A Trial to Evaluate the Efficacy and Safety of Sibeprenlimab Administered Subcutaneously in Participants With Sjögren's (EnVISage)

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Sibeprenlimab Administered Subcutaneously in Participants With Sjögren's

This is a phase 2 study to evaluate the effects of sibeprenlimab 400 mg administered subcutaneously (SC) every 4 (Q4) weeks as an add-on to background treatment in participants with Sjögren's disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Sjogren Disease
• Intervention / Treatment: Biological: Sibeprenlimab; Other: Placebo

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled, proof-of-concept study followed by an optional open-label extension to evaluate the efficacy and safety of sibeprenlimab 400 mg administered SC Q4 weeks as an add-on to background treatment in participants with Sjögren's disease.

The primary objective is to compare the effect of sibeprenlimab versus placebo added to background treatment on European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) scores at 28 weeks.

The key secondary objective is to compare the effect of sibeprenlimab versus placebo added to background treatment on European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index (ESSPRI) at 28 weeks.

Approximately 80 participants who have a diagnosis of Sjögren's disease according to the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria will be randomized with approximately 40 participants in the sibeprenlimab group and 40 participants in the placebo group.

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1111AAH
    • DOM Centro de Reumatología
  • Buenos Aires, Argentina, C1406AGA
    • Aprillus Asistencia e Investigacion de Arcis Salud SRL
  • Buenos Aires, Argentina, C1128AAF
    • Expertia S.A- Mautalen Salud e Investigación
  • Buenos Aires, Argentina, C1180AAD
    • Maffei Centro Médico
  • San Juan, Argentina, J5402
    • Centro Polivalente de Asistencia e Investigacion Clinica - CER San Juan
  • Buenos Aires
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1426ABP
      • Consultorios Médicos Dr. Doreski - Fundacion Respirar - PPDS
    • Quilmes, Buenos Aires, Argentina, B1878DVB
      • Instituto CER S.A.
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2000DEJ
      • Instituto Medico de La Fundacion Estudios Clinicos
  • Tucumán Province
    • San Miguel de Tucumán, Tucumán Province, Argentina, T4000IHE
      • Clínica Mayo de U.M.C.B. S.R.L
    • San Miguel de Tucumán, Tucumán Province, Argentina, T4000
      • Centro de Investigaciones Médicas Tucumán - PPDS
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Medical center Medconsult Pleven OOD
  • Plovdiv, Bulgaria, 4002
    • University Multiprofile Hospital for Active Treatment Sveti Georgi EAD-15 A Vassil Aprilov Boulevard
  • Sofia, Bulgaria, 1407
    • Medical Center Excelsior OOD - PPDS
  • Sofia, Bulgaria, 1680
    • Diagnostic- Consultative Center Convex EOOD
  • Varna, Bulgaria, 9000
    • Medical Center- Nova Clinic
• Germany
  • Hamburg, Germany, 22391
    • Mvz Rheumatologie Und Autoimmunmedizin Hamburg Gmbh
  • München, Germany, 81667
    • Medicover München Ost MVZ
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
      • Universitatsklinikum Freiburg
  • North Rhine-Westphalia
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Universitatsklinikum Koln
• Greece
  • Achaïa
    • Pátrai, Achaïa, Greece, 264 43
      • Olympion General Clinic
  • Attica
    • Athens, Attica, Greece, 115 27
      • Laiko General Hospital of Athens (Site 1)
    • Athens, Attica, Greece, 115 27
      • Laiko General Hospital of Athens (Site 2)
    • Voula, Attica, Greece, 166 73
      • General Hospital ''Asklepieio Voulas''
• Poland
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki nr 2 im. dr Jana Biziela w Bydgoszczy
  • Bydgoszcz, Poland, 85-065
    • MICS Centrum Medyczne Bydgoszcz
  • Katowice, Poland, 40-600
