Ankylosing Spondylitis
Conditions
Brief summary
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
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.
Interventions
DRUGInfliximab (BCD-055)
infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha
Sponsors
Biocad
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration of Infliximab After the Single Infusion of BCD-055/Remicade | 2 weeks | 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. |
| 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 | — |
| 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 | — |
| 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 | — |
Other
| Measure | Time frame |
|---|---|
| Maximum Concentration at Steady State | 28 weeks |
| Area Under the Plasma Concentration-time Curve at Steady State Phase | 28 weeks |
Countries
Belarus, Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
Infliximab (BCD-055): infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha | 45 |
| 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
Infliximab (Remicade) | 45 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
Baseline characteristics
| Characteristic | BCD-055 Group | Remicade Group | Total |
|---|---|---|---|
| Age, Continuous | 38 years | 38 years | 38 years |
| Sex: Female, Male Female | 12 Participants | 14 Participants | 26 Participants |
| Sex: Female, Male Male | 33 Participants | 31 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 45 | 4 / 45 |
| serious Total, serious adverse events | 0 / 45 | 1 / 45 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Zero (0) Hours to 336 Hours After the Single Infusion of BCD-055/Remicade
Time frame: 2 weeks
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BCD-055 Group | Area Under the Plasma Concentration-time Curve From Zero (0) Hours to 336 Hours After the Single Infusion of BCD-055/Remicade | 26282582 (ng/ml)*hour |
| Remicade Group | Area Under the Plasma Concentration-time Curve From Zero (0) Hours to 336 Hours After the Single Infusion of BCD-055/Remicade | 25914888 (ng/ml)*hour |
Secondary
Average Concentration of Infliximab at Steady State Phase
Time frame: 28 weeks
Secondary
Frequency of AE/SAE After the Single Infusion of BCD-055/Remicade
Time frame: 2 weeks
Secondary
Frequency of Early Withdrawal Due to AE/SAE
Time frame: 30 weeks
Secondary
Half Life of Infliximab After the 1st and 5th Infusion of BCD-055/Remicade
Time frame: 2 weeks / 28 weeks
Secondary
Maximum Concentration of Infliximab After the 1st, 2nd, 3rd, 4th and 5th Infusion of BCD-055/Remicade
Time frame: 28 weeks
Secondary
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.
Time frame: 2 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BCD-055 Group | Maximum Concentration of Infliximab After the Single Infusion of BCD-055/Remicade | 174638 ng/ml |
| Remicade Group | Maximum Concentration of Infliximab After the Single Infusion of BCD-055/Remicade | 195434 ng/ml |
Secondary
Mean Change of BASDAI Score Compared With Baseline
Time frame: 14 weeks / 30 weeks
Secondary
Mean Change of BASFI Score Compared With Baseline
Time frame: 14 weeks / 30 weeks
Secondary
Mean Change of BASMI Score Compared With Baseline
Time frame: 14 weeks / 30 weeks
Secondary
Mean Change of Chest Expansion Compared With Baseline
Time frame: 14 weeks / 30 weeks
Secondary
Mean Change of MASES Score Compared With Baseline
Time frame: 14 weeks / 30 weeks
Secondary
Mean Change of SF36 Score Compared With Baseline
Time frame: 14 weeks / 30 weeks
Secondary
Minimum Concentration of Infliximab After the 1st, 2nd, 3rd, 4th and 5th Infusion of BCD-055/Remicade
Time frame: 28 weeks
Secondary
Percentage of Patients in Each Group Achieving ASAS20
Time frame: 14 weeks / 30 weeks
Secondary
Percentage of Patients in Each Group Achieving ASAS40
Time frame: 14 weeks / 30 weeks
Secondary
Percentage of Patients in Whom Bind or Neutralizing Antibodies to Infliximab Were Detected
Time frame: screening / 14 weeks / 30 weeks
Secondary
Time of Maximum Concentration of Infliximab After the1st, 2nd, 3rd, 4th and 5th Infusion of BCD-055/Remicade
Time frame: 28 weeks
Secondary
Time of Maximum Concentration of Infliximab After the Single Infusion of BCD-055/Remicade
Time frame: 2 weeks
Secondary
Total Frequency of AE/SAE Within the Whole Time of the Study
Time frame: 30 weeks
Secondary
Total Frequency of Grade 3-4 Laboratory Abnormalities Within the Whole Time of the Study
Time frame: 30 weeks
Other Pre-specified
Area Under the Plasma Concentration-time Curve at Steady State Phase
Time frame: 28 weeks
Other Pre-specified
Maximum Concentration at Steady State
Time frame: 28 weeks