This study is intended to treat ankylosing spondylitis (AS). AS is a form of arthritis that primarily affects the spine. It is characterized by inflammation of the spinal joints that can lead to severe pain, and in more advanced cases, ankylosis (sections of the spine fuse in a fixed, immobile position). The study will be an ascending single and multiple-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of subcutaneous KIN-1901 in healthy subjects and subjects with AS.
KIN-1901 is a fully human immunoglobulin monoclonal antibody (mAb) directed towards a proinflammatory cytokine that is believed to have a role in inflammation and autoimmunity, and is found in synovial fluid from patients with spondyloarthritis. Therefore, neutralization of this cytokine activity by specific monoclonal antibodies (mAbs) could be beneficial in treating certain spondyloarthropathies such as ankylosing spondylitis (AS). The primary objective of the study is to evaluate the safety and tolerability of escalating single-dose or once-weekly repeat-dose subcutaneous (SC) administration of KIN-1901 in healthy subjects (Cohorts 1 through 4) and in subjects with AS (Cohort 5). The secondary objective of the study is to evaluate the pharmacokinetics (PK) of escalating single-dose and once-weekly repeat-dose SC administration of KIN-1901 in healthy subjects (Cohorts 1 through 4) and in subjects with AS (Cohort 5). The following exploratory objectives will also be evaluated: (1) To explore the pharmacodynamic (PD) effects of escalating single-dose and once-weekly repeat-dose SC administration of KIN-1901 in healthy subjects (Cohorts 1 through 4), (2) To explore the PD effects and changes in disease activity by Assessment in Ankylosing Spondylitis Criteria ASAS 20/40 (and components) and Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP) of once-weekly repeat-dose SC administration of KIN-1901 in subjects with AS (Cohort 5), (3) To assess biomarkers of efficacy and safety after once-weekly repeat-dose SC administration of KIN-1901 in subjects with AS (Cohort 5).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
Altasciences Clinical Research
Montreal, Quebec, Canada
Incidence of treatment-emergent adverse events
Time frame: Up to 57 days (Cohort 1 and 2); Up to 78 days (Cohorts 3, 4, and 5)
Change from baseline in QTcF interval
Time frame: Up to 57 days (Cohort 1 and 2); Up to 78 days (Cohorts 3, 4, and 5)
Change in clinical chemistry parameter hsCRP determined by laboratory testing
Time frame: Up to 57 days (Cohort 1 and 2); Up to 78 days (Cohorts 3, 4, and 5)
Incidence of serum anti-drug antibodies
Time frame: Up to 57 days (Cohort 1 and 2); Up to 78 days (Cohorts 3, 4, and 5)
Serum Cmax
Maximum observed concentration
Time frame: Up to 57 days (Cohort 1 and 2); Up to 78 days (Cohorts 3, 4, and 5)
Serum tmax
Time to Cmax
Time frame: Up to 57 days (Cohort 1 and 2); Up to 78 days (Cohorts 3, 4, and 5)
Serum AUC
Area under the concentration-time curve
Time frame: Up to 57 days (Cohort 1 and 2); Up to 78 days (Cohorts 3, 4, and 5)
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QUADRUPLE
Enrollment
36