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

• ClinicalTrials.gov Identifier: NCT01782235
• Recruitment Status: Completed
• First Posted: February 1, 2013
• Last Update Posted: August 21, 2019
• Sponsor: University Hospital, Strasbourg, France
• Information provided by (Responsible Party): University Hospital, Strasbourg, France

Tracking Information

• First Submitted Date: January 30, 2013
• First Posted Date: February 1, 2013
• Last Update Posted Date: August 21, 2019
• Actual Study Start Date: July 24, 2013
• Actual Primary Completion Date: July 16, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 11, 2014)

Improvement of the ESSDAI score equal to or greater than 3 points compared to enrollment. [ Time Frame: 24 weeks ]

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.

• Original Primary Outcome Measures (submitted: January 30, 2013): Proportion of patient with an enhancement superior or equal to 30% of the ESSPRI (EULAR Sjogren's Syndrome Patient Reported Index) score. [ Time Frame: 28 weeks ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy of Tocilizumab in Primary Sjögren's Syndrome.
• Official Title: A Randomized, Double-blind, Parallel, Placebo-controlled Trial to Evaluate the Efficacy of Tocilizumab for the Treatment of Primary Sjögren's Syndrome.

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Primary Sjögren's Syndrome (pSS)

Intervention

• Drug: Tocilizumab
• Drug: Placebo

Study Arms

• Experimental: Tocilizumab arm
  Tocilizumab arm will receive tocilizumab.
  Intervention: Drug: Tocilizumab
• Placebo Comparator: Placebo arm
  Placebo arm will receive placebo.
  Intervention: Drug: Placebo

• Publications *: Felten R, Devauchelle-Pensec V, Seror R, Duffau P, Saadoun D, Hachulla E, Pierre Yves H, Salliot C, Perdriger A, Morel J, Mekinian A, Vittecoq O, Berthelot JM, Dernis E, Le Guern V, Dieude P, Larroche C, Richez C, Martin T, Zarnitsky C, Blaison G, Kieffer P, Maurier F, Dellal A, Rist S, Andres E, Contis A, Chatelus E, Sordet C, Sibilia J, Arnold C, Tawk MY, Aberkane O, Holterbach L, Cacoub P, Saraux A, Mariette X, Meyer N, Gottenberg JE. Interleukin 6 receptor inhibition in primary Sjogren syndrome: a multicentre double-blind randomised placebo-controlled trial. Ann Rheum Dis. 2021 Mar;80(3):329-338. doi: 10.1136/annrheumdis-2020-218467. Epub 2020 Nov 18.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 11, 2014): 110
• Original Estimated Enrollment (submitted: January 30, 2013): 80
• Actual Study Completion Date: July 16, 2018
• Actual Primary Completion Date: July 16, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria :

• Patient with primary Sjögren's syndrome according to the European - American consensus group criteria.
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT01782235
• Other Study ID Numbers: 5206; 2012-002045-37 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: University Hospital, Strasbourg, France
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital, Strasbourg, France
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jacques-Eric Gottenberg; Hôpitaux Universitaires de Strasbourg

• PRS Account: University Hospital, Strasbourg, France
• Verification Date: August 2019