Ciclosporin Followed by Low-dose IL-2 in Patients With Recently Diagnosed Type 1 Diabetes

NCT05153070 | Recruiting Phase 2 DMC

• 1 other identifier: P120142
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Type 1 diabetes (T1D) is caused by the destruction of insulin-producing cells by effector T cells (Teffs), due to a deficiency of regulatory T cells (Tregs). Ciclosporin effectively blocks the Teffs and controls diabetes, but cannot be considered as a long-term treatment. Low-dose interleukin-2 (ld IL-2) activates and expands Tregs in humans. Hence, Ld IL-2 in patients in whom the autoimmune process was blocked early by a short treatment (2 months) of cyclosporine should restore immune homeostasis and maintain some insulin production over the long term.

Conditions

Type 1 Diabetes

Keywords

Interleukin 2; Ciclosporin; Auto-immune disease; Diabetes; Regulatory T cells; Immune tolerance; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Treg variation

  Change in Tregs values at Day 67 compared to Day 63 (post-ciclosporin value)

  From Day 63 to Day 67

Secondary Outcomes (41)

• Change in Area under curve (AUC (T0-T120) of serum C-peptide at month 6

  up to month 6

• Change in Area under curve (AUC (T0-T120) of serum C-peptide at month 12

  up to month 12

• Change in Area under curve (AUC (T0-T120) of serum C-peptide at month 24

  up to month 24

• Variation in HbA1c value (in %) during the treatment period and during the 1-year follow-up period compared to Baseline at day 63,

  up to day 63

• Variation in HbA1c value (in %) during the treatment period and during the 1-year follow-up period compared to Baseline at month 3

  up to month 3

Study Arms (2)

Ciclosporin/ILT-101

EXPERIMENTAL

Ciclosporin during 2 months (for all patients) followed by ILT-101 during 10 months

Drug: Cyclosporin; Drug: ILT101

Ciclosporin/placebo

PLACEBO COMPARATOR

Ciclosporin during 2 months (for all patients) followed by placebo during 10 months

Drug: Cyclosporin; Drug: Placebo

Interventions

Cyclosporin DRUG

• Ciclosporin: 5mg/kg, twice a day, oral, between Day 1 and Day 60

Ciclosporin/ILT-101; Ciclosporin/placebo

ILT101 DRUG

• ILT-101: 1MIU/day in a volume of 1 ml; subcutaneous injection every day during 5 consecutive days and then every week between Day 63 and Day 354.

Ciclosporin/ILT-101

Placebo DRUG

• Placebo with an identical formulation and regimen of injections i.e. Subcutaneous injection every day (5 consecutive days) then then every week between Day 63 and Day 354.

Ciclosporin/placebo

Eligibility Criteria

• Age: 16 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Type 1 diabetes according to ADA criteria, with at least 1 positive autoantibody among the following: anti-islet, anti-GAD, anti-IA2, anti-ZnT8 and anti-insulin.
• Diagnosis ≤ 3 months
• No acid ketosis
• No weight loss \> 10% OR with fasting C-peptide ≥ 0.1 nmol/L (after a period of ≥ 15 days following the initiation of insulin therapy
• Absence of clinically significant biological abnormalities on hematological, biochemical, hepatic, renal and thyroid tests.
• No documented history of heart disease, no family history of sudden death, AND normal ECG.
• Effective contraception in men and women of childbearing potential \> 2 weeks prior to first administration of the investigational drug and throughout the treatment period (if sexually active). Specifically for women of childbearing age and sexually active, they must use an effective contraceptive method (Pearl Index \< 1). The following methods are acceptable: oral hormonal contraceptives, injectable, or implanted (with the exception of oral minipills: i.e. low doses of gestagens which are not acceptable (lynestrenol and norestisteron), intrauterine contraceptives (e.g. progestin-release systems)),
• Free, informed and written consent, signed by the patient and the investigator, prior to any examination required by the trial.
• If the patient is a minor, the signatures of both parents and of the child will be collected (or the legal representative if only one parent is alive).

You may not qualify if:

• Known contraindications to IL2 treatment:
• Hypersensitivity to the active substance or to one of the excipients.
• Signs of active infection requiring antibiotics
• Documented history of clinical autoimmune disease
• Oxygen saturation ≤ 90%
• Existence of a serious dysfunction in a vital organ
• History of organ allograft,
• Known contraindications to treatment with cyclosporine
• Presence of unauthorized treatment, i.e. cytotoxic drugs, products known for their impact on blood glucose levels or for their interactions with the treatments under trial
• Patients who have received anti-diabetic treatment other than insulin for more than 3 consecutive months.
• EBV viral load \> 2000 IU/ml
• CMV viral load \> 400 IU/ml
• HBV, HCV or HIV infection
• Lymphopenia ≤ 1000/ mm3
• Presence or history of cancer that has been cured for less than five years, except in situ cervical or basal cell carcinoma in early stage management,

Sponsors & Collaborators

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

Study Sites (1)

Lorenzon Roberta

Paris, 75013, France

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Interventions

Cyclosporine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• David Klatzmann, MD, Ph.D

  APHP(ASSISTANCE PUBLIQUE DES HOPITAUX DE PARIS

  STUDY DIRECTOR

• Agnès Hartmann, MD, Ph.D

  APHP(ASSISTANCE PUBLIQUE DES HOPITAUX DE PARIS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Klatzmann, MD, Ph.D

CONTACT

01 42 17 74 61; david.klatzmann@sorbonne-universite.fr

Roberta Lorenzon, MD

CONTACT

01 42 17 65 16; roberta.lorenzon@sorbonne-universite.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: all participant receive the treatment with Ciclosporin and double Blind for the treatment with IL-2
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single group during ciclosporin treatment and parallel group during ILT-101 treatment

Study Record Dates

• First Submitted: April 16, 2021
• First Posted: December 10, 2021
• Study Start: September 21, 2022
• Primary Completion: April 21, 2026
• Study Completion (Estimated): April 21, 2028
• Last Updated: June 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)