Back to resultsClinical Trial to Evaluate Efficacy and Safety of Acellbia® (JSC "BIOCAD") With Methotrexate in First Line Biological Therapy of Patients With Active Rheumatoid Arthritis (ALTERRA)
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Acellbia
Placebo
Methotrexate
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring rheumatoid arthritis, rheumatism, Acellbia, methotrexate, biologic therapy, monoclonal antibody, rituximab
Eligibility 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Acellbia + methotrexate
Placebo + methotrexate
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Percentage of patients who developed ACR20 response on 24 week of therapy
The proportion of patients achieving at least a 20% improvement in ACR criteria at 24 weeks of therapy.
Secondary Outcome Measures
Percentage of patients who developed ACR50 and ACR70 response on 24 week of therapy
The proportion of patients achieving at least 50% and 70% improvement in ACR criteria at 24 weeks of therapy.
Percentage of patients who developed ACR20, ACR50 and ACR70 response on 16 week of therapy
The proportion of patients achieving at least 20%, 50% and 70% improvement in ACR criteria after 16 weeks of therapy.
Change in average DAS28-4 (ESR) score after 24 weeks of therapy
Change in average DAS28-4 (ESR) score after 24 weeks of therapy
Change in average HAQ-DI score after 24 weeks of therapy
Change in average score according to modified Sharp method of assessment after 24 weeks of therapy
Change in average score of erosions according to modified Sharp method of assessment after 24 weeks of therapy
Change in average score of joint spase narrowing according to modified Sharp method of assessment after 24 weeks of therapy
Percentage of patients with progression of disease according to modified Steinbrocker method of assessment after 24 weeks of treatment
Percentage of patients who developed ACR20, ACR50 and ACR70 response on 52 week of therapy
The proportion of patients achieving at least 20%, 50% and 70% improvement in ACR criteria after 52 weeks of therapy.
Change in average DAS28-4 (ESR) score after 52 weeks of therapy
Change in average DAS28-4 (ESR) score after 52 weeks of therapy
Change in average HAQ-DI score after 52 weeks of therapy
Change in average score according to modified Sharp method of assessment after 52 weeks of therapy
Change in average score of erosions according to modified Sharp method of assessment after 52 weeks of therapy
Change in average score of joint space narrowing according to modified Sharp method of assessment after 52 weeks of therapy
Percentage of patients with progression of disease according to modified Steinbrocker method of assessment after 52 weeks of treatment
Frequency and severity of AE/SAE
Frequency and severity of AE/SAE in patients who received at least one injection of study drug/placebo
Frequency of AE 3-4 grade CTCAE 4.03
Frequency of AE 3-4 grade CTCAE 4.03 in patients who received at least one injection of study drug/placebo
Frequency of premature withdrawal due to AE/SAE
Percentage of patients who have developed binding and neutralizing antibodies to rituximab on week 24 and week 52
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02744196
Brief Title
Clinical Trial to Evaluate Efficacy and Safety of Acellbia® (JSC "BIOCAD") With Methotrexate in First Line Biological Therapy of Patients With Active Rheumatoid Arthritis
Acronym
ALTERRA
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
January 2015 (Actual)
Primary Completion Date
February 2017 (Actual)
Study Completion Date
August 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biocad
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
rheumatoid arthritis, rheumatism, Acellbia, methotrexate, biologic therapy, monoclonal antibody, rituximab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
159 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Acellbia + methotrexate
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo + methotrexate
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Acellbia
Other Intervention Name(s)
rituximab
Intervention Description
Acellbia is rituximab biosimilar, monoclonal antibody which binds CD20.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo solution will look identical to the Acellbia solution.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Primary Outcome Measure Information:
Title
Percentage of patients who developed ACR20 response on 24 week of therapy
Description
The proportion of patients achieving at least a 20% improvement in ACR criteria at 24 weeks of therapy.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Percentage of patients who developed ACR50 and ACR70 response on 24 week of therapy
Description
The proportion of patients achieving at least 50% and 70% improvement in ACR criteria at 24 weeks of therapy.
Time Frame
Week 24
Title
Percentage of patients who developed ACR20, ACR50 and ACR70 response on 16 week of therapy
Description
The proportion of patients achieving at least 20%, 50% and 70% improvement in ACR criteria after 16 weeks of therapy.
Time Frame
Week 16
Title
Change in average DAS28-4 (ESR) score after 24 weeks of therapy
Description
Change in average DAS28-4 (ESR) score after 24 weeks of therapy
Time Frame
Week 24
Title
Change in average HAQ-DI score after 24 weeks of therapy
Time Frame
Week 24
Title
Change in average score according to modified Sharp method of assessment after 24 weeks of therapy
Time Frame
Week 24
Title
Change in average score of erosions according to modified Sharp method of assessment after 24 weeks of therapy
Time Frame
Week 24
Title
Change in average score of joint spase narrowing according to modified Sharp method of assessment after 24 weeks of therapy
Time Frame
Week 24
Title
Percentage of patients with progression of disease according to modified Steinbrocker method of assessment after 24 weeks of treatment
Time Frame
Week 24
Title
Percentage of patients who developed ACR20, ACR50 and ACR70 response on 52 week of therapy
Description
The proportion of patients achieving at least 20%, 50% and 70% improvement in ACR criteria after 52 weeks of therapy.
Time Frame
Week 52
Title
Change in average DAS28-4 (ESR) score after 52 weeks of therapy
Description
Change in average DAS28-4 (ESR) score after 52 weeks of therapy
Time Frame
Week 52
Title
Change in average HAQ-DI score after 52 weeks of therapy
Time Frame
Week 52
Title
Change in average score according to modified Sharp method of assessment after 52 weeks of therapy
Time Frame
Week 52
Title
Change in average score of erosions according to modified Sharp method of assessment after 52 weeks of therapy
Time Frame
Week 52
Title
Change in average score of joint space narrowing according to modified Sharp method of assessment after 52 weeks of therapy
Time Frame
Week 52
Title
Percentage of patients with progression of disease according to modified Steinbrocker method of assessment after 52 weeks of treatment
Time Frame
Week 52
Title
Frequency and severity of AE/SAE
Description
Frequency and severity of AE/SAE in patients who received at least one injection of study drug/placebo
Time Frame
52 weeks
Title
Frequency of AE 3-4 grade CTCAE 4.03
Description
Frequency of AE 3-4 grade CTCAE 4.03 in patients who received at least one injection of study drug/placebo
Time Frame
52 weeks
Title
Frequency of premature withdrawal due to AE/SAE
Time Frame
52 weeks
Title
Percentage of patients who have developed binding and neutralizing antibodies to rituximab on week 24 and week 52
Time Frame
Week 24, Week 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roman Ivanov, PhD
Organizational Affiliation
JCS BIOCAD
Official's Role
Study Chair
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Clinical Trial to Evaluate Efficacy and Safety of Acellbia® (JSC "BIOCAD") With Methotrexate in First Line Biological Therapy of Patients With Active Rheumatoid Arthritis
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