Clinical trial NCT06800157: Comparison of LW402 Vs. Placebo, for the Treatment of Rheumatoid Arthritis in China
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Phase IIa Clinical Study Evaluating the Initial Efficacy, Safety, and Tolerability of LW402 Tablets in Patients with Moderate and Severe Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Arthritis, Rheumatoid
Lead sponsor: Shanghai Longwood Biopharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-01-29
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the dose-response relationship of LW402 tablets in adults with active rheumatoid arthritis combined with methotrexate, in a 12-week therapy


Eligibility criteria: Inclusion Criteria:

1. Signed informed consent;
2. The patient voluntarily accept and is able to follow the protocol procedures including medication and follow-up examination;
3. Age from 18 to 65 years old (including critical value), male or female;
4. Have a diagnosis of adult-onset rheumatoid arthritis (RA) as defined by American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) 2010 criteria for the classification of RA;
5. Diagnosisof moderately to severely active rheumatoid arthritis who also meets the following disease activity criteria at screening:

   * 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) ;C-Reactive Protein (CRP) ≥ 10 mg/L or Eerythrocyte sedimentation rate（ESR）≥ 28 mm/h; DAS28-CRP\>3.2；
6. Subjects had been on methotrexate (MTX) for ≥12 weeks and on a stable oral dose (7.5-25 mg/ week) of MTX for ≥4 weeks prior to randomization and are able to continue a stable dose of MTX during the study.

Exclusion Criteria:

1. Suspected or confirmed allergy to investigational drugs (including excipient and similar drugs) ,and other serious allergic diseases (except RA) judged by the investigator that may impair the safety of the subjects;
2. Had any inflammatory joint disease or autoimmune disease other than RA at screening (such as Gout, Reactive arthritis, Psoriatic arthritis, Spinal arthritis, Systemic lupus erythematosus, Mixed connective tissue diseases, etc.);
3. Have a history of lymphoproliferative disease; or have a current malignancy or history of malignancy (except Cutaneous squamous cell carcinoma in situ, Basal cell carcinoma or cervical carcinoma in situ, which have not shown any signs of recurrence for more than 5 years after achieving complete remission following radical treatment);
4. Have a history of major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell or bone marrow transplant;
5. Patients with Active tuberculosis at screening should be excluded.After a minimum of 4 weeks of treatment with 0.3g qd of isoniazid(or other prophylactic anti-tuberculosis treatments) for latent tuberculosis infection, continued screening could be considered when the investigator reassessed that the risk was controlled;
6. Presence of active infection, or have a history of: Systemic anti-infective treatment within 4 weeks prior to randomization; Sore throat, nasal congestion, acute upper respiratory tract infection, or systemic acute infection within 2 weeks prior to randomization; Presence of recurrent, chronic or other active infections in the screening period which may increase the risk of the subjects according to the evaluation of the investigators;
7. Have a history of recurrent herpes zoster, disseminated herpes zoster, or disseminated herpes simplex, or have a history of herpes zoster or herpes simplex within 2 months before randomization;
8. Presence of other diseases at screening that may interfere with the study evaluation;
9. Abnormal laboratory values at screening:

   Hemoglobin \<10.0g/dL（100.0g/L） for male or \< 9.0g/dL (90.0g/L) for female;WBC count \<3.0×109/L;Neutrophil count \<1.5×109/L; Platelet count \<100×109/L; Lymphocyte count \<0.5×109/L; Alanine transaminase (ALT) and/or Serum aspartate transaminase (AST) \>1.5 upper limit of normal (ULN); Serum creatinine \>1.5×upper limit of normal (ULN).
10. Positive for hepatitis B surface antigen and/or positive for hepatitis B core antibody (except HBV DNA negative or less than 500IU/ml) , positive for hepatitis C virus (HCV) antibody, positive for anti-human immunodeficiency virus (HIV) antibody, or anti-syphilis spiral antibody (except for TP-Ab positive but RPR or TRUST negative) at screening；
11. Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the investigator , are clinically significant and indicate an unacceptable risk for the participant's participation in the study;
12. Previous use of any of the following medications or treatments:

