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Rheumatoid ArthritisPhase 3NCT03478111

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

A Phase 3 study testing CMAB008, MTX and Remicade in people with Rheumatoid Arthritis, run by Shanghai Biomabs Pharmaceutical Co., Ltd. at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
CMAB008, MTX and Remicade
Could I receive a placebo?
No, everyone receives an active treatment
How many people
390 participants
Where
1 siteChina
Study dates
30 Mar 2018to 27 Aug 2019
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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.

Who cannot join

  • 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;
  • 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;
  • 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;
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  • 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;
  • 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);
  • Concurrent or previous demyelinating diseases of the central nervous system (e.g., multiple sclerosis);
  • Concurrent or previous congestive heart failure;
  • Concurrent or previous other autoimmune disease, and may be expected to affect the assessment of investigational drug;
  • 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;
  • 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);
  • 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;
  • Allergic reaction against human immunoglobulin, infliximab or other ingredient;
  • Participation in another drug clinical trial in the last 30 days before screening or within 5 half-lives of drug (longer time shall prevail).

Trial locations and contacts

1 site in 1 country.

China1 site

  • Peking University People's Hospital

    Beijing, Beijing Municipality, 100044

Other trials in China

About this study

Official 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

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.

Read the 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.

Being tested
CMAB008, MTX, Remicade
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CMAB008Drug

    Also called infliximab

    the study drug

  • MTXDrug

    Also called methotrexate

    basic therapy drug

  • RemicadeDrug

    Also called infliximab

    active comparator

Study groups in NCT03478111
Study groupRoleWhat they receive
CMAB008+MTXExperimentalDrug: 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.
Receives: Drug: CMAB008; Drug: MTX
Remicade+MTXActive comparatorDrug: 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.
Receives: Drug: MTX; Drug: Remicade

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The percentage of subjects achieving ACR20

    Defined as the percentage of subjects achieving ACR20 of all subjects

    Measured: Baseline up to 30 weeks

Secondary outcomes (7)

  1. The percentage of subjects achieving ACR20

    Defined as the percentage of subjects achieving ACR20 of all subjects

    Measured: Baseline up to 2,6,14,22 weeks

  2. The percentage of subjects achieving ACR50,70

    Defined as the percentage of subjects achieving ACR50,70 of all subjects

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

  3. Improvement rate of the duration of morning stiffness

    Improvement rate=(before the treatment - after the treatment)/before the treatment *100%

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

  4. Improvement rate of the number of joint swelling or tenderness

    Improvement rate=(before the treatment - after the treatment)/before the treatment *100%

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

  5. Improvement rate of Visual Analogue Scale (VAS)

    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

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

  6. Improvement rate of Health Assessment Questionnaire (HAQ) score

    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).

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

  7. Improvement rate of physicochemical indexes of curative effect (ESR, CRP)

    Improvement rate=(before the treatment - after the treatment)/before the treatment *100%

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Mar 2018
  2. Study start30 Mar 2018
  3. Primary completion23 Jun 2019
  4. Study completion27 Aug 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
390 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03478111
Sponsor's protocol ID
C008RAIII
Status last verified
Mar 2020
First submitted
16 Mar 2018
Last updated
18 Mar 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 36964872

  • 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.

    PubMed 36607544

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing CMAB008, MTX and Remicade in people with Rheumatoid Arthritis, run by Shanghai Biomabs Pharmaceutical Co., Ltd. at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The percentage of subjects achieving ACR20 (time frame: Baseline up to 30 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03478111, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2020.

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