A Study of CC-99677 in Participants With Active Ankylosing Spondylitis (AS SpA axSpA)

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

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.

Study Overview

• Status: Terminated
• Conditions: Spondylitis, Ankylosing
• Intervention / Treatment: Drug: CC-99677; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangzhou, China, 510630
    • Local Institution - 151
  • Hangzhou, China, 310014
    • Local Institution - 152
  • Huangpu District, China, 200000
    • Local Institution - 153
  • Wuhan, China, 430030
    • Local Institution - 150
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Local Institution - 154
• Czechia
  • Brno, Czechia, 61141
    • Local Institution - 205
  • Ostrava, Czechia, 702 00
    • Local Institution - 206
  • Ostrava, Czechia, 702 00
    • Local Institution - 207
  • Pardubice, Czechia, 530 02
    • Local Institution - 201
  • Praha 11, Czechia, 148 00
    • Local Institution - 211
  • Praha 3, Czechia, 13000
    • Local Institution - 202
  • Praha 4, Czechia, 140 00
    • Local Institution - 203
  • Uherské Hradište, Czechia, 686 01
    • Local Institution - 204
• Germany
  • Herne, Germany, 44649
    • Local Institution - 900
• Poland
  • Bialystok, Poland, 15-077
    • Local Institution - 311
  • Bialystok, Poland, 15-351
    • Local Institution - 315
  • Bydgoszcz, Poland, 85-065
    • Local Institution - 305
  • Bydgoszcz, Poland, 85-168
    • Local Institution - 302
  • Elblag, Poland, 82-300
    • Local Institution - 301
  • Katowice, Poland, 40-282
    • Local Institution - 307
  • Krakow, Poland, 30-002
    • Local Institution - 300
  • Krakow, Poland, 30-363
    • Local Institution - 308
  • Nowa Sol, Poland, 67-100
    • Local Institution - 310
  • Onyksowa 10, Poland, 20-582
    • Local Institution - 313
  • Sochaczew, Poland, 96-500
    • Local Institution - 312
  • Torun, Poland, 87-100
    • Local Institution - 306
  • Warsaw, Poland, 02-691
    • Local Institution - 303
  • Wroclaw, Poland, 52-416
    • Local Institution - 309
• Romania
  • Brasov, Romania, 500283
    • Local Institution - 400
  • Bucuresti, Romania, 011025
    • Local Institution - 404
  • Bucuresti, Romania, 011172
    • Local Institution - 402
  • Bucuresti, Romania, 011172
    • Local Institution - 403
• Spain
  • A Coruña, Spain, 15006
    • Local Institution - 604
  • Barcelona, Spain, 08035
    • Local Institution - 607
  • Cordoba, Spain, 14001
    • Local Institution - 606
  • Merida, Spain, 06800
    • Local Institution - 605
  • Sabadell, Spain, 8208
    • Local Institution - 601
  • Santiago De Compostela, Spain, 15706
    • Local Institution - 602
  • Sevilla, Spain, 41013
    • Local Institution - 603
• Turkey
  • Adapazari, Turkey, 54100
    • Local Institution - 702
  • Altındağ/Ankara, Turkey, 06230
    • Local Institution - 707
  • Ankara, Turkey, 06100
    • Local Institution - 700
  • Edirne, Turkey, 22030
    • Local Institution - 701
  • Istanbul, Turkey, 34098
    • Local Institution - 705
  • Izmir, Turkey, 35100
    • Local Institution - 706
  • Karabaglar, Turkey, 35360
    • Local Institution - 704
  • Trabzon, Turkey, 61080
    • Local Institution - 703
• United States
  • Arizona
    • Flagstaff, Arizona, United States, 86001
      • Local Institution - 024
    • Gilbert, Arizona, United States, 58297
      • Local Institution - 021
    • Phoenix, Arizona, United States, 95037
      • Local Institution - 022
    • Tucson, Arizona, United States, 85704
      • Local Institution - 025
  • California
    • Tustin, California, United States, 92780
      • Local Institution - 017
  • Michigan
    • Saint Clair Shores, Michigan, United States, 48081
      • Local Institution - 026
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Local Institution - 028
    • Dayton, Ohio, United States, 45417
      • Local Institution - 004
  • Oregon
    • Portland, Oregon, United States, 97239
      • Local Institution - 009
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Local Institution - 003
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Local Institution - 005
    • Memphis, Tennessee, United States, 38119
      • Local Institution - 002
  • Texas
    • Austin, Texas, United States, 78731
      • Local Institution - 029
    • Colleyville, Texas, United States, 76034
      • Local Institution - 006
    • Fort Worth, Texas, United States, 76107
      • Local Institution - 019
    • Houston, Texas, United States, 77099
      • Local Institution - 008

