Moderate to severe active rheumatoid arthritis
Conditions
Interventions
Test group:LZM008, 8 mg/kg, administrated once every 4 weeks and in combination with methotrexate (7.5-25mg/week)
Control group:Tocilizumab Injection (ACTEMRA?), 8 mg/kg, administrated once every 4 weeks and in combination with methotrexate (7.5-25mg/week)
Sponsors
Huashan Hospital, Fudan University / Peking University, Reople’s Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1.Participants who fully understand the objectives, nature, methods and possible adverse reactions of the trial, voluntarily participate in the trial, and sign the ICF before the start of any trial procedure; 2.18–70 years old (both inclusive; participant to the day of signing the ICF); 3.Diagnosis of moderately or severely active RA according to the 2010 ACR/EULAR classification and diagnostic criteria and previous diagnosis of RA for >= 6 months; 4.Swollen joints >= 6 (66 joints) and tender joints >= 6 (68 joints) during the screening period; if the same joint has both swelling and tenderness, this joint will be included in both swollen and tender joint counts (except for joint prosthesis); 5.Central laboratory test value of high-sensitivity CRP >= 4 mg/L or local laboratory test value of ESR >= 28 mm/h during the screening period; 6.Reception of DMARD treatment for at least 3 months before screening visit; 7.Reception of at least one non-biological DMARD (including MTX) that failed prior to screening visit; 8.Reception of oral MTX (>= 7.5 mg/week) for at least 12 weeks before randomized administration and a stable dose (dosage of MTX : 7.5–25 mg/week, including cut-off value) for at least 4 weeks before randomized administration; Note: Before the screening visit, participants with a history of parenteral use of MTX (subcutaneously, intramuscularly or intravenously) are eligible for the trial. However, before randomized administration, these patients must have received a stable dose of oral MTX (7.5–25 mg/week, including critical values) for at least 4 weeks; 9.Reception of or willing to receive oral folic acid (at least 5 mg/week or a dose determined according to local medical practice) or equivalent drugs (concomitant medication required for the MTX treatment) during the entire process of the trial, with the dosage of folic acid or equivalent drugs stable for at least 2 weeks before randomized administration; 10.Withdrawal of all non-biological DMARDs (except for MTX) for at least 2 weeks before randomized administration; Note: Drug withdrawal = 8 weeks: leflunomide; but if the participant has received standard cholestyramine therapy* or washout with activated charcoal, leflunomide should be withdrawn at least 2 weeks before randomized administration; Drug withdrawal >= 4 weeks: azathioprine *Standard cholestyramine therapy: cholestyramine 8 g po, tid, for 11 consecutive days. 11.Withdrawal of all biological DMARDs for at least 2 weeks before randomized administration; Note: Drug withdrawal >= 8 weeks: adalimumab, certolizumab, infliximab, and golimumab; Drug withdrawal >= 4 weeks: etanercept (Enbrel, Ecep and Qiangke) 12.Withdrawal of all RA-treating Chinese herbal medicines, Chinese patent medicines and crude drugs for at least 1 week before randomized administration; 13.Eligible for oral corticosteroid use (excluding intra-articular administration or injection) and maintenance of a stable dose for at least 4 weeks before randomized administration. administration of prednisone at a dose of <= 10 mg/day (or administration of other glucocorticoids at an equivalent dose); 14.Reception of a stable dose of non-steroidal anti-inflammatory drugs for at least 2 weeks before randomized administration; 15.Women and men of childbearing age who agree to take effective contraceptive measures (including abstinence, tubal ligation, male sterilization, hormone implants, correct use of compound oral or injectable hormonal contraceptiv
Exclusion criteria
