Efficacy and Safety of S95011 in Primary Sjögren's Syndrome Patients

A Phase IIa Efficacy and Safety Trial With Intravenous S95011 in Primary Sjögren's Syndrome Patients: An International, Multicentre, Randomised, Double-blind, Placebo-controlled Study

The purpose of this study is to assess the effect of multiple intravenous infusions of S95011 compared to placebo in reducing disease activity in patients with primary Sjögren's syndrome.

Study Overview

• Status: Completed
• Conditions: Primary Sjögren's Syndrome
• Intervention / Treatment: Drug: S95011 concentrate for solution for infusion; Drug: Placebo concentrate for solution for infusion

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Institut de Recherches Internationales Servier Clinical Studies Department; Phone Number: +33 1 55 72 43 66; Email: scientificinformation@servier.com

Study Locations

• Australia
  • Woodville, Australia, 5011
    • The Queen Elizabeth Hospital Rheumatology Unit
• France
  • Bordeaux, France, 33000
    • Hôpital Saint-André
  • Le Kremlin-Bicêtre, France, 94275
    • CHU de Bicêtre
  • Paris, France, 75571
    • Hopital Saint Antoine
  • Paris, France, 75013
    • Hôpital Pitié-Salpétrière
  • Paris, France, 75010
    • Hôpital Laribiosière
• Germany
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen Medizinische Klinik 3 Rheumatologie und Immunologie
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg Department Innere Medizin Klinik für Rheumatologie und Klinische Immunologie
• Hungary
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Orvos és Egészségtudományi Centrum Belgyógyászat C épület - Klinikai Immunológiai Tanszék
  • Gyula, Hungary, 5700
    • Békés Megyei Központi Kórház, Pándy Kálmán Tagkórház, Infektológia-Hepatológia
  • Székesfehérvár, Hungary, 8000
    • Vita Verum Medical Bt. Berényi u. 72-100. 95. számú épület 16. Rendelő
• Spain
  • Barcelona, Spain, 08022
    • CLINICA SAGRADA FAMILIA Servicio de Reumatología y Unidad de Ensayos Clínicos
  • Santiago De Compostela, Spain, 15702
    • CLINICAL GAIAS SANTIAGO Servicio de Reumatología
  • Sevilla, Spain, 41010
    • Hospital Infanta Luisa Quirón Salud Servicio de Reumatología
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital, University Hospital Southampton NHS Trust
• United States
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Colorado Arthritis Associates
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of primary Sjögren's Syndrome based on 2016 American College of Rheumatology-EULAR criteria
2. ESSDAI total score ≥ 6 during screening, with at least 6 points scored within the 7 following domains: constitutional, lymphadenopathy, glandular, articular, cutaneous, hematologic and biologic,
3. Positive anti-Sjögren's Syndrome A (Ro) antibodies or anti-nuclear antibodies (ANA) ≥ 1:320 or rheumatoid factor (RF) >20 IU/ml during screening period, measured in a central laboratory
4. Stimulated whole salivary flow rate > 0 mL/minute

Exclusion Criteria:

1. Prior administration within the timeframe described in the protocol of any of the following:

   • Belimumab,
   • Rituximab or other B cell depleting agents,
   • Abatacept,
   • Tumor necrosis factor inhibitors,
   • Tocilizumab,
   • Cyclophosphamide,
   • Cyclosporine (except for eye drops), tacrolimus, sirolimus, mycophenolate mofetil (MMF), azathioprine, or leflunomide
   • Janus kinase (JAK) inhibitors

