Back to resultsA Proof-of-Concept Study of AC-201 Controlled-Release Tablet (CR Tablet) in Patients With Hemophilic Arthropathy
Primary Purpose
Hemophilic Arthropathy
Status
Completed
Phase
Phase 2
Locations
Taiwan
Study Type
Interventional
Intervention
Placebo
AC-201CR
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilic Arthropathy
Eligibility Criteria
Inclusion Criteria:
- Male age 20 to 65 years, inclusive
- Diagnosis of Hemophilia A or B
- Clinical diagnosis of hemophilic arthropathy in the knee(s) for at least 6 months
- Pettersson score (based on X-ray) of 0 to 4 in at least one knee within 1 year of screening
- IPSG (2012) overall score of 3 to 9 (based on MRI) in at least one knee at screening
- Is able to read, understand, and sign the Informed Consent Form (ICF), communicate with the investigator, complete study diaries, and understand and comply with protocol requirements
Exclusion Criteria:
- Total knee replacement in the primary knee
- Presence of joint infections in the primary knee
- Knee surgery within 6 months prior to screening in the primary knee
- Intra-articular hyaluronic acid (IAHA) or platelet-rich plasma (PRP) injection in the primary knee within 6 months prior to screening
Use of any of the following medications after the screening visit:
- NSAID injection (oral NSAIDs including COX-2 inhibitors allowed)
- Glucosamine or chondroitin
- History of high responder inhibitory antibodies to factor VIII or factor IX clotting factor, with titer >5 Bethesda units (BU), OR clinical evidence for presence of factor inhibitor
- History of rheumatoid arthritis or gouty arthropathy
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) concentration >2x the upper limit of laboratory normal range (ULN), or bilirubin >1.5x ULN at screening
- Positive test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or TB
Sites / Locations
- Tri-Service General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
AC-201CR 72mg
Arm Description
Subjects will initiate blinded study medication at a once daily (QD) regimen for 4 weeks, then titrate to twice daily (BID) for the remainder of the 24-week blinded treatment period. At Week 24, subjects will discontinue blinded study medication and start open-label treatment with AC-201CR. All subjects will initiate open-label AC-201CR QD for 4 weeks, then titrate to BID for the remainder of the study.
Subjects will initiate blinded study medication at a once daily (QD) regimen for 4 weeks, then titrate to twice daily (BID) for the remainder of the 24-week blinded treatment period. At Week 24, subjects will discontinue blinded study medication and start open-label treatment with AC-201CR. All subjects will initiate open-label AC-201CR QD for 4 weeks, then titrate to BID for the remainder of the study.
Outcomes
Primary Outcome Measures
Change from baseline in IPSG (MRI) score for primary knee
Knee arthropathy will be evaluated according to the 2012 IPSG (International Prophylaxis Study Group) rating scale. This scale is an additive scale with maximum value up to 17 points, comprising 2 subscores of soft tissue changes (maximum 9 points) and osteochondral changes (maximum 8 points).
Secondary Outcome Measures
Change from baseline in IPSG (MRI) score for non-primary knee
Change from baseline in IPSG score by knee
Change from baseline in IPSG component scores by knee
Change from baseline in MRI-measured synovial thickness by knee
Change from baseline in ultrasonographic synovial thickness by knee
Change from baseline in ultrasonographic hyperemia score by knee
Change from baseline in knee pain (by VAS) by knee
Change from baseline in Short Form-36 score
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02994147
Brief Title
A Proof-of-Concept Study of AC-201 Controlled-Release Tablet (CR Tablet) in Patients With Hemophilic Arthropathy
Official Title
A Proof-of-Concept Study of AC-201 Controlled-Release Tablet (CR Tablet) in Patients With Hemophilic Arthropathy
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
March 21, 2017 (Actual)
Primary Completion Date
April 18, 2019 (Actual)
Study Completion Date
October 2, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
TWi Biotechnology, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Repeated joint bleeding leads to hemophilic arthropathy (HA), which manifests with chronic synovitis, cartilage damage and bony destruction. Currently available treatments of HA, including analgesics, NSAIDs, and hyaluronic acid, are predominantly directed toward the symptomatic relief of pain and inflammation, with no or little effect on joint cartilage degeneration. AC201CR, a control released formulation of AC-201, demonstrates anti-inflammatory effects by reducing NLRP3 inflammasome assembly. AC-201 is also unique in that it influences both the anabolism and catabolism of chondrocytes in vitro and has shown cartilage-sparing properties in animal studies. The study is designed to evaluate the joint structure-modifying and symptom-relieving effects, safety, and tolerability of AC-201CR in subjects with HA.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilic Arthropathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects will initiate blinded study medication at a once daily (QD) regimen for 4 weeks, then titrate to twice daily (BID) for the remainder of the 24-week blinded treatment period.
