Back to resultsClinical Trial to Evaluate Efficacy and Safety of Multiple Subcutaneous Injections of Various Doses of BCD-085 in Patients With Active Ankylosing Spondylitis
Primary Purpose
Ankylosing Spondylitis
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
BCD-085
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Ankylosing Spondylitis focused on measuring ankylosing spondylitis, interleukin 17, monoclonal antibody
Eligibility Criteria
Inclusion Criteria:
- Written informed consent
- Age between 18 and 65 years
- Active ankylosing spondylitis according to modified criteria of New York classification (1984), that was diagnosed at least 3 months prior to screening.
- Active disease according to BASDAI (score 4 or more) if nonsteroidal antiinflammatory drugs were used in the last 3 month prior to screening.
- Mean backache intensity equals 4 points or more.
- If patient have had biologic therapy to treat ankylosing spondylitis for at least 3 months, there was no positive results of such treatment or patient revealed intolerance to the drug. This therapy must be discontinued at least 12 weeks before enrollment in the study.
- Female patients have negative urine pregnancy test.
- Patient has no history of tuberculosis.
- Patients have negative results of Diaskintest.
- Patient has no history of alcohol or drug abuse.
Exclusion Criteria:
- Total spinal ankylosis.
- Allergy or intolerance of monoclonal antibodies or any excipients of study drugs.
- Previous receipt of anti-interleukin 17 drugs or anti-interleukin 17 receptor drugs.
- Prior use of two or more biologics to tumor necrosis factor alfa.
- Prior use of two or more biologics to other targets. Previous receipt of monoclonal antibodies if they were cancelled less that in 12 weeks before signing informed consent.
- Patient is taking corticosteroids for up to 4 weeks in a dose more than 10 mg (recalculated to prednisolone) before signing informed consent and during screening, or in a dose less than 10 mg (recalculated to prednisolone) if it was not stable.
- Prior use of disease-modifying antirheumatic drugs including methotrexate, sulfasalazin, chloroquine or hydroxychloroquine for up to 4 weeks before randomization, if their dose was not stable for up to 4 weeks before signing informed consent and during screening.
- Prior use of live or attenuated vaccines for up to 8 weeks before signing informed consent.
- Prior use of alkylating agents for up to 12 months prior to signing informed consent.
- Intraarticular use of corticosteroids for up to 4 weeks before randomization.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
BCD-085, 40 mg
BCD-085, 80 mg
BCD-085, 120 mg
Placebo
Arm Description
Patient will receive 40 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12.
Patient will receive 80 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12.
Patient will receive 120 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12.
Patient will receive placebo subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12.
Outcomes
Primary Outcome Measures
Ratio of patients with ASAS20 response after 16 weeks of therapy
Ratio of patients who developed a decrease in ankylosing spondylitis assessment score (ASAS) by 20% or more after 16 weeks of therapy with BCD-085.
Secondary Outcome Measures
Ratio of patients with ASAS20 response after 4, 8, 12 weeks of therapy
Ratio of patients who developed a decrease in ankylosing spondylitis assessment score (ASAS) by 20% or more after 4, 8, 12 weeks of therapy with BCD-085.
Ratio of patients with ASAS40 response after 4, 8, 12, 16 weeks of therapy
Ratio of patients who developed a decrease in ankylosing spondylitis assessment score (ASAS) by 40% or more after 4, 8, 12, 16 weeks of therapy with BCD-085.
Ratio of patients with ASAS5/6 response after 4, 8, 12, 16 weeks of therapy
Ratio of patients who developed a response in at least 5 of 6 criteria of ankylosing spondylitis assessment score (ASAS) after 4, 8, 12, 16 weeks of therapy with BCD-085.
