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

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ClinicalTrials.gov Identifier: NCT01712204
Recruitment Status : Completed
First Posted : October 23, 2012
Results First Posted : December 1, 2014
Last Update Posted : May 22, 2018
Sponsor:
Information provided by (Responsible Party):
TWi Biotechnology, Inc.

Tracking Information
First Submitted Date  ICMJE October 19, 2012
First Posted Date  ICMJE October 23, 2012
Results First Submitted Date  ICMJE November 24, 2014
Results First Posted Date  ICMJE December 1, 2014
Last Update Posted Date May 22, 2018
Study Start Date  ICMJE January 2013
Actual Primary Completion Date September 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 22, 2012)
Number of Gout Flares Per Subject [ Time Frame: 16 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01712204 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Proof-of-Concept Study of AC-201 to Prevent Gout Flares
Official Title  ICMJE 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 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE Gout Flares
Intervention  ICMJE
  • Drug: Placebo
    Placebo Capsule BID for 16 Weeks
    Other Name: PBO
  • Drug: AC-201
    AC-201 50mg Capsule BID for 16 Weeks
  • Drug: Febuxostat
    Febuxostat 80 mg QD for 16 Weeks
    Other Name: ULT
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo plus Febuxostat
    Interventions:
    • Drug: Placebo
    • Drug: Febuxostat
  • Experimental: AC-201
    AC-201 plus Febuxostat
    Interventions:
    • Drug: AC-201
    • Drug: Febuxostat
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 24, 2014)
82
Original Estimated Enrollment  ICMJE
 (submitted: October 22, 2012)
80
Actual Study Completion Date  ICMJE September 2013
Actual Primary Completion Date September 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01712204
Other Study ID Numbers  ICMJE AC-201-GOU-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party TWi Biotechnology, Inc.
Study Sponsor  ICMJE TWi Biotechnology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account TWi Biotechnology, Inc.
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP