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Clinical Trial to Evaluate Efficacy and Safety of Acellbia® (JSC "BIOCAD") With Methotrexate in First Line Biological Therapy of Patients With Active Rheumatoid Arthritis (ALTERRA)

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ClinicalTrials.gov Identifier: NCT02744196
Recruitment Status : Completed
First Posted : April 20, 2016
Last Update Posted : January 25, 2018
Sponsor:
Information provided by (Responsible Party):
Biocad

Brief Summary:
The mail goal of this study is to establish superiority in efficacy of Acellbia® applied in a dose of 600 mg (Day 1 and Day 15) in combination with methotrexate in patients with active RA seropositive previously untreated with biological therapy, compared to standard therapy with methotrexate.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Biological: Acellbia Drug: Placebo Drug: Methotrexate Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 159 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Multicenter Comparative Randomised Double-blind Placebo-controlled Clinical Trial to Evaluate Efficacy and Safety of Acellbia® (JSC "BIOCAD") With Methotrexate in First Line of Biological Therapy of Patients With Active Rheumatoid Arthritis
Actual Study Start Date : January 2015
Actual Primary Completion Date : February 2017
Actual Study Completion Date : August 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Acellbia + methotrexate

106 patients of this group will receive methotrexate in combination with a drug Acellbia to be used at a dose of 600 mg as a slow intravenous infusion carried out on day 1 and day 15.

If a follow-up examination at 24 weeks or later (up to 48 weeks) reveals that the patient still has active arthritis (evaluation index DAS28-4 (ESR)> 2,6 points), the therapy with Acellbia is repeated by the same scheme - 2 infusion at a dose of 600 mg at intervals of 14 days.

Biological: Acellbia
Acellbia is rituximab biosimilar, monoclonal antibody which binds CD20.
Other Name: rituximab

Drug: Methotrexate
Placebo Comparator: Placebo + methotrexate

53 patients of this group will receive methotrexate in combination with a placebo to be used as a slow intravenous infusion carried out on day 1 and day 15.

If a follow-up examination at 24 weeks or later (up to 48 weeks) reveals that the patient still has active arthritis (evaluation index DAS28-4 (ESR)> 2,6 points), the patient receives open therapy with Acellbia is initiated: 2 infusion at a dose of 600 mg at intervals of 14 days.

Biological: Acellbia
Acellbia is rituximab biosimilar, monoclonal antibody which binds CD20.
Other Name: rituximab

Drug: Placebo
Placebo solution will look identical to the Acellbia solution.

Drug: Methotrexate



Primary Outcome Measures :
  1. Percentage of patients who developed ACR20 response on 24 week of therapy [ Time Frame: Week 24 ]
    The proportion of patients achieving at least a 20% improvement in ACR criteria at 24 weeks of therapy.


Secondary Outcome Measures :
  1. Percentage of patients who developed ACR50 and ACR70 response on 24 week of therapy [ Time Frame: Week 24 ]
    The proportion of patients achieving at least 50% and 70% improvement in ACR criteria at 24 weeks of therapy.

  2. Percentage of patients who developed ACR20, ACR50 and ACR70 response on 16 week of therapy [ Time Frame: Week 16 ]
    The proportion of patients achieving at least 20%, 50% and 70% improvement in ACR criteria after 16 weeks of therapy.

  3. Change in average DAS28-4 (ESR) score after 24 weeks of therapy [ Time Frame: Week 24 ]
    Change in average DAS28-4 (ESR) score after 24 weeks of therapy

  4. Change in average HAQ-DI score after 24 weeks of therapy [ Time Frame: Week 24 ]
  5. Change in average score according to modified Sharp method of assessment after 24 weeks of therapy [ Time Frame: Week 24 ]
  6. Change in average score of erosions according to modified Sharp method of assessment after 24 weeks of therapy [ Time Frame: Week 24 ]
  7. Change in average score of joint spase narrowing according to modified Sharp method of assessment after 24 weeks of therapy [ Time Frame: Week 24 ]
  8. Percentage of patients with progression of disease according to modified Steinbrocker method of assessment after 24 weeks of treatment [ Time Frame: Week 24 ]
  9. Percentage of patients who developed ACR20, ACR50 and ACR70 response on 52 week of therapy [ Time Frame: Week 52 ]
    The proportion of patients achieving at least 20%, 50% and 70% improvement in ACR criteria after 52 weeks of therapy.

