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

This study has been completed.
Information provided by (Responsible Party):
TWi Biotechnology, Inc.
ClinicalTrials.gov Identifier:
First received: October 19, 2012
Last updated: November 24, 2014
Last verified: November 2014
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.

Condition Intervention Phase
Gout Flares
Drug: Placebo
Drug: AC-201
Drug: Febuxostat
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Randomized, Double-Blind, Placebo-Controlled Trial Of AC-201 In Subjects With Gout Initiating Urate-Lowering Therapy

Resource links provided by NLM:

Further study details as provided by TWi Biotechnology, Inc.:

Primary Outcome Measures:
  • Number of Gout Flares Per Subject [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of Subjects Experiencing ≥1 or ≥2 Gout Flares [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Time to First Gout Flare [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Gout Flare Days Per Subject [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Duration of Gout Flares [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline in Serum Uric Acid Concentration [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Proportion of Subjects Achieving Serum Uric Acid Concentration <6.0 or <5.0 mg/dL [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Mean Pain Visual Analog Scale Score Associated With Gout Flares [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Enrollment: 82
Study Start Date: January 2013
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo plus Febuxostat
Drug: Placebo
Placebo Capsule BID for 16 Weeks
Other Name: PBO
Drug: Febuxostat
Febuxostat 80 mg QD for 16 Weeks
Other Name: ULT
Experimental: AC-201
AC-201 plus Febuxostat
Drug: AC-201
AC-201 50mg Capsule BID for 16 Weeks
Drug: Febuxostat
Febuxostat 80 mg QD for 16 Weeks
Other Name: 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.

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01712204

Veterans General Hospital
Taipei, Taiwan
Sponsors and Collaborators
TWi Biotechnology, Inc.
  More Information

Responsible Party: TWi Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT01712204     History of Changes
Other Study ID Numbers: AC-201-GOU-001 
Study First Received: October 19, 2012
Results First Received: November 24, 2014
Last Updated: November 24, 2014
Health Authority: United States: Food and Drug Administration
Taiwan: Taiwan Food and Drug Administration (TFDA)

Keywords provided by TWi Biotechnology, Inc.:
Prophylaxis of Acute Gout Flares
Urate-Lowering Therapy
Gouty arthritis

Additional relevant MeSH terms:
Genetic Diseases, Inborn
Joint Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Musculoskeletal Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Rheumatic Diseases
Antirheumatic Agents
Gout Suppressants

ClinicalTrials.gov processed this record on May 26, 2016