Mean BASDAI score at screening and after 4, 8, 12, 16 weeks of therapy
Mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score at screening and after 4, 8, 12, 16 weeks of therapy
Mean BASMI score at screening and after 4, 8, 12, 16 weeks of therapy
Mean Bath Ankylosing Spondylitis Metrology Index (BASMI) score at screening and after 4, 8, 12, 16 weeks of therapy
Mean MASES score at screening and after 4, 8, 12, 16 weeks of therapy
Mean Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at screening and after 4, 8, 12, 16 weeks of therapy
Mean chest excursion at screening and after 4, 8, 12, 16 weeks of therapy
Mean chest excursion at screening and after 4, 8, 12, 16 weeks of therapy measured by Cloth Tape Measure Technique
Mean BASFI score at screening and after 4, 8, 12, 16 weeks of therapy
Mean Bath Ankylosing Spondylitis Functional Index (BASFI) score at screening and after 4, 8, 12, 16 weeks of therapy
Mean ASDAS-CRP score at screening and after 4, 8, 12, 16 weeks of therapy
Mean Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP) score at screening and after 4, 8, 12, 16 weeks of therapy
Mean SF-36 score at screening and after 8 and 16 weeks of therapy
Mean Short Form-36 (SF36) score at screening and after 8, 16 weeks of therapy
Mean pain score during a day at screening and after 1, 2, 4, 8, 12, 16 weeks of therapy
Mean pain score during a day at screening and after 1, 2, 4, 8, 12, 16 weeks of therapy measured by Visual Analog Scale for Pain
Proportion of patients with deterioration of roentgenologic signs of sacroileitis after 16 weeks of treatment
Mean C-reactive protein concentration at screening and after 4, 8, 12 and 16 weeks of treatment.
Frequency of AE/SAE
Frequency of local reactions
Frequency of AE/SAE 3-4 grade CTCAE 4.03
Frequency of withdrawals due to AE/SAE
Cmin
Minimal concentration of BCD-085 in blood after drug injection
AUC (0-168h)
Area under curve from 0 to 168 hours of BCD-085 in blood after drug injection
AUC0-∞
Area under curve from 0 to infinity of BCD-085 in blood after drug injection
Cmax
Maximal concentration of BCD-085 in blood after drug injection
Тmax
Time before Cmax of BCD-085 is reached in blood after drug injection
Т½
Half-life of BCD-085 in blood after drug injection
Кel
Elimination rate constant of BCD-085 in blood after drug injection
Cl
Clearance of BCD-085 in blood after drug injection
Proportion of patients who developed binding and neutralizing antibodies to BCD-085
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02763111
Brief Title
Clinical Trial to Evaluate Efficacy and Safety of Multiple Subcutaneous Injections of Various Doses of BCD-085 in Patients With Active Ankylosing Spondylitis
Official Title
International Multi-center Comparative Randomized Double-blind Placebo-controlled Clinical Trial to Evaluate Efficacy and Safety of Multiple Subcutaneous Injections of BCD-085 in Various Doses in Patients With Active Ankylosing Spondylitis
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
September 2016 (undefined)
Primary Completion Date
June 2017 (Actual)
Study Completion Date
June 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biocad
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
BCD-085-3 is a next step in clinical investigation of BCD-085. BCD-085 is a monoclonal antibody to interleukin 17. During the trial patients with active ankylosing spondylitis will receive 40, 80 or 120 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12. Efficacy and safety parameters will be evaluated.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ankylosing Spondylitis
Keywords
ankylosing spondylitis, interleukin 17, monoclonal antibody
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
88 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BCD-085, 40 mg
Arm Type
Experimental
Arm Description
Patient will receive 40 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12.
Arm Title
BCD-085, 80 mg
Arm Type
Experimental
Arm Description
Patient will receive 80 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12.
Arm Title
BCD-085, 120 mg
Arm Type
Experimental
Arm Description
Patient will receive 120 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patient will receive placebo subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12.
Intervention Type
Drug
Intervention Name(s)
BCD-085
Intervention Type
Other
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Ratio of patients with ASAS20 response after 16 weeks of therapy
Description
Ratio of patients who developed a decrease in ankylosing spondylitis assessment score (ASAS) by 20% or more after 16 weeks of therapy with BCD-085.
