ABY-035 in the Treatment of Subjects With Ankylosing Spondylitis

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

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.

Study Overview

• Status: Terminated
• Conditions: Ankylosing Spondylitis
• Intervention / Treatment: Drug: ABY-035; Drug: Placebo

Detailed Description

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:

1. Screening Period: Up to 35 days prior to baseline randomization.

2. 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.

3. 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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China
      • The First affiliated hospital of bengbu medical college
    • Hefei, Anhui, China
      • Anhui Provincial Hospital
  • Beijing
    • Beijing, Beijing, China
      • Beijing Chao-Yang Hospital,Capital medical university
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen Memorial Hospital Sun Yat-sen University
    • Shenzhen, Guangdong, China
      • ShenZhen People's Hospital
  • Henan
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China
      • Tong Ji Hospital TongJi Medical Colleague of HUST
  • Hunan
    • Zhuzhou, Hunan, China
      • Zhuzhou Hospital Affiliated to Xiangya School of Medicine
  • Inner Mongolia
    • Baotou, Inner Mongolia, China
      • The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China
      • The Affiliated Drum Tower Hospital of Nanjing University Medical School
    • Suzhou, Jiangsu, China
      • The First Affiliated Hospital of Soochow University
  • Jiangxi
    • Nanchang, Jiangxi, China
      • The First Affiliated Hospital Of NanChang University
  • Jilin
    • Changchun, Jilin, China
      • The First Hospital of Jilin University
  • Shandong
    • Linyi, Shandong, China
      • Linyi People's Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai Changzheng Hospital
    • Shanghai, Shanghai, China
      • Changhai Hospital of Shanghai
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital of Sichuan University
  • Taiwan
    • Gaoxiong, Taiwan, China
      • Kaohsiung Chang Gung Memorial Hospital ，Chang Gung Medical Foundation
    • Gaoxiong, Taiwan, China
      • Kaohsiung Veterans General Hospital
    • Taibei, Taiwan, China
      • National Taiwan University Hospital (NTUH)
    • Taibei, Taiwan, China
      • Tri-Service General Hospital
    • Taizhong, Taiwan, China
      • China Medical University Hospital (CMUH)
    • Taizhong, Taiwan, China
      • Chung Shan Medical University Hospital (CSMHU)
  • The Affiliated Hospital Of Inner Mongolia Medical University
    • Hohhot, The Affiliated Hospital Of Inner Mongolia Medical University, China
      • The Affiliated Hospital of The Affiliated Hospital of Inner Mongolia Medical University Medical University
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University General Hospital
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of
    • Ajou University Hospital
  • Gyeonggi-do, Korea, Republic of
    • Bundang Seoul National University Hospital
  • Incheon, Korea, Republic of
    • Inha University Hospital
  • Seoul, Korea, Republic of
    • SNU Boramae Medical Center
  • Seoul, Korea, Republic of
    • KyungHee University Hospital
  • Seoul, Korea, Republic of
    • Hanyang University Seoul Hospital
  • Gwangju
    • Gwangju,, Gwangju, Korea, Republic of
      • Chonnam National University Hospital
• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Arizona Arthritis & Rheumatology Research, PLLC
  • California
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research
    • Huntington Beach, California, United States, 92648
      • Newport Huntington Medical Group
    • Palm Desert, California, United States, 92260
      • Desert Medical Advances
  • Florida
    • Aventura, Florida, United States, 33180
      • Arthritis and Rheumatic Disease Specialties
    • Sarasota, Florida, United States, 34293
      • Drucker Sarasota Arthritis Research Center
  • Illinois
    • Schaumburg, Illinois, United States, 60195
      • Greater Chicago Specialty Physicians/ Clinical Investigation Specialists, Inc.
    • Skokie, Illinois, United States, 60076
      • Clinic of Robert Hozman, MD / Clinical Investigation Specialists,
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Klein & Associates, M.D., P.A.
    • Wheaton, Maryland, United States, 20902
      • The Center for Rheumatology and Bone Research
  • North Carolina
    • Durham, North Carolina, United States, 27704
      • M3 Emerging Medical Research, LLC
  • Ohio
    • Perrysburg, Ohio, United States, 43551
      • Clinical Research Source, Inc.
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • Texas
    • Dallas, Texas, United States, 75240
      • HRMD Research
  • Washington
    • Seattle, Washington, United States, 98122
      • Seattle Rheumatology Associates

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or female at least 18 years of age.

2. 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.

3. Subjects have moderate to severe active disease
4. Subjects must have inadequate response or intolerance to at least 2 NSAIDs, or contraindication to NSAID therapy.
5. Subjects may be TNFα inhibitor-naïve or may have received up to 2 prior TNFα inhibitor(s)..

Exclusion Criteria:

1. Subjects have active fibromyalgia or total spinal ankylosis ('bamboo spine'), or any other inflammatory arthritis.
2. Subjects have used medications in the manner as detailed by the exclusion criteria as detailed in the study protocol.
3. Subjects have received technetium-99 conjugated with methylene diphosphonate other than for diagnostic purpose within 5 years prior to baseline.
4. Have received any live (includes attenuated) vaccination within the 12 weeks prior to the baseline.
5. 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).
6. Subject has an active infection or history of infections
7. Have evidence of or test positive for hepatitis B virus (HBV)
8. Have evidence of or test positive for hepatitis C virus (HCV).
9. Have a historically positive human immunodeficiency virus (HIV) test or test positive at screening for HIV.
10. Subjects have known tuberculosis (TB) infection, at high risk of acquiring TB infection, or current or history of nontuberculous mycobacterium (NTMB) infection, or LTB.
11. Have a history of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease.
12. Subjects have active Crohn's disease (CD) or active ulcerative colitis (UC).
13. Subjects have active uveitis within 6 weeks prior to baseline.
14. Subjects have laboratory abnormalities at Screening.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

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

What is the study measuring?

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
AEs leading to withdrawal from investigational medicinal product (IMP)	Safety information	74 weeks
Incidence of serious adverse events (SAEs) and adverse events of special interests (AESIs)	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

Collaborators and Investigators

• Sponsor: Inmagene LLC
• Collaborators: Affibody
• Investigators: Study Director: Lawrence He, SVP, Global Regulatory Head

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2021
• Primary Completion (Actual): July 11, 2022
• Study Completion (Actual): August 30, 2022

Study Registration Dates

• First Submitted: March 3, 2021
• First Submitted That Met QC Criteria: March 10, 2021
• First Posted (Actual): March 12, 2021

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 6, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• 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: ABY-035-204

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No