At Week 24, subjects will discontinue blinded study medication and start open-label treatment with AC-201CR. All subjects will initiate open-label AC-201CR QD for 4 weeks, then titrate to BID for the remainder of the study.
Arm Title
AC-201CR 72mg
Arm Type
Experimental
Arm Description
Subjects will initiate blinded study medication at a once daily (QD) regimen for 4 weeks, then titrate to twice daily (BID) for the remainder of the 24-week blinded treatment period.
At Week 24, subjects will discontinue blinded study medication and start open-label treatment with AC-201CR. All subjects will initiate open-label AC-201CR QD for 4 weeks, then titrate to BID for the remainder of the study.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo-only control study medication is the same formulation as active treatment without active ingredient
Intervention Type
Drug
Intervention Name(s)
AC-201CR
Intervention Description
The investigational product is formulated as controlled-release (CR) tablets
Primary Outcome Measure Information:
Title
Change from baseline in IPSG (MRI) score for primary knee
Description
Knee arthropathy will be evaluated according to the 2012 IPSG (International Prophylaxis Study Group) rating scale. This scale is an additive scale with maximum value up to 17 points, comprising 2 subscores of soft tissue changes (maximum 9 points) and osteochondral changes (maximum 8 points).
Time Frame
24 Weeks
Secondary Outcome Measure Information:
Title
Change from baseline in IPSG (MRI) score for non-primary knee
Time Frame
24 Weeks
Title
Change from baseline in IPSG score by knee
Time Frame
48 Weeks
Title
Change from baseline in IPSG component scores by knee
Time Frame
24 Weeks and 48 Weeks
Title
Change from baseline in MRI-measured synovial thickness by knee
Time Frame
24 Weeks and 48 Weeks
Title
Change from baseline in ultrasonographic synovial thickness by knee
Time Frame
24 Weeks and 48 Weeks
Title
Change from baseline in ultrasonographic hyperemia score by knee
Time Frame
24 Weeks and 48 Weeks
Title
Change from baseline in knee pain (by VAS) by knee
Time Frame
4, 12, 24, 28, 36 and 48 Weeks
Title
Change from baseline in Short Form-36 score
Time Frame
24 Weeks and 48 Weeks
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male age 20 to 65 years, inclusive
Diagnosis of Hemophilia A or B
Clinical diagnosis of hemophilic arthropathy in the knee(s) for at least 6 months
Pettersson score (based on X-ray) of 0 to 4 in at least one knee within 1 year of screening
IPSG (2012) overall score of 3 to 9 (based on MRI) in at least one knee at screening
Is able to read, understand, and sign the Informed Consent Form (ICF), communicate with the investigator, complete study diaries, and understand and comply with protocol requirements
Exclusion Criteria:
Total knee replacement in the primary knee
Presence of joint infections in the primary knee
Knee surgery within 6 months prior to screening in the primary knee
Intra-articular hyaluronic acid (IAHA) or platelet-rich plasma (PRP) injection in the primary knee within 6 months prior to screening
Use of any of the following medications after the screening visit:
NSAID injection (oral NSAIDs including COX-2 inhibitors allowed)
Glucosamine or chondroitin
History of high responder inhibitory antibodies to factor VIII or factor IX clotting factor, with titer >5 Bethesda units (BU), OR clinical evidence for presence of factor inhibitor
History of rheumatoid arthritis or gouty arthropathy
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) concentration >2x the upper limit of laboratory normal range (ULN), or bilirubin >1.5x ULN at screening
Positive test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or TB
Facility Information:
Facility Name
Tri-Service General Hospital
City
Taipei
Country
Taiwan
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Proof-of-Concept Study of AC-201 Controlled-Release Tablet (CR Tablet) in Patients With Hemophilic Arthropathy
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