Time Frame
Week 16
Secondary Outcome Measure Information:
Title
Ratio of patients with ASAS20 response after 4, 8, 12 weeks of therapy
Description
Ratio of patients who developed a decrease in ankylosing spondylitis assessment score (ASAS) by 20% or more after 4, 8, 12 weeks of therapy with BCD-085.
Time Frame
Week 4, Week 8, Week 12
Title
Ratio of patients with ASAS40 response after 4, 8, 12, 16 weeks of therapy
Description
Ratio of patients who developed a decrease in ankylosing spondylitis assessment score (ASAS) by 40% or more after 4, 8, 12, 16 weeks of therapy with BCD-085.
Time Frame
Week 4, Week 8, Week 12, Week 16
Title
Ratio of patients with ASAS5/6 response after 4, 8, 12, 16 weeks of therapy
Description
Ratio of patients who developed a response in at least 5 of 6 criteria of ankylosing spondylitis assessment score (ASAS) after 4, 8, 12, 16 weeks of therapy with BCD-085.
Time Frame
Week 4, Week 8, Week 12, Week 16
Title
Mean BASDAI score at screening and after 4, 8, 12, 16 weeks of therapy
Description
Mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score at screening and after 4, 8, 12, 16 weeks of therapy
Time Frame
Screening, Week 4, Week 8, Week 12, Week 16
Title
Mean BASMI score at screening and after 4, 8, 12, 16 weeks of therapy
Description
Mean Bath Ankylosing Spondylitis Metrology Index (BASMI) score at screening and after 4, 8, 12, 16 weeks of therapy
Time Frame
Screening, Week 4, Week 8, Week 12, Week 16
Title
Mean MASES score at screening and after 4, 8, 12, 16 weeks of therapy
Description
Mean Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at screening and after 4, 8, 12, 16 weeks of therapy
Time Frame
Screening, Week 4, Week 8, Week 12, Week 16
Title
Mean chest excursion at screening and after 4, 8, 12, 16 weeks of therapy
Description
Mean chest excursion at screening and after 4, 8, 12, 16 weeks of therapy measured by Cloth Tape Measure Technique
Time Frame
Screening, Week 4, Week 8, Week 12, Week 16
Title
Mean BASFI score at screening and after 4, 8, 12, 16 weeks of therapy
Description
Mean Bath Ankylosing Spondylitis Functional Index (BASFI) score at screening and after 4, 8, 12, 16 weeks of therapy
Time Frame
Screening, Week 4, Week 8, Week 12, Week 16
Title
Mean ASDAS-CRP score at screening and after 4, 8, 12, 16 weeks of therapy
Description
Mean Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP) score at screening and after 4, 8, 12, 16 weeks of therapy
Time Frame
Screening, Week 4, Week 8, Week 12, Week 16
Title
Mean SF-36 score at screening and after 8 and 16 weeks of therapy
Description
Mean Short Form-36 (SF36) score at screening and after 8, 16 weeks of therapy
Time Frame
Screening, Week 8, Week 16
Title
Mean pain score during a day at screening and after 1, 2, 4, 8, 12, 16 weeks of therapy
Description
Mean pain score during a day at screening and after 1, 2, 4, 8, 12, 16 weeks of therapy measured by Visual Analog Scale for Pain
Time Frame
Screening, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16
Title
Proportion of patients with deterioration of roentgenologic signs of sacroileitis after 16 weeks of treatment
Time Frame
Week 16
Title
Mean C-reactive protein concentration at screening and after 4, 8, 12 and 16 weeks of treatment.
