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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Collaborator:
ILTOO Pharma
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01988506
First received: November 7, 2013
Last updated: February 6, 2014
Last verified: January 2014
  Purpose

TRANSREG will assess the safety and biological efficacy of low-dose IL2 as a Treg inducer in a set of 11 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 Intervention 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
Drug: Interleukin 2
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Induction of Regulatory t Cells by Low Dose IL2 in Autoimmune and Inflammatory Diseases: a Transnosographic Approach

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Percentages of Tregs [ Time Frame: Day8 ] [ Designated as safety issue: No ]
    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:
  • Percentages of Tregs [ Time Frame: Day 15, 29, 85, 183 and 240 ] [ Designated as safety issue: No ]
    Changes in Treg percentage at Day 15, 29, 85, 183 and 240 compared to baseline (Day0)

  • CRP, CRP ulta sensible, PCT, Albumin, LDH, anemia [ Time Frame: Day 0, 1, 8, 15, 29, 85, 183 and 240 ] [ Designated as safety issue: Yes ]
    Changes in levels of inflammation markers

  • Number of relapses [ Time Frame: up to Day240 ] [ Designated as safety issue: Yes ]
  • CGI-sev and CGI-eff scales [ Time Frame: Day 85, 183 and 240 ] [ Designated as safety issue: No ]
    Change in the clinical global impression severity and efficacy scale (CGI-sev and scale, CGI-eff scales) at Day 85, 183 and 240 compared to baseline (Day1)

  • EuroQL-5 scale [ Time Frame: Day 183 ] [ Designated as safety issue: No ]
    Change in the quality of life (EuroQL-5 scale)

  • Evolution of clinical, biological or radiological criteria specific to each disease [ Time Frame: up to Day 240 ] [ Designated as safety issue: No ]
    Changes in disease-specific score and/or evolution of clinical, biological or radiological criteria specific to each disease

  • Safety Assessment [ Time Frame: up to Day 240 ] [ Designated as safety issue: Yes ]
    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 2 months after IL2- treatment stop.


Estimated Enrollment: 132
Study Start Date: January 2014
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Interleukin 2
Interleukin 2, 1MUI.= Proleukin®
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 for 6 months

Detailed Description:

Protocol: TRANSREG is a multicentric, uncontrolled, open-label study, comparing biological and clinical responses to the administration of low doses IL2 across 11 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, and sclerosing cholangitis.Methods: Each patient will receive 1MUI /day of IL2 from Day-1 to Day-5 (the induction period), and then every 2 weeks from Day-15 to Day-180 (the maintenance period). Patients will thereafter be followed up for 2 months (Day-181-Day-240). For each pathology, 6 patients will be included at Pitié-Salpêtrière, Cochin and Saint Antoine hospitals in Paris. 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 66 patients and up to 132 patients will be enrolled in this study. Primary efficacy endpoint is the Treg response at Day-8. Secondary endpoints are:- 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age > 18 year
  • male or female
  • documented diagnosis of one AIID among the 11 diseases selected (following consensual specific criteria)
  • stable or moderately active disease under standard treatment (≥ 2 months) at the time of inclusion,
  • 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 <100 000/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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01988506

Contacts
Contact: David KLATZMANN, MD, PhD +33(0) 1 42 17 74 61 david.klatzmann@upmc.fr
Contact: Roberta LORENZON, MD +33(0) 1 42 17 74 61 rolorenzon@gmail.com

Locations
France
Service de Dermatologie - Hôpital COCHIN Not yet recruiting
Paris, Ile de France, France, 75014
Contact: Salim Aractingi, MD, PhD    + 33 1 56 01 64 62    selim.aractingi@gmail.com   
Principal Investigator: ARACTINGI Selim, MD, PhD         
Service de Gastro Entérologie - Hôpital SAINT-ANTOINE Recruiting
Paris, Ile de France, France, 75012
Contact: Laurent Beaugerie, MD, PhD    33 1 .49.28.31.71    laurent.beaugerie@sat.aphp.fr   
Principal Investigator: Laurent BEAUGERIE, MD, PhD         
Service de Rhumatologie - Hôpital SAINT-ANTOINE Not yet recruiting
Paris, Ile de France, France, 75012
Contact: Francis Berenbaum, MD, PhD    33 1 .49.28.25.20    francis.berenbaum@sat.aphp.fr   
Principal Investigator: Francis. BERENBAUM, MD, PhD         
Service d' Hépato Gastro Entérologie - Hôpital SAINT-ANTOINE Not yet recruiting
Paris, Ile de France, France, 75012
Contact: Olivier CHAZOUILLERES, MD, PhD    33 1.49.28.23.78    olivier.chazouilleres@sat.aphp.fr   
Principal Investigator: Olivier CHAZOUILLERES, MD, PhD         
Service de Médecine Interne - Hôpital PITIE SALPETRIERE Not yet recruiting
Paris, Ile de France, France, 75013
Contact: Patrice CACOUB, MD, PhD    33 1 42.17.80.09    patrice.cacoub@psl.aphp.fr   
Principal Investigator: Patrice CACOUB, MD, PhD         
Service de Rhumatologie - Hôpital PITIE SALPETRIERE Not yet recruiting
Paris, Ile de France, France, 75013
Contact: Bruno FAUTREL, MD, PhD    33 1 .42.17.76.20    bruno.fautrel@psl.aphp.fr   
Principal Investigator: Bruno FAUTREL, MD, PhD         
CIC - Hôpital PITIE SALPETRIERE Not yet recruiting
Paris, Ile de France, France, 75013
Contact: Nathalie Nicolas, MD    33 1 .42.17.85.33    nath.nicolas@psl.aphp.fr   
Principal Investigator: Nathalie Nicolas, MD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
ILTOO Pharma
Investigators
Principal Investigator: David KLATZMANN, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01988506     History of Changes
Other Study ID Numbers: P130101, 2013-001232-22
Study First Received: November 7, 2013
Last Updated: February 6, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
IL2,
Interleukin 2,
IL-2,
Proleukin®
Auto-immune disease
Inflammatory disease
Inflammation
Regulatory T cells,
Treg
Immunoregulation
Immune tolerance

Additional relevant MeSH terms:
Bile Duct Diseases
Arthritis
Arthritis, Rheumatoid
Behcet Syndrome
Cholangitis
Cholangitis, Sclerosing
Colitis
Colitis, Ulcerative
Crohn Disease
Hepatitis
Hepatitis A
Lupus Erythematosus, Systemic
Psoriasis
Spondylitis
Spondylitis, Ankylosing
Aortic Arch Syndromes
Takayasu Arteritis
Ulcer
Wegener Granulomatosis
Hepatitis, Autoimmune
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Mouth Diseases
Stomatognathic Diseases
Uveitis, Anterior
Panuveitis

ClinicalTrials.gov processed this record on September 14, 2014