Low-dose rhIL-2 in Patients With Recently-diagnosed Type 1 Diabetes (DIABIL-2)
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ClinicalTrials.gov Identifier: NCT02411253 |
Recruitment Status :
Completed
First Posted : April 8, 2015
Last Update Posted : August 14, 2023
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Tracking Information | ||||
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First Submitted Date ICMJE | March 23, 2015 | |||
First Posted Date ICMJE | April 8, 2015 | |||
Last Update Posted Date | August 14, 2023 | |||
Actual Study Start Date ICMJE | June 2015 | |||
Actual Primary Completion Date | November 2020 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
AUC (T0-T120) of serum C-peptide, determined after a mixed meal tolerance test at month 12, compared to baseline. [ Time Frame: Baseline, month12 ] | |||
Original Primary Outcome Measures ICMJE | Same as current | |||
Change History | ||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | |||
Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Low-dose rhIL-2 in Patients With Recently-diagnosed Type 1 Diabetes | |||
Official Title ICMJE | European Phase-IIb Clinical Trial Evaluating Efficacy of Low Dose rhIL-2 in Patients With Recently-diagnosed Type 1 Diabetes DIABIL-2 | |||
Brief Summary | Type 1diabetes (T1D) is caused by autoimmune destruction of the pancreatic islet ß-cells, leading to an absolute deficiency in insulin. In health, regulatory T cells (Tregs) suppress immune responses against normal tissues, and likewise prevent autoimmune diseases. Tregs are insufficient in T1D. The investigators previously showed that administration of low doses of IL-2 induces selective expansion and activation of Tregs in mice and humans. The investigators hypothesize that Tregs expansion and activation with low doses of IL2 could block the ongoing autoimmune destruction of insulin producing cells in patients with recently diagnosed T1D. |
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Detailed Description | Scientific justification: Clinical and preclinical studies, together with supportive mechanistic data showing that Tregs are activated by much lower IL-2 concentration than effector T cells (Teffs), provide a strong rationale for studying efficacy of low dose IL2 to stop the autoimmune destruction of insulin-secreting beta cells in patient with recently diagnosed with T1D. Primary objective:
Primary assessment criterion: AUC (T0-T120) of serum C-peptide, determined after a mixed meal tolerance test at month 12, compared to baseline. Secondary objectives:
Secondary assessment criteria:
Pharmacokinetic of IL2 will be performed (in patients from regimen A only) on day 1 at T0, T60min (1h), T120min (2h), T240min (4h), T360min (6h), T600min (10h), T1440min (24h=day2) on day 4, V8 (D29±1day) and V54 (day 351±3 days) at the same time points in 27 patients of regimen A. • Safety parameters will be evaluated by clinical examination (including height/weight and pubertal stage especially for children and adolescents), routine laboratory tests, ILT-101 auto-antibodies, ancillary investigations and adverse event. Experimental design: This is a multicenter European, sequential-group, randomized, double-blind trial evaluating IL-2 versus placebo Population involved: Male or female, aged between 6 and 35 years, with type 1 diabetes diagnosed for less than two months. Number of subjects: 138 Inclusion period: 49 months Duration of patient participation: 24 months (treatment period: 12 months, follow-up period: 12months) Total duration of the study: 73 months Statistical analysis: The principal efficacy analysis will be drawn from the intention to treat group. The per-protocol analysis will be used to confirm the intention to treat analysis. For each regimen: - MMTT: C-peptide concentrations will be summarized by the AUC from T0 to T+120 min. Before statistical analysis, log (x+1) normalizing transformation will be used, and IL-2 and placebo treated patients will be compared using a mixed model of ANCOVA including baseline value as covariate and factor pubertal stage group. Quantitative endpoints will be analyzed using same methods as primary endpoint. Categorical endpoints will be analyzed using multivariate logistic regression models. Subgroups analyses: Response to treatment will be analysed according to criteria such as:
Funding source: European Commission under the Health Cooperation Programme of the Seventh Framework Programme (Grant Agreement n°305380-2). |
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Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 2 | |||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
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Condition ICMJE | Type 1 Diabetes | |||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Completed | |||
Actual Enrollment ICMJE |
141 | |||
Original Estimated Enrollment ICMJE |
138 | |||
Actual Study Completion Date ICMJE | November 2022 | |||
Actual Primary Completion Date | November 2020 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion criteria
Exclusion criteria
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Sex/Gender ICMJE |
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Ages ICMJE | 6 Years to 35 Years (Child, Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | Belgium, France, Germany, Netherlands, Sweden, Switzerland | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT02411253 | |||
Other Study ID Numbers ICMJE | P121001 | |||
Has Data Monitoring Committee | Yes | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE | Not Provided | |||
Current Responsible Party | Assistance Publique - Hôpitaux de Paris | |||
Original Responsible Party | Same as current | |||
Current Study Sponsor ICMJE | Assistance Publique - Hôpitaux de Paris | |||
Original Study Sponsor ICMJE | Same as current | |||
Collaborators ICMJE | Iltoo Pharma | |||
Investigators ICMJE |
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PRS Account | Assistance Publique - Hôpitaux de Paris | |||
Verification Date | August 2023 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |