Induction of Regulatory t Cells by Low Dose il2 in Autoimmune and Inflammatory Diseases (TRANSREG)

July 19, 2021 updated by: Assistance Publique - Hôpitaux de Paris

Induction of Regulatory t Cells by Low Dose IL2 in Autoimmune and Inflammatory Diseases: a Transnosographic Approach

TRANSREG will assess the safety and biological efficacy of low-dose IL2 as a Treg inducer in a set of 14 autoimmune and auto-inflammatory diseases, with the aim to select diseases in which further therapeutic development will be performed. Extensive biological- and immune-monitoring pre- and post-IL2 will contribute (i) to define the common or distinct processes responsible for the breakdown of immunological tolerance in these pathologies and (ii) to discover potential biomarkers of the IL2 response.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Protocol: TRANSREG is a multicentric, uncontrolled, open-label study, comparing biological and clinical responses to the administration of low doses IL2 across 14 selected pathologies: rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Behcet's disease, Wegener's granulomatosis, Takayasu's disease, Crohn's disease, ulcerative colitis, autoimmune hepatitis, sclerosing cholangitis, Gougerot-sjögren, Systemic Sclerosis and Idiopathic Thrombocytopenic Purpura. Methods: Each patient will receive 1MUI /day of IL2 from Day-1 to Day-5 (the induction period), and then every 2 weeks (except systemic lupus erythematosus's patients will received every week) from Day-15 to Day-180 (the maintenance period). Patients will thereafter be followed up for 12 months (Day-181-Day-540). For each pathology, 6 patients will be included at Pitié-Salpêtrière, Cochin, Saint Antoine, Paul Brousse and Henri Mondor hospitals in Paris and Créteil, France. An interim analysis will be performed in each pathology group when the first six patients have received at least 3 months of treatment. In those pathology groups in which a Treg response will be documented, six additional patients will be included. In total, a minimum of 84 patients and up to 132 patients will be enrolled in this study. Primary efficacy endpoint is the Treg response at Day-8 compared to baseline. Secondary efficacy endpoints are:- evolution of the Treg response during the maintenance period,- the changes in markers of inflammation - the clinical response, evaluated by means of global generic scales [Clinical Global Impression severity scale (CGI-sev) and Clinical Global Impression efficacy index (CGI-eff)] as well as specific clinical and biological evaluations for each disease, - the frequency of relapses, - the assessment of quality of life (scale EuroQL-5). Expected Results: TRANSREG will define which patients respond to IL2, whether per pathology or according to pre-treatment phenomics, allowing to guide further clinical development of low dose IL2 in autoimmune and auto-inflammatory diseases.

Study Type

Interventional

Enrollment (Actual)

81

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Créteil, France, 94010
        • Henri Mondor - Médecine Interne
      • Paris, France, 75012
        • Médecine interne - Hôpital Saint-Antoine
      • Paris, France, 75015
        • Service de médecine vasculaire - HEGP
    • Ile De France
      • Paris, Ile De France, France, 75012
        • Service d' Hépato Gastro Entérologie - Hôpital SAINT-ANTOINE
      • Paris, Ile De France, France, 75012
        • Service de Gastro Entérologie - Hôpital SAINT-ANTOINE
      • Paris, Ile De France, France, 75012
        • Service de Rhumatologie - Hôpital Saint-Antoine
      • Paris, Ile De France, France, 75013
        • CIC - Hôpital PITIE SALPETRIERE
      • Paris, Ile De France, France, 75013
        • Service de Médecine Interne - Hôpital PITIE SALPETRIERE
      • Paris, Ile De France, France, 75013
        • Service de Rhumatologie - Hôpital PITIE SALPETRIERE
      • Paris, Ile De France, France, 75014
        • Service de Dermatologie - Hôpital COCHIN
      • Villejuif, Ile De France, France, 94800
        • Centre Hépato-biliaire - Hôpital Paul Brousse

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • age > 18 year
  • male or female
  • documented diagnosis of one AIID among the 14 diseases selected (following consensual specific criteria)
  • stable or moderately active disease (except Lupus) under standard treatment (≥ 2 months) at the time of inclusion (except Sclerosing Cholangitis, Gougerot-sjögren, Takayasu's Disease and Systemic Sclerosis)
  • normal thyroid function (with or without treatment)
  • effective contraception for more than two weeks at inclusion and negative beta HCG test for women of childbearing potential,
  • affiliated to the social security system
  • written informed consent form.

