Type 1 DiabetesPhase 2DIABIL-2NCT02411253
Low-dose rhIL-2 in Patients With Recently-diagnosed Type 1 Diabetes
A Phase 2 study testing rhIL-2 in people with Type 1 Diabetes, run by Assistance Publique - Hôpitaux de Paris at 34 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 35 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- rhIL-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 141 participants
- Where
- 34 sitesin 6 countries
- Study dates
- Jun 2015to Nov 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age 6-35 years old.
- Male or female both using effective methods of contraception during treatment if sexually active.
- Specifically; Females (if sexually active) with childbearing potential must use contraceptive methods that are considered as highly-effective (pearl index < 1). The following methods are acceptable: Oral , injectable, or implanted hormonal contraceptives (with the exception of oral minipills ie low-dose gestagens which are not acceptable (lynestrenol and norestisteron), Intrauterine device, Intrauterine system (for example, progestin-releasing toit),
- beta HCG negative at inclusion;
- With type-1 diabetes:
- Newly diagnosed (ADA criteria, see annexe 19.6) at most three months between insulin initiation and anticipated start of experimental treatment.
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- Positive for one or more of the autoantibodies typically associated with T1D (anti-islet, -insulin, -GAD, -IA2, -ZnT8)
- With a detectable peak C-peptide concentration during a standardised MMTT at Visit MMTT (≥0.2pmol/ml);
- patients with a stable blood glucose level and seric glycaemia between 60 mg/dL and 250 mg/dL verified at MMTT visit
- Absence of clinically significant abnormal laboratory values (out of range and associated with clinical symptoms or signs) in haematology, biochemistry, thyroid, liver and kidney function;
- Normal cardiac function: no documented history of heart disease and absence of family history of sudden death, normal ECG especially QTc duration within normal value (<480ms);
- Free, informed and written consent, signed by the patient and investigator before any Study examination. If the patient is a minor by child and both parents or child and the legal representative in case only one parent is alive. (Journal officiel des communautés européennes (1.5.2001)
- NB: patient with history of thyroidism on treatment at the inclusion and with normal thyroid hormone values (TSH+T4) can be included.
Who cannot join
- Children under the age of 6 years old cannot be included
- Patient who, before inclusion, have been treated with other anti-diabetic medication than Insulin for more than 3 months consecutively
- Chronic adrenal insufficiency known or fasting ACTH ≥2.5 ULN normal at inclusion after control;
- Anti TPO present at inclusion and abnormal TSH and T4
- Anti-transglutaminase positive at inclusion
- Hypersensitivity to the active substance or to any of the excipients
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- Any major health problem including: any major auto-immune/auto-inflammatory disease (other than type 1 diabetes) present at inclusion, any significant respiratory disease (such as moderate or severe COPD or asthma) requiring the chronic use of corticosteroids (whatever route of administration) and serious digestive malfunctions.
- Patient with existing malignancy or history of malignancy
- Major psychosocial instability with expected lack of compliance with insulin treatment, psychiatric pathology of patient or parents, or major problems of family dynamics;
- Signs of active infection;
- Any patient with obesity defined as BMI ≥ 35
- Existence of a serious malfunction of a vital organ;
- History of organ allograft;
- Use of treatments not allowed in the Study (see Section 8.4.2);
- Vaccination with alive attenuated virus within 4 weeks of the first injection of the induction period and during the whole maintenance period
- Pregnant female (confirmed by laboratory testing) or lactating
- Participation in another clinical trial in the previous 3 months;
- Lack of affiliation to a social security scheme (as a beneficiary or assignee).
Trial locations and contacts
34 sites in 6 countries.