    • NZOZ Holsamed - Oddzial Libero
  • Lublin, Poland, 20-607
    • Zespol Poradni Specjalistycznych REUMED- Wallenroda 2F/4
  • Poznan, Poland, 60-192
    • Pratia Poznan - PPDS
  • Warsaw, Poland, 02-677
    • ETG Warszawa - PPDS
  • Greater Poland Voivodeship
    • Poznan, Greater Poland Voivodeship, Poland, 60-693
      • Med-Polonia Sp. z o.o.
    • Poznan, Greater Poland Voivodeship, Poland, 60-324
      • Twoja Przychodnia PCM
  • Lower Silesian Voivodeship
    • Wroclaw, Lower Silesian Voivodeship, Poland, 50-570
      • Pracownia Badan Klinicznych Salus - ul. Ołtaszyńska 92c/3
  • Masovian Voivodeship
    • Siedlce, Masovian Voivodeship, Poland, 08-110
      • ETG Siedlce - PPDS
    • Warsaw, Masovian Voivodeship, Poland, 02-665
      • Klinika Reuma Park sp . zoo Sp.k.
    • Wołomin, Masovian Voivodeship, Poland, 05-200
      • Centrum Medyczne K2J2 - Wołomin
• Romania
  • Bucharest, Romania, 20125
    • Colentina Clinical Hospital
  • Bucharest, Romania, 11172
    • Sf.Maria Clinical Hospital
  • Cluj-Napoca, Romania, 400006
    • Cluj-Napoca Emergency Clinical County Hospital
  • Râmnicu Vâlcea, Romania, 240226
    • Medart Cliniq
  • Timiș County
    • Timișoara, Timiș County, Romania, 300133
      • Policlinica SelfMed Clinique
• Spain
  • Castelló, Spain, 12004
    • Hospital General Universitari de Castelló
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Torrevieja, Spain, 3186
    • Hospital de Torrevieja
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
• United States
  • California
    • Riverside, California, United States, 92508
      • Medvin Clinical Research - Riverside
    • Tujunga, California, United States, 91042
      • Medvin Clinical Research - Tujunga
  • Florida
    • Brandon, Florida, United States, 33511
      • Bay Area Arthritis And Osteoporosis
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida Inc
    • Cooper City, Florida, United States, 33024
      • GNP Research - Florida
    • Tampa, Florida, United States, 33606
      • Vantage Clinical Trials - Tampa - ClinEdge - PPDS
  • Illinois
    • Rockford, Illinois, United States, 61114-4937
      • OrthoIllinois, LTD
    • Skokie, Illinois, United States, 60076
      • Arnold Arthritis and Rheumatology
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70836
      • Ochsner Clinic Foundation
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts University School of Dental Medicine
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Center for Rheumatology
  • New York
    • The Bronx, New York, United States, 34205-1704
      • Bradenton Research Center Inc
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • DJL Clinical Research PLLC
  • Ohio
    • Vandalia, Ohio, United States, 45377
      • Stat Research
  • Texas
    • Allen, Texas, United States, 75013
      • Allen Arthritis
    • Austin, Texas, United States, 78745
      • Tekton Research, LLC
    • Houston, Texas, United States, 77058
      • Advanced Rheumatology of Houston
    • Houston, Texas, United States, 77089
      • Accurate Clinical Research - Houston
    • Katy, Texas, United States, 77450
      • R & H Clinical Research
    • Katy, Texas, United States, 77449
      • Accurate Clinical Management, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Diagnosed with Sjögren's disease.
• ESSDAI score (which measures disease activity) must be 5 or higher.
• Salivary flow rate must be at least 0.05 mL/min.
• Serum IgG level must be higher than 900 mg/dL.
• Must be able to communicate well with the investigator and agree to follow the trial requirements.
• Participants can continue certain medications (hydroxychloroquine, methotrexate, leflunomide, or azathioprine) if they have been on a stable dose for at least 30 days.
• Corticosteroid dose must be stable and no more than 10 mg/day for at least 30 days.
• Test positive for anti-Ro52 and/or anti-Ro60 antibodies.

Key Exclusion Criteria:

