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

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Brief Title

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

Official Title

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

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.
    

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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Percentages of Tregs

Secondary Outcome

 Percentages of Tregs

Condition

Rheumatoid Arthritis

Intervention

Interleukin 2

Study Arms / Comparison Groups

 Interleukin 2
Description:  Interleukin 2, 1MUI.= Proleukin®, RhIL-2

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

81

Start Date

January 6, 2014

Completion Date

March 31, 2021

Primary Completion Date

October 16, 2019

Eligibility Criteria

        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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

David KLATZMANN, MD, PhD, , 

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT01988506

Organization ID

P130101

Secondary IDs

2013-001232-22

Responsible Party

Sponsor

Study Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

 Iltoo Pharma

Study Sponsor

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


Verification Date

August 2020