Exclusion Criteria:

  • known intolerance for IL2 (see SPC),
  • administration of a non-authorized treatment and/or IV bolus of corticosteroids in the last 2 months,
  • vaccination with live attenuated virus in the months preceding the inclusion or planned during the study
  • other severe or progressive autoimmune/inflammatory pathology,
  • low white blood cell count<2000/mm3, lymphocytes <600/mm3, platelets <80 000/mm3,
  • heart failure (≥ grade III NYHA), renal insufficiency (Cockcroft< 60ml/mn except patients with lupus or Wegener's granulomatosis) or hepatic insufficiency (transaminases> 5N except for patients with autoimmune hepatitis), or lung failure,
  • significant abnormality in chest X-ray other than these linked to the diseases under investigation
  • cancer or history of cancer cured for less than five years (except in situ carcinoma of the cervix or basocellular carcinoma)
  • poor venous access not allowing repeated blood tests,
  • restrictive diet or parenteral nutrition,
  • surgery during the last 2 months or surgery planned during the study,
  • participation in other biomedical research in the last 3 months or planned during the study.
  • pregnant or lactating women,
  • concomitant psychiatric disease or any other chronic illness or drug-abuse that could interfere with the ability to comply with the protocol or to give informed consent,
  • positive HIV serology, active hepatitis B or EBV infection,
  • patients under a measure of legal protection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Interleukin 2
Interleukin 2, 1MUI.= Proleukin®, RhIL-2
Drug: Interleukin 2
Induction period: repeated administration of low-dose IL-2 (1MUI/day, sc) during 5 consecutive days.Maintenance period: treatment with IL-2, 1MUI once every 15 days (except systemic lupus erythematosus's patients every 7 days) for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentages of Tregs
Time Frame: Day8
Change in Treg percentage (percentages of Tregs within the CD4+ lymphocytes) at Day-8 after administration of low-dose of IL2 compared to baseline (Day0)
Day8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentages of Tregs
Time Frame: Day 15, 29, 85, 183, 240, 360 and 540
Changes in Treg percentage at Day 15, 29, 85, 183, 240, 360 and 540 compared to baseline (Day0)
Day 15, 29, 85, 183, 240, 360 and 540
inflammation markers (CRP and CRP ultra sensible)
Time Frame: Day 0, 1, 8, 15, 29, 85, 183, 240, 360 and 540
Changes in levels of inflammation markers
Day 0, 1, 8, 15, 29, 85, 183, 240, 360 and 540
markers of inflammatory anemia (Hemoglobin, serum iron level, transferrin) ferritin
Time Frame: Day 0, 1, 8, 15, 29, 85, 183, 240, 360 and 540
Changes in levels of inflammation markers
Day 0, 1, 8, 15, 29, 85, 183, 240, 360 and 540
Number of relapses
Time Frame: up to Day540
up to Day540
CGI-sev, CGI-activity and CGI-eff scales
Time Frame: Day 85, 183, 240, 360 and 540
Change in the clinical global impression severity and efficacy scale (CGI-sev, CGI-act and CGI-eff scales) at Day 85, 183, 240, 360 and 540 compared to baseline (Day1)
Day 85, 183, 240, 360 and 540
EuroQL-5 scale
Time Frame: Day 183
Change in the quality of life (EuroQL-5 scale)
Day 183
Evolution of clinical, biological or radiological criteria specific to each disease
Time Frame: up to Day 540
Changes in disease-specific score and/or evolution of clinical, biological or radiological criteria specific to each disease
up to Day 540
Safety Assessment
Time Frame: up to Day 540
Safety Assessment all along the observation period (Day-1 to Day-240): Safety assessment will include vital signs, adverse events and concomitant medications collection as well as biology during the 6 months of the treatment period; .In addition, the evolution of the disease will be followed up to 1 year after IL2- treatment stop.
up to Day 540

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Iltoo Pharma

Investigators

  • Principal Investigator: David KLATZMANN, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 6, 2014

Primary Completion (Actual)

October 16, 2019

Study Completion (Actual)

April 1, 2021

Study Registration Dates

First Submitted

November 7, 2013

First Submitted That Met QC Criteria

November 13, 2013

First Posted (Estimate)

November 20, 2013

Study Record Updates

Last Update Posted (Actual)

July 20, 2021

Last Update Submitted That Met QC Criteria

July 19, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P130101
  • 2013-001232-22 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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