ABY-035 in the Treatment of Subjects With Ankylosing Spondylitis

• ClinicalTrials.gov Identifier: NCT04795141
• Recruitment Status: Terminated
• First Posted: March 12, 2021
• Last Update Posted: September 22, 2022
• Sponsor: Inmagene Biopharmaceuticals
• Collaborator: Affibody
• Information provided by (Responsible Party): Inmagene Biopharmaceuticals

Tracking Information

• First Submitted Date: March 3, 2021
• First Posted Date: March 12, 2021
• Last Update Posted Date: September 22, 2022
• Actual Study Start Date: August 24, 2021
• Actual Primary Completion Date: July 11, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 10, 2021)

Proportion of subjects achieving an ASAS40 response [ Time Frame: 16 weeks ]

The treatment effect

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 10, 2021)

• Change from baseline in BASDAI [ Time Frame: 16 weeks ]
  The treatment effect
• Change from baseline in BASFI [ Time Frame: 16 weeks ]
  The treatment effect
• Proportion of subjects reaching ASDAS-MI [ Time Frame: 16 weeks ]
  The treatment effect
• Incidence of AEs [ Time Frame: 74 weeks ]
  Safety information
• Incidence of serious adverse events (SAEs) [ Time Frame: 74 weeks ]
  Safety information
• AEs leading to withdrawal from investigational medicinal product (IMP) [ Time Frame: 74 weeks ]
  Safety information
• Proportion of subjects achieving an ASAS40 response at Week 2, 24 and 52 [ Time Frame: 52 weeks ]
  The treatment effect
• Change from baseline in BASDAI at Week 2, 24 and 52 [ Time Frame: 52 weeks ]
  The treatment effect
• Change from baseline in BASFI at Week 2, 24 and 52 [ Time Frame: 52 weeks ]
  The treatment effect
• Proportion of subjects reaching ASDAS-MI at Week 24 and 52 [ Time Frame: 52 weeks ]
  The treatment effect

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Eligible subjects will be randomized 1:1:1:1 to receive 1 of 4 treatments (ABY-035 80 mg Q2W, ABY-035 160 mg Q4W, ABY-035 40 mg Q2W, or placebo), 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 Subjects will continue their original treatment of Treatment Period 1 in a double-blinded manner.

Subjects who couldn't achieve an ASAS20 response from baseline are defined as non-responders and eligible for rescue treatment after Week 16 (Visit 9).

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

2. Treatment Period 1 (Placebo-Controlled, Double-Blind Period): Day 0 to Week 16 Cohort 1: Eligible subjects will be randomized 1:1:1:1 to receive 1 of 4 treatments, and will remain on their allowable background medication.

Cohort 2: Eligible subjects will be randomized 1:1:1 to receive 1 of 3 treatments , and will remain on their allowable background medication.

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 (Open-label Extension Period): Week 16 to Week 52 Cohort 1: Subjects will receive Group A treatment in an open-label manner. Cohort 2: Subjects will receive Group A treatment in an open-label manner. At Week 24, subjects who could not achieve an ASAS20 response from baseline are defined as non-responders and will discontinue the study treatment.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Ankylosing Spondylitis

Intervention

• Drug: ABY-035
  ABY-035 Duration: 52 weeks
  Other Name: Izokibep
• Drug: Normal saline
  Dosage form: Solution for injection; Duration: 52 weeks
  Other Name: placebo

Study Arms

• Active Comparator: Group A
  ABY-035 SC injection Cohort 1
  Intervention: Drug: ABY-035
• Active Comparator: Group B
  ABY-035 SC injection Cohort 1
  Intervention: Drug: ABY-035
• Active Comparator: Group C
  ABY-035 SC injection Cohort 1
  Intervention: Drug: ABY-035
• Placebo Comparator: Group D
  Placebo injection Cohort 1
  Intervention: Drug: Normal saline
• Active Comparator: Group E
  ABY-035 SC injection Cohort 2
  Intervention: Drug: ABY-035
• Active Comparator: Group F
  ABY-035 SC injection Cohort 2
  Intervention: Drug: ABY-035
• Placebo Comparator: Group G
  Placebo injection Cohort 2
  Intervention: Drug: Normal saline

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: September 21, 2022): 25
• Original Estimated Enrollment (submitted: March 10, 2021): 300
• Actual Study Completion Date: August 30, 2022
• Actual Primary Completion Date: July 11, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China, Korea, Republic of, United States
• Removed Location Countries: Cayman Islands

Administrative Information

• NCT Number: NCT04795141
• Other Study ID Numbers: ABY-035-204
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Inmagene Biopharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Inmagene Biopharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Affibody

Investigators

• Study Director: Sammy Zhu; clinical medical director

• PRS Account: Inmagene Biopharmaceuticals
• Verification Date: September 2022