A Study of LNK01001 Capsule in Moderately to Severely Active Rheumatoid Arthritis

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Multicenter Study of LNK01001 Capsule in Moderately to Severely Active Rheumatoid Arthritis Patients With Inadequate Response or Intolerance to csDMARDs

This study includes two periods. In Period 1, Participants who meet eligibility criteria will be randomized in a 1:1:1 ratio to receive a twice-daily oral LNK01001 Dose A or LNK01001 Dose B or a matching placebo for 12 weeks. Participants who receive a placebo in Period 1 will be re-randomized at Week 13 in a 1:1 ratio to receive a twice-daily oral LNK01001 Dose A or LNK01001 Dose B for 12 weeks (period 2). Participants who receive LNK01001 ( Dose A and Dose B) in Period 1 will maintain the treatment dose in Period 2.

This study includes a 35-day screening period; a 12-week randomized, double-blind, parallel-group, placebo-controlled treatment period (Period 1); a 12-week double-blind period (Period 2); and a 28 to 35-day follow-up period (FU).

Participants who meet eligibility criteria will be randomized in a ratio of 1：1：1 to 3 treatment groups in period 1， the placebo group will be rerandomized in a 1:1 ratio to LNK01001 Dose A or LNK01001 Dose B at week 13.

1. Group 1: LNK01001 Dose A BID (Day 1 to Week 12)， LNK01001 Dose A BID (Week 13 and thereafter)
2. Group 2：LNK01001 Dose B BID (Day 1 to Week 12)， LNK01001 Dose B BID (Week 13 and thereafter)
3. Group 3: Placebo (Day 1 to Week12) ， LNK01001 Dose A BID (Week 13 and thereafter)
4. Group 4: Placebo (Day 1 to Week12) ， LNK01001 Dose B BID (Week 13 and thereafter)

Participants who complete the Week 12 visit (end of Period 1) will enter Period 2, and continue to receive LNK01001 Dose A or Dose B treatment. Starting at Week 12, rescue therapy is allowed.

Inclusion Criteria:

• Participants between ≥ 18 and ≤70 years of age.
• Diagnosis of RA for ≥ 3 months at screening visit who also fulfill the 2010 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification criteria for RA.
• ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and baseline visit.
• High-sensitivity C-Reactive Protein (hsCRP) ≥ ULN at Screening.
• Participants have been receiving csDMARD therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug.

Exclusion Criteria:

• Subjects who are allergy to any component of the study drug.
• Subjects who are ACR functional class IV or long-term bedridden/long-term wheelchair.
• Prior exposure to Janus Kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
• Subjects who received intra-articular, intramuscular, intravenous, trigger point or tender point, intracapsular, or intra-tendon injections of glucocorticoids within 8 weeks before randomization.
• Current use of oral or inhaled glucocorticoids and the daily dose is >10 mg of prednisone (or equivalent dose) or on a not stable dose within 4 weeks before randomization.
• Current use of Non-steroidal anti-inflammatory drugs and on a not stable dose within 4 weeks before randomization.
• Subjects who received iguratimod treatment within 4 weeks before randomization.
• Subjects who received interferon treatment within 4 weeks before randomization.
• Current diagnosis of systemic inflammatory disease other than RA.
• History of malignancy or current diagnosis of malignancy within 5 years before screening visit.
• Uncontrolled diabetes, hypertension, kidney disease, liver disease, severe heart disease.
• Subject with any major surgery within 4 weeks before randomization or planned major surgery during study; history of chronic pain that may affect study evaluation; previous recipient of an organ transplant.
• Any clinically significant laboratory or ECG abnormal value, as determined by the Investigator, may interfere with the evaluation of the study results.