A Phase 2a/b Study to Assess the Efficacy, Safety and Tolerability of DDY391 in Participants With Sjögren's Disease

This study is a Phase 2a/b, randomized, double-blind, placebo-controlled, multi-center trial involving participants with SjD. The study consists of three parts (Part A, Part B, and Part C).

The study includes a screening period of up to 8 weeks to assess eligibility, a 52-week treatment period, and a 4-week safety follow-up period after the last dose of study treatment.

• DDY391 (Drug): DDY391 dose level 1 DDY391 dose level 2 DDY391 dose level 3
• Placebo (Drug): Matching Placebo

Primary outcomes

• Part A and B: Change from baseline in ESSDAI score [Baseline, Week 24]: EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) is a validated tool for assessing disease activity in SjD. Score range is 0-123. Higher scores on the ESSDAI scale are associated with poorer health states. A negative change from baseline indicates improvement in disease status.
• Part C: Change from baseline in ESSPRI [Baseline, Week 24]: EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is a validated disease outcome measure for SjD. It consists of three domains of dryness, pain, and fatigue. The participant will assess severity of symptoms they experienced over the last 14 days on a single 0-10 numerical rating scale for each of the three domains. The ESSPRI score is defined as the mean of scores from the three scales: (dryness + pain + fatigue) /3. The total ESSPRI score ranges from 0 (no symptoms) to 10 (maximal symptom severity).

Secondary outcomes

• Part A and B: Change from baseline in ESSPRI [Baseline, Week 24]: EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is a validated disease outcome measure for SjD. It consists of three domains of dryness, pain, and fatigue. The participant will assess severity of symptoms they experienced over the last 14 days on a single 0-10 numerical rating scale for each of the three domains. The ESSPRI score is defined as the mean of scores from the three scales: (dryness + pain + fatigue) /3. The total ESSPRI score ranges from 0 (no symptoms) to 10 (maximal symptom severity).
• Part A, B and C: Change from baseline in SSSD [Baseline, Week 24]: Sjögren's Syndrome Symptom Diary (SSSD) includes six items specific to SjD (eye dryness, mouth dryness skin dryness, tiredness, muscle and/or joint pain, and genital dryness). The total score ranges from 0 (no symptoms) to 10 (maximal symptom severity).
• Part A, B and C: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to Week 52]: To evaluate the safety and tolerability of multiple doses of DDY391.

Sex: All, ages: 18 Years to 100 Years

Key Inclusion Criteria:

• Participants must have a diagnosis of SjD according to the ACR/EULAR 2016 classification criteria at screening:

\- Positive anti-Ro (SSA) antibodies at screening. Participants negative for anti-Ro/SSA antibodies are eligible if they have documented previous biopsy showing evidence of salivary gland inflammation consistent with SjD.

Key Exclusion Criteria:

* Presence of another autoimmune rheumatic disease that is active at screening and constitutes the principal illness.
* Exclusion based on medications being used for SjD:

  * Participants taking > 400 mg/day hydroxychloroquine are excluded. Participants taking ≤400 mg/day hydroxychloroquine should be on a stable dose for at least 4 weeks prior to randomization.
  * Participants taking > 400 mg/day hydroxychloroquine are excluded. Participants on ≤ 400 mg/day of hydroxychloroquine should be on a stable dose for at least 4 weeks prior to randomization.
* Prior treatment with any of the following within 3 months prior to randomization: belimumab, abatacept, anti-tumor necrosis factor alpha biologic agents, immunoglobulins, plasmapheresis, intravenous (i.v.) or oral cyclophosphamide, mycophenolate mofetil, i.v. or oral cyclosporine A, or any other immunosuppressants (e.g., JAK inhibitors or other kinase inhibitors, IL-2, anti-IL-6, anti-IL-17).
* Previous treatment with any cell-depleting therapies, including but not limited to anti-CD20, unless ≥ 12 months prior to screening.
* Any viral, bacterial or other infections at the time of screening or randomization, or history of recurrent clinically significant infection or of recurrent bacterial infection.
* History of malignancy of any organ system (other than localized non melanoma carcinoma of the skin or in situ cervical cancer) within the last five years of randomization or any malignancy not in remission.

Other protocol-defined inclusion/exclusion criteria may apply.

NIH grants: 2025