Clinical trial NCT06099535: A Study of LNK01001 Capsule in Moderately to Severely Active Rheumatoid Arthritis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Lynk Pharmaceuticals Co., Ltd
Sponsor class: INDUSTRY
First posted: 2023-10-25
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at week 12
timeFrame: week 12
Secondary outcomes:
measure: Percentage of Participants With an ACR50
timeFrame: Week1,2,4,8,12
measure: Percentage of Participants With an ACR20
timeFrame: Week1,2,4,8
measure: Change From Baseline in Disease Activity Score 28 (DAS28)-CRP
timeFrame: Week1,2,4,8,12
measure: Change From Baseline in Disease Activity Score 28 (DAS28)-ESR
timeFrame: Week1,2,4,8,12
measure: Change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI).
timeFrame: Week1,2,4,8,12
measure: Percentage of Participants With an ACR70
timeFrame: Week1,2,4,8,12
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
Study officials:
affiliation: Peking Union Medical College Hospital
name: Xiaofeng Zeng
role: PRINCIPAL_INVESTIGATOR
References: