Low-dose rhIL-2 in Patients With Recently-diagnosed Type 1 Diabetes

NCT02411253 | Completed Phase 2 DMC

• 1 other identifier: P121001
• Study Type: interventional
• Target: 141
• Locations: 6 countries
• Sites: 34

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.

Conditions

Type 1 Diabetes

Keywords

IL2; Interleukin 2; IL-2; Auto-immune disease; Insulin; Diabetes; Regulatory T cells; Treg; Immunoregulation; Immune tolerance; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• AUC (T0-T120) of serum C-peptide, determined after a mixed meal tolerance test at month 12, compared to baseline.

  Baseline, month12

Secondary Outcomes (21)

• Serum concentrations of C-peptide

  month 3, month 6, month 9, month 15

• AUC (T0-T120) of serum C-peptide after a mixed meal tolerance test after treatment discontinuation

  month 15

• Diabetic monitoring (insulin use)

  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

  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.

  baseline, Day 1, Day 5, month 1, month 3, month 6, month 9, month 12, month 15, month 18, month 21

Study Arms (2)

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

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

Drug: Placebo

Interventions

rhIL-2 DRUG

Subcutaneous injections of IL2 according to regimen A Subcutaneous injections of IL2 according to regimen B

rhIL-2

Placebo DRUG

Subcutaneous injections of Placebo according to regimen A Subcutaneous injections of Placebo according to regimen B

Placebo

Eligibility Criteria

• Age: 6 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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),
• 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.
• 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)

You may not qualify if:

• Children under the age of 6 years old cannot be included
• Hypersensitivity to the active substance or to any of the excipients
• 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).

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Iltoo Pharma: collaborator

Study Sites (34)

Pediatric Department, Centre Hospitalier Régional de la Citadelle

Liège, Province De Liège, 4000, Belgium

Location

UZ - Diabetes voor Kinderen en Adolescenten-Leuven

Leuven, 3000, Belgium

Location

CHU UCL Namur - site Godinne

Yvoir, 1-B-5530, Belgium

Location

Centre d'Investigations Cliniques, CHU-HOPITAL HAUTEPIERRE

Strasbourg, Alsace, 67098, France

Location

Centre d'Investigations Cliniques, HÔPITAL CIVIL

Strasbourg, Alsace, 67098, France

Location

Service de pédiatrie 1CHU de HAUTEPIERRE

Strasbourg, Alsace, 67098, France

Location

Structure d'Endocrinologie-Diabète-Nutrition et Addictologie HOPITAUX UNIVERSITAIRES NHC

Strasbourg, Alsace, BP421 - 67091, France

Location

Service d'endocrinologie, diabétologie, maladies métaboliques, et nutrition, CHU de Bordeaux, Hôpital Haut Levêque

Pessac, Aquitaine, 33604, France

Location

Service d' Endocrinologie HOPITAL CAVALE BLANCHE

Brest, Brittany Region, 29609, France

Location

Service de Pédiatrie, HOPITAL MORVAN

Brest, Brittany Region, 29609, France

Location

Service de Pédiatrie CHRU DE NANTES

Nantes, Brittany Region, 44093, France

Location

Service d' Endocrinologie Diabétologie CHRU DE RENNES

Rennes, Brittany Region, 35033, France

Location

Médecine pédiatrique, CHU Jean Minjoz

Besançon, Franche-Compté, 59037, France

Location

Service Diabétologie -Endocrinologie, CHU Jean Minjoz

Besançon, Franche-Comté, 59037, France

Location

CHRU de Lille, Hôpital Claude Huriez Service d'endocrinologie

Lille, Hauts-de-France, 59037, France

Location

Service Pédiatrie - Gastro-entérologie, Hépatologie, Nutrition, Diabétologie, Hôpital des Enfants Pôle Enfants

Toulouse, Midi Pyrénnées, 31059 Toulouse cedex 9, France

Location

Service d' Endocrinologie, maladies métaboliques HOPITAL NORD

Marseille, PACA, 13015, France

Location

Service de Nutrition - Maladies Métaboliques - Endocrinologie HOPITAL DE LA CONCEPTION

Marseille, PACA, 13385, France

Location

Hopital G&R Laënnec , Endocrinologie, Maladies Métaboliques et Nutrition

Saint-Herblain, Pays de la Loire Region, 44093 NANTES Cedex 1, France

Location

Unité d'Endocrinologie et Diabétologie Pédiatriques, CHU de Marseille, Hôpital La Timone Enfants

Marseille, Provence-Alpes-Côte d'Azur Region, 13385 Marseille Cedex 5, France

Location

Endocrinologie-Diabétologie-Maladies de la nutrition, Centre Hospitalier Lyon-Sud

Lyon, Rhones-Alpes, 69495, France

Location

Service d'Endocrinologie pédiatrique - HFME

Bron, 69677, France

Location

CIC Paris-Est (Adultes), Hôpitaux Universitaires Pitié-Salpêtrière, Charles Foix

Paris, Île-de-France Region, 75013, France

Location

Institut E3M, Hôpital Pitié-Salpêtrière

Paris, Île-de-France Region, 75013, France

Location

CIC pédiatrique Hôpital Necker Enfants Malades

Paris, Île-de-France Region, 75015, France

Location

Endocrinologie gynécologie diabétologie pédiatriques, Hôpital Universitaire Necker Enfants Malades.

Paris, Île-de-France Region, 75015, France

Location

CIC Pédiatrique, Hôpital d'enfants Robert Debré

Paris, Île-de-France Region, 75019, France

Location

Service d'Endocrinologie Pédiatrique, Hôpital d'enfants Robert Debré

Paris, Île-de-France Region, 75019, France

Location

Division of Endocrinology and Diabetology, Department of Internal Medicine II, University Hospital of Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Division of Endocrinology, Diabetology and Metabolic Diseases, University Hospital of Freiburg, Department for children and adolescents

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Institute of Diabetes Research, Helmholtz Zentrum München

München, Bavaria, D 80804, Germany

Location

Center for Pediatric and Adolescent Diabetes Care and Research

Rotterdam, Randstad Holland, 3011 TG Rotterdam, Netherlands

Location

Dept. of Clinical Sciences Lund University, Skåne University Hospital.

Malmo, Öresund Region, 205 02 Malmö, Sweden

Location

Endocrinology and Diabetes department, University Hospital of Basel

Basel, Canton of Basel-City, 4031 Basel, Switzerland

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Study Officials

• David Klatzmann, MD, Ph.D.

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2015
• First Posted: April 8, 2015
• Study Start: June 1, 2015
• Primary Completion: November 1, 2020
• Study Completion: November 1, 2022
• Last Updated: August 14, 2023

Record last verified: 2023-08

Locations

BE (3); NL (1); CH (1); SE (1); DE (3); FR (25)