34 sites in 6 countries
France25 sites
Médecine pédiatrique, CHU Jean Minjoz
Besançon, Franche-Compté, 59037
Service Diabétologie -Endocrinologie, CHU Jean Minjoz
Besançon, Franche-Comté, 59037
Service d' Endocrinologie HOPITAL CAVALE BLANCHE
Brest, Brittany Region, 29609
Service de Pédiatrie, HOPITAL MORVAN
Brest, Brittany Region, 29609
Service d'Endocrinologie pédiatrique - HFME
Bron, 69677
CHRU de Lille, Hôpital Claude Huriez Service d'endocrinologie
Lille, Hauts-de-France, 59037
Endocrinologie-Diabétologie-Maladies de la nutrition, Centre Hospitalier Lyon-Sud
Lyon, Rhones-Alpes, 69495
Service d' Endocrinologie, maladies métaboliques HOPITAL NORD
Marseille, PACA, 13015
Service de Nutrition - Maladies Métaboliques - Endocrinologie HOPITAL DE LA CONCEPTION
Marseille, PACA, 13385
Unité d'Endocrinologie et Diabétologie Pédiatriques, CHU de Marseille, Hôpital La Timone Enfants
Marseille, Provence-Alpes-Côte d'Azur Region, 13385 Marseille Cedex 5
Service de Pédiatrie CHRU DE NANTES
Nantes, Brittany Region, 44093
CIC Paris-Est (Adultes), Hôpitaux Universitaires Pitié-Salpêtrière, Charles Foix
Paris, Île-de-France Region, 75013
Institut E3M, Hôpital Pitié-Salpêtrière
Paris, Île-de-France Region, 75013
CIC pédiatrique Hôpital Necker Enfants Malades
Paris, Île-de-France Region, 75015
Endocrinologie gynécologie diabétologie pédiatriques, Hôpital Universitaire Necker Enfants Malades.
Paris, Île-de-France Region, 75015
CIC Pédiatrique, Hôpital d'enfants Robert Debré
Paris, Île-de-France Region, 75019
Service d'Endocrinologie Pédiatrique, Hôpital d'enfants Robert Debré
Paris, Île-de-France Region, 75019
Service d'endocrinologie, diabétologie, maladies métaboliques, et nutrition, CHU de Bordeaux, Hôpital Haut Levêque
Pessac, Aquitaine, 33604
Service d' Endocrinologie Diabétologie CHRU DE RENNES
Rennes, Brittany Region, 35033
Hopital G&R Laënnec , Endocrinologie, Maladies Métaboliques et Nutrition
Saint-Herblain, Pays de la Loire Region, 44093 NANTES Cedex 1
Centre d'Investigations Cliniques, CHU-HOPITAL HAUTEPIERRE
Strasbourg, Alsace, 67098
Centre d'Investigations Cliniques, HÔPITAL CIVIL
Strasbourg, Alsace, 67098
Service de pédiatrie 1CHU de HAUTEPIERRE
Strasbourg, Alsace, 67098
Structure d'Endocrinologie-Diabète-Nutrition et Addictologie HOPITAUX UNIVERSITAIRES NHC
Strasbourg, Alsace, BP421 - 67091
Service Pédiatrie - Gastro-entérologie, Hépatologie, Nutrition, Diabétologie, Hôpital des Enfants Pôle Enfants
Toulouse, Midi Pyrénnées, 31059 Toulouse cedex 9
Belgium3 sites
UZ - Diabetes voor Kinderen en Adolescenten-Leuven
Leuven, 3000
Pediatric Department, Centre Hospitalier Régional de la Citadelle
Liège, Province De Liège, 4000
CHU UCL Namur - site Godinne
Yvoir, 1-B-5530
Germany3 sites
Division of Endocrinology and Diabetology, Department of Internal Medicine II, University Hospital of Freiburg
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Division of Endocrinology, Diabetology and Metabolic Diseases, University Hospital of Freiburg, Department for children and adolescents
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Institute of Diabetes Research, Helmholtz Zentrum München
München, Bavaria, D 80804
Netherlands1 site
Center for Pediatric and Adolescent Diabetes Care and Research
Rotterdam, Randstad Holland, 3011 TG Rotterdam
Sweden1 site
Dept. of Clinical Sciences Lund University, Skåne University Hospital.
Malmö, Öresund Region, 205 02 Malmö
Switzerland1 site
Endocrinology and Diabetes department, University Hospital of Basel
Basel, Canton of Basel-City, 4031 Basel
About this study
Official title: European Phase-IIb Clinical Trial Evaluating Efficacy of Low Dose rhIL-2 in Patients With Recently-diagnosed Type 1 Diabetes DIABIL-2
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.