    1. Have received potent opioids within 1 week before randomization;
    2. Have received any JAK inhibitor within 2 weeks before randomization;
    3. Have received any drugs that may interact with this product within 4 weeks before randomization, such as potent inhibitors of CYP3A4 (such as ketoconazole, itraconazole, clarithromycin, nefazodone, telithromycin, etc.), potent inducers of CYP3A4 (such as rifampicin);
    4. Have received disease-modifying antirheumatic drugs (DMARDs) or biological agents other than MTX. before randomization:

       Have received sulfasalazine, antimalarial drugs, penicillamine, oral gold salts, cyclosporine, azathioprine, cyclophosphamide, iguratimod, etc., within 4 weeks before randomization or no more than 5 half-life periods; Have received herbal medicines (including tripterygium wilfordii preparations, total glucosides of paeony, sinomenine and/or Chinese herbs) within 4 weeks before randomization; Have received Flunomide within 8 weeks before randomization; Have received TNF-α inhibitor (fusion protein) within 4 weeks, or received TNF-α inhibitor (monoclonal antibody) or abatacept within 12 weeks prior to randomization have received Tocilizumab within 10 weeks prior to randomization; Have received Rituximab within 24 weeks, or received another biologic agent with no more than 5 half-life periods before randomization.
    5. Are currently receiving receiving non-steroidal anti-inflammatory drugs (NSAIDs) before randomization with an unstable dosing regimen within 4 weeks before randomization;
    6. Are currently receiving corticosteroids at doses \>10 mg per day of prednisone (or equivalent) or have been receiving an unstable dosing regimen of corticosteroids t within 4 weeks before randomization;
    7. Has been treated with intra-articular, intramuscular, intravenous, trigger point or tender point, intra-bursa, or intra-tendon sheath corticosteroids in the preceding 4 weeks prior to randomization;
13. Have been enrolled in another clinical study within 4 weeks or been treated by the last dose of any investigational drug within 5 half-lives prior to randomization;
14. Have been exposed to a live/attenuated vaccine within 8 weeks prior to randomization or are expected to need/receive a live/attenuated vaccine during the course of the study;
15. Have a history of drug or alcohol abuse (defined as consuming more than 28 units of alcohol per week. 1 unit =285ml beer or 25ml spirits containing at least 40% alcohol or 1 glass of wine) within the last 6 months.
16. Have donated ≥300mL of blood within 4 weeks prior to screening (except physiological blood loss in female) or plan to donate blood during or within 4 weeks after the study;
17. Women and/or men of childbearing potential and their partners who refuse to use effective contraception from the time they sign the informed consent until 6 months after the last dose, or who are planning to have children, donate eggs (women) or donate sperm (men);
18. Female who is pregnant or breastfeeding;
19. Other situations which are not suitable for the study per Investigator judgment.

Primary outcomes:
measure: Change from Baseline in DAS28 (CRP) at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Change from Baseline in DAS28 (CRP) at Weeks 2，4 and 8
timeFrame: Weeks 2，4，and 8
measure: Change from Baseline in DAS28 (ESR) at Weeks 2，4， 8 and 12
timeFrame: Weeks 2，4， 8 and 12
measure: Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response
timeFrame: Weeks 2, 4, 8 and 12
measure: Percentage of Participants Achieving American College of Rheumatology 70% (ACR20) Response
timeFrame: Weeks 2, 4, 8 and 12
measure: Percentage of Participants Achieving American College of Rheumatology 50% (ACR20) Response
timeFrame: Weeks 2, 4, 8 and 12
measure: Percentage of Participants Who Achieved DAS28 (CRP) ≤ 3.2 at Weeks 2, 4, 8 and 12
timeFrame: Weeks 2, 4, 8 and 12
measure: Change From Baseline in Individual ACR Component: HAQ-DI at Weeks 2, 4, 8 and 12
timeFrame: Weeks 2, 4, 8 and 12
measure: Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8 and 12
timeFrame: Weeks 2, 4, 8 and 12
measure: Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8 and 12
timeFrame: Weeks 2, 4, 8 and 12
measure: Adverse events, clinical Lab testing, vital signs, Electrocardiogram (ECG), physical examination, etc.
timeFrame: From first dose up to 28 days after the last dose of study drug
Other outcomes:
measure: Pharmacokinetics of LW402 and its main metabolite LW40241
timeFrame: W0~W12
measure: Pharmacodynamics
timeFrame: W0~W12
Locations:
city: Peking
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
References: