DFIL2-REP - Study of the clinical and biological response to repeated administration of low-dose interleukin-2 in patients with type 1 diabetes who have retained residual insulin secretion

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

21 Sep 2022 → ongoing

Decision date (initial)

2024-07-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

DGOS

External identifiers

EU CT number

2024-514043-29-00

EudraCT number

2020-005068-70

ClinicalTrials.gov

NCT05153070

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Evaluation of the Tregs lymphocyte response profile between D63 and D70, after 5 administrations of low-dose IL-2 (1MUI/day) in patients with type 1 diabetes of recent onset who had received ciclosporin treatment for 2 months.

Secondary objectives 4

1. Evolution of residual insulin secretion
2. Change in Tregs values at M3 (J88), M6 (J179), M9 (J270), M12 (J361) and after treatment discontinuation at M18 (J536) and M24 (J719) compared to baseline and post ciclosporin values (J63)
3. Compliance with ciclosporin and ILT-101/placebo
4. Tolerance of trial treatments from D1 to D719

Conditions and MedDRA coding

Patient with newly diagnosed (≤ 3 months) type 1 diabetes stage 3

Regulatory references

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age at inclusion between ≥ 16 years (Tanner 5 pubertal stage) and ≤ 45 years
2. Type 1 diabetes according to ADA criteria, with at least 1 positive autoantibody (AAC) among the following AACs: anti-islet, anti-GAD, anti-IA2, anti-ZnT8 and anti-insulin
3. Diabetes stage 3 ≤ 3 months and without ketoacidosis and without weight loss > 10% OR with fasting C-peptide ≥ 0.1nmol/L (after a delay ≥ 15days following initiation of insulin therapy).
4. Absence of clinically significant biological abnormalities in hematology, biochemistry, liver, kidney and thyroid function tests
5. No documented history of heart disease and ECG without clinically significant abnormalities
6. Effective contraception for men and women of childbearing age > 2 weeks before the first administration of the investigational drug and throughout the treatment period (if sexually active). Sexually active women of childbearing age must use an effective contraceptive method. The following methods are acceptable: oral, injectable or implanted hormonal contraceptives. The minipill and copper IUD are tolerated28
7. Free, informed and written consent, signed by the patient and the investigator, before any examination required by the trial. If the patient is a minor, the signatures of the 2 parents and the child will be collected (or the legal representative if only one parent is alive).

Exclusion criteria 19

1. Known contraindications to IL-2 therapy
2. Known contraindications to ciclosporin treatment
3. Presence of unauthorized treatments, i.e. cytotoxics, products known to have an impact on glycemia or to interact with trial treatments
4. Patients who have received anti-diabetic treatment other than insulin for more than 3 consecutive months
5. Positivity of at least one thyroid-specific antibody (anti-TPO, anti-TG or anti-TRAKS) associated with an abnormal thyroid workup (TSH, T3, or T4) at inclusion
6. Anti-transglutaminase positive at inclusion
7. EBV viral load > 2000 IU/ml
8. CMV viral load > 400 IU/ml
9. HBV, HCV or HIV infection
10. Lymphopenia ≤ 1000/ mm3
11. Presence or history of cancer cured within the last five years, except in situ cervical cancer or basal cell cancer managed at an early stage
12. Participation in other research relating to a clinical trial of a medicinal product for human use< 3 months
13. Pregnant or breast-feeding women
14. No social security coverage (as beneficiary or beneficiary's beneficiary)
15. Vaccination with live attenuated virus in the last 4 weeks before starting experimental treatment and throughout the treatment phase
16. Patient with active SARS-CoV-2 infection
17. Patients with chronic respiratory disease
18. Subject under legal protection (such as guardianship, curatorship or safeguarding)
19. Subject hospitalized without consent, unable to express consent or deprived of liberty

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Variation in Tregs values at D70 compared with post-ciclosporin values (D63)

Secondary endpoints 4

1. Compliance with ciclosporin and ILT-101/placebo
2. Tolerance: tolerance will be assessed from D1 to D719 by means of a clinical examination, measurement of vital signs, a systematic biological check-up and collection of adverse events at every visit.
3. Evolution of residual insulin secretion
4. Change in Tregs values at M3 (J88), M6 (J179), M9 (J270), M12 (J361) and after treatment discontinuation at M18 (J536) and M24 (J719) compared to baseline and post-ciclosporin values (J63)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr David Klatzmann

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr David Klatzmann

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications