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

This study is currently recruiting participants.
Verified April 2013 by TWi Biotechnology, Inc.
Sponsor:
Information provided by (Responsible Party):
TWi Biotechnology, Inc.
ClinicalTrials.gov Identifier:
NCT01712204
First received: October 19, 2012
Last updated: April 7, 2013
Last verified: April 2013
History of Changes
  Purpose

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: AC-201 50mg Capsule BID for 16 Weeks
Drug: Placebo Capsule BID for 16 Weeks
 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:

MedlinePlus related topics: Gout
U.S. FDA Resources

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 ]

Estimated Enrollment: 80
Study Start Date: January 2013
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AC-201
AC-201 50mg Capsule BID for 16 Weeks
 Drug: AC-201 50mg Capsule BID for 16 Weeks
Placebo Comparator: Placebo
Placebo Capsule BID for 16 Weeks
 Drug: Placebo Capsule BID for 16 Weeks

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.

  Eligibility

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

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

Contacts
Contact: Emily Lin 886-2-26573350 ext 364 emily.lin@twipharma.com

Locations
Taiwan
Veterans General Hospital Recruiting
Taipei, Taiwan
Contact: Emily Lin     886-2-26573350 ext 364     emily.lin@twipharma.com    
Sponsors and Collaborators
TWi Biotechnology, Inc.
  More Information

No publications provided

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
Last Updated: April 7, 2013
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
Hyperuricemia
Gouty arthritis

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

ClinicalTrials.gov processed this record on May 16, 2013