Abatacept restores immune system equilibrium

Phase 2

• Conditions: D83; Common variable immunodeficiency

• Registration Number: DRKS00027556
• Lead Sponsor: niversitätsklinikum Freiburg

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-05-11
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Pending
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Diagnosis of CVID according to ESID/PAGID criteria or diagnosis of related disorders which fulfill the diagnostic criteria for CVID
2. A) Interstitial lung disease or granuloma diagnosed by chest CT positive for nodules, lines or ground-glass signs OR
B) Celiac-like enteropathy diagnosed by histologically proven lymphocytic enteropathy
3. Male and female patients of age 18 years and above
4. Signed written informed consent
5. Patient able to understand and willing to follow the protocol, including s.c. application and adequate storage of study drug
6. Patients receiving regular immunoglobulin replacement therapy with trough levels of IgG above 4g/l
7. Patients have failed steroid monotherapy (including topical steroids for enteropathy) for a minimum of three months or do not tolerate steroid treatment.
8. Need for intervention due to pulmonary manifestation measured by either reduced oxygen saturation, drop of oxygen saturation under exercise or reduced DLCOcSB
OR
progress of interstitial lung disease measured by progressive
changes in the CT scan of the lung
OR
Need for intervention due to gastrointestinal manifestation measured by stool frequency above three stools/day OR signs of malabsorption OR severe bloating
OR
Marsh score of 3 in the duodenal histology

Exclusion Criteria

1. Patient without legal capacity who is unable to understand the nature, significance and consequences of the study
2. Known diagnosis of a monogenic defect in CTLA-4 or LRBA
3. Other immunosuppressive therapy including biologicals beyond steroid at screening phase. 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 3 months before inclusion into trial.
4. Previous treatment with abatacept
5. Chronic or active infection or any major episode of infection requiring hospitalization or treatment with intravenous (i.v.) antibiotics within 30 days prior to baseline
6. Acute or uncontrolled chronic bacterial including tuberculosis or viral infection (including HIV, HBV; HCV, HEV, SARS-CoV2. Patients with a chronic Norovirus infection can be included).
7. Subjects who have a present malignancy or previous malignancy within the last 5 years prior to screening (except documented history of cured non-metastatic squamous or basal cell skin carcinoma or cervical carcinoma in situ). Subjects who had a screening procedure that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations.
8. Receipt of a live replication-competent virus vaccine within 3 months prior to first application of trial medication.
9. Serious uncontrolled concomitant disease not caused by CVID.
10. Prior hematopoietic stem cell transplantation (HSCT) or HSCT planned within next 12 months
11. Known intolerance to study medication or any of the excipients
12. Current or planned pregnancy, nursing period; WOCBP need to keep anti-conceptive measures until 14 weeks after EOT.

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The hypothesis of the study is that the immunosuppressive medication abatacept restores immune homeostasis in patients with CVID and immune dysregulation due to autoimmune manifestations like interstitial lung disease or enteropathy and that these changes can be measured and some of them used as biomarkers of restoration. The primary endpoint is to identify predictive, early markers of immune restoration under abatacept therapy in patients with CVID and related disorders and to generate a marker panel indicative of (early) immune reconstitution under abatacept treatment at 3 months of treatment.