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

NCT03478111 | Completed Phase 3

• 1 other identifier: C008RAIII
• Study Type: interventional
• Target: 390
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• The percentage of subjects achieving ACR20

  Defined as the percentage of subjects achieving ACR20 of all subjects

  Baseline up to 30 weeks

Secondary Outcomes (7)

• The percentage of subjects achieving ACR20

  Baseline up to 2,6,14,22 weeks

• The percentage of subjects achieving ACR50,70

  Baseline up to 2,6,14,22,30 weeks

• Improvement rate of the duration of morning stiffness

  Baseline up to 2,6,14,22,30 weeks

• Improvement rate of the number of joint swelling or tenderness

  Baseline up to 2,6,14,22,30 weeks

• Improvement rate of Visual Analogue Scale (VAS)

  Baseline up to 2,6,14,22,30 weeks

Study Arms (2)

CMAB008+MTX

EXPERIMENTAL

Drug: CMAB008 (recombinant chimeric anti-TNF-α monoclonal antibody injection) infusion of 3mg/kg in Week 0, 2, 6, 14, 22, 30. Drug: MIX (methotrexate) will be oral administered at a dose of 7.5mg\~15mg weekly from Week 0 to 38.

Drug: CMAB008; Drug: MTX

Remicade+MTX

ACTIVE COMPARATOR

Drug: Remicade (recombinant chimeric anti-TNF-α monoclonal antibody injection) infusion of 3mg/kg in Week 0, 2, 6, 14, 22, 30. Drug: MIX (methotrexate) will be oral administered at a dose of 7.5mg\~15mg weekly from Week 0 to 38.

Drug: MTX; Drug: Remicade

Interventions

CMAB008 DRUG

the study drug

Also known as: infliximab

CMAB008+MTX

MTX DRUG

basic therapy drug

Also known as: methotrexate

CMAB008+MTX; Remicade+MTX

Remicade DRUG

active comparator

Also known as: infliximab

Remicade+MTX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age≥18 years, males or females;
• 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;
• 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);
• 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;
• 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;
• 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;
• 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;
• Non-use of Chinese medicine (e.g., Tripterygium, Total Glucosides of Paeony Capsules) for rheumatoid arthritis in the last 4 weeks before screening;
• 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;
• Signed the informed consent form;
• Can participate in visits on schedule;
• Can understand and complete assessment forms correctly.

You may not qualify if:

• Weight\>75Kg;
• Inoculated live (attenuated) viral/bacterial vaccine in the last 4 weeks before screening;
• Use of biologicals (including but nor limited to Infliximab, Etanercept, Adalimumab, Tocilizumab, Rituximab etc.) for rheumatoid arthritis in the last 3 months before screening;
• 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,;
• 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;
• History of prosthetic joint infections, or suspicious prosthetic joint infections with antibiotic therapy and unremoved prosthetic joint;
• 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;
• AIDS-infected patient or HIVpositive;
• One of the following situations relating to tuberculosis:
• 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;
• 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;
• 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;
• 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;
• History of organ allograft operation (except for keratoplasty more than 3 months before the first use of investigational drug);
• 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;

Sponsors & Collaborators

• Shanghai Biomabs Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

Location

Related Publications (2)

• Ye H, Liu S, Xu J, Chai K, He D, Fang Y, Xie Q, Liu H, Liu Y, Hua B, Hu J, Zhang Z, Zhou M, Zhao D, Li Y, Jiang Z, Wang M, Li J, Zhang Z, Li X, Li Y, Sun E, Bi L, Wei W, Tie N, He L, Huang X, Zhang Y, Huang Q, Wang X, Liu X, Li J, Su Y. Efficacy and Safety of CMAB008 Compared with Innovator Infliximab in Patients with Moderate-to-Severe Rheumatoid Arthritis Receiving Concomitant Methotrexate: A Randomized, Double-blind, Multi-center, Phase III Non-inferiority Study. Rheumatol Ther. 2023 Jun;10(3):757-773. doi: 10.1007/s40744-023-00544-2. Epub 2023 Mar 25.

  PMID: 36964872 DERIVED

• Su Y, Li J, Wang C, Zhang X, Hou S, Guo H, Deng C, Ou L, Wang J. Population Pharmacokinetics of CMAB008 (an Infliximab Biosimilar) and Remicade(R) in Healthy Subjects and Patients with Moderately to Severely Active Rheumatoid Arthritis. Adv Ther. 2023 Mar;40(3):1005-1018. doi: 10.1007/s12325-022-02396-8. Epub 2023 Jan 6.

  PMID: 36607544 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Infliximab; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Yin Su, Ph.D

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2018
• First Posted: March 27, 2018
• Study Start: March 30, 2018
• Primary Completion: June 23, 2019
• Study Completion: August 27, 2019
• Last Updated: March 18, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)