Time Frame
Screening, Week 4, Week 8, Week 12, Week 16
Title
Frequency of AE/SAE
Time Frame
16 weeks
Title
Frequency of local reactions
Time Frame
16 weeks
Title
Frequency of AE/SAE 3-4 grade CTCAE 4.03
Time Frame
16 weeks
Title
Frequency of withdrawals due to AE/SAE
Time Frame
16 weeks
Title
Cmin
Description
Minimal concentration of BCD-085 in blood after drug injection
Time Frame
0 to 168 hours post-dose
Title
AUC (0-168h)
Description
Area under curve from 0 to 168 hours of BCD-085 in blood after drug injection
Time Frame
0 to 168 hours post-dose
Title
AUC0-∞
Description
Area under curve from 0 to infinity of BCD-085 in blood after drug injection
Time Frame
0 to 168 hours post-dose
Title
Cmax
Description
Maximal concentration of BCD-085 in blood after drug injection
Time Frame
0 to 168 hours post-dose
Title
Тmax
Description
Time before Cmax of BCD-085 is reached in blood after drug injection
Time Frame
0 to 168 hours post-dose
Title
Т½
Description
Half-life of BCD-085 in blood after drug injection
Time Frame
0 to 168 hours post-dose
Title
Кel
Description
Elimination rate constant of BCD-085 in blood after drug injection
Time Frame
0 to 168 hours post-dose
Title
Cl
Description
Clearance of BCD-085 in blood after drug injection
Time Frame
0 to 168 hours post-dose
Title
Proportion of patients who developed binding and neutralizing antibodies to BCD-085
Time Frame
16 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent
Age between 18 and 65 years
Active ankylosing spondylitis according to modified criteria of New York classification (1984), that was diagnosed at least 3 months prior to screening.
Active disease according to BASDAI (score 4 or more) if nonsteroidal antiinflammatory drugs were used in the last 3 month prior to screening.
Mean backache intensity equals 4 points or more.
If patient have had biologic therapy to treat ankylosing spondylitis for at least 3 months, there was no positive results of such treatment or patient revealed intolerance to the drug. This therapy must be discontinued at least 12 weeks before enrollment in the study.
Female patients have negative urine pregnancy test.
Patient has no history of tuberculosis.
Patients have negative results of Diaskintest.
Patient has no history of alcohol or drug abuse.
Exclusion Criteria:
Total spinal ankylosis.
Allergy or intolerance of monoclonal antibodies or any excipients of study drugs.
Previous receipt of anti-interleukin 17 drugs or anti-interleukin 17 receptor drugs.
Prior use of two or more biologics to tumor necrosis factor alfa.
Prior use of two or more biologics to other targets. Previous receipt of monoclonal antibodies if they were cancelled less that in 12 weeks before signing informed consent.
Patient is taking corticosteroids for up to 4 weeks in a dose more than 10 mg (recalculated to prednisolone) before signing informed consent and during screening, or in a dose less than 10 mg (recalculated to prednisolone) if it was not stable.
Prior use of disease-modifying antirheumatic drugs including methotrexate, sulfasalazin, chloroquine or hydroxychloroquine for up to 4 weeks before randomization, if their dose was not stable for up to 4 weeks before signing informed consent and during screening.
Prior use of live or attenuated vaccines for up to 8 weeks before signing informed consent.
Prior use of alkylating agents for up to 12 months prior to signing informed consent.
Intraarticular use of corticosteroids for up to 4 weeks before randomization.
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
No
Citations:
PubMed Identifier
31025924
Citation
Erdes S, Nasonov E, Kunder E, Pristrom A, Soroka N, Shesternya P, Dubinina T, Smakotina S, Raskina T, Krechikova D, Povarova T, Plaksina T, Gordeev I, Mazurov V, Reshetko O, Zonova E, Eremeeva A, Chernyaeva E, Makulova T, Ivanov R. Primary efficacy of netakimab, a novel interleukin-17 inhibitor, in the treatment of active ankylosing spondylitis in adults. Clin Exp Rheumatol. 2020 Jan-Feb;38(1):27-34. Epub 2019 Apr 16.
Results Reference
result
Learn more about this trial
Clinical Trial to Evaluate Efficacy and Safety of Multiple Subcutaneous Injections of Various Doses of BCD-085 in Patients With Active Ankylosing Spondylitis
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