
treatment with intravenous (i.v.) antibiotics within 30 days prior to baseline
6. Chronic infection requiring hospitalization or treatment with i.v. antibiotics
within 30 days prior to baseline (does not apply for patients already
pretreated with abatacept)
7. Acute bacterial or viral infection (patients with a chronic and clinically
controlled infection can be included).
8. Patient on antiviral cytomegalovirus (CMV) prophylaxis within 28 days prior
to baseline visit.
9. Any malignancies within the last 4 years with the exception of basal cell
carcinoma and precancerous conditions (does not apply for patients already
pretreated with abatacept)
10. Current or planned pregnancy, nursing period
11. Epstein-Barr virus (EBV) load of = 5.000 IU/ml or CMV load of = 1.000 IU/ml
in plasma at screening
12. Receipt of a live virus vaccine within 3 month prior to first application of trial
medication
13. Serious uncontrolled concomitant disease not caused by
CTLA4 insufficiency or LRBA deficiency.
14. Known HIV infection, infectious hepatitis (type A or C) or another
uncontrolled infection
15. Prior hematopoietic stem cell transplantation (HSCT) or HSCT planned
within next 12 months
16. Known intolerance to study medication or any of the excipients

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
umber of episodes of failed infection control under therapy with abatacept during the trial period of one year.

Secondary Outcome Measures

Name	Time	Method
- Number of severe infections (i.e. hospitalisation required, or an infection requiring i.v. antibiotic, i.v. antifungal or i.v. antiviral treatment)<br>- Characterization (including pathogen type and affected organ system) of severe infections during study treatment with Abatacept.<br>•Number of episodes of failed infection control exceeding 3 months under therapy with abatacept during the trial period of one year. <br><br>- overall survival<br>- event-free survival<br>- treatment failure, defined as premature discontinuation of study treatment for any reason<br>- cumulative steroid dose<br>- cumulative dose of concomitant drugs to alleviate symptoms, such as diarrhoea or pain medication<br>- Clinical Global Impression – Improvement Skala (CGI-I)<br>- quality of life measured by SF 36<br>- CHAI-Morbidity Score<br>- laboratory parameters