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

NCT01988506 | Completed Phase 2 DMC

• 2 other identifiers: P1301012013-001232-22
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 11

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.

Conditions

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

Keywords

IL2,; Interleukin 2,; ILT101; Proleukin®, RhIL-2; Auto-immune disease; Inflammatory disease; Inflammation; Regulatory T cells,; Treg; Immunoregulation; Immune tolerance

Outcome Measures

Primary Outcomes (1)

• Percentages of Tregs

  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 Outcomes (8)

• Percentages of Tregs

  Day 15, 29, 85, 183, 240, 360 and 540

• inflammation markers (CRP and CRP ultra sensible)

  Day 0, 1, 8, 15, 29, 85, 183, 240, 360 and 540

• markers of inflammatory anemia (Hemoglobin, serum iron level, transferrin) ferritin

  Day 0, 1, 8, 15, 29, 85, 183, 240, 360 and 540

• Number of relapses

  up to Day540

• CGI-sev, CGI-activity and CGI-eff scales

  Day 85, 183, 240, 360 and 540

Study Arms (1)

Interleukin 2

EXPERIMENTAL

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

Drug: Interleukin 2

Interventions

Interleukin 2 DRUG

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

Interleukin 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age \> 18 year
• male or female
• documented diagnosis of one AIID among the 14 diseases selected (following consensual specific criteria)
• normal thyroid function (with or without treatment)
• affiliated to the social security system
• written informed consent form.

You may not qualify if:

• known intolerance for IL2 (see SPC),
• administration of a non-authorized treatment and/or IV bolus of corticosteroids in the last 2 months,
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Iltoo Pharma: collaborator

Study Sites (11)

Henri Mondor - Médecine Interne

Créteil, 94010, France

Location

Médecine interne - Hôpital Saint-Antoine

Paris, 75012, France

Location

Service de médecine vasculaire - HEGP

Paris, 75015, France

Location

Service d' Hépato Gastro Entérologie - Hôpital SAINT-ANTOINE

Paris, Île-de-France Region, 75012, France

Location

Service de Gastro Entérologie - Hôpital SAINT-ANTOINE

Paris, Île-de-France Region, 75012, France

Location

Service de Rhumatologie - Hôpital SAINT-ANTOINE

Paris, Île-de-France Region, 75012, France

Location

CIC - Hôpital PITIE SALPETRIERE

Paris, Île-de-France Region, 75013, France

Location

Service de Médecine Interne - Hôpital PITIE SALPETRIERE

Paris, Île-de-France Region, 75013, France

Location

Service de Rhumatologie - Hôpital PITIE SALPETRIERE

Paris, Île-de-France Region, 75013, France

Location

Service de Dermatologie - Hôpital COCHIN

Paris, Île-de-France Region, 75014, France

Location

Centre Hépato-Biliaire - Hôpital Paul Brousse

Villejuif, Île-de-France Region, 94800, France

Location

Related Publications (1)

• Rosenzwajg M, Lorenzon R, Cacoub P, Pham HP, Pitoiset F, El Soufi K, RIbet C, Bernard C, Aractingi S, Banneville B, Beaugerie L, Berenbaum F, Champey J, Chazouilleres O, Corpechot C, Fautrel B, Mekinian A, Regnier E, Saadoun D, Salem JE, Sellam J, Seksik P, Daguenel-Nguyen A, Doppler V, Mariau J, Vicaut E, Klatzmann D. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial. Ann Rheum Dis. 2019 Feb;78(2):209-217. doi: 10.1136/annrheumdis-2018-214229. Epub 2018 Nov 24.

  PMID: 30472651 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid; Spondylitis, Ankylosing; Lupus Erythematosus, Systemic; Psoriasis; Behcet Syndrome; Granulomatosis with Polyangiitis; Aortic Arch Syndromes; Crohn Disease; Colitis, Ulcerative; Hepatitis, Autoimmune; Cholangitis, Sclerosing; Purpura, Thrombocytopenic, Idiopathic; Scleroderma, Systemic; Inflammation

Interventions

Interleukin-2

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Axial Spondyloarthritis; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Ankylosis; Skin Diseases, Papulosquamous; Skin Diseases; Mouth Diseases; Stomatognathic Diseases; Uveitis, Anterior; Panuveitis; Uveitis; Uveal Diseases; Eye Diseases; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Skin Diseases, Vascular; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Aortic Diseases; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases; Hepatitis, Chronic; Hepatitis; Liver Diseases; Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• David KLATZMANN, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2013
• First Posted: November 20, 2013
• Study Start: January 6, 2014
• Primary Completion: October 16, 2019
• Study Completion: April 1, 2021
• Last Updated: July 20, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11)