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

• Status: Not yet recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Iltoo Pharma
• Treatments: Cyclosporine; Cyclosporins

Criteria

Inclusion Criteria:

• • Age at inclusion between ≥ 16 years old (Tanner 5 pubertal stage) and ≤ 35 years old

• 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%

• 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).

Exclusion Criteria:

• 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.

• Anti-thyroperoxidase positive and abnormal TSH and T4 at inclusion

• Anti-transglutaminase positive at inclusion

• 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,

• Participation in other intervention research involving humans < 3 months,

• Pregnant or breastfeeding women

• Lack of social security affiliation (as a beneficiary or assignee)

• Vaccination with live attenuated virus during the last 4 weeks before the start of the experimental treatment and during the entire treatment phase.

• Patient with active SARS-CoV-2 infection

• Patient with chronic respiratory disease

• Subject under legal protection (such as tutorship, curatorship, or judicial safeguard)

• Subject hospitalized without consent, unable to express consent or deprived of liberty