CMAB008 With MTX Therapy in Adult Patients With Moderately to Severely Active Rheumatoid Arthritis

• Status: Completed
• Trial end date: 2019-08-27
• Target enrollment: 0
• Participant gender: All

Summary

CMAB008 is an infliximab biosimilar candidate. The host cell of Remicade is mouse myeloma SP2/0 cell, however, the host cell of CMAB008 is CHO (Chinese hamster ovary cell). It seems that CMAB008 has lower immunogenicity and higher safety, because Remicade comprises more complex-type and hybrid-type glycans than CMAB008. However, it is not yet known whether CMAB008 is not inferior to Remicade. This randomized, double-blind trial investigates the efficacy and safety of CMAB008 for moderately to severely active rheumatoid arthritis, compared to Remicade.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shanghai Biomabs Pharmaceutical Co., Ltd.
• Treatments: Infliximab; Methotrexate

Criteria

Inclusion Criteria:

1. Age≥18 years, males or females;

2. Diagnosis of rheumatoid arthritis according to American College of Rheumatology (ACR) 1987 Revised Criteria for the Classification of Rheumatoid Arthritis, and in moderately to severely active stage during screening;

3. Have had one or more DMARDs failure (defined as "failure of traditional/conventional DMARD(s) due to lack of efficacy/desired response or side effects" according to 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis);

4. Non-use of DMARDs (including: Chloroquine, Hydroxychloroquine, Gold Compound, Penicillamine, Salicylazosulfapyridine, Azathioprine, Cyclophosphamide, Cyclosporine A, Leflunomide, Thalidomide etc.) except for MTX in the last 4 weeks before screening;

5. Have completed at least 3 months of treatment with MTX, and steadily at the dosage of 7.5mg~15mg/w at least 4 weeks prior to screening;

6. Non-use of Non-steroidal Anti-inflammatory Drugs (NSAIDs) in the last 2 weeks before enrollment, or if using NSAIDs, should stabilize dose at least 2 weeks;

7. Non-use of glucocorticoid (including intramuscular corticotropin) systematically (e.g., oral administration, intramuscular or intravenous injection) or intra-articular injection; or if concurrent taking glucocorticoid orally, dose (equivalent to the dose of Prednisone) should stabilize≤10mg/d at least 4 weeks;

8. Non-use of Chinese medicine (e.g., Tripterygium, Total Glucosides of Paeony Capsules) for rheumatoid arthritis in the last 4 weeks before screening;

9. Pregnancy test should be negative for procreative female, or not lactating. Both male and female subjects should consent to take effective contraception throughout the study and at least 6 months after the study;

10. Signed the informed consent form;

11. Can participate in visits on schedule;

12. Can understand and complete assessment forms correctly.

Exclusion Criteria:

1. Weight>75Kg;

2. Inoculated live (attenuated) viral/bacterial vaccine in the last 4 weeks before screening;

3. Use of biologicals (including but nor limited to Infliximab, Etanercept, Adalimumab, Tocilizumab, Rituximab etc.) for rheumatoid arthritis in the last 3 months before screening;

4. Severe infection (e.g., acute hepatitis, pneumonia, acute pyelonephritis) in the last 2 months before enrollment, or previous hospitalization due to infection, or previous use of antibiotics, antifungal or antiviral drugs due to infection. However, low-grade infection (e.g., acute upper respiratory infections, simplex urinary tract infection) is not considered as exclusion criteria, whether the subject can be chosen depends on investigator;

5. Suffering from acute infection or recurrent infections disease during screening, e.g., respiratory system infection (influenza, upper respiratory infection, bronchiectasia etc.), acute episode of chronic pyelonephritis, infectious skin wound etc,;

6. Previous opportunistic infection (e.g., herpes zoster, active cytomegalovirus, mycoplasma, pneumocystis pneumonia, histoplasma, aspergillus, mycobacteria except for mycobacterium tuberculosis) in the last 6 months before screening;

7. History of prosthetic joint infections, or suspicious prosthetic joint infections with antibiotic therapy and unremoved prosthetic joint;

8. History of severe hepatic diseases; or HbsAg positive; or only HbcAb positive in Second Liver 5 Indexes, and HBV-DNA positive; or HCV-infected patient;

9. AIDS-infected patient or HIVpositive;

10. One of the following situations relating to tuberculosis:

1. Concurrent or previous active tuberculosis. Chest X-ray examination (suggest chest anteroposterior and lateral position films) should be performed in the last 3 months before screening, to provide evidence for concurrent or previous tuberculosis;

2. Intimate contact with active tuberculosis patient recently; or high-risk and/or immunocompromised group (e.g., long-term use of glucocorticoids, immunosuppressor), and with any signs of latent tuberculosis infection;

3. PPD test (inject 5IU TB-PPD intradermally, measure the diameter of skin induration 72 hours later) performed in the last 3 weeks before screening: diameter of induration≤15mm, and with vesicle or necrosis; or diameter of induration>15mm;

4. If cannot perform PPD test, perform T-SPOT test: T-SPOT test positive, chest file and clinical evidence indicate that the patient is unsuitable for participation;

11. History of organ allograft operation (except for keratoplasty more than 3 months before the first use of investigational drug);

12. Concurrent or previous malignant tumor (except for total excision and no recurrence of cutaneous squamous cell carcinoma, basal-cell carcinoma or carcinoma in situ of cervix) in the last 5 years before screening;

13. History of lymphoid malignancies (lymphoma) or lymphoproliferative disease; or symptoms and signs indicate that may be lymphoproliferative disease (e.g., lymph node enlargement at neck, clavicle or axilla) during screening; or splenomegaly (≥subcostal 2cm);

14. Concurrent or previous demyelinating diseases of the central nervous system (e.g., multiple sclerosis);

15. Concurrent or previous congestive heart failure;

16. Concurrent or previous other autoimmune disease, and may be expected to affect the assessment of investigational drug;

17. Severe, progressive, uncontrolled cardiovascular, hepatic, renal, pulmonic, gastrointestinal, hematopoietic, endocrine, neural diseases, or other situations that the patient is considered as unsuitable for participation by investigator;

18. History of severe drug or alcohol abuse with clinical symptoms; history of poor drug compliance; or other situations that may interfere protocol compliance (e.g., mental disease, frequent travel, lack of willingness);

19. Laboratory tests results meet one of the following indexes: HGB<8.5g/dL, WBC<3.5*10^9/L, PLT<80*10^9/L, ALT/AST>2*upper limit of normal value, CREA>upper limit of normal value;

20. Allergic reaction against human immunoglobulin, infliximab or other ingredient;

21. Participation in another drug clinical trial in the last 30 days before screening or within 5 half-lives of drug (longer time shall prevail).