Exclusion criteria: 1.Participants classified as Class IV according to the ACR Criteria for Classification of Functional Status in RA; 2.Body weight of >= 100 kg; 3.History of past or current inflammatory joint diseases (such as gout, reactive arthritis, psoriatic arthritis, spondyloarthritis and Lyme disease) other than RA, except for secondary Sjogren syndrome accompanied by RA; or other systemic autoimmune diseases (such as systemic lupus erythematosus, scleroderma, inflammatory myopathy, mixed connective tissue disease or other overlap syndromes); or uncontrolled diseases, such as asthma, psoriasis or inflammatory bowel disease that usually require oral or parenteral corticosteroid treatment in case of onset; 4.History of malignancies (including solid tumors, hematologic tumor and carcinoma-in-situ); Note: Basal cell carcinoma or squamous cell carcinoma that have been removed or cured, or cervical dysplasia or Grade I cervical cancer in situ that have been treated within 6 to 12 months before the screening visit are not included. 5.Serious poorly controlled concomitant diseases that are believed to be clinically significant by the investigators, such as (but not limited to) disorders of the nervous system, kidney, liver, endocrine or gastrointestinal tract; 6.Cardiovascular diseases meeting any of the following conditions: moderate congestive heart failure (New York Heart Association Class III or IV); severe arrhythmia requiring medical treatment; acute myocardial infarction, severe or unstable angina pectoris occurring within 6 months before the first administration; 7.Interstitial lung disease diagnosed by chest X-ray or chest CT (except for mild cases, as determined by the investigator); 8.History of severe allergies or allergic reactions to human, humanized or murine monoclonal antibodies; 9.Any congenital or acquired neurological disease, vascular disease or systemic disease (such as Parkinson's disease, cerebral palsy and diabetic neuropathy) that may affect efficacy evaluation in this trial (especially joint pain and swelling); or neuropathy or other painful conditions that may interfere with pain evaluation; 10.Infections or the history of infections: recurrent active bacteria, viruses, fungi, mycobacteria or other infections, including but not limited to tuberculosis (TB) and atypical mycobacteria, granulomatous disease and herpes zoster diagnosed by chest X-ray (CXR) or chest CT; Note: Fungal infection of the nail bed is not included. 11.Severe infections occurring within 4 weeks before the screening visit and requiring hospitalization or intravenous anti-infective treatment; reception of oral anti-infective treatment within 2 weeks before the screening visit; 12.History of deep space/tissue infections (such as fasciitis, abscess and osteomyelitis) 52 weeks before the screening visit; 13.History of severe infection or opportunistic infection in the past 2 years as evaluated by the investigators; 14.History of chronic infections (such as chronic pyelonephritis, bronchiectasis, or osteomyelitis); 15.Suspected active or latent tuberculosis, including purified protein derivative positive (positive for TB) or TB-interferon positive, and reception of no treatment or preventive treatment for TB infection. Latent tuberculosis requiring preventive treatment for at least 4 weeks before the first administration in this trial; willing to complete the entire course of treatment; 16.History of past or current primary or secondary immunodeficiency, includin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The percentage of participants achieving ACR20 response criteria at W24; | — |
Secondary
| Measure | Time frame |
|---|---|
| The percentage of participants achieving ACR50 at W24;The percentage of participants achieving ACR70 at W24;ACR core measures (High sensitivity C-reactive protein [CRP], Erythrocyte sedimentation rate [ESR], Tender joint count in 68 joints [TJC], Swollen joint count in 66 joints [SJC], Pain assessment, Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment Of Disease Activity (PhGADA),Health Asse;DAS28 Mean change of DAS28-CRP from baseline at W24 Proportion of participants achieving DAS28 remission (DAS28-ESR < 2.6) at W24;EULAR response criteria Number of EULAR good, moderate or non-responders at W24;Bone mineral density;HAQ-DI (included in ACR core measures) SF-36 (including physical component score (PCS) and mental component scores (MCS));Adverse Events (AEs), Laboratory test, Vital signs, ECG, Physical examination; | — |
Countries
China
Contacts
Public ContactZou hejian
Huashan Hospital, Fudan University
Outcome results
None listed