Read the 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:
- To evaluate efficacy of low dose IL-2 for the preservation of residual pancreatic β cells function
- To select the optimal regimen of administration of IL-2
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:
- To assess Tregs expansion after an induction period and during maintenance therapy
- To assess safety of IL-2 during the treatment period (1 year) and 1 year after its discontinuation
- To assess the relation between Tregs expansion and preservation of residual pancreatic β cells function
- To assess clinical and biological responses according to (i) pubertal stage group, (i) time from diagnosis to treatment initiation, (iii) biomarkers of responses
- To assess effects of IL-2 on disease-specific immune responses
- To identify biomarkers for predicting/monitoring safety and efficacy of IL-2.
Secondary assessment criteria:
- Serum concentrations of C-peptide
- AUC (T0-T120) of serum C-peptide after a mixed meal tolerance test after treatment discontinuation
- Diabetic monitoring (insulin use)
- HbA1c and IDAA1c score
- Number of hypoglycaemic episodes (< 0.5 g/L on capillary sample) over 15 days before each visit.
- Number of clinically significant symptomatic episodes of hypoglycaemia between each visit.
- Change in Tregs (expressed as percentage of CD4 and absolute numbers) at day 5 compared to baseline.
- Change in trough level of Tregs (%CD4+ and absolute numbers) at month 1, month 3, month 6, month 9, month 12, compared to baseline; and then month 15 and 24 after treatment discontinuation.
- Change in Foxp3 gene methylation
- Cytokines and chemokines assays at day 5, month 1, month 3, month 6, month 9, and month 12 compared to baseline and then month 15 and month 24 after treatment discontinuation.
- Transcriptome analysis.
- Genotyping at baseline
- Treg phenotype and functionality in adults and adolescents only including pStat5 analysis
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:
- Pubertal stage, age, gender, BMI…
- Biomarkers (identified in previous studies as predictive of patients' response to treatment)
Funding source: European Commission under the Health Cooperation Programme of the Seventh Framework Programme (Grant Agreement n°305380-2).
- Conditions
- Type 1 Diabetes
- Being tested
- rhIL-2, Placebo
- Keywords
- IL2, Interleukin 2, IL-2, Auto-immune disease, Insulin, Diabetes, Regulatory T cells, Treg, Immunoregulation, Immune tolerance, Immunotherapy
- Medical subject headings
- Diabetes Mellitus, Type 1, Insulin Resistance, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rhIL-2Drug
Subcutaneous injections of IL2 according to regimen A Subcutaneous injections of IL2 according to regimen B
PlaceboDrug
Subcutaneous injections of Placebo according to regimen A Subcutaneous injections of Placebo according to regimen B
| Study group | Role | What they receive |
|---|---|---|
| rhIL-2 | Experimental | * 0.5 MIU/m²/day of IL2 with a maximum of 1MIU/day in a volume of 1 ml for children and adolescents,
* 1MIU/day for adults.
Subcutaneous injection every day (5 days) then:
* Regimen A injection every two weeks between D15 and D351,
* Regimen B injections every week between D15 and D351 Receives: Drug: rhIL-2 |
| Placebo | Placebo comparator | Placebo with a identical formulation and regimen of injections i.e. Subcutaneous injection every day (5 days) then:
* Regimen A injection every two weeks between D15 and D351
* Regimen B injections every week between D15 and D351 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC (T0-T120) of serum C-peptide, determined after a mixed meal tolerance test at month 12, compared to baseline.
Measured: Baseline, month12
Secondary outcomes (21)
Serum concentrations of C-peptide
Measured: month 3, month 6, month 9, month 15
AUC (T0-T120) of serum C-peptide after a mixed meal tolerance test after treatment discontinuation
Measured: month 15
Diabetic monitoring (insulin use)
Measured: baseline, Day 1, Day 5, month 1, month 3, month 6, month 9, month 12, month 15, month 18, month 21.
HbA1c and IDAA1c score
Measured: baseline, month 3, month 6, month 9, month 12, month 15
Number of hypoglycaemic episodes (< 0.5 g/L on capillary sample) over 15 days before each visit.
Measured: baseline, Day 1, Day 5, month 1, month 3, month 6, month 9, month 12, month 15, month 18, month 21
Number of clinically significant symptomatic episodes of hypoglycaemia between each visit.
Measured: baseline, Day 1, Day 5, month 1, month 3, month 6, month 9, month 12, month 15, month 18, month 21
Change in Tregs (expressed as percentage of CD4 and absolute numbers) at day 5 compared to baseline.
Measured: Baseline, Day 5.
Change in trough level of Tregs (%CD4+ and absolute numbers) at month 1, month 3, month 6, month 9, month 12, compared to baseline; and then month 15 and 24 after treatment discontinuation.
Measured: Baseline, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 24
Change in Foxp3 gene methylation
Measured: Day 1, Day 5, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15
Cytokines and chemokines assays at day 5, month 1, month 3, month 6, month 9, and month 12 compared to baseline and then month 15 and month 24 after treatment discontinuation.
Measured: Baseline, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 24
Transcriptome analysis.
Transcriptome analysis on whole PBMCs will allow analysis of changes in inflammation-related signatures, as already described in Saadoun et al. NEJM, 2011.
Measured: Baseline, Month 6, Month 12
Genotyping at baseline
Genotyping will be used to assess genetic variation (polymorphisms) associated with T1D, such as those linked to IL2RA, PTPN22, CTLA-4...
Measured: baseline
Treg phenotype and functionality in adults and adolescents only including pStat5 analysis
Measured: Day 1, Day 5, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15
Clinical examination.
Measured: Baseline Day 1, Day 5, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Height/weight and pubertal stage especially for children and adolescents.
Based on Tanner staging (Tanner J. M. 1986).
Measured: Baseline, Month 12, Month 24
Routine laboratory tests
Biochemistry, Liver function
Measured: Baseline Day 1, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Haematology
Measured: Baseline Day 1, Day 5, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Detection of IL-2 auto-antibodies
Measured: Day1, Month 6, Month 12
T cells repertory
Measured: Day 1, Day 5, Month 6, Month 12
Intestinal microbiota.
Measured: Baseline, Month 6, Month 12
Adverse event.
Throughout the study.
Measured: Baseline, Day 1, 2, 3, 4, 5, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2015 (estimated)
- Study startJun 2015
- Primary completionNov 2020
- Study completionNov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 141 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Iltoo Pharma
- Responsible party
- Sponsor
- Investigators
- David Klatzmann, MD, Ph.D., Study director, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02411253
- Sponsor's protocol ID
- P121001
- Acronym
- DIABIL-2
- Status last verified
- Aug 2023
- First submitted
- 23 Mar 2015
- Last updated
- 14 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Rosenzwajg M, Hartemann A, Halbron M, Amouyal C, Thivolet C, Rigalleau V, Fontaine P, Mignot B, Reynaud R, Carel JC, Bismuth E, Storey C, Bourdet K, Sonnet E, Baron S, Nicolino M, Perge K, Chaillous L, Kessler L, Mansilla M, Achenbach P, Ziegler AG, Aanstoot HJ, Mouraux T, Casteels K, Donath MY, Roep BO, Lorenzon R, Ribet C, Salem JE, Pitoiset F, Roux A, Vicaut E, Klatzmann D; DIABIL-2 investigators. Efficacy and safety of low-dose IL-2 in people with newly diagnosed type 1 diabetes (DIABIL-2): a double-blind, multicentre, randomised, placebo-controlled, phase 2b trial. Lancet Diabetes Endocrinol. 2026 Oct 1:S2213-8587(26)00191-9. doi: 10.1016/S2213-8587(26)00191-9. Online ahead of print.
