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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03478111
• Date of registration: 16/03/2018
• Prospective Registration: Yes
• Primary sponsor: Shanghai Biomabs Pharmaceutical Co., Ltd.
• Public title: CMAB008 With MTX Therapy in Adult Patients With Moderately to Severely Active Rheumatoid Arthritis
• Scientific title: A Randomized, Double-blind, Methotrexate (MTX) Based, Parallel-group, Multicenter Phase III Study to Evaluate Efficacy and Safety of CMAB008 in Adult Patients With Moderately to Severely Active Rheumatoid Arthritis, Compared to Remicade
• Date of first enrolment: March 30, 2018
• Target sample size: 390
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03478111
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

China

Contacts

• Name: Yin Su, Ph.D
• Affiliation: Peking University People's Hospital

Key inclusion & exclusion 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).



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: MTX

Drug: Remicade

Drug: CMAB008

Primary Outcome(s)

The percentage of subjects achieving ACR20 [Time Frame: Baseline up to 30 weeks]

Secondary Outcome(s)

Improvement rate of physicochemical indexes of curative effect (ESR, CRP) [Time Frame: Baseline up to 2,6,14,22,30 weeks]

The percentage of subjects achieving ACR50,70 [Time Frame: Baseline up to 2,6,14,22,30 weeks]

Improvement rate of Health Assessment Questionnaire (HAQ) score [Time Frame: Baseline up to 2,6,14,22,30 weeks]

Improvement rate of the number of joint swelling or tenderness [Time Frame: Baseline up to 2,6,14,22,30 weeks]

Improvement rate of Visual Analogue Scale (VAS) [Time Frame: Baseline up to 2,6,14,22,30 weeks]

The percentage of subjects achieving ACR20 [Time Frame: Baseline up to 2,6,14,22 weeks]

Improvement rate of the duration of morning stiffness [Time Frame: Baseline up to 2,6,14,22,30 weeks]

Secondary ID(s)

C008RAIII

Source(s) of Monetary Support

Please refer to primary and secondary sponsors