Efficacy of Tocilizumab in Primary Sjögren's Syndrome. (ETAP)

This study is currently recruiting participants.
Verified March 2014 by University Hospital, Strasbourg, France
Sponsor:
Information provided by (Responsible Party):
University Hospital, Strasbourg, France
ClinicalTrials.gov Identifier:
NCT01782235
First received: January 30, 2013
Last updated: March 11, 2014
Last verified: March 2014
  Purpose

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration leading to destruction of acinar and ductal cells and loss of glandular parenchyma. The main symptoms of pSS are dry eyes and dry mouth, diffuse pain, and fatigue. One third of patients develop systemic features, the most severe being lymphomas.

Serum IL-6 is increased in serum, saliva, and tears of patients with pSS. IL-6 plays a pivotal role in B-cell activation, a hallmark of the pathogenesis of pSS, and in T-cell differentiation. Tocilizumab, a recombinant humanised monoclonal antibody acts as an IL-6R antagonist. The aim of this randomised double blind placebo controlled trial iss to evaluate the efficacy of tocilizumab for the treatment of pSS.


Condition Intervention Phase
Primary Sjögren's Syndrome (pSS)
Drug: Tocilizumab
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Parallel, Placebo-controlled Trial to Evaluate the Efficacy of Tocilizumab for the Treatment of Primary Sjögren's Syndrome.

Resource links provided by NLM:


Further study details as provided by University Hospital, Strasbourg, France:

Primary Outcome Measures:
  • Improvement of the ESSDAI score equal to or greater than 3 points compared to enrollment. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Improvement of the ESSDAI score equal to or greater than 3 points compared to enrollment, with no new domain with high activity of the ESSDAI compared to enrollment, and no clinical worsening according to the clinician (no worsening compared to enrollment greater than 1 point of the Systemic Activity 0-10 VAS according to the physician.


Estimated Enrollment: 110
Study Start Date: July 2013
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tocilizumab arm
Tocilizumab arm will receive tocilizumab.
Drug: Tocilizumab
Placebo Comparator: Placebo arm
Placebo arm will receive placebo.
Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria :

  • Patient with primary Sjögren's syndrome according to the European - American consensus group criteria.
  • Presence of anti SSA (Ro) or of anti-SSA and anti-SSB(La) antibodies
  • ESSDAI score ≥ 5.
  • In women in childbearing age, effective contraception during treatment and 3 months following treatment discontinuation.

Exclusion Criteria:

  • Patient with previous history of therapy with tocilizumab.
  • Prednisone treatment introduced two weeks before inclusion or a change in this drug dose within two weeks before inclusion.
  • A prednisone dose ≥ 15 mg per day.
  • Non-steroidal anti-inflammatory drugs, pilocarpine hydrochloride, cyclosporine, cimeviline if introduced within two weeks before inclusion.
  • Therapy with methotrexate, Hydroxychloroquine, chloroquine, quinacrine, leflunomide, psychoactive drug if introduced within 8 weeks before inclusion or a dose change within 8 weeks before inclusion.
  • Treatment with azathioprine or mycophenolate mofetil within 8 weeks before inclusion.
  • Live and live attenuated vaccines given within 4 weeks before inclusion.
  • Any biologic treatment within 6 month before inclusion.
  • Treatment with cyclophosphamide, intravenous immunoglobulin therapy or plasmapharese therapy in the last 6 months before inclusion.
  • Systemic auto-immune disease.
  • Patient with previous history of diverticular perforations, complications of diverticulitis, peritonite or inflammatory bowel disease (such as Crohn's disease and Colitis ulcerative).
  • Patient with history of severe infection within 4 weeks before inclusion.
  • Patient with history of infection within 2 weeks before inclusion.
  • Patient with chronic infection or infection returns (e.g. tuberculose, VHB, VHC…).
  • Positive serology tests for HIV, HBV, HCV.
  • Severe uncontrolled dyslipidemia.
  • Hepatocellular insufficiency.
  • Unstable cardiovascular disease.
  • Severe or chronic kidney disease, severe or chronic lung disease, severe or chronic endocrine disorder, severe or chronic neurological disease ( not related to the SJP).
  • Patient with history of solid organ transplantation or haematopoietic stem cell transplantation.
  • Patient with history of lymphoma, neoplasia diagnosed 5 years before inclusion except squamous and basal cell cancers and carcinoma in situ of the uterine cervix.
  • Severe complications of SJp at the inclusion: vasculitis with renal neurologic, digestive or cardiac involvement, interstitial lung disease, symptomatic cryoglobulinemia with severe neurologic involvement, renal function impairment, severe myositis, corticotherapy ≥ 1 mg/kg in the last 30 days before inclusion.
  • Neutropenia < 1000*10^6 .
  • Thrombocytopenia < 50 000/µl
  • ALT or AST > 3 x ULN
  • alcohol and drug addiction : withdrawal at least one year before inclusion
  • A major surgical procedure in the 8 weeks before inclusion or a scheduled major surgery
  • Pregnant woman, breast feeding woman
  • Adults under supervision or guardianship
  • Patient taking part in another clinical trial
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01782235

Contacts
Contact: Jacques-Eric GOTTENBERG 3 88 12 81 89 ext 0033 jacques-eric.gottenberg@chru-strasbourg.fr

Locations
France
Hôpitaux Universitaires de Strasbourg Recruiting
Strasbourg, France, 67098
Contact: Jacques-Eric Gottenberg    3 88 12 81 89 ext 0033    jacques-eric.gottenberg@chru-strasbourg.fr   
Principal Investigator: Jacques-Eric Gottenberg         
Sponsors and Collaborators
University Hospital, Strasbourg, France
Investigators
Principal Investigator: Jacques-Eric Gottenberg Hôpitaux Universitaires de Strasbourg
  More Information

No publications provided

Responsible Party: University Hospital, Strasbourg, France
ClinicalTrials.gov Identifier: NCT01782235     History of Changes
Other Study ID Numbers: 5206, 2012-002045-37
Study First Received: January 30, 2013
Last Updated: March 11, 2014
Health Authority: FRANCE:ANSM

Additional relevant MeSH terms:
Sjogren's Syndrome
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Xerostomia
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Dry Eye Syndromes
Lacrimal Apparatus Diseases
Eye Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on April 14, 2014