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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Gout Flares	Drug: Placebo; Drug: AC-201; Drug: Febuxostat	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	82 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Prevention
Official Title:	A Randomized, Double-Blind, Placebo-Controlled Trial Of AC-201 In Subjects With Gout Initiating Urate-Lowering Therapy
Study Start Date :	January 2013
Actual Primary Completion Date :	September 2013
Actual Study Completion Date :	September 2013

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
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

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Number of Gout Flares Per Subject [ Time Frame: 16 weeks ]

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Mean Pain Visual Analog Scale Score Associated With Gout Flares [ Time Frame: 16 weeks ]

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	20 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Taiwan
Veterans General Hospital
Taipei, Taiwan

Sponsors and Collaborators

TWi Biotechnology, Inc.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	TWi Biotechnology, Inc.
ClinicalTrials.gov Identifier:	NCT01712204 History of Changes
Other Study ID Numbers:	AC-201-GOU-001
First Posted:	October 23, 2012
Results First Posted:	December 1, 2014
Last Update Posted:	December 1, 2014
Last Verified:	November 2014

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; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors	Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Febuxostat; Gout Suppressants; Antirheumatic Agents