Clinical trial NCT02994147: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemophilic Arthropathy
Lead sponsor: TWi Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2016-12-15
Enrollment: 22
Sex: MALE
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Male age 20 to 65 years, inclusive
2. Diagnosis of Hemophilia A or B
3. Clinical diagnosis of hemophilic arthropathy in the knee(s) for at least 6 months
4. Pettersson score (based on X-ray) of 0 to 4 in at least one knee within 1 year of screening
5. IPSG (2012) overall score of 3 to 9 (based on MRI) in at least one knee at screening
6. 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:

1. Total knee replacement in the primary knee
2. Presence of joint infections in the primary knee
3. Knee surgery within 6 months prior to screening in the primary knee
4. Intra-articular hyaluronic acid (IAHA) or platelet-rich plasma (PRP) injection in the primary knee within 6 months prior to screening
5. Use of any of the following medications after the screening visit:

   1. NSAID injection (oral NSAIDs including COX-2 inhibitors allowed)
   2. Glucosamine or chondroitin
6. 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
7. History of rheumatoid arthritis or gouty arthropathy
8. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) concentration \>2x the upper limit of laboratory normal range (ULN), or bilirubin \>1.5x ULN at screening
9. Positive test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or TB

Primary outcomes:
measure: Change from baseline in IPSG (MRI) score for primary knee
timeFrame: 24 Weeks
Secondary outcomes:
measure: Change from baseline in IPSG (MRI) score for non-primary knee
timeFrame: 24 Weeks
measure: Change from baseline in IPSG score by knee
timeFrame: 48 Weeks
measure: Change from baseline in IPSG component scores by knee
timeFrame: 24 Weeks and 48 Weeks
measure: Change from baseline in MRI-measured synovial thickness by knee
timeFrame: 24 Weeks and 48 Weeks
measure: Change from baseline in ultrasonographic synovial thickness by knee
timeFrame: 24 Weeks and 48 Weeks
measure: Change from baseline in ultrasonographic hyperemia score by knee
timeFrame: 24 Weeks and 48 Weeks
measure: Change from baseline in knee pain (by VAS) by knee
timeFrame: 4, 12, 24, 28, 36 and 48 Weeks
measure: Change from baseline in Short Form-36 score
timeFrame: 24 Weeks and 48 Weeks
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
Study officials:
References: