Clinical trial NCT02763111: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ankylosing Spondylitis
Keywords: ankylosing spondylitis
interleukin 17
monoclonal antibody
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2016-05-05
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Ratio of patients with ASAS20 response after 16 weeks of therapy
timeFrame: Week 16
Secondary outcomes:
measure: Ratio of patients with ASAS20 response after 4, 8, 12 weeks of therapy
timeFrame: Week 4, Week 8, Week 12
measure: Ratio of patients with ASAS40 response after 4, 8, 12, 16 weeks of therapy
timeFrame: Week 4, Week 8, Week 12, Week 16
measure: Ratio of patients with ASAS5/6 response after 4, 8, 12, 16 weeks of therapy
timeFrame: Week 4, Week 8, Week 12, Week 16
measure: Mean BASDAI score at screening and after 4, 8, 12, 16 weeks of therapy
timeFrame: Screening, Week 4, Week 8, Week 12, Week 16
measure: Mean BASMI score at screening and after 4, 8, 12, 16 weeks of therapy
timeFrame: Screening, Week 4, Week 8, Week 12, Week 16
measure: Mean MASES score at screening and after 4, 8, 12, 16 weeks of therapy
timeFrame: Screening, Week 4, Week 8, Week 12, Week 16
measure: Mean chest excursion at screening and after 4, 8, 12, 16 weeks of therapy
timeFrame: Screening, Week 4, Week 8, Week 12, Week 16
measure: Mean BASFI score at screening and after 4, 8, 12, 16 weeks of therapy
timeFrame: Screening, Week 4, Week 8, Week 12, Week 16
measure: Mean ASDAS-CRP score at screening and after 4, 8, 12, 16 weeks of therapy
timeFrame: Screening, Week 4, Week 8, Week 12, Week 16
measure: Mean SF-36 score at screening and after 8 and 16 weeks of therapy
timeFrame: Screening, Week 8, Week 16
measure: Mean pain score during a day at screening and after 1, 2, 4, 8, 12, 16 weeks of therapy
timeFrame: Screening, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16
measure: Proportion of patients with deterioration of roentgenologic signs of sacroileitis after 16 weeks of treatment
timeFrame: Week 16
measure: Mean C-reactive protein concentration at screening and after 4, 8, 12 and 16 weeks of treatment.
timeFrame: Screening, Week 4, Week 8, Week 12, Week 16
measure: Frequency of AE/SAE
timeFrame: 16 weeks
measure: Frequency of local reactions
timeFrame: 16 weeks
measure: Frequency of AE/SAE 3-4 grade CTCAE 4.03
timeFrame: 16 weeks
measure: Frequency of withdrawals due to AE/SAE
timeFrame: 16 weeks
measure: Cmin
timeFrame: 0 to 168 hours post-dose
measure: AUC (0-168h)
timeFrame: 0 to 168 hours post-dose
measure: AUC0-∞
timeFrame: 0 to 168 hours post-dose
measure: Cmax
timeFrame: 0 to 168 hours post-dose
measure: Тmax
timeFrame: 0 to 168 hours post-dose
measure: Т½
timeFrame: 0 to 168 hours post-dose
measure: Кel
timeFrame: 0 to 168 hours post-dose
measure: Cl
timeFrame: 0 to 168 hours post-dose
measure: Proportion of patients who developed binding and neutralizing antibodies to BCD-085
timeFrame: 16 weeks
Other outcomes:
Locations:
Study officials:
affiliation: JCS BIOCAD
name: Roman Ivanov, PhD
role: STUDY_CHAIR
References:
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.