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

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: 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:

MedlinePlus related topics: Gout

Drug Information available for: Febuxostat

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 ]


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 Other Name: AC-201 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.

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

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

Locations


Taiwan
Veterans General Hospital
Taipei, Taiwan

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
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 Hyperuricemia Gouty arthritis

Additional relevant MeSH terms:


Febuxostat Antirheumatic Agents Gout Suppressants Pharmacologic Actions Therapeutic Uses

ClinicalTrials.gov processed this record on March 01, 2015