Phase 3 Study of Telitacicept in Active Primary Sjögren's Disease

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.

Primary Outcome Measures

1. 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.

Secondary Outcome Measures

1. 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.
2. 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.
3. 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
4. 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
5. 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
6. 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.