Phase 3 Study of Telitacicept in Active Primary Sjögren's Disease (UPSTREAM SjD)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Telitacicept in Adult Participants With Active Primary Sjögren's Disease

Phase 3 Study of Telitacicept in Active Primary Sjögren's Disease (UPSTREAM SjD)

Study Overview

• Status: Recruiting
• Conditions: Primary Sjogren's Disease
• Intervention / Treatment: Drug: Placebo; Biological: Telitacicept

Detailed Description

Telitacicept (RC18) is a recombinant fusion protein designed to target B-cell-mediated immune pathways. It consists of the extracellular domain of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) linked to the Fc portion of human immunoglobulin G1 (IgG1).

Telitacicept binds with high affinity to the cytokines B-lymphocyte stimulator (BLyS, also known as BAFF) and A Proliferation-Inducing Ligand (APRIL). By binding these soluble factors, telitacicept prevents their interaction with cell-surface receptors on B cells, including TACI, B-cell maturation antigen (BCMA), and BAFF receptor (BAFF-R).

This inhibition reduces BLyS/APRIL signaling, leading to decreased B-cell survival, reduced differentiation of B cells into immunoglobulin-producing plasma cells, and lowering of autoantibody production, increased BLyS and APRIL levels, B-cell hyperactivity, and autoantibody production are associated with multiple autoimmune diseases.

Modulation of the BLyS/APRIL pathway is intended to reduce pathogenic B-cell activity and downstream immune effects that contribute to disease manifestations in Sjogren's disease and other B-cell-mediated autoimmune conditions.

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jeremy Sokolove; Phone Number: 6176556580; Email: Study@vorbio.com

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85225
      • Recruiting
      • Arizona Arthritis & Rheumatology Associates P.C.
    • Flagstaff, Arizona, United States, 86001
      • Recruiting
      • Arizona Arthritis & Rheumatology Associates P.C.
    • Glendale, Arizona, United States, 85306
      • Recruiting
      • Arizona Arthritis & Rheumatology Associates, PLLC
    • Phoenix, Arizona, United States, 85392
      • Recruiting
      • Arizona Arthritis & Rheumatology Associates P.C.
    • Tucson, Arizona, United States, 85704
      • Recruiting
      • Arizona Arthritis & Rheumatology Associates, P.C.
  • California
    • Beverly Hills, California, United States, 90210
      • Recruiting
      • Wallace Rheumatic Study Center
  • Florida
    • Green Acres, Florida, United States, 33467
      • Recruiting
      • Finlay Medical Research Corp
    • New Port Richey, Florida, United States, 34652
      • Recruiting
      • Suncoast Clinical Research Inc.
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Recruiting
      • Chicago Clinical Research Institute Inc
    • Schaumburg, Illinois, United States, 60195
      • Recruiting
      • Clinical Investigation Specialist
    • Willowbrook, Illinois, United States, 60527
      • Recruiting
      • Willow Rheumatology & Wellness
  • Louisiana
    • Lake Charles, Louisiana, United States, 70605
      • Recruiting
      • Accurate Clinical Research, Inc.
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Recruiting
      • Arthritis and Rheumatism Associates
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Recruiting
      • Altoona Center for Clinical Research, P.C.
  • Texas
    • Allen, Texas, United States, 75013
      • Recruiting
      • Allen Arthritis
    • Allen, Texas, United States, 75013
      • Recruiting
      • Arthritis and Rheumatology Research Institute, PLLC
    • Baytown, Texas, United States, 77521
      • Recruiting
      • Accurate Clinical Research
    • Bellaire, Texas, United States, 77401
      • Recruiting
      • Novel Research LLC
    • Euless, Texas, United States, 76040
      • Recruiting
      • Precision Comprehensive Clinical Research Solutions
    • Fort Worth, Texas, United States, 76109
      • Recruiting
      • Lone Star Arthritis & Rheumatology
    • Houston, Texas, United States, 77089
      • Recruiting
      • Accurate Clinical Research, Inc.
    • Katy, Texas, United States, 77450
      • Recruiting
      • R&H Clinical Research Inc.
    • Waco, Texas, United States, 76710
      • Recruiting
      • Velocity Clinical Research, Waco
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Recruiting
      • Tidewater Clinical Research

