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

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ClinicalTrials.gov Identifier: NCT01988506
Recruitment Status : Completed
First Posted : November 20, 2013
Last Update Posted : July 20, 2021
Iltoo Pharma
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Idiopathic Thrombocytopenic Purpura Systemic Sclerosis Drug: Interleukin 2 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 81 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Induction of Regulatory t Cells by Low Dose IL2 in Autoimmune and Inflammatory Diseases: a Transnosographic Approach
Actual Study Start Date : January 6, 2014
Actual Primary Completion Date : October 16, 2019
Actual Study Completion Date : April 1, 2021

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

Primary Outcome Measures :
  1. 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)

Secondary Outcome Measures :
  1. 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)

  2. 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

  3. 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

  4. Number of relapses [ Time Frame: up to Day540 ]
  5. 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)

  6. EuroQL-5 scale [ Time Frame: Day 183 ]
    Change in the quality of life (EuroQL-5 scale)

  7. 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

  8. 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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01988506

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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, 75012
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, 75013
Service de Dermatologie - Hôpital COCHIN
Paris, Ile De France, France, 75014
Centre Hépato-Biliaire - Hôpital Paul Brousse
Villejuif, Ile De France, France, 94800
Henri Mondor - Médecine Interne
Créteil, France, 94010
Médecine interne - Hôpital Saint-Antoine
Paris, France, 75012
Service de médecine vasculaire - HEGP
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Iltoo Pharma
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Principal Investigator: David KLATZMANN, MD, PhD Assistance Publique - Hôpitaux de Paris
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01988506    
Other Study ID Numbers: P130101
2013-001232-22 ( EudraCT Number )
First Posted: November 20, 2013    Key Record Dates
Last Update Posted: July 20, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Interleukin 2,
Proleukin®, RhIL-2
Auto-immune disease
Inflammatory disease
Regulatory T cells,
Immune tolerance
Additional relevant MeSH terms:
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Spondylitis, Ankylosing
Crohn Disease
Cholangitis, Sclerosing
Hepatitis, Autoimmune
Behcet Syndrome
Granulomatosis with Polyangiitis
Takayasu Arteritis
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Lupus Erythematosus, Systemic
Scleroderma, Systemic
Liver Diseases
Digestive System Diseases
Joint Diseases
Musculoskeletal Diseases
Pathologic Processes
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Skin Diseases
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Intestinal Diseases
Bone Diseases, Infectious