• Another active autoimmune rheumatic disease.
• Prior use of B-cell depleting therapy or prohibited immunosuppressants.
• Significant comorbidities including uncontrolled type 2 diabetes, malignancy, and chronic and/or acute infections.
• Suicidal ideation or behavior based on the Patient Health Questionnaire-9 (PHQ-9).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Administered SC Q4 weeks
Experimental: 400 mg Sibeprenlimab	Biological: Sibeprenlimab; 400 mg administered SC Q4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) score	Higher scores on the ESSDAI indicate a worse outcome, as they reflect higher disease activity. Minimum value is 0 and the maximum value is 123.	28 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index (ESSPRI) score	Higher scores on the ESSPRI indicate a worse outcome, as they reflect higher levels of patient-reported symptoms. Minimum value is 0, maximum value is 10.	28 weeks
Incidence of treatment-emergent adverse events (TEAEs)		28 weeks
Incidence of treatment-emergent adverse events (TEAEs) by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade		28 weeks
Incidence of treatment-emergent adverse events (TEAEs) with an outcome of death		28 weeks
Incidence of serious treatment-emergent adverse events (TEAEs)		28 weeks
Incidence of treatment-emergent adverse events (TEAEs) leading to discontinuation of the investigational medicinal product (IMP)		28 weeks
Proportion of participants with minimal clinical improvement defined as European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) reduction ≥ 3 points from baseline	Higher scores on the ESSDAI indicate a worse outcome, as they reflect higher disease activity. Minimum value is 0 and the maximum value is 123.	At 28 weeks
Proportion of participants with minimal clinical improvement defined as European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index (ESSPRI) reduction ≥ 1 point from baseline	Higher scores on the ESSPRI indicate a worse outcome, as they reflect higher levels of patient-reported symptoms. Minimum value is 0, maximum value is 10.	At 28 weeks
Change from baseline in individual European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) domains	Higher scores on the ESSDAI indicate a worse outcome, as they reflect higher disease activity. Minimum value is 0 and the maximum value is 123.	At 28 weeks
Change from baseline in salivary flow rate		At 28 weeks
Change from baseline in tear flow rate		At 28 weeks
Change from baseline in Clinical European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ClinESSDAI) score	Higher scores on the ClinESSDAI indicate a worse outcome, as they reflect higher disease activity. Minimum value is 0 and the maximum value is 123.	At 28 weeks
Change from baseline in Physician Global Assessment (PhGA) score	Higher scores on the PhGA indicate a worse outcome, as they reflect a higher assessment of disease activity or severity by the physician. Minimum value is 0 and the maximum value is 10.	At 28 weeks
Change from baseline in Patient Global Assessment (PaGA) score of participant outcomes	Higher scores on the PaGA indicate a worse outcome, as they reflect a higher assessment of disease severity or impact by the patient. Minimum value is 0 and the maximum value is 10.	At 28 weeks
Change from baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) score	Higher FACIT-Fatigue scores indicate a better outcome, as they reflect less fatigue. Minimum value is 0 and the maximum value is 52.	At 28 weeks
Change from baseline in 36 Item Short-Form Survey Version 2 (SF-36v2) Physical Component Summary Scale score and Mental Component Summary Scale score	Higher scores on the SF-36v2 indicate a better outcome, as they reflect better health status and quality of life. Minimum value is 0 and the maximum value is 100.	At 28 weeks
Change from baseline in patient-reported Sjögren's disease diary score	Higher diary score indicates more severe symptoms and greater impact on the patient's daily life. Minimum value is 0 and the maximum value is 10.	At 28 weeks
Proportion of participants with minimal clinical improvement, defined as Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) score increase of ≥ 4 from baseline	Higher FACIT-Fatigue scores indicate a better outcome, as they reflect less fatigue. Minimum value is 0 and the maximum value is 52.	At 28 weeks
Time to the first occurrence of minimal clinical improvement in ESSDAI		Week 28
Time to the first occurrence of minimal clinical improvement in ESSPRI		Week 28
Percent change from baseline in total serum IgA		Week 28
Percent change from baseline in total serum IgG		Week 28
Percent change from baseline in total serum IgM		Week 28
Percent change from baseline in total serum free APRIL (a proliferation-inducing ligand) concentrations		Week 28
Cmax of sibeprenlimab		28 weeks
Tmax of sibeprenlimab		28 weeks
Area Under the Curve (AUC) of sibeprenlimab		28 weeks
Serum concentration of sibeprenlimab		28 weeks
Presence or absence of serum antidrug antibody (ADA) to sibeprenlimiab		28 weeks

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2025
• Primary Completion (Estimated): March 13, 2027
• Study Completion (Estimated): June 4, 2027

Study Registration Dates

• First Submitted: March 25, 2025
• First Submitted That Met QC Criteria: April 7, 2025
• First Posted (Actual): April 15, 2025

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Immune System Diseases; Autoimmune Diseases; Dry Eyes; Immunoglobulin G; Dry Mouth; Sibeprenlimab; Salivary Gland Disorders; Lacrimal Gland Disorders; EnVISage
• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Eye Diseases; Lacrimal Apparatus Diseases; Autoimmune Diseases; Dry Eye Syndromes; Immune System Diseases; Salivary Gland Diseases; Xerostomia
• Other Study ID Numbers: 417-201-00042

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
• IPD Sharing Time Frame: Data will be available after marketing approval in global markets or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• IPD Sharing Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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