Study Evaluating AGG-523 in Subjects With Severe Osteoarthritis Requiring Total Knee Replacement

A Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Regimen, Parallel-Group Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AGG-523 Administered Orally to Subjects With Severe Osteoarthritis

The main purpose of the study is to find out if, after 4 weeks of dosing, signs of the investigational drug AGG-523, or its effects, can be measured in urine, blood, or the knee joint. A secondary purpose is to evaluate the safety of taking the drug either once a day or twice a day for 4 weeks.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: AGG-523 (Aggrecanase Inhibitor)

Detailed Description

This is a multicenter study of 2 dosing regimens of AGG-523, an investigational aggrecanase inhibitor that is taken orally. Potential study subjects are those with severe Osteoarthritis (OA) of the knee who are scheduled to undergo total joint replacement surgery.

Study subjects will be randomly assigned to 1 of 2 dosing regimens (once-daily or twice-daily dosing) of either 1800 mg AGG-523 or placebo, which will be taken during the 4-week period before having the total knee replacement. The treatments will be assigned using a 4:1 ratio of active to placebo treatment, which means that more subjects will receive the active treatment than the placebo (see below).

• AGG-523 1800 mg once a day (32 subjects)
• AGG-523 900 mg twice a day (32 subjects)
• Placebo once a day (8 subjects)
• Placebo twice a day (8 subjects)

Study subjects will have weekly evaluations as outpatients during the 4-week dosing period. The purpose of these evaluations is to monitor for potential complications, ensure compliance with taking the study drug, ask about the use of other medications, and, when necessary, replenish the supply of study drug. These assessments may be conducted by telephone, as a home visit, or by having the subject travel to the clinic for an outpatient office visit. A final (in person) visit will happen 2 weeks after having total knee replacement surgery.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02120
    • Boston, Massachusetts, United States, 02215
    • Newton, Massachusetts, United States, 02462
    • Winchester, Massachusetts, United States, 01801
    • Worcester, Massachusetts, United States, 01655

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Generally healthy, men or women, at least 55 years old
• Osteoarthritis of the knee requiring total knee replacement surgery

Exclusion Criteria:

• Other types of arthritis, like rheumatoid arthritis
• Recent major surgery (in past 3 months)
• Recent knee injections (in past 6 months)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; AGG-523 1800 mg QD PO (12 capsules) for 28 days	Drug: AGG-523 (Aggrecanase Inhibitor)
Active Comparator: B; AGG-523 900 mg BID PO (12 capsules) for 28 days	Drug: AGG-523 (Aggrecanase Inhibitor)
Placebo Comparator: C; Placebo QD PO (12 capsules) for 28 days	Drug: AGG-523 (Aggrecanase Inhibitor)
Placebo Comparator: D; Placebo BID PO (12 capsules) for 28 days	Drug: AGG-523 (Aggrecanase Inhibitor)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Using parts of the knee joint and the surrounding fluid that is taken out at the time of knee replacement, measure 1) the activity of aggrecansase (an enzyme that breaks down cartilage) and 2) the amount of study drug using lab tests.	4 weeks

Collaborators and Investigators

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Investigators: Study Director: Medical Montior, Wyeth is now a wholly owned subsidiary of Pfizer

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: March 29, 2007
• First Submitted That Met QC Criteria: March 29, 2007
• First Posted (Estimate): March 30, 2007

Study Record Updates

• Last Update Posted (Estimate): July 29, 2009
• Last Update Submitted That Met QC Criteria: July 28, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: Arthritis; Severe Osteoarthritis
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: 3189A1-106