NCT01712204

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

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 82 (actual)
• Sponsor: TWi Biotechnology, Inc. · Industry
• Sex: All
• Age: 20 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Gout Flares

Interventions

Type	Name	Description
DRUG	Placebo	Placebo Capsule BID for 16 Weeks
DRUG	AC-201	AC-201 50mg Capsule BID for 16 Weeks
DRUG	Febuxostat	Febuxostat 80 mg QD for 16 Weeks

Timeline

• Start date: 2013-01-01
• Primary completion: 2013-09-01
• Completion: 2013-09-01
• First posted: 2012-10-23
• Last updated: 2018-05-22
• Results posted: 2014-12-01

Locations

1 site across 1 country: Taiwan