A Proof-of-Concept Study of AC-201 Controlled-Release Tablet (CR Tablet) in Patients With Hemophilic Arthropathy

Hemophilic Arthropathy Clinical Trial

Official title:

A Proof-of-Concept Study of AC-201 Controlled-Release Tablet (CR Tablet) in Patients With Hemophilic Arthropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02994147
• Other study ID #: AC-201CR-HA-001
• Status: Completed
• Phase: Phase 2
• Start date: March 21, 2017
• Est. completion date: October 2, 2019

Study information

• Verified date: July 2020
• Source: TWi Biotechnology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: October 2, 2019
• Est. primary completion date: April 18, 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 20 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemophilic Arthropathy
• Joint Diseases

Intervention

Drug:
• Placebo
Placebo-only control study medication is the same formulation as active treatment without active ingredient
• AC-201CR
The investigational product is formulated as controlled-release (CR) tablets

Locations

Country	Name	City	State
Taiwan	Tri-Service General Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
TWi Biotechnology, Inc.

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	24 Weeks
Secondary	Change from baseline in IPSG (MRI) score for non-primary knee		24 Weeks
Secondary	Change from baseline in IPSG score by knee		48 Weeks
Secondary	Change from baseline in IPSG component scores by knee		24 Weeks and 48 Weeks
Secondary	Change from baseline in MRI-measured synovial thickness by knee		24 Weeks and 48 Weeks
Secondary	Change from baseline in ultrasonographic synovial thickness by knee		24 Weeks and 48 Weeks
Secondary	Change from baseline in ultrasonographic hyperemia score by knee		24 Weeks and 48 Weeks
Secondary	Change from baseline in knee pain (by VAS) by knee		4, 12, 24, 28, 36 and 48 Weeks
Secondary	Change from baseline in Short Form-36 score		24 Weeks and 48 Weeks