PubMed 42822480
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- European Phase-IIb Clinical Trial Evaluating Efficacy of Low Dose rhIL-2 in Patients With Recently-diagnosed Type 1 Diabetes DIABIL-2
- ClinicalTrials.gov ID
- NCT02411253
- Acronym / sponsor ID
- DIABIL-2 / P121001
- Conditions
- Type 1 Diabetes
- Keywords
- IL2, Interleukin 2, IL-2, Auto-immune disease, Insulin, Diabetes, Regulatory T cells, Treg
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 141 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Iltoo Pharma
- Study start
- Jun 2015 (actual)
- Primary completion
- Nov 2020 (actual)
- Study completion
- Nov 2022 (actual)
- First posted
- 8 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- To evaluate efficacy of low dose IL-2 for the preservation of residual pancreatic β cells function
- To select the optimal regimen of administration of IL-2
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:
- To assess Tregs expansion after an induction period and during maintenance therapy
- To assess safety of IL-2 during the treatment period (1 year) and 1 year after its discontinuation
- To assess the relation between Tregs expansion and preservation of residual pancreatic β cells function
- To assess clinical and biological responses according to (i) pubertal stage group, (i) time from diagnosis to treatment initiation, (iii) biomarkers of responses
- To assess effects of IL-2 on disease-specific immune responses
- To identify biomarkers for predicting/monitoring safety and efficacy of IL-2.
Secondary assessment criteria:
- Serum concentrations of C-peptide
- AUC (T0-T120) of serum C-peptide after a mixed meal tolerance test after treatment discontinuation
- Diabetic monitoring (insulin use)
- HbA1c and IDAA1c score
- Number of hypoglycaemic episodes (< 0.5 g/L on capillary sample) over 15 days before each visit.
- Number of clinically significant symptomatic episodes of hypoglycaemia between each visit.
- Change in Tregs (expressed as percentage of CD4 and absolute numbers) at day 5 compared to baseline.
- Change in trough level of Tregs (%CD4+ and absolute numbers) at month 1, month 3, month 6, month 9, month 12, compared to baseline; and then month 15 and 24 after treatment discontinuation.
- Change in Foxp3 gene methylation
- Cytokines and chemokines assays at day 5, month 1, month 3, month 6, month 9, and month 12 compared to baseline and then month 15 and month 24 after treatment discontinuation.
- Transcriptome analysis.
- Genotyping at baseline
- Treg phenotype and functionality in adults and adolescents only including pStat5 analysis
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:
- Pubertal stage, age, gender, BMI…
- Biomarkers (identified in previous studies as predictive of patients' response to treatment)
Funding source: European Commission under the Health Cooperation Programme of the Seventh Framework Programme (Grant Agreement n°305380-2).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rhIL-2 | Experimental | Drug: rhIL-2* 0.5 MIU/m²/day of IL2 with a maximum of 1MIU/day in a volume of 1 ml for children and adolescents, * 1MIU/day for adults. Subcutaneous injection every day (5 days) then: * Regimen A injection every two weeks between D15 and D351, * Regimen B injections every week between D15 and D351 |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo with a identical formulation and regimen of injections i.e. Subcutaneous injection every day (5 days) then: * Regimen A injection every two weeks between D15 and D351 * Regimen B injections every week between D15 and D351 |
Who may qualify
- Ages
- 6 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- Age 6-35 years old.
- Male or female both using effective methods of contraception during treatment if sexually active.
- Specifically; Females (if sexually active) with childbearing potential must use contraceptive methods that are considered as highly-effective (pearl index < 1). The following methods are acceptable: Oral , injectable, or implanted hormonal contraceptives (with the exception of oral minipills ie low-dose gestagens which are not acceptable (lynestrenol and norestisteron), Intrauterine device, Intrauterine system (for example, progestin-releasing toit),
- beta HCG negative at inclusion;
- With type-1 diabetes:
Key exclusion criteria (18 listed)
- Children under the age of 6 years old cannot be included
- Patient who, before inclusion, have been treated with other anti-diabetic medication than Insulin for more than 3 months consecutively
- Chronic adrenal insufficiency known or fasting ACTH ≥2.5 ULN normal at inclusion after control;
- Anti TPO present at inclusion and abnormal TSH and T4
- Anti-transglutaminase positive at inclusion
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rhIL-2Subcutaneous injections of IL2 according to regimen A Subcutaneous injections of IL2 according to regimen B | Drug | rhIL-2 |
| PlaceboSubcutaneous injections of Placebo according to regimen A Subcutaneous injections of Placebo according to regimen B | Drug | Placebo |
Primary outcome
AUC (T0-T120) of serum C-peptide, determined after a mixed meal tolerance test at month 12, compared to baseline.
Time frame: Baseline, month12
21 secondary outcomes
Serum concentrations of C-peptide
Time frame: month 3, month 6, month 9, month 15
AUC (T0-T120) of serum C-peptide after a mixed meal tolerance test after treatment discontinuation
Time frame: month 15
Diabetic monitoring (insulin use)
Time frame: baseline, Day 1, Day 5, month 1, month 3, month 6, month 9, month 12, month 15, month 18, month 21.
HbA1c and IDAA1c score
Time frame: baseline, month 3, month 6, month 9, month 12, month 15
Number of hypoglycaemic episodes (< 0.5 g/L on capillary sample) over 15 days before each visit.
Time frame: baseline, Day 1, Day 5, month 1, month 3, month 6, month 9, month 12, month 15, month 18, month 21
Number of clinically significant symptomatic episodes of hypoglycaemia between each visit.
Time frame: baseline, Day 1, Day 5, month 1, month 3, month 6, month 9, month 12, month 15, month 18, month 21
Change in Tregs (expressed as percentage of CD4 and absolute numbers) at day 5 compared to baseline.
Time frame: Baseline, Day 5.
Change in trough level of Tregs (%CD4+ and absolute numbers) at month 1, month 3, month 6, month 9, month 12, compared to baseline; and then month 15 and 24 after treatment discontinuation.
Time frame: Baseline, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 24
Change in Foxp3 gene methylation
Time frame: Day 1, Day 5, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15
Cytokines and chemokines assays at day 5, month 1, month 3, month 6, month 9, and month 12 compared to baseline and then month 15 and month 24 after treatment discontinuation.
Time frame: Baseline, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 24
Transcriptome analysis.
Time frame: Baseline, Month 6, Month 12
Genotyping at baseline
Time frame: baseline
Treg phenotype and functionality in adults and adolescents only including pStat5 analysis
Time frame: Day 1, Day 5, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15
Clinical examination.
Time frame: Baseline Day 1, Day 5, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Height/weight and pubertal stage especially for children and adolescents.
Time frame: Baseline, Month 12, Month 24
Routine laboratory tests
Time frame: Baseline Day 1, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Haematology
Time frame: Baseline Day 1, Day 5, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Detection of IL-2 auto-antibodies
Time frame: Day1, Month 6, Month 12
T cells repertory
Time frame: Day 1, Day 5, Month 6, Month 12
Intestinal microbiota.
Time frame: Baseline, Month 6, Month 12
Adverse event.
Time frame: Baseline, Day 1, 2, 3, 4, 5, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2023.
- Derived from this study: PubMed 42822480Rosenzwajg M, Hartemann A, Halbron M, Amouyal C, Thivolet C, Rigalleau V, Fontaine P, Mignot B, Reynaud R, Carel JC, Bismuth E, Storey C, Bourdet K, Sonnet E, Baron S, Nicolino M, Perge K, Chaillous L, Kessler L, Mansilla M, Achenbach P, Ziegler AG, Aanstoot HJ, Mouraux T, Casteels K, Donath MY, Roep BO, Lorenzon R, Ribet C, Salem JE, Pitoiset F, Roux A, Vicaut E, Klatzmann D; DIABIL-2 investigators. Efficacy and safety of low-dose IL-2 in people with newly diagnosed type 1 diabetes (DIABIL-2): a double-blind, multicentre, randomised, placebo-controlled, phase 2b trial. Lancet Diabetes Endocrinol. 2026 Oct 1:S2213-8587(26)00191-9. doi: 10.1016/S2213-8587(26)00191-9. Online ahead of print.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Klatzmann, MD, Ph.D. study director
Assistance Publique - Hôpitaux de Paris
34 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rhIL-2 in people with Type 1 Diabetes, run by Assistance Publique - Hôpitaux de Paris at 34 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in France, Belgium, Germany, Netherlands, Sweden and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC (T0-T120) of serum C-peptide, determined after a mixed meal tolerance test at month 12, compared to baseline. (time frame: Baseline, month12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02411253, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2023.