A Study of CC-99677 in Participants With Active Ankylosing Spondylitis

Study Overview
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Brief Summary
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This study is designed to learn about response to CC-99677 treatment by measuring signs and symptoms of Ankylosing Spondylitis (AS), objective measures of disease activity, quality of life assessments, pharmacokinetics, safety, and tolerability over a 12-week double-blind period.

Official Title
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A Phase 2 Multicenter, Randomized, Double-Blinded, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of CC-99677 in Subjects With Active Ankylosing Spondylitis

Conditions
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Spondylitis, Ankylosing

Intervention / Treatment
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* Drug: CC-99677
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Ankylosing Spondylitis (AS) fulfilling the modified New York criteria Active axial disease at Screening and Baseline defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 and Total Back Pain ≥ 4 Failed prior treatment with at least 2 NSAIDs for at least 4 weeks each Participant has never received a biologic therapy eg, tumor necrosis factor (TNF) antagonist or monoclonal antibody [mAb] against IL-17A (biologic naive main study), or have taken more than one biologic therapy (biologic-failure substudy) for the treatment of AS Exclusion Criteria: Radiographic evidence of total ankylosis of the spine Clinically significant back pain caused by diseases other than AS Concurrent treatment or treatment within the 6 months prior to Baseline with cell depleting biologic agents Participation in any study of an investigational drug, including those for COVID-19 History of malignancy Oral corticosteroids (prednisone or equivalent) > 10 mg/day systemically for ≥ 2 weeks prior to Baseline Visit

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Administration of CC-99677 150 mg QD PO<br>49 participants will be randomized to CC-99677 150 mg in biologic naive main study | Drug: CC-99677<br>* Oral<br>|
| Experimental: Administration of CC-99677 60mg QD PO<br>49 participants will be randomized to CC-99677 60 mg in biologic naive main study | Drug: CC-99677<br>* Oral<br>|
| Placebo Comparator: Administration of Placebo QD PO<br>49 participants will be randomized to placebo in biologic naive main study | Other: Placebo<br>* Oral<br>|
| Experimental: Administration of CC-99677 150 mg QD PO.<br>20 participants will be randomized to CC-99677 150 mg in biologic-failure substudy | Drug: CC-99677<br>* Oral<br>|
| Experimental: Administration of CC-99677 60mg QD PO.<br>20 participants will be randomized to CC-99677 60 mg in biologic-failure substudy | Drug: CC-99677<br>* Oral<br>|
| Placebo Comparator: Placebo additional dose cohort<br>10 participants will be randomized to placebo in biologic-failure substudy | Other: Placebo<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of ASAS 20 | The Assessment In Spondyloarthritis International Society (ASAS) 20 is defined as improvement ≥ 20% and ≥ 1 unit on a scale of 0 to 10 in each of the 3 domains, with no worsening in the fourth, where the domains are physical function, total back pain, patient global assessment of disease, and inflammation. | Up to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of ASAS 40 | The Assessment In Spondyloarthritis International Society (ASAS) 40 is defined as improvement ≥ 40% and ≥ 2 units on a scale of 0 to 10 in each of the 3 domains, with no worsening in the fourth, where the domains are physical function, total back pain, patient global assessment of disease, and inflammation. | Up to week 12 | 
| Assessment of ASDAS-CRP | The Ankylosing Spondylitis Disease Activity with C-reactive protein as the acute-phase reactant (ASDAS-CRP)is a validated disease activity index in AS that combines participant reported assessments of back pain, morning stiffness, joint pain and/or swelling and general wellbeing. | Up to week 12 | 
| Assessment of BASDAI | The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a composite score based on a participant self-administered survey of six questions using a 0 to 10 unit numerical rating scale (NRS) that assesses the participant major symptoms of AS. | Up to week 12 | 
| Assessment of BASFI | The Bath Ankylosing Spondylitis Functional Index (BASFI) is a composite score based on a participant self-administered survey of ten questions using a 0 to 10 unit numerical rating scale (NRS) that assesses a participant's degree of mobility and functional ability. | Up to week 12 | 
| SPARCC score for the total spine and sacroiliac joints | Spinal and sacroiliac joint inflammation as measured by Spondyloarthritis Research Consortium of Canada (SPARCC) magnetic resonance imaging (MRI) score of sacroiliac joints and spine. | Up to week 12 | 
| High-sensitivity C-reactive protein (hsCRP) | High-sensitivity C-reactive protein (hsCRP) provides an objective measure of disease activity in participants. | Up to week 12 | 
| Incidence of Adverse Events (AEs) | An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre-existing condition) should be considered an AE. | From enrollment until at least 28 days after completion of study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CC-99677, MK2inhibitor, Spinal Diseases, Ankylosing Spondylitis, Bone Diseases, Musculoskeletal Diseases, Arthritis, Joint Diseases