Clinical trial NCT04795141: ABY-035 in the Treatment of Subjects With Ankylosing Spondylitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ankylosing Spondylitis
Lead sponsor: Inmagene LLC
Sponsor class: INDUSTRY
Collaborators: name: Affibody
First posted: 2021-03-12
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of subjects achieving an ASAS40 response
timeFrame: 16 weeks
Secondary outcomes:
measure: Change from baseline in BASDAI
timeFrame: 16 weeks
measure: Change from baseline in BASFI
timeFrame: 16 weeks
measure: Proportion of subjects reaching ASDAS-MI
timeFrame: 16 weeks
measure: Incidence of AEs
timeFrame: 74 weeks
measure: Incidence of serious adverse events (SAEs) and adverse events of special interests (AESIs)
timeFrame: 74 weeks
measure: AEs leading to withdrawal from investigational medicinal product (IMP)
timeFrame: 74 weeks
measure: Change in safety laboratory parameters and vital signs compared to baseline
timeFrame: 74 weeks
measure: Proportion of subjects achieving an ASAS40 response, ASAS20 response, ASAS partial remission, and ASAS 5/6 response respectively at required timepoints
timeFrame: 52 weeks
measure: Change from baseline in BASDAI and BASFI at required timepoints
timeFrame: 52 weeks
measure: Proportion of subjects reaching BASDAI50 and ASDAS-MI at required timepoints
timeFrame: 52 weeks
measure: Proportion of subjects experiencing clinically important improvement at required timepoints
timeFrame: 52 weeks
measure: ASDAS-CRP and ASDAS status at required timepoints
timeFrame: 52 weeks
measure: Change from baseline in total and nocturnal pain at required timepoints
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Arizona Arthritis & Rheumatology Research, PLLC
state: Arizona
city: Canoga Park
country: United States
facility: Hope Clinical Research
state: California
city: Huntington Beach
country: United States
facility: Newport Huntington Medical Group
state: California
city: Palm Desert
country: United States
facility: Desert Medical Advances
state: California
city: Aventura
country: United States
facility: Arthritis and Rheumatic Disease Specialties
state: Florida
city: Sarasota
country: United States
facility: Drucker Sarasota Arthritis Research Center
state: Florida
city: Schaumburg
country: United States
facility: Greater Chicago Specialty Physicians/ Clinical Investigation Specialists, Inc.
state: Illinois
city: Skokie
country: United States
facility: Clinic of Robert Hozman, MD / Clinical Investigation Specialists,
state: Illinois
city: Hagerstown
country: United States
facility: Klein & Associates, M.D., P.A.
state: Maryland
city: Wheaton
country: United States
facility: The Center for Rheumatology and Bone Research
state: Maryland
city: Durham
country: United States
facility: M3 Emerging Medical Research, LLC
state: North Carolina
city: Perrysburg
country: United States
facility: Clinical Research Source, Inc.
state: Ohio
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Dallas
country: United States
facility: HRMD Research
state: Texas
city: Seattle
country: United States
facility: Seattle Rheumatology Associates
state: Washington
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital,Capital Medical University
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital Sun Yat-Sen University
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Tong Ji Hospital TongJi Medical Colleague of HUST
state: Hubei
city: Zhuzhou
country: China
facility: Zhuzhou Hospital Affiliated to Xiangya School of Medicine
state: Hunan
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and TechNology
state: Inner Mongolia
city: Nanjing
country: China
facility: The Affiliated Drum Tower Hospital of Nanjing University Medical School
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Shanghai
country: China
facility: Changhai Hospital of Shanghai
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Gaoxiong
country: China
facility: Kaohsiung Chang Gung Memorial Hospital ，Chang Gung Medical Foundation
state: Taiwan
city: Gaoxiong
country: China
facility: Kaohsiung Veterans General Hospital
state: Taiwan
city: Taibei
country: China
facility: National Taiwan University Hospital (NTUH)
state: Taiwan
city: Taibei
country: China
facility: Tri-Service General Hospital
state: Taiwan
city: Taizhong
country: China
facility: China Medical University Hospital (CMUH)
state: Taiwan
city: Taizhong
country: China
facility: Chung Shan Medical University Hospital (CSMHU)
state: Taiwan
city: Hohhot
country: China
facility: The Affiliated Hospital of The Affiliated Hospital of Inner Mongolia Medical University Medical University
state: The Affiliated Hospital Of Inner Mongolia Medical University
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Gwangju,
country: Korea, Republic of
facility: Chonnam National University Hospital
state: Gwangju
city: Gyeonggi-do
country: Korea, Republic of
facility: Ajou University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Bundang Seoul National University Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Kyunghee University Hospital
city: Seoul
country: Korea, Republic of
facility: SNU Boramae Medical Center
Study officials:
affiliation: SVP, Global Regulatory Head
name: Lawrence He
role: STUDY_DIRECTOR
References: