Rheumatoid Arthritis
Conditions
Brief 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.
Detailed description
This is a non-inferiority trial. The primary outcome is the percentage of subjects achieving ACR20. According to the global instruction of Remicade, the effective rate of Remicade is 50%, and the placebo is 20%. Calculate the critical value δ=（50%-20%）×50%=15%, one-side α=0.025, β=0.20, experimental group : control group = 1:1, the results are: CMAB008 group 175 participants, control group 175 participants, 350 participants in total. Take 10% drop-out into consideration, the finial sample sizes are: CMAB008 group 196 participants, control group 196 participants, 392 participants in total. During the entire duration of the study, all adverse events (AE) and all serious adverse events (SAEs) are collected, fully investigated and documented in source documents and case report forms (CRF). Study duration encompassed the time from when the participant sign the informed consent until the last protocol-specific procedure has been completed, including a safety follow up period. This study will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the guidelines of Good Clinical Practice (GCP) as well as all national legal and regulatory requirements.
Interventions
Sponsors
Shanghai Biomabs Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The percentage of subjects achieving ACR20 | Baseline up to 30 weeks | Defined as the percentage of subjects achieving ACR20 of all subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The percentage of subjects achieving ACR50,70 | Baseline up to 2,6,14,22,30 weeks | Defined as the percentage of subjects achieving ACR50,70 of all subjects |
| Improvement rate of the duration of morning stiffness | Baseline up to 2,6,14,22,30 weeks | Improvement rate=(before the treatment - after the treatment)/before the treatment \*100% |
| Improvement rate of the number of joint swelling or tenderness | Baseline up to 2,6,14,22,30 weeks | Improvement rate=(before the treatment - after the treatment)/before the treatment \*100% |
| The percentage of subjects achieving ACR20 | Baseline up to 2,6,14,22 weeks | Defined as the percentage of subjects achieving ACR20 of all subjects |
| Improvement rate of Health Assessment Questionnaire (HAQ) score | Baseline up to 2,6,14,22,30 weeks | Improvement rate=(before the treatment - after the treatment)/before the treatment \*100%. The Health Assessment Questionnaire (HAQ) Disability Index assesses a patient's level of functional ability. There are 20 questions in eight categories of functioning which represent a comprehensive set of functional activities - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The patient's responses are made on a scale from zero (no disability) to three (completely disabled). |
| Improvement rate of physicochemical indexes of curative effect (ESR, CRP) | Baseline up to 2,6,14,22,30 weeks | Improvement rate=(before the treatment - after the treatment)/before the treatment \*100% |
| Improvement rate of Visual Analogue Scale (VAS) | Baseline up to 2,6,14,22,30 weeks | Improvement rate=(before the treatment - after the treatment)/before the treatment \*100%. Visual Analogue Scale(VAS) is designed to present to the respondent a rating scale. Respondents mark the location on the 10-centimeter line corresponding to the amount of pain they experienced. VAS data of this type is recorded as the number of centimeters from the left of the line with the range 0-10. No pain \<-- 10 cm. --\> Pain as bad as possible |
Countries
China
Outcome results
None listed