ABY-035 in the Treatment of Subjects With Ankylosing Spondylitis

Study Overview
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Brief Summary
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ABY-035-204 is a clinical study to assess the efficacy of IL-17 blocker ABY-035 in ankylosing spondylitis(AS). The primary objective is to estimate the relationship between different dose regimens of ABY-035 and clinical response as assessed by Assessment of Spondyloarthritis International Society 40 (ASAS40) response at Week 16 in subjects with active AS.

Detailed Description
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ABY-035-204 is a double-blind, randomized, parallel-group, placebo-controlled study. The primary objective is to estimate the relationship between different dose regimens of ABY-035 and clinical response as assessed by Assessment of Spondyloarthritis International Society 40 (ASAS40) response at Week 16 in subjects with active AS. The study will include the following 3 periods: Screening Period: Up to 35 days prior to baseline randomization. Treatment Period 1: Day 0-Week 16 Cohort 1: Eligible subjects will be randomized 1:1:1:1 to receive 1 of 4 treatments (ABY-035 High Dose every 2 weeks (Q2W), ABY-035 Low Dose every 2 weeks (Q2W), ABY-035 High Dose every 4 weeks (Q4W), or placebo Q2W), and will remain on their allowable background medication. Cohort 2: Eligible subjects will be randomized 1:1:1 to receive 1 of 3 treatments (ABY-035 High Dose every week (QW), ABY-035 Low Dose every week (QW), or placebo QW), and will remain on their allowable background medication. Randomization will be stratified by region (North Eastern Asia and North America) and previous tumor necrosis factor alpha (TNFα) inhibitor exposure (TNFα inhibitor treated or TNFα inhibitor naïve). Maximum 30% of subjects will be TNFα inhibitor-treated subjects to ensure a representative population for the assessment of efficacy and safety. Treatment Period 1 ends at Week 16 after all trial assessments have been done and Treatment Period 2 starts at Week 16 with the IMP injection. Treatment Period 2 (Extension Period): Week 16-Week 52 Cohort 1: Subjects will receive ABY-035 High Dose Q2W treatment in an open-label manner. Cohort 2: Subjects will receive ABY-035 High Dose QW treatment in an open-label manner. At Week24, subjects who could not achieve an ASAS20 response from baseline are defined as non-responders and will discontinue the study treatment.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of ABY-035 in the Treatment of Subjects With Ankylosing Spondylitis

Conditions
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Ankylosing Spondylitis

Intervention / Treatment
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* Drug: ABY-035
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female at least 18 years of age. Subjects with active AS, determined by documented radiologic evidence (X-ray) fulfilling the Modified New York criteria for AS (1984). AND At least one SpA feature, according to ASAS criteria. Subjects have moderate to severe active disease Subjects must have inadequate response or intolerance to at least 2 NSAIDs, or contraindication to NSAID therapy. Subjects may be TNFα inhibitor-naïve or may have received up to 2 prior TNFα inhibitor(s).. Exclusion Criteria: Subjects have active fibromyalgia or total spinal ankylosis ('bamboo spine'), or any other inflammatory arthritis. Subjects have used medications in the manner as detailed by the exclusion criteria as detailed in the study protocol. Subjects have received technetium-99 conjugated with methylene diphosphonate other than for diagnostic purpose within 5 years prior to baseline. Have received any live (includes attenuated) vaccination within the 12 weeks prior to the baseline. Subjects have received any non-biological therapy for AS not listed as detailed in the study protocol within or outside a clinical study in the 3 months or within 5 half-lives prior to the Baseline Visit (whichever is longer). Subject has an active infection or history of infections Have evidence of or test positive for hepatitis B virus (HBV) Have evidence of or test positive for hepatitis C virus (HCV). Have a historically positive human immunodeficiency virus (HIV) test or test positive at screening for HIV. Subjects have known tuberculosis (TB) infection, at high risk of acquiring TB infection, or current or history of nontuberculous mycobacterium (NTMB) infection, or LTB. Have a history of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease. Subjects have active Crohn's disease (CD) or active ulcerative colitis (UC). Subjects have active uveitis within 6 weeks prior to baseline. Subjects have laboratory abnormalities at Screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: #1: Cohort 1-High Dose Q2W<br>Cohort 1: ABY-035 High Dose, every 2 weeks, subcutaneous injection | Drug: ABY-035<br>* ABY-035 Solution for injection<br>* Other names: Izokibep;|
| Experimental: #2: Cohort 1-High Dose Q4W<br>Cohort 1: ABY-035 High Dose, every 4 weeks, subcutaneous injection | Drug: ABY-035<br>* ABY-035 Solution for injection<br>* Other names: Izokibep;|
| Experimental: #3: Cohort 1-Low Dose Q2W<br>Cohort 1: ABY-035 Low Dose, every 2 weeks, subcutaneous injection | Drug: ABY-035<br>* ABY-035 Solution for injection<br>* Other names: Izokibep;|
| Experimental: #4: Cohort 2-Low Dose QW<br>Cohort 2: ABY-035 Low Dose, every week, subcutaneous injection | Drug: ABY-035<br>* ABY-035 Solution for injection<br>* Other names: Izokibep;|
| Experimental: #5: Cohort 2-High Dose QW<br>Cohort 2: ABY-035 High Dose, every week, subcutaneous injection | Drug: ABY-035<br>* ABY-035 Solution for injection<br>* Other names: Izokibep;|
| Placebo Comparator: #1: Cohort 1-Placebo Q2W<br>Cohort 1: Placebo, every 2 weeks, subcutaneous injection | Drug: Placebo<br>* Normal Saline for injection<br>* Other names: Normal Saline;|
| Placebo Comparator: #2: Cohort 2-Placebo QW<br>Cohort 2: Placebo, every week, subcutaneous injection | Drug: Placebo<br>* Normal Saline for injection<br>* Other names: Normal Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving an ASAS40 response | The treatment effect | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in BASDAI | The treatment effect | 16 weeks | 
| Change from baseline in BASFI | The treatment effect | 16 weeks | 
| Proportion of subjects reaching ASDAS-MI | The treatment effect | 16 weeks | 
| Incidence of AEs | Safety information | 74 weeks | 
| Incidence of serious adverse events (SAEs) and adverse events of special interests (AESIs) | Safety information | 74 weeks | 
| AEs leading to withdrawal from investigational medicinal product (IMP) | Safety information | 74 weeks | 
| Change in safety laboratory parameters and vital signs compared to baseline | Safety information | 74 weeks | 
| Proportion of subjects achieving an ASAS40 response, ASAS20 response, ASAS partial remission, and ASAS 5/6 response respectively at required timepoints | The treatment effect | 52 weeks | 
| Change from baseline in BASDAI and BASFI at required timepoints | The treatment effect | 52 weeks | 
| Proportion of subjects reaching BASDAI50 and ASDAS-MI at required timepoints | The treatment effect | 52 weeks | 
| Proportion of subjects experiencing clinically important improvement at required timepoints | The treatment effect | 52 weeks | 
| ASDAS-CRP and ASDAS status at required timepoints | The treatment effect | 52 weeks | 
| Change from baseline in total and nocturnal pain at required timepoints | The treatment effect | 52 weeks |