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

TWi Biotechnology

Status and phase: Completed; Phase 2

Conditions: Hemophilic Arthropathy

Treatments: Drug: Placebo; Drug: AC-201CR

Study type: Interventional

Funder types: Industry

Identifiers

NCT02994147

AC-201CR-HA-001

Details and patient eligibility

About

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.

Enrollment: 22 patients

Sex: Male

Ages: 20 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

22 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

1. 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. 2. 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.

Treatment:

Drug: Placebo

AC-201CR 72mg

Experimental group

Description:

1. 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. 2. 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.

Treatment:

Drug: AC-201CR