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Administration of CC-99677 150 mg QD PO; 49 participants will be randomized to CC-99677 150 mg in biologic naive main study	Drug: CC-99677; Oral
Experimental: Administration of CC-99677 60mg QD PO; 49 participants will be randomized to CC-99677 60 mg in biologic naive main study	Drug: CC-99677; Oral
Placebo Comparator: Administration of Placebo QD PO; 49 participants will be randomized to placebo in biologic naive main study	Other: Placebo; Oral
Experimental: Administration of CC-99677 150 mg QD PO.; 20 participants will be randomized to CC-99677 150 mg in biologic-failure substudy	Drug: CC-99677; Oral
Experimental: Administration of CC-99677 60mg QD PO.; 20 participants will be randomized to CC-99677 60 mg in biologic-failure substudy	Drug: CC-99677; Oral
Placebo Comparator: Placebo additional dose cohort; 10 participants will be randomized to placebo in biologic-failure substudy	Other: Placebo; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieve ASAS 20 at Week 12	Percentage of participants who achieve an improvement in disease activity from baseline of ≥ 20% and ≥ 1 unit in at least 3 of the 4 SpondyloArthritis International Society (ASAS) domains on a scale of 0 to 10, and no worsening from baseline of ≥ 20% and ≥ 1 unit in the remaining domain on a scale of 0 to 10. Baseline is the last non-missing value on or before the date of the first dose of investigational product. The four ASAS Domains are: Patient Global Assessment of Disease (0 to 10 unit Numerical Rating Scale [NRS]);; Total Back Pain NRS;; Function (the Bath Ankylosing Spondylitis Functional Index [BASFI] score NRS);; Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] NRS Questions #5 and #6 for morning stiffness).	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieve ASAS 40 at Week 12	Percentage of participants who achieve an improvement in disease activity from baseline of ≥ 40% and ≥ 2 unit in at least 3 of the 4 SpondyloArthritis International Society (ASAS) domains on a scale of 0 to 10, and no worsening at all from baseline in the remaining domain. Baseline is the last non-missing value on or before the date of the first dose of investigational product. The four ASAS Domains are: Patient Global Assessment of Disease (0 to 10 unit Numerical Rating Scale [NRS]);; Total Back Pain NRS;; Function (the Bath Ankylosing Spondylitis Functional Index [BASFI] score NRS);; Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] NRS Questions #5 and #6 for morning stiffness).	Week 12
Change From Baseline in Ankylosing Spondylitis Disease Activity Score With CRP (ASDAS-CRP) at Week 12	ASDAS-CRP is a score of disease activity that combines patient reported assessments of back pain (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] question 2), duration of morning stiffness (BASDAI question 6), peripheral joint pain and/or swelling (BASDAI question 3), general wellbeing, and CRP in a weighted manner. The cut-off values for disease activity states and improvement scores are defined as follows: <1.3 inactive disease, ≥1.3 and <2.1 low disease activity, ≥2.1 and ≤3.5 high disease activity and 3.5 very high disease activity. The minimum clinically important difference (MCID) are defined as: change of at least 1.1 unit for 'clinically important improvement' and change of at least 2.0 units for 'major improvement'. Baseline is the last non-missing value on or before the date of the first dose of investigational product. ASDAS-CRP Formula: 0.12xBack Pain+0.06xDuration of Morning Stiffness+0.11xPatient Global+0.07xPeripheral Pain/Swelling+0.58xln(CRP+1)	Baseline and Week 12
