CVID patients confirmed according to ESID/PAGID criteria or related disorders which fulfill the diagnostic criteria for CVID and interstitial lung disease or granuloma diagnosed by chest CT positive for nodules, lines or ground-glass signs. OR CVID patients confirmed according to ESID/PAGID criteria or related disorders which fulfill the diagnostic criteria for CVID and Enteropathy diagnosed by endoscopy, clinical manifestation of diarrhea, severe bloating or/and malabsorption. MedDRA versi
Conditions
Interventions
Trade Name: ORENCIA® Injektionslösung in einer Fertigspritze
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Abatacept
CAS Number: 332348-12-6
Concentration unit
Sponsors
Universitätsklinikum Freiburg
Eligibility
Sex/Gender
All
Inclusion criteria
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 AND/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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 9 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 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 registration 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. Lack of consent to perform gastroscopy including biopsies in a patient with enteropathy 13. Current or planned pregnancy, nursing period; WOCBP need to keep anti-conceptive measures until 14 weeks after EOT
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To identify predictive, early markers of immune restoration under abatacept therapy in patients with CVID and related disorders. ;Secondary Objective: 1) To molecularly describe immune restoration in CVID patients undergoing abatacept treatment by deep phenotyping 2) To document safety of abatacept treatment in CVID patients with interstitial lung disease and /or autoimmune enteropathy 3) To document efficacy of abatacept treatment in CVID patients with interstitial lung disease and /or autoimmune enteropathy ;Primary end point(s): Identification of predictive, early markers of immune restoration under abatacept therapy in patients with CVID and related disorders.;Timepoint(s) of evaluation of this end point: After 6 months of treatment with Orencia within the clinical trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) In regard to immune reconstitution: - Differential signatures of RNA seq profiles of peripheral blood B and T cell populations before vs after treatment - Differential immune phenotype of peripheral blood B and T cell populations before vs after treatment - Differential serum protein composition before vs. after treatment 2) In regard to safety: Number and type of severe infections (requiring intravenous treatment, hospitalization, ER and ICU treatment, opportunistic infection, death) and number, type and severity of all other (serious) adverse events ((S)AE) in relation to study drug 3) In regard to efficacy in patients with ILD: - Borg Dyspnea scale - Lung function parameter (DLCOcSBVA), FVC, DLCOc/VA, TLC SB, pO2 at rest and under exercise (six-minute walking test) - Laboratory parameters: sIL-2-Receptor, Neopterin - CT scan lung: Global and specific scores for nodules, lines, consolidation and ground glass 4) In regard to efficacy in patients with autoimmune enteropathy: - Stool frequency and consistency - Inflammatory Bowel Disease Questionnaire (IBDQ) - Gastrointestinal histology (for screening historical biopsies can be used) 5) In regard to efficacy in all patients: - Relative reduction of steroid dose - Quality of life measured by SF-36, Chronic fatigue score(FACIT) - Overall survival;Timepoint(s) of evaluation of this end point: After 6 months of treatment with Orencia within the clinical trial. | — |
Countries
Germany
Contacts
Public ContactCoordinating Investigator
Universitätsklinikum Freiburg
Outcome results
None listed