Clinical trial NCT06276998: A Study of LNK01001 Capsule in Subjects With Active Rheumatoid Arthritis
Official title: A Randomized, Double-blind Study to Compare LNK01001 to Placebo in Adults With Rheumatoid Arthritis (RA) on a Stable Dose of csDMARDs Who Have an Inadequate Response or Intolerance to bDMARDs
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Lynk Pharmaceuticals Co., Ltd
Sponsor class: INDUSTRY
First posted: 2024-02-26
Enrollment: 430
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Brief Summary: This is a randomized, double-blind study comparing LNK01001 to placebo in Chinese participants with moderately to severely active rheumatoid arthritis who are on a stable dose of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and have an inadequate response or Intolerance to biologic DMARDs(bDMARDs).

The study objective of Period 1 (Day 1 to Week 24) is to compare the safety and efficacy of LNK01001 12 mg twice daily (BID) versus placebo for the treatment of signs and symptoms of participants with moderately to severely active rheumatoid arthritis (RA) who are on a stable dose of csDMARDs and had an inadequate response to or intolerance to at least 1 bDMARD.

The study objective of Period 2 (Week 24 to Week 76) is to evaluate the long-term safety, tolerability, and efficacy of LNK01001 12 mg BID in participants with RA who completed Period 1.

Detailed description: This study includes a 35-day screening period; a 24-week randomized, double-blind, parallel-group, placebo-controlled treatment period (Period 1); a 52-week open label long-term extension period (Period 2); and a 28 to 35-day follow-up period (FU).

Participants who meet eligibility criteria will be randomized in a 1:1 ratio to two treatment groups:

Group 1: LNK01001 12 mg BID (Day 1 to Week 24)， LNK01001 12 mg BID (Week 24 and thereafter)

Group 2: Placebo (Day 1 to Week 24)， LNK01001 12 mg BID (Week 24 and thereafter)

Participants who complete the Week 24 visit (end of Period 1) will enter the extension portion of the study, Period 2, and continue to receive LNK01001 12 mg BID treatment. Starting at Week 12, rescue therapy is allowed if there's less than 20% improvement in both swollen joint count (SJC) and tender joint count (TJC) compared to Baseline. Starting at Week 24, initiation of or change in corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or adding or increasing doses in up to 2 csDMARDs (concomitant use of up to 2 csDMARDs except the combination of methotrexate and leflunomide) is allowed.

Eligibility criteria: Inclusion Criteria:

* Participants aged 18 and above.
* Diagnosis of rheumatoid arthritis (RA) for ≥ 3 months.
* ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and baseline visit.
* Erythrocyte sedimentation rate (ESR) ≥ 28mm/h or 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.
* Have an inadequate response to ≥ 1 bDMARD.

Exclusion Criteria:

* Subjects who were prior exposure to Janus Kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib) and have evidence showing an inadequate response or intolerance.
* Subjects who received intra-articular, intramuscular, intravenous, trigger point or tender point, intracapsular, or intra-tendon injections of glucocorticoids 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.

Primary outcomes:
measure: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 24
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Change from Baseline in Disease Activity Score 28 (DAS28) (CRP) at week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants with an American College of Rheumatology 50% (ACR50) Response at week 24
timeFrame: Baseline and Week 24
measure: Change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at all visits.
timeFrame: Baseline to Week 76.
measure: Percentage of Participants with an American College of Rheumatology 70% (ACR70) Response at all visits.
timeFrame: Baseline to Week 76.
measure: Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at all visits.
timeFrame: Baseline to Week 76.
measure: Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at all visits
timeFrame: Baseline to Week 76.
measure: Percentage of Participants with an American College of Rheumatology 20% (ACR20) Response at all visits (except week 24).
timeFrame: Baseline to Week 76 (except week 24).
measure: Change from Baseline in the Severity of Morning Stiffness at all visits.
timeFrame: Baseline to Week 76.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
Study officials:
affiliation: Lynk Pharmaceuticals
name: Linda Wei
role: STUDY_DIRECTOR
References: