A Proof-of-Concept Study of AC-201 to Prevent Gout Flares

Gout Flares Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled Trial Of AC-201 In Subjects With Gout Initiating Urate-Lowering Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01712204
• Other study ID #: AC-201-GOU-001
• Status: Completed
• Phase: Phase 2
• Start date: January 2013
• Est. completion date: September 2013

Study information

• Verified date: April 2018
• Source: TWi Biotechnology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Initiation of ULT for gout increases the occurrence of acute gouty arthritis flares due to mobilization of urate from tissue deposits. IL-1β plays a key role in mediating the inflammatory response in gouty arthritis. The efficacy of IL-1β blockade in the prophylaxis of gouty flares during initiation of ULT has been validated in multiple trials of IL-1β inhibitor therapies. Therefore, it is believed that IL-1β is a relevant therapeutic target for gout flares. AC-201 is an IL-1β modulator indicated for the treatment of osteoarthritis with good safety record and very few contraindications to the co-morbidities commonly among gout patients. AC-201 has also been demonstrated to have uric acid-lowering effects in clinical trials. The favorable product profile of AC-201 overall provides a strong rationale for investigating its clinical utility as prophylaxis against flares when initiating ULT.

Description:

Clinical trials have demonstrated that anti-IL-1 agents (IL-1Ra, IL-1 Trap, and anti-IL-1β monoclonal antibody) can reduce the frequency of gout flares during the initial period of treatment with urate-lowering therapy and prevent of gout flares in gout patients with frequent flares. AC-201 is an oral IL-1 modulator but with a mechanism distinct from that of existing anti-IL-1 agents. The active metabolite of AC-201 has been shown in vitro and in vivo to inhibit the production and activity of IL-1, down-regulate IL-1 receptors, and increase IL1-Ra. Molecular research further suggests that these effects are mediated upstream via inhibition of MAPK signaling pathways and binding of NF-κB and AP-1 transcription factors that encode for a range of pro-inflammatory factors, including IL-1β, TNF-α, IL-6, IL-8, iNOS, and MMPs, which have been implicated in gout flares. AC-201 has also been demonstrated to have uric acid-lowering effects in clinical trials. The favorable product profile of AC-201 overall provides a strong rationale for investigating its clinical utility as prophylaxis against flares when initiating ULT.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

• Male or female age 20 to 80 years, inclusive

• Meets at least 6 of the 12 American College of Rheumatology preliminary criteria (1977) for the classification of acute arthritis of primary gout, OR have proven tophus or documented monosodium urate (MSU) crystals in the joint fluid

• Serum uric acid =7.5 mg/dL at screening

• Experienced =2 gouty arthritis flares within one year prior to screening

Exclusion Criteria:

• Occurrence of a gouty arthritis flare ongoing at screening or during the screening period through baseline

• Use of allopurinol, febuxostat, benzbromarone, probenecid, or sulfinpyrazone within 4 weeks prior to screening

• Use of colchicine, glucocorticoids, NSAIDs, or COX-2 inhibitors within 1 week prior to screening

• Other (non-gout) chronic arthritis, acute inflammatory arthritis, autoimmune diseases with arthritis, or any condition requiring chronic daily use of pain medication

• History of allergy to any components of study medication, including diacerein

• Allergy, contraindication, or intolerance to febuxostat

• Contraindication or allergy to NSAIDs

• Severe renal impairment

• Any prior use of biologic anti-inflammatory therapy, such as IL-1 modulators, tumor necrosis factor inhibitors, IL-6 inhibitors, or T-cell costimulation modulator

Related Conditions & MeSH terms

• Gout
• Gout Flares

Intervention

Drug:
• Placebo
Placebo Capsule BID for 16 Weeks
• AC-201
AC-201 50mg Capsule BID for 16 Weeks
• Febuxostat
Febuxostat 80 mg QD for 16 Weeks

Locations

Country	Name	City	State
Taiwan	Veterans 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	Number of Gout Flares Per Subject		16 weeks