Change From Baseline in BASDAI at Week 12	Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a composite score based on a self-administered survey of six questions using a 0 to 10 unit numerical rating scale (NRS) that assesses five major symptoms of AS during the last week: 1) fatigue; 2) spinal pain; 3) peripheral joint pain/swelling; 4) areas of localized tenderness; 5a) morning stiffness severity upon wakening; 5b) morning stiffness duration upon wakening. To give each of the five symptoms equal weighting, the mean of the two scores relating to morning stiffness is taken. The resulting 0 to 50 score is divided by 5 to give a final 0 to 10 BASDAI score. A BASDAI score of 4 or greater is considered to be indicative of active AS disease. Baseline is the last non-missing value on or before the date of the first dose of investigational product.	Baseline and Week 12
Change From Baseline in BASFI at Week 12	Bath Ankylosing Spondylitis Functional Index (BASFI) is a composite score based on a self administered survey of ten questions using a 0 to 10 unit numerical rating scale (NRS) that assesses degree of mobility and functional ability during the last week. The questionnaire consists of eight questions regarding function in AS and the two last questions reflecting ability to cope with everyday life. The left-hand box of 0 represents "easy," and the right-hand box represents "impossible." The resulting 0 to 100 score is divided by 10 to give a final 0 to 10 BASFI score. A higher BASFI score correlates to reduced functional ability. Baseline is the last non-missing value on or before the date of the first dose of investigational product.	Baseline and Week 12
Change From Baseline in the SPARCC SI Joint Score at Week 12	Change from Baseline in the Spondyloarthritis Research Consortium of Canada (SPARCC) scores of the sacroiliac joints. The SPARCC assesses 16 sites for enthesitis using a score of "0" for no activity or "1" for activity. Sites assessed include Medial epicondyle (left/right [L/R]), Lateral epicondyle (L/R), Supraspinatus insertion into greater tuberosity of humerus (L/R), Greater trochanter (L/R), Quadriceps insertion into superior border of patella (L/R), Patellar ligament insertion into inferior pole of patella or tibial tubercle (L/R), Achilles tendon insertion into calcaneum (L/R), and Plantar fascia insertion into calcaneum (L/R). The SPARCC is the sum of all site scores (range 0 to 16). Higher scores indicate more severe enthesitis. Baseline is the last non-missing value on or before the date of the first dose of investigational product.	Baseline and Week 12
Change From Baseline in the SPARCC Spine Score at Week 12	Change from Baseline in the Spondyloarthritis Research Consortium of Canada (SPARCC) scores of the total spine. All 23 disco-vertebral units (DVU) of the spine (from C2 to S1) were scored for bone marrow edema. A single DVU has 18 scoring units, and each has score of 0 or 1, bringing the maximum total score to 414, the sum ranges from 0 to 414 with higher scores reflecting worse disease. Baseline is the last non-missing value on or before the date of the first dose of investigational product.	Baseline and Week 12
Percent Change From Baseline in hsCRP at Week 12	Percent change from baseline in high-sensitivity C-reactive protein (hsCRP). Baseline is the last non-missing value on or before the date of the first dose of investigational product.	Baseline and Week 12

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Bristol-Myers Squibb, MD, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• FDA Safety Alerts and Recalls
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2021
• Primary Completion (Actual): February 21, 2023
• Study Completion (Actual): February 21, 2023

Study Registration Dates

• First Submitted: June 23, 2021
• First Submitted That Met QC Criteria: June 23, 2021
• First Posted (Actual): July 1, 2021

Study Record Updates

• Last Update Posted (Actual): May 1, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Arthritis; Joint Diseases; Musculoskeletal Diseases; Bone Diseases; Ankylosing Spondylitis; CC-99677; MK2inhibitor; Spinal Diseases
• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Axial Spondyloarthritis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing
• Other Study ID Numbers: CC-99677-AS-001; U1111-1265-3951 (Registry Identifier: UTN Number); 2019-004108-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No