Low-dose Interleukin-2 in Women With Unexplained Miscarriages

NCT ID: NCT03970954

Last Updated: 2025-09-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-05
• Study Completion Date: 2024-03-20

Brief Summary

The purpose of this study is to demonstrate the ability of low dose IL-2 to stimulate peripheral blood Tregs of women with unexplained repeated early spontaneous miscarriages for development of a therapy to prevent fetal rejection by low dose IL-2.

Detailed Description

About 1 to 3% of women of childbearing age have repeated early spontaneous miscarriages that may be related to parental chromosomal abnormalities, uterine abnormalities, hormonal causes, infectious etiology, thrombophilia ... When one of these known causes is excluded, it is unexplained miscarriages of which half would be due to an immunological deregulation of the mother causing a decrease of the tolerance to the fetus.

In this context, the stimulation of regulatory T cells (Tregs) by low dose IL-2 is a therapeutic option with a rational, preclinical and clinical data very favorable.

In humans, low dose IL-2 allows preferential activation of Tregs and is very well tolerated. Several therapeutic trials have shown its efficiencies.

These elements make it possible to envisage the development of a therapeutic to prevent fetal rejection by IL2-fd on the women with spontaneous miscarriages by an immunological deregulation.

Conditions

Recurrent Miscarriage

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Low-dose IL-2

Group Type: EXPERIMENTAL

low-dose IL-2

Intervention Type: DRUG

Subcutaneous injection of low dose of IL-2 for induction course of 5 days, the 10th day after the beginning of periods. At most 5 courses of low dose of IL-2.

Interventions

low-dose IL-2

Subcutaneous injection of low dose of IL-2 for induction course of 5 days, the 10th day after the beginning of periods. At most 5 courses of low dose of IL-2.

Intervention Type: DRUG

Other Intervention Names

interleukin-2

Eligibility Criteria

Inclusion Criteria

• Woman with at least 5 consecutive early miscarriages less than 14 weeks of amenorrhea and unexplained after the usual check-up;
• Volunteer to participate in the trial and having given written consent after appropriate information.

Exclusion Criteria

• Uterine or pelvic abnormality: uterine malformation, intracavitary fibroid, synechiae, polyp, hydrosalpinx;
• Balanced translocations in both spouses;
• Diabetes type I or II;
• Sickle cell disease;
• Contraindication to pregnancy;
• Constitutional or acquired thrombophilia (protein deficit C, S, ATIII, homozygous factor V or II deficiency, antiphospholipid syndrome, antithyroid antibodies positive, celiac disease, hyperhomocysteinemia);
• Ovarian insufficiency (AMH <1 ng/ml); AFC < 4
• Significant spermogram abnormalities and DNA fragmented more than 30%
• Active HIV or HCV infection;
• Main known contraindications to treatment with IL-2:
• Hypersensitivity to the active substance or to any of the excipients;
• Signs of progressive infection requiring antibiotic therapy;
• History of organ allograft;
• Pre-existing autoimmune disease;
• Leukocytes <4000 / mm3; platelets <100,000 / mm3; hematocrit <30%;
• hepatic or renal insufficiency;
• depression;
• significant history or existence of a serious heart disease (in doubtful cases, perform a stress test);
• patients with autoimmune disease;
• patients with an infection (septicemia, bacterial endocarditis, septic thrombophlebitis, peritonitis and pneumonia);
• pregnancy;
• Treatment with immunomodulators, immunosuppressants (class L04A of the ATC classification), in particular systemic corticosteroids, as well as aspirin and low molecular weight heparin;
• No affiliation to a social security;
• Person who has already been included in this study or in another at the same time;
• Major incapacitated patient (tutorship / curatorship);
• Patient with an allergy to taking IL2-fd;
• Participants who would present professional risk factors (eg ionizing exposure);

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Iltoo Pharma

INDUSTRY

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Klatzmann, Pr

Role: PRINCIPAL_INVESTIGATOR

Pitié Salpètrière APHP Paris

Arsene Mékinian, Dr

Role: STUDY_DIRECTOR

Saint Antoine APHP Paris

Gilles Kayem, Pr

Role: STUDY_DIRECTOR

Trousseau APHP Paris

Locations

Mekinian

Paris, Hopital Saint Antoine, France

Bornes

Paris, Hopital Tenon, France

Kayem

Paris, Hopital Trousseau, France

Countries

France

Other Identifiers

APHP180256

Identifier Type: -

Identifier Source: org_study_id