Clinical Trial to Evaluate Efficacy and Safety of Multiple Subcutaneous Injections of Various Doses of BCD-085 in Patients With Active Ankylosing Spondylitis

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

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.

Study Overview

• Status: Completed
• Conditions: Ankylosing Spondylitis
• Intervention / Treatment: Other: Placebo; Drug: BCD-085

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BCD-085, 40 mg; Patient will receive 40 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12.	Drug: BCD-085
Experimental: BCD-085, 80 mg; Patient will receive 80 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12.	Drug: BCD-085
Experimental: BCD-085, 120 mg; Patient will receive 120 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12.	Drug: BCD-085
Placebo Comparator: Placebo; Patient will receive placebo subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12.	Other: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 4, Week 8, Week 12
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.	Week 4, Week 8, Week 12, Week 16
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.	Week 4, Week 8, Week 12, Week 16
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	Screening, Week 4, Week 8, Week 12, Week 16
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	Screening, Week 4, Week 8, Week 12, Week 16
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	Screening, Week 4, Week 8, Week 12, Week 16
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	Screening, Week 4, Week 8, Week 12, Week 16
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	Screening, Week 4, Week 8, Week 12, Week 16
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	Screening, Week 4, Week 8, Week 12, Week 16
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	Screening, Week 8, Week 16
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	Screening, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16
Proportion of patients with deterioration of roentgenologic signs of sacroileitis after 16 weeks of treatment		Week 16
Mean C-reactive protein concentration at screening and after 4, 8, 12 and 16 weeks of treatment.		Screening, Week 4, Week 8, Week 12, Week 16
Frequency of AE/SAE		16 weeks
Frequency of local reactions		16 weeks
Frequency of AE/SAE 3-4 grade CTCAE 4.03		16 weeks
Frequency of withdrawals due to AE/SAE		16 weeks
Cmin	Minimal concentration of BCD-085 in blood after drug injection	0 to 168 hours post-dose
AUC (0-168h)	Area under curve from 0 to 168 hours of BCD-085 in blood after drug injection	0 to 168 hours post-dose
AUC0-∞	Area under curve from 0 to infinity of BCD-085 in blood after drug injection	0 to 168 hours post-dose
Cmax	Maximal concentration of BCD-085 in blood after drug injection	0 to 168 hours post-dose
Тmax	Time before Cmax of BCD-085 is reached in blood after drug injection	0 to 168 hours post-dose
Т½	Half-life of BCD-085 in blood after drug injection	0 to 168 hours post-dose
Кel	Elimination rate constant of BCD-085 in blood after drug injection	0 to 168 hours post-dose
Cl	Clearance of BCD-085 in blood after drug injection	0 to 168 hours post-dose
Proportion of patients who developed binding and neutralizing antibodies to BCD-085		16 weeks

Collaborators and Investigators

• Sponsor: Biocad

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: April 3, 2016
• First Submitted That Met QC Criteria: May 3, 2016
• First Posted (Estimate): May 5, 2016

Study Record Updates

• Last Update Posted (Actual): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 25, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: monoclonal antibody; ankylosing spondylitis; interleukin 17
• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing
• Other Study ID Numbers: BCD-085-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No