ABY-035 in the Treatment of Subjects With Ankylosing Spondylitis

Phase 2

Terminated

Conditions: Ankylosing Spondylitis

Interventions: Drug: ABY-035
Drug: Placebo

Registration Number: NCT04795141

Lead Sponsor: Inmagene LLC

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 25

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
#1: Cohort 1-High Dose Q2W	ABY-035	Cohort 1: ABY-035 High Dose, every 2 weeks, subcutaneous injection
#4: Cohort 2-Low Dose QW	ABY-035	Cohort 2: ABY-035 Low Dose, every week, subcutaneous injection
#2: Cohort 2-Placebo QW	Placebo	Cohort 2: Placebo, every week, subcutaneous injection
#1: Cohort 1-Placebo Q2W	Placebo	Cohort 1: Placebo, every 2 weeks, subcutaneous injection
#5: Cohort 2-High Dose QW	ABY-035	Cohort 2: ABY-035 High Dose, every week, subcutaneous injection
#2: Cohort 1-High Dose Q4W	ABY-035	Cohort 1: ABY-035 High Dose, every 4 weeks, subcutaneous injection
#3: Cohort 1-Low Dose Q2W	ABY-035	Cohort 1: ABY-035 Low Dose, every 2 weeks, subcutaneous injection

Primary Outcome Measures

Name	Time	Method
Proportion of subjects achieving an ASAS40 response	16 weeks	The treatment effect

Secondary Outcome Measures

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

Trial Locations

Locations (47): Newport Huntington Medical Group
🇺🇸
Huntington Beach, California, United States
Desert Medical Advances
🇺🇸
Palm Desert, California, United States
Hope Clinical Research
🇺🇸
Canoga Park, California, United States
Greater Chicago Specialty Physicians/ Clinical Investigation Specialists, Inc.
🇺🇸
Schaumburg, Illinois, United States
The Center for Rheumatology and Bone Research
🇺🇸
Wheaton, Maryland, United States
Altoona Center for Clinical Research
🇺🇸
Duncansville, Pennsylvania, United States
Ajou University Hospital
🇰🇷
Gyeonggi-do, Korea, Republic of
Clinical Research Source, Inc.
🇺🇸
Perrysburg, Ohio, United States
Bundang Seoul National University Hospital
🇰🇷
Gyeonggi-do, Korea, Republic of
Tong Ji Hospital TongJi Medical Colleague of HUST
🇨🇳
Wuhan, Hubei, China
The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and TechNology
🇨🇳
Baotou, Inner Mongolia, China
Inha University Hospital
🇰🇷
Incheon, Korea, Republic of
The First Affiliated Hospital of Bengbu Medical College
🇨🇳
Bengbu, Anhui, China
Anhui Provincial Hospital
🇨🇳
Hefei, Anhui, China
Shenzhen People's Hospital
🇨🇳
Shenzhen, Guangdong, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳
Zhengzhou, Henan, China
Sun Yat-Sen Memorial Hospital Sun Yat-Sen University
🇨🇳
Guangzhou, Guangdong, China
Beijing Chao-Yang Hospital,Capital Medical University
🇨🇳
Beijing, Beijing, China
Zhuzhou Hospital Affiliated to Xiangya School of Medicine
🇨🇳
Zhuzhou, Hunan, China
The First Affiliated Hospital of Soochow University
🇨🇳
Suzhou, Jiangsu, China
The First Affiliated Hospital of Nanchang University
🇨🇳
Nanchang, Jiangxi, China
The First Hospital of Jilin University
🇨🇳
Changchun, Jilin, China
The Affiliated Drum Tower Hospital of Nanjing University Medical School
🇨🇳
Nanjing, Jiangsu, China
Linyi People's Hospital
🇨🇳
Linyi, Shandong, China
West China Hospital of Sichuan University
🇨🇳
Chengdu, Sichuan, China
Kaohsiung Chang Gung Memorial Hospital ，Chang Gung Medical Foundation
🇨🇳
Gaoxiong, Taiwan, China
Kaohsiung Veterans General Hospital
🇨🇳
Gaoxiong, Taiwan, China
Changhai Hospital of Shanghai
🇨🇳
Shanghai, Shanghai, China
Shanghai Changzheng Hospital
🇨🇳
Shanghai, Shanghai, China
National Taiwan University Hospital (NTUH)
🇨🇳
Taibei, Taiwan, China
Tri-Service General Hospital
🇨🇳
Taibei, Taiwan, China
China Medical University Hospital (CMUH)
🇨🇳
Taizhong, Taiwan, China
Chung Shan Medical University Hospital (CSMHU)
🇨🇳
Taizhong, Taiwan, China
The Affiliated Hospital of The Affiliated Hospital of Inner Mongolia Medical University Medical University
🇨🇳
Hohhot, The Affiliated Hospital Of Inner Mongolia Medical University, China
Tianjin Medical University General Hospital
🇨🇳
Tianjin, Tianjin, China
Hanyang University Seoul Hospital
🇰🇷
Seoul, Korea, Republic of
SNU Boramae Medical Center
🇰🇷
Seoul, Korea, Republic of
Arizona Arthritis & Rheumatology Research, PLLC
🇺🇸
Glendale, Arizona, United States
Kyunghee University Hospital
🇰🇷
Seoul, Korea, Republic of
Chonnam National University Hospital
🇰🇷
Gwangju,, Gwangju, Korea, Republic of
Arthritis and Rheumatic Disease Specialties
🇺🇸
Aventura, Florida, United States
Drucker Sarasota Arthritis Research Center
🇺🇸
Sarasota, Florida, United States
Seattle Rheumatology Associates
🇺🇸
Seattle, Washington, United States
Clinic of Robert Hozman, MD / Clinical Investigation Specialists,
🇺🇸
Skokie, Illinois, United States
Klein & Associates, M.D., P.A.
🇺🇸
Hagerstown, Maryland, United States
M3 Emerging Medical Research, LLC
🇺🇸
Durham, North Carolina, United States
HRMD Research
🇺🇸
Dallas, Texas, United States