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or female aged 18 to 75 years of age (both inclusive) at screening
2. Participants must meet the 2016 American College of Rheumatology (ACR)/EULAR classification criteria for primary Sjogren's Syndrome at the time of screening.
3. ESSDAI ≥5 at screening (score calculated excluding renal, pulmonary and neurological domains)
4. Participants are seropositive for antibodies to Sjogren's Syndrome A (SSA)/Anti-Sjogren's Syndrome A (Ro) at the Screening Visit.

Additional inclusion criteria are defined in the protocol

Exclusion Criteria:

1. Participants who have a systemic autoimmune disease other than Primary Sjogren's Disease, such as rheumatoid arthritis, systemic lupus erythematosus, or systemic sclerosis, that can better explain the majority of the symptoms (i.e., secondary Sjogren's Disease)
2. Participants who have another autoimmune disease or inflammatory condition that could interfere with assessment of response of Primary Sjogren's Disease to therapy (e.g., systemic sclerosis, inflammatory bowel disease, gout).
3. Participants with severe fibromyalgia that could interfere with the assessment of response of Primary Sjogren's Disease to therapy
4. Active life-threatening or organ-threatening complications of Primary Sjogren's Disease at the time of screening based on investigator evaluation
5. Significant, uncontrolled medical disease in any organ system not related to Primary Sjogren's Disease (e.g., poorly controlled asthma, cardiovascular disease, accelerated hypertension, major depression, etc.) that in the opinion of the investigator would preclude participant participation.

Additional exclusion criteria are defined in the protocol

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
Placebo Comparator: Placebo	Drug: Placebo; Subcutaneous injection
Experimental: Telitacicept	Biological: Telitacicept; Subcutaneous injection; Other Names: RC18; RC18-L

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the efficacy of telitacicept versus placebo at Week 48 in the change from baseline in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score at Week 48.	Change from baseline in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score at Week 48.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the efficacy of telitacicept versus placebo at Week 48 in the treatment of adult participants with pSD.	To evaluate the efficacy of telitacicept versus placebo at Week 48 in the treatment of adult participants with pSD.	Week 48
To evaluate the efficacy of telitacicept versus placebo in improving glandular function during the trial.	Change from baseline in the stimulated whole salivary flow at Week 48.	Week 48
To evaluate the effect of telitacicept versus placebo in improving patient-reported outcomes (i.e., how participants feel and function) during the trial.	Change from baseline in the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score at Week 48	Week 48
To evaluate the efficacy of telitacicept versus placebo at Week 48 in the change from baseline in the physician's global assessment of disease activity (Physician GDA) score at Week 48	Change from baseline in the physician's global assessment of disease activity (Physician GDA) score at Week 48	Week 48
To evaluate the efficacy of telitacicept versus placebo at Week 48 in the change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score at Week 48	Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score at Week 48	Week 48
To evaluate the efficacy of telitacicept versus placebo at Week 48 in the change from baseline in the participant's global assessment of disease activity (Patient GDA) at Week 48.	Change from baseline in the participant's global assessment of disease activity (Patient GDA) at Week 48.	Week 48

Collaborators and Investigators

• Sponsor: Vor Biopharma

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: February 4, 2026
• First Submitted That Met QC Criteria: February 4, 2026
• First Posted (Actual): February 12, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Sjogren's Syndrome; Primary Sjogren's Syndrome; Sjögren's Disease; pSD; SjD
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Mouth Diseases; Stomatognathic Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Skin and Connective Tissue Diseases; Sjogren's Syndrome; telitacicept
• Other Study ID Numbers: RC18G007; pSD (Registry Identifier: Active Primary Sjögren's Disease); Telitacicept (Other Identifier: Vor Biopharma Inc.); UPSTREAM SjD (Other Identifier: Vor Biopharma Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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