Low-dose Interleukin-2 in Women With Unexplained Miscarriages (FaCIL-2)

Regulatory T-cell Induction by Low-dose Interleukin-2 in Women With Unexplained Repeated Spontaneous Early Miscarriages

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Miscarriage
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Hopital Saint Antoine
    • Paris, Hopital Saint Antoine, France, 75012
      • Mekinian
  • Hopital Tenon
    • Paris, Hopital Tenon, France, 75020
      • Bornes
  • Hopital Trousseau
    • Paris, Hopital Trousseau, France, 75012
      • Kayem

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No

Description

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);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Low-dose IL-2	Drug: 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.; Other Names: interleukin-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variation of rate of blood circulating T regulator lymphocytes(expressed in % of CD4 and total)	Change of Tregs at Day 14 of cycles under low dose of IL-2 compared to the baseline of the first cycle without low dose of IL-2	At the day 38 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 1]
Variation of rate of blood circulating T regulator lymphocytes(expressed in % of CD4 and total)	Change of Tregs at Day 14 of cycles under low dose of IL-2 compared to the baseline of the first cycle without low dose of IL-2	At the day 66 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 1
Variation of rate of blood circulating T regulator lymphocytes(expressed in % of CD4 and total)	Change of Tregs at Day 14 of cycles under low dose of IL-2 compared to the baseline of the first cycle without low dose of IL-2	At the day 94 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 1
Variation of rate of blood circulating T regulator lymphocytes(expressed in % of CD4 and total)	Change of Tregs at Day 14 of cycles under low dose of IL-2 compared to the baseline of the first cycle without low dose of IL-2	At the day 122 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 1
Variation of rate of blood circulating T regulator lymphocytes(expressed in % of CD4 and total)	Change of Tregs at Day 14 of cycles under low dose of IL-2 compared to the baseline of the first cycle without low dose of IL-2	At the day 150 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 11

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variation of rate of blood circulating T regulator lymphocytes(expressed in absolute numbers)	Change of Tregs at Day 14 of cycles under low dose of IL-2 compared to the baseline of the first cycle without low dose of IL-2	At the day 38 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 1
Variation of rate of blood circulating T regulator lymphocytes(expressed in absolute numbers)	Change of Tregs at Day 14 of cycles under low dose of IL-2 compared to the baseline of the first cycle without low dose of IL-2	At the day 66 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 1
Variation of rate of blood circulating T regulator lymphocytes(expressed in absolute numbers)	Change of Tregs at Day 14 of cycles under low dose of IL-2 compared to the baseline of the first cycle without low dose of IL-2	At the day 94 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 1
Variation of rate of blood circulating T regulator lymphocytes(expressed in absolute numbers)	Change of Tregs at Day 14 of cycles under low dose of IL-2 compared to the baseline of the first cycle without low dose of IL-2	At the day 122 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 1
Variation of rate of blood circulating T regulator lymphocytes(expressed in absolute numbers)	Change of Tregs at Day 14 of cycles under low dose of IL-2 compared to the baseline of the first cycle without low dose of IL-2	At the day 150 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 11

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Iltoo Pharma
• Investigators: Principal Investigator: David Klatzmann, Pr, Pitié Salpètrière APHP Paris; Study Director: Arsene Mékinian, Dr, Saint Antoine APHP Paris; Study Director: Gilles Kayem, Pr, Trousseau APHP Paris

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2021
• Primary Completion (Actual): July 28, 2023
• Study Completion (Actual): March 20, 2024

Study Registration Dates

• First Submitted: March 14, 2019
• First Submitted That Met QC Criteria: May 29, 2019
• First Posted (Actual): June 3, 2019

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 10, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Miscarriage; Regulatory T cells; Low-dose Interleukin-2
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Abortion, Spontaneous; Abortion, Habitual; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Intercellular Signaling Peptides and Proteins; Cytokines; Interleukins; Lymphokines; Interleukin-2
• Other Study ID Numbers: APHP180256

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No