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

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

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.

Study Overview

• Status: Completed
• Conditions: Ankylosing Spondylitis
• Intervention / Treatment: Drug: Infliximab (BCD-055); Drug: Infliximab (Remicade)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belarus
  • Vitebsk, Belarus
    • Vitebsk Regional Clinical Hospital
• Russian Federation
  • Chelyabinsk, Russian Federation
    • Chelyabinsk Regional Clinical Hospital
  • Moscow, Russian Federation
    • Research Institute of Rheumotology
  • N.Novgorod, Russian Federation
    • Nizhegorodskaya Regional Clinical Hospital named after N.A. Semashko
  • Smolensk, Russian Federation
    • Local hospital at the station Smolensk OAO RZD
  • St.Petersburg, Russian Federation
    • North-Western State Medical University n.a. I.I.Mechnikov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BCD-055 group; 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); infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha; Other Names: Remicade; BCD-055
Active Comparator: Remicade group; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
Maximum Concentration at Steady State	28 weeks
Area Under the Plasma Concentration-time Curve at Steady State Phase	28 weeks

Collaborators and Investigators

• Sponsor: Biocad
• Investigators: Study Chair: Ivanov Roman, PhD, JCS BIOCAD

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: January 30, 2015
• First Submitted That Met QC Criteria: February 5, 2015
• First Posted (Estimate): February 10, 2015

Study Record Updates

• Last Update Posted (Estimate): June 8, 2016
• Last Update Submitted That Met QC Criteria: May 3, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: BCD-055-1/ASART-1