A Phase I-IIa trial on low-dose IL-2 (Aldesleukin) treatment for immunological dysregulation in common variable immunodeficiency (CVID)

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 6

Inclusion Criteria

1.Patient with a diagnosis of CVID according to the ESID/PAGID criteria
2.Sufficient IgG replacement therapy for at least 6 months with IgG trough levels above 6g/l.
3.Diagnosis of autoimmune enteropathy of the upper gastrointestinal tract proven by histology. Last biopsy <6 months before study inclusion.
4.Clinical activity of enteropathy within the last month before inclusion defined as = 3 loose stools per day on more than half of the days.
5.Report of negative culture for pathogenic intestinal bacteria within one month before study inclusion.
6.Failure of topic or systemic steroid treatment or contraindications for steroid therapy or unacceptable side effects of steroid treatment.
7.Daily dose of glucocorticosteroids = 20mg prednisolone (or equivalent) at the day of baseline visit.

Exclusion Criteria

1.Need for a scheduled application of contrast agent during the trial.
2.Patients with malignant neoplasm within the last 5 years prior to visit 1 (except adequately treated basal cell carcinoma or squamous cell carcinoma of the skin and carcinoma in situ of the uterine cervix).
3.Patients with an ECOG = 2.
4.Patients with a history of or current severe cardiac or pulmonary disease or uncontrolled pericardial or pleural effusion.
5.Patients with thrombosis or thromboembolic event < 6 months before study inclusion.
6.Patients with active CNS involvement (e.g. intracranial granulomata, multiple sclerosis, vasculitis or other autoinflammatory CNS disease) or recurrent seizures.
7.Uncontrolled chronic infectious disease (including HIV, EBV, CMV, HCV, HBV, tuberculosis) or conditions which represent a high risk for infection (i.e. severe bronchiectasis) which might interfere with the study at the discretion of the investigator.
8. Major infection requiring antibiotic therapy or infection requiring hospitalization within the last 4 weeks prior to the baseline visit.
9.Treatment with any immunosuppressive, cytotoxic drug within the last 4 weeks prior to visit 1 (except prednisolone = 20mg or equivalent).
10.Patients with allogenic organ transplants.
11.Active autoimmue manifestation requiring treatment (except autoimmune enteropathy).
12.Clinically relevant chronic or acute renal (creatinine >1.25 ULN), hepatic (AST > 3 ULN, bilirubin > 1.5 x ULN) or other severe organ impairment.
13.Preexisting cytopenia (hematocrit <30%, thrombocytes <100.000/µl, leukocytes <3.000/µl or neutrophils <1.500/µl or CD4 cell counts <100/ µl.

Study & Design

Study Type: interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To assess the safety:<br>Adverse events will be recorded according to GCP guidelines during the treatment and follow-up phase at every site visit (every two weeks). <br>Autoantibodies will be measured before and after the therapy. <br>Differential blood count (eosinophil counts), lymphocyte subsets as well as liver enzymes, creatinine and coagulation parameters will be measured every two weeks. <br>

Secondary Outcome Measures

Name	Time	Method
To assess the optimal dose for expansion of Treg cells:<br>- % of Tregs will be measured before each cycle and on day 4 of every cycle and on day 6 of the induction cycle(s). <br><br>To assess the impact of low-dose Aldesleukin on chronic diarrhoea:<br>- Disease activity will be assessed with a self-administered questionnaire (IBDQ) and a stool diary filled in by patients.<br>

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