Back to resultsLow-dose Interleukin-2 in Women With Unexplained Miscarriages (FaCIL-2)
Primary Purpose
Recurrent Miscarriage
Status
Active
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
low-dose IL-2
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent Miscarriage focused on measuring Low-dose Interleukin-2, Miscarriage, Regulatory T cells
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);
Sites / Locations
- Mekinian
- Bornes
- Kayem
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Low-dose IL-2
Outcomes
Primary Outcome Measures
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
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
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
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
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
Secondary Outcome Measures
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
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
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
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
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
Full Information
NCT ID
NCT03970954
First Posted
March 14, 2019
Last Updated
July 10, 2023
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Iltoo Pharma
1. Study Identification
Unique Protocol Identification Number
NCT03970954
Brief Title
Low-dose Interleukin-2 in Women With Unexplained Miscarriages
Acronym
FaCIL-2
Official Title
Regulatory T-cell Induction by Low-dose Interleukin-2 in Women With Unexplained Repeated Spontaneous Early Miscarriages
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 5, 2021 (Actual)
Primary Completion Date
February 5, 2024 (Anticipated)
Study Completion Date
February 5, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Iltoo Pharma
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Miscarriage
Keywords
Low-dose Interleukin-2, Miscarriage, Regulatory T cells
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Low-dose IL-2
Intervention Type
Drug
Intervention Name(s)
low-dose IL-2
Other Intervention Name(s)
interleukin-2
Intervention Description
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.
Primary Outcome Measure Information:
Title
Variation of rate of blood circulating T regulator lymphocytes(expressed in % of CD4 and total)
Description
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
Time Frame
At the day 38 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 1]
Title
Variation of rate of blood circulating T regulator lymphocytes(expressed in % of CD4 and total)
Description
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
Time Frame
At the day 66 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 1
Title
Variation of rate of blood circulating T regulator lymphocytes(expressed in % of CD4 and total)
Description
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
Time Frame
At the day 94 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 1
Title
Variation of rate of blood circulating T regulator lymphocytes(expressed in % of CD4 and total)
Description
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
Time Frame
At the day 122 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 1
Title
Variation of rate of blood circulating T regulator lymphocytes(expressed in % of CD4 and total)
Description
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
Time Frame
At the day 150 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 11
Secondary Outcome Measure Information:
Title
Variation of rate of blood circulating T regulator lymphocytes(expressed in absolute numbers)
Description
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
Time Frame
At the day 38 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 1
Title
Variation of rate of blood circulating T regulator lymphocytes(expressed in absolute numbers)
Description
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
Time Frame
At the day 66 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 1
Title
Variation of rate of blood circulating T regulator lymphocytes(expressed in absolute numbers)
Description
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
Time Frame
At the day 94 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 1
Title
Variation of rate of blood circulating T regulator lymphocytes(expressed in absolute numbers)
Description
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
Time Frame
At the day 122 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 1
Title
Variation of rate of blood circulating T regulator lymphocytes(expressed in absolute numbers)
Description
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
Time Frame
At the day 150 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 11
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
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);
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Klatzmann, Pr
Organizational Affiliation
Pitié Salpètrière APHP Paris
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Arsene Mékinian, Dr
Organizational Affiliation
Saint Antoine APHP Paris
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Gilles Kayem, Pr
Organizational Affiliation
Trousseau APHP Paris
Official's Role
Study Director
Facility Information:
Facility Name
Mekinian
City
Paris
State/Province
Hopital Saint Antoine
ZIP/Postal Code
75012
Country
France
Facility Name
Bornes
City
Paris
State/Province
Hopital Tenon
ZIP/Postal Code
75020
Country
France
Facility Name
Kayem
City
Paris
State/Province
Hopital Trousseau
ZIP/Postal Code
75012
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Low-dose Interleukin-2 in Women With Unexplained Miscarriages
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