Comparative Evaluation of Pharmacokinetics and Safety of BCD-055 and Remicade in Patients With Ankylosing Spondylitis

Study Overview
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Brief Summary
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ASART-1 clinical study is a phase 1 study which carried out to establish the pharmacokinetic equivalence and equal safety profile of BCD-055 (infliximab manufactured by JSC BIOCAD, Russia) and Remicade when used as multiple IV infusions for the treatment of ankylosing spondylitis.

Detailed Description
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ASART-1 study is the first step of clinical evaluation of infliximab biosimilar manufactured by JSC BIOCAD, Russia.The aim of this study is to establish that BCD-055 is equivalent to Remicade in terms of pharmacokinetics and safety when used by the standard regimen in patients with ankylosing spondylitis (AS). The study will enroll 90 patients with active AS, who will be randomized into 2 groups (1:1 ratio): patients from the first group will receive BCD-055 IV at a dose 5 mg/kg on week 0, 2, 6, 14 and 22; patients from the second group will receive Remicade at the same regimen.

Official Title
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International Multicenter Comparative Double Blind Study of Pharmacokinetics and Safety of BCD-055 and Remicade in Patients With Ankylosing Spondylitis

Conditions
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Ankylosing Spondylitis

Intervention / Treatment
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* Drug: Infliximab (BCD-055)
* Drug: Infliximab (Remicade)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signed informed consent active ankylosing spondylitis, which exists in patient within last 3 months BASDAI score > or equal to 4 points, spinal pain (by VAS) > or equal to 4 points history of NSAID use for the treatment of AS within last 3 months adequate renal and liver function absence of severe abnormalities in complete blood count consent to use adequate contraception ability to follow Protocol procedures Exclusion Criteria: previously use of any biologic for AS treatment total ankylosing of the spine known allergy to chimeric proteins or any excipients of BCD-055/Remicade hepatitis B, active hepatitis C, HIV, syphilis known tuberculosis latent forms of tuberculosis any bacterial infection diagnosed within last month which required oral antibiotics (within last 2 weeks) or parenteral antibiotics (within last 4 weeks) drug or alcohol abuse any other disease which can affect assessments or masking some symptoms of AS (severe osteoarthrosis, nervous disorders with impairment of sensory or motor functions, another inflammatory joint disease apart from AS, etc.) severe uncontrolled hypertension chronic heart failure decompensated renal or liver disorders severe uncontrolled diabetes mellitus chronic obstructive lung disease, atopic bronchial asthma, angioedema in anamnesis any mental disorder, incl. severe depression or/and suicide thoughts/actions in anamnesis unstable angina pectoris myocardial infarction within last 12 months Other exclusion criteria could be found in the Full Study Protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCD-055 group<br>BCD-055 (infliximab) at a dose of 5 mg/kg, administered as a slow intravenous infusion, which will be performed on week 0, 2, 6, 14 and 22 | Drug: Infliximab (BCD-055)<br>* infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha<br>* Other names: BCD-055;|
| Active Comparator: Remicade group<br>Remicade (infliximab) at a dose of 5 mg/kg, administered as a slow intravenous infusion, which will be performed on week 0, 2, 6, 14 and 22 | Drug: Infliximab (Remicade)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-time Curve From Zero (0) Hours to 336 Hours After the Single Infusion of BCD-055/Remicade |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Concentration of Infliximab After the Single Infusion of BCD-055/Remicade | Patients who received at least 1 injection. From BCD-055 group 1 patient was excluded because of violation of timing of blood collection. From Remicade group 2 patients were excluded due to AE/SAE. | 2 weeks | 
| Time of Maximum Concentration of Infliximab After the Single Infusion of BCD-055/Remicade |  | 2 weeks | 
| Maximum Concentration of Infliximab After the 1st, 2nd, 3rd, 4th and 5th Infusion of BCD-055/Remicade |  | 28 weeks | 
| Minimum Concentration of Infliximab After the 1st, 2nd, 3rd, 4th and 5th Infusion of BCD-055/Remicade |  | 28 weeks | 
| Time of Maximum Concentration of Infliximab After the1st, 2nd, 3rd, 4th and 5th Infusion of BCD-055/Remicade |  | 28 weeks | 
| Half Life of Infliximab After the 1st and 5th Infusion of BCD-055/Remicade |  | 2 weeks / 28 weeks | 
| Average Concentration of Infliximab at Steady State Phase |  | 28 weeks | 
| Percentage of Patients in Each Group Achieving ASAS20 |  | 14 weeks / 30 weeks | 
| Percentage of Patients in Each Group Achieving ASAS40 |  | 14 weeks / 30 weeks | 
| Mean Change of BASDAI Score Compared With Baseline |  | 14 weeks / 30 weeks | 
| Mean Change of BASMI Score Compared With Baseline |  | 14 weeks / 30 weeks | 
| Mean Change of BASFI Score Compared With Baseline |  | 14 weeks / 30 weeks | 
| Mean Change of MASES Score Compared With Baseline |  | 14 weeks / 30 weeks | 
| Mean Change of SF36 Score Compared With Baseline |  | 14 weeks / 30 weeks | 
| Mean Change of Chest Expansion Compared With Baseline |  | 14 weeks / 30 weeks | 
| Frequency of AE/SAE After the Single Infusion of BCD-055/Remicade |  | 2 weeks | 
| Total Frequency of AE/SAE Within the Whole Time of the Study |  | 30 weeks | 
| Total Frequency of Grade 3-4 Laboratory Abnormalities Within the Whole Time of the Study |  | 30 weeks | 
| Percentage of Patients in Whom Bind or Neutralizing Antibodies to Infliximab Were Detected |  | screening / 14 weeks / 30 weeks | 
| Frequency of Early Withdrawal Due to AE/SAE |  | 30 weeks |