Status and phase
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About
The aim of the study is to evaluate the efficacy, safety, immunogenicity, pharmacokinetics and pharmacodynamics of a fixed dose of study drug (BCD-180) in comparison with placebo in patients with active axial spondyloarthritis (axSpA). The study will include HLA-B27+ patients with radiographic (r-axSpA) and non-radiographic (nr-axSpA) who had no response to prior therapy with non-steroidal anti-rheumatic drugs (NSAIDs), have not received biologic disease-modifying anti-rheumatic drugs (bDMARDs) or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), and subjects with insufficient efficacy and/or loss of efficacy on bDMARDs and/or tsDMARDs.
Full description
Subjects meeting the eligibility criteria will be randomized in 2 groups:bDMARDs and/or tsDMARD naive subjects and bDMARDs and/or tsDMARD experienced subjects will be randomized independently of each other.
bDMARDs and tsDMARD-naive subjects (naïve) will be randomized into 3 groups:
bDMARDs and/or tsDMARD experienced subjects (exp) will be randomized into 2 groups:
After the primary endpoint assessment all subjects will be switched to BCD-180.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Signed Informed Consent Form for participation in the study.
Men and women aged >18 years of age at the time of signing the Informed Consent Form for participation.
Positive test result for HLA-B27.
Presence of r-axSpA OR nr-axSpA according to the criteria provided below:
Active disease at the screening and the randomization visit diagnosed based on both criteria:
For subjects with nr-axSpA: presence of objective MRI signs of sacroiliitis (according to ASAS/OMERACT) as assessed by the central review AND/OR based on hsCRP level >1.5 ULN at screening.
For subjects with r-axSpA: hsCRP level ˃1.5 ULN at screening.
Duration of back pain ≥3 months, age <45 years at the onset of the axSpA-associated back pain.
Meeting at least one of the following criteria based on the Investigator's assessment:
For bDMARDs-experienced and/or targeted synthetic DMARD-experienced subjects (tsDMARD): meeting at least one of the following criteria based on the Investigator's assessment:
For subjects continuing to receive NSAIDs or COX-2 inhibitors: the drug dose shall be steady for at least 14 days prior to Visit 1/Week 0.
For women: negative pregnancy test result at screening (the test is not performed in women who have been postmenopausal for at least 2 years or are surgically sterile) .
The ability of the subject to follow the Protocol procedures, according to the Investigator.
Willingness of subjects and their sexual partners of childbearing potential to use reliable methods of contraception from the date of signing the ICF, throughout the study, and for 8 weeks after the last administration of BCD-180/placebo (infusions)/adalimumab/placebo (subcutaneously). This requirement does not apply to subjects who have had operative sterilization and women who have been postmenopausal for more than 2 years.
For participants of childbearing potential, from signing the informed consent form, throughout the study, and for 8 weeks after the last dose of BCD-180/placebo (intravenously)/adalimumab/placebo (subcutaneous):
Exclusion criteria
Refusal to take NSAIDs for the treatment of axSpA for any subjective reasons that do not have a clinical justification.
Use of the following medicines/procedures:
Exception: the medicinal products listed below if their dose was stable for 4 weeks before signing the ICF and during the screening period:
oral or parenteral methotrexate at a dose ≤25 mg/week, therapy shall be started at least 8 weeks before signing the ICF;
5-aminosalicylic acid and its derivatives, including sulfasalazine, at a dose not exceeding 3 g/day, provided that therapy was started at least 8 weeks before signing the ICF. Subjects with inflammatory bowel disease (IBD) may be treated with topical 5-aminosalicylic acid at therapeutic doses;
Vaccination with any vaccines within 12 weeks prior to signing the ICF.
Documented presence of one or more of the listed conditions:
Clarification: for subjects with IBD: IBD therapy must be stable for 8 weeks prior to signing the ICF. For subjects with psoriasis: topical products may be used.
A current diagnosis or a history of a severe immunodeficiency of any origin.
A diagnosis of HIV infection, hepatitis B, hepatitis C.
The following laboratory test results at screening:
Clinically significant thyroid disease and/or clinically significant deviation of the TSH level from the reference values at screening.
Diagnosis of active or latent tuberculosis, including a history of tuberculosis .
Major surgery within 4 weeks prior to signing the ICF or major surgery planned for the period of participation in the study.
Documented diagnosis of infectious mononucleosis within 8 weeks prior to signing the ICF and during the screening period, any active infection or recurrent infection within 4 weeks prior to signing the ICF and during the screening period, including fever ≥38°C at the Randomization Visit.
Documented diagnosis of any other chronic infection that, in the opinion of the investigator, can increase the risk of infectious complications.
Severe infectious diseases (requiring hospitalization, parenteral use of antibacterial, antimycotic or antiprotozoal drugs) within 8 weeks prior to signing the ICF and during the screening period.
Systemic antibacterial, antimycotic or antiprotozoal therapy within 8 weeks prior to signing the ICF and during the screening period.
Epileptic seizures, a history of seizures.
A history of or current (at the time of signing the ICF and during the screening period) significant uncontrolled neuropsychiatric disorders, severe depression and/or suicide attempts, a risk of suicide and/or any psychiatric illness that, in the opinion of the investigator, may pose an excessive risk to the subject or have an impact on the subject's ability to follow the protocol.
Known (including from historical data) alcohol or drug dependence, psychoactive substance or drug abuse, evidence of alcohol/drug dependence or current abuse that, in the investigator's opinion, is a contraindication to AS therapy or limits treatment adherence.
The following diseases:
Exception: the following subjects may be included in the study:
Comorbidities (including, but not limited to, metabolic, hematological, renal, hepatic, pulmonary, neurological, endocrine, cardiac, infectious, gastrointestinal disorders), including disorders ongoing at the time of screening, which, in the opinion of the investigator, may affect the course of radiographic axSpA, the results of assessment of its symptoms, or create an unacceptable risk to the subject from study therapy.
Known allergy or intolerance to any component of the test drug, premedication drugs used in this clinical study. For bDMARDs and/or tsDMARD-naive subjects: known allergy or intolerance of any components of adalimumab.
For bDMARDs and/or tsDMARD-naive subjects: contraindications for the use of adalimumab.
A history of angioedema.
Fibromyalgia, or other conditions associated with chronic pain .
Lymphoproliferative diseases or malignancies with a remission duration of less than 5 years, with the exception of cured basal cell carcinoma and cervical cancer in situ.
Pregnancy, pregnancy planning (including pregnancy of female sexual partners of male study subjects) less than 8 weeks after the last administration of BCD-180/placebo (intravenously)/adalimumab/placebo (subcutaneous), breastfeeding.
Contraindications to MRI.
Simultaneous participation in other clinical studies, as well as previous participation in other clinical studies less than 3 months before signing the ICF, prior participation in this study.
Exception: subjects who dropped out of this study at screening.
Primary purpose
Allocation
Interventional model
Masking
421 participants in 5 patient groups, including a placebo group
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Central trial contact
Galina Vinderskaya, MD; Maria Morozova, PhD, MD
Data sourced from clinicaltrials.gov
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