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)

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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Methotrexate; Biological: Acellbia; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 159
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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.	Drug: Methotrexate; Biological: Acellbia; Acellbia is rituximab biosimilar, monoclonal antibody which binds CD20.; Other Names: rituximab
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.	Drug: Methotrexate; Biological: Acellbia; Acellbia is rituximab biosimilar, monoclonal antibody which binds CD20.; Other Names: rituximab; Drug: Placebo; Placebo solution will look identical to the Acellbia solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 24
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.	Week 16
Change in average DAS28-4 (ESR) score after 24 weeks of therapy	Change in average DAS28-4 (ESR) score after 24 weeks of therapy	Week 24
Change in average HAQ-DI score after 24 weeks of therapy		Week 24
Change in average score according to modified Sharp method of assessment after 24 weeks of therapy		Week 24
Change in average score of erosions according to modified Sharp method of assessment after 24 weeks of therapy		Week 24
Change in average score of joint spase narrowing according to modified Sharp method of assessment after 24 weeks of therapy		Week 24
Percentage of patients with progression of disease according to modified Steinbrocker method of assessment after 24 weeks of treatment		Week 24
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.	Week 52
Change in average DAS28-4 (ESR) score after 52 weeks of therapy	Change in average DAS28-4 (ESR) score after 52 weeks of therapy	Week 52
Change in average HAQ-DI score after 52 weeks of therapy		Week 52
Change in average score according to modified Sharp method of assessment after 52 weeks of therapy		Week 52
Change in average score of erosions according to modified Sharp method of assessment after 52 weeks of therapy		Week 52
Change in average score of joint space narrowing according to modified Sharp method of assessment after 52 weeks of therapy		Week 52
Percentage of patients with progression of disease according to modified Steinbrocker method of assessment after 52 weeks of treatment		Week 52
Frequency and severity of AE/SAE	Frequency and severity of AE/SAE in patients who received at least one injection of study drug/placebo	52 weeks
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	52 weeks
Frequency of premature withdrawal due to AE/SAE		52 weeks
Percentage of patients who have developed binding and neutralizing antibodies to rituximab on week 24 and week 52		Week 24, Week 52

Collaborators and Investigators

• Sponsor: Biocad

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: April 4, 2016
• First Submitted That Met QC Criteria: April 15, 2016
• First Posted (Estimate): April 20, 2016

Study Record Updates

• Last Update Posted (Actual): January 25, 2018
• Last Update Submitted That Met QC Criteria: January 24, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: rheumatoid arthritis; monoclonal antibody; rituximab; methotrexate; rheumatism; biologic therapy; Acellbia
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: BCD-020-4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED