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

Primary Purpose

Gout Flares

Status

Completed

Phase

Phase 2

Locations

Taiwan

Study Type

Interventional

Intervention

Placebo

AC-201

Febuxostat

About this trial

This is an interventional prevention trial for Gout Flares focused on measuring Prophylaxis of Acute Gout Flares, Urate-Lowering Therapy, Hyperuricemia, Gouty arthritis

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Veterans General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

AC-201

Arm Description

Placebo plus Febuxostat

AC-201 plus Febuxostat

Outcomes

Primary Outcome Measures

Number of Gout Flares Per Subject

Secondary Outcome Measures

Full Information

NCT ID

NCT01712204

First Posted

October 19, 2012

Last Updated

April 24, 2018

Sponsor

TWi Biotechnology, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01712204

Brief Title

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

Official Title

A Randomized, Double-Blind, Placebo-Controlled Trial Of AC-201 In Subjects With Gout Initiating Urate-Lowering Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

April 2018

Overall Recruitment Status

Completed

Study Start Date

January 2013 (undefined)

Primary Completion Date

September 2013 (Actual)

Study Completion Date

September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

TWi Biotechnology, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gout Flares

Keywords

Prophylaxis of Acute Gout Flares, Urate-Lowering Therapy, Hyperuricemia, Gouty arthritis

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

82 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo plus Febuxostat

Arm Title

AC-201

Arm Type

Experimental

Arm Description

AC-201 plus Febuxostat

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

PBO

Intervention Description

Placebo Capsule BID for 16 Weeks

Intervention Type

Drug

Intervention Name(s)

AC-201

Intervention Description

AC-201 50mg Capsule BID for 16 Weeks

Intervention Type

Drug

Intervention Name(s)

Febuxostat

Other Intervention Name(s)

ULT

Intervention Description

Febuxostat 80 mg QD for 16 Weeks

Primary Outcome Measure Information:

Title

Number of Gout Flares Per Subject

Time Frame

16 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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

Facility Information:

Facility Name

Veterans General Hospital

City

Taipei

Country

Taiwan

12. IPD Sharing Statement

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

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