  10. Change in average DAS28-4 (ESR) score after 52 weeks of therapy [ Time Frame: Week 52 ]
    Change in average DAS28-4 (ESR) score after 52 weeks of therapy

  11. Change in average HAQ-DI score after 52 weeks of therapy [ Time Frame: Week 52 ]
  12. Change in average score according to modified Sharp method of assessment after 52 weeks of therapy [ Time Frame: Week 52 ]
  13. Change in average score of erosions according to modified Sharp method of assessment after 52 weeks of therapy [ Time Frame: Week 52 ]
  14. Change in average score of joint space narrowing according to modified Sharp method of assessment after 52 weeks of therapy [ Time Frame: Week 52 ]
  15. Percentage of patients with progression of disease according to modified Steinbrocker method of assessment after 52 weeks of treatment [ Time Frame: Week 52 ]
  16. Frequency and severity of AE/SAE [ Time Frame: 52 weeks ]
    Frequency and severity of AE/SAE in patients who received at least one injection of study drug/placebo

  17. Frequency of AE 3-4 grade CTCAE 4.03 [ Time Frame: 52 weeks ]
    Frequency of AE 3-4 grade CTCAE 4.03 in patients who received at least one injection of study drug/placebo

  18. Frequency of premature withdrawal due to AE/SAE [ Time Frame: 52 weeks ]
  19. Percentage of patients who have developed binding and neutralizing antibodies to rituximab on week 24 and week 52 [ Time Frame: Week 24, Week 52 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Written informed consent. Age from 18 to 80 years. Rheumatoid arthritis diagnosed at least 6 months before informed consent signing Presence of more than 8 swollen and more than 8 painful joints at screening. C-reactive protein 7 mg/l or more AND/OR erythrocyte sedimentation rate 28 mm/hour or more.

Antibodies to citrullinated cyclic peptide 20 U/ml or more AND/OR rheumatoid factor-IgM higher than upper normal limit.

Documented regular methotrexate intake for 12 weeks, stable dose from 10 to 25 mg/week during last 4 weeks before signing informed consent.

Exclusion Criteria:

Methotrexate intolerance. Felty's syndrome. Patient functional status - IV class according to ACR. Previous use of biologic drugs to treat rheumatoid arthritis, biologic drugs that deplete CD20-lymphocytes, azathioprine use in the last 28 days prior to informed consent signing, leflunomide use in the last 8 weeks prior to informed consent signing, sulphasalazine/hydroxyquinoline use in the last 28 days prior to informed consent signing, intraarticular use of corticosteroids in the last 4 weeks prior to informed consent signing, patient requires prednisolone (or analogues) in a dose more than 10 mg/day or dose is unstable during 4 weeks prior to informed consent signing, requirement in non-steroid antiinflammatory drugs if their dose was not stable during last 8 weeks prior to informed consent signing.

Patient has inflammatory joint disease otherwise than rheumatoid arthritis or systemic autoimmune diseases.

Full list of inclusion and exclusion criteria can be found in Study Protocol.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02744196


Sponsors and Collaborators
Biocad
Investigators
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Study Chair: Roman Ivanov, PhD JCS BIOCAD

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Responsible Party: Biocad
ClinicalTrials.gov Identifier: NCT02744196     History of Changes
Other Study ID Numbers: BCD-020-4
First Posted: April 20, 2016    Key Record Dates
Last Update Posted: January 25, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Biocad:
rheumatoid arthritis
rheumatism
Acellbia
methotrexate
biologic therapy
monoclonal antibody
rituximab
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Methotrexate
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Nucleic Acid Synthesis Inhibitors