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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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 Summary: 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.
Sponsor: TWi Biotechnology, Inc.

Current Primary Outcome: Number of Gout Flares Per Subject [ Time Frame: 16 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Proportion of Subjects Experiencing ≥1 or ≥2 Gout Flares [ Time Frame: 16 weeks ]
  • Time to First Gout Flare [ Time Frame: 16 weeks ]
  • Gout Flare Days Per Subject [ Time Frame: 16 weeks ]
  • Duration of Gout Flares [ Time Frame: 16 weeks ]
  • Change From Baseline in Serum Uric Acid Concentration [ Time Frame: 16 weeks ]
  • Proportion of Subjects Achieving Serum Uric Acid Concentration <6.0 or <5.0 mg/dL [ Time Frame: 16 weeks ]


Original Secondary Outcome:

Information By: TWi Biotechnology, Inc.

Dates:
Date Received: October 19, 2012
Date Started: January 2013
Date Completion:
Last Updated: November 24, 2014
Last Verified: November 2014