2. Meeting any of the following conditions:

   • Corticosteroids: > 10 mg/day oral prednisone (or equivalent) within 4 weeks prior to randomisation (W000); Any change or initiation of new dose of oral prednisone (or equivalent) within 4 weeks prior to randomisation (W000); Intramuscular, IV, or intra-articular corticosteroids within 4 weeks prior to randomisation (W000); Any change or initiation of new dose of topical corticosteroids within 2 weeks prior to randomisation (W000),
   • Antimalarials: any change or initiation of new dose of antimalarials (e.g. chloroquine, hydroxychloroquine, quinacrine) within 16 weeks prior to randomisation (W000),
   • Methotrexate: > 25 mg/week of methotrexate; any initiation or change of dose of methotrexate within 12 weeks prior to randomisation (W000); any change in route of administration within 4 weeks prior to randomisation (W000),
   • Non-steroidal anti-inflammatory drugs (NSAIDs): Any change or initiation of new dose of regularly scheduled NSAIDs within 2 weeks prior to randomisation (W000),
   • Cevimeline or pilocarpine and cyclosporine eye drops (Restasis) and lifitegrast: any increase or initiation of new doses within 2 weeks prior to randomisation (W000).
3. Secondary Sjögren's Syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S95011 concentrate for solution for infusion; S95011 is administrated by one IV infusion every 2 weeks for the first month and then every 3 weeks.	Drug: S95011 concentrate for solution for infusion; IV administration every 2 weeks until week 4 and then every 3 weeks until week 10.
Placebo Comparator: S95011 Placebo concentrate for solution for infusion; S95011 placebo is administrated by one IV infusion every 2 weeks for the first month and then every 3 weeks.	Drug: Placebo concentrate for solution for infusion; IV administration every 2 weeks until week 4 and then every 3 weeks until week 10.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ESSDAI Total Score	Efficacy criterion Eular Sjögren Syndrome Disease Activity index (ESSDAI) is a physician-administered clinical index which has been validated to objectively assess systemic manifestations in Primary Sjögren's Syndrome patients. Scores range from 0 - 123, with a lower score representing less disease activity.	From baseline to week 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ESSDAI Score by Domain and Total Score	Efficacy criterion Eular Sjögren Syndrome Disease Activity index (ESSDAI) is a physician-administered clinical index which has been validated to objectively assess systemic manifestations in Primary Sjögren's Syndrome patients. There are 12 organ-specific domains and for each domain, features of disease activity are scored according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score. The total score ranges from 0 to 123. A higher score always represents a more severe disease activity. The domain [weight] and score range are as follows: Constitutional [3] 0-2; Lymphadenopathy and lymphoma [4] 0-3; Glandular [2] 0-2; Articular [2] 0-3; Cutaneous [3] 0-3; Pulmonary [5] 0-3; Renal [5] 0-3; Muscular [6] 0-3; PNS [5] 0-3; CNS [5] 0-3; Hematological [2] 0-3; Biological [1] 0-2.	At baseline, week 4 and week 13
ESSPRI Score by Symptom and Total Score	Efficacy criterion EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is an index designed to measure patients' symptoms in primary Sjögren's Syndrome. The three domains included in this scale are dryness, fatigue, and pain, each of which are scored on a scale of 0-10. The total score is calculated as the average of the three domain scores and therefore the maximum total score is 10. The higher score represents more severe symptoms.	At baseline, week 4 and week 13
Quality of Life (SF-36)	Efficacy criterion The Short Form (SF-36) Health Survey is a 36-item, patient-reported survey of patient health to asses QoL. Scores for each subscale range from 0 - 100, with a lower number representing a worse quality of life.	At baseline and week 13
Fatigue (MFI)	Efficacy criterion Modified Fatigue Impact Scale (MFI) is a 20-item survey to evaluate five dimensions of fatigue. Scores range from 4 to 20 for each sub-score, with a lower score representing less fatigue.	At baseline and week 13
Physician's Global Assessment (PhGA) of the Disease Activity	Efficacy criterion Physician's global assessment (PhGA) of the disease activity is a 0 to 10 numerical rating scale (NRS), with a lower score representing less disease activity.	At baseline and week 13
Patient's Global Assessment (PGA) of the Disease Activity	Efficacy criterion Patient's global assessment (PGA) of the disease activity is a 0 to 10 numerical rating scale (NRS), with a lower score representing less disease activity.	At baseline and week 13
Number of Participants With Adverse Events (AEs)	Safety criterion	Through study completion, up to Week 28

Collaborators and Investigators

• Sponsor: Institut de Recherches Internationales Servier
• Collaborators: ADIR, a Servier Group company

Publications and helpful links

Helpful Links

• Find Results on Servier Clinical Trial Data website

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2021
• Primary Completion (Actual): January 16, 2023
• Study Completion (Actual): May 9, 2023

Study Registration Dates

• First Submitted: October 19, 2020
• First Submitted That Met QC Criteria: October 27, 2020
• First Posted (Actual): October 28, 2020

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Arthritis; Monoclonal antibody; Xerostomia; Systemic; Autoimmune disease; Sjögren's Syndrome; xerophthalmia; Joint disease; Sjögren; Salivary gland disease
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Syndrome; Sjogren's Syndrome; Pharmaceutical Solutions
• Other Study ID Numbers: CL2-95011-001; 2020-001526-59 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

• used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• where Servier is the Marketing Authorization Holder (MAH).

The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

• sponsored by Servier
• with a first patient enrolled as of 1 January 2004 onwards
• for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

• IPD Sharing Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• IPD Sharing Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Individual Participant Data Set
2. Study Protocol
3. Statistical Analysis Plan
4. Informed Consent Form
5. Clinical Study Report
6. study-level clinical trial data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No