Study of AA4500 in the Treatment of Peyronie's Disease

NCT01221623 | Completed Phase 3 Results

• 1 other identifier: AUX-CC-804
• Study Type: interventional
• Target: 418
• Locations: 2 countries
• Sites: 34

Brief Summary

This study is a Phase 3, double-blind, randomized, placebo-controlled study of the safety and efficacy of AA4500 0.58 mg in subjects with Peyronie's disease. Approximately 300 (200 AA4500 and 100 placebo) men will be randomized. Subjects will be screened for study eligibility within 21 days before the initial injection of study drug in the first treatment cycle. Before dosing, subjects will be stratified by degree of penile curvature (ie, 30º to 60º or 61º to 90º) and then randomized into two treatment groups to receive in a 2:1 ratio either AA4500 0.58 mg or placebo. In this study, qualified subjects may receive up to four treatment cycles; each cycle will be separated by a period of 42 days (± 5 days). During each treatment cycle, subjects will receive two injections of study drug with at least 24 hours but not more than 72 hours between injections. After the final injection of each treatment cycle, the investigator or qualified designee will model the penile plaque in an attempt to stretch or elongate the plaque. If the subject's penile curvature is reduced to \< 15 degrees after the first, second, or third cycle of injections or if the investigator determines further treatment is not clinically indicated (eg, adverse events; allergic reaction), subsequent treatment cycles will not be administered. Following the maximum of four treatment cycles, each subject will be followed for additional safety and efficacy assessments on Days 169 (± 7 days), 232 (± 7 days), 295 (± 7 days), 365 (± 7 days) (nominal weeks 24, 33, 42 and 52). Subjects randomized to placebo may receive open-label AA4500 treatment after completing this study as part of another protocol.

Conditions

Peyronie's Disease

Keywords

Peyronie's Disease; penile plaque; penile curvature

Outcome Measures

Primary Outcomes (2)

• Percentage Change From Baseline in Penile Curvature

  A negative value in the percentage change from baseline in penile curvature deformity (angle measured in degrees) indicates less curvature.

  Baseline and Week 52

• Change From Baseline in the Peyronie's Disease Bother Domain of the Peyronie's Disease Questionnaire (PDQ)

  Peyronie's disease bother score range 0 (no issue or not at all bothered) to 4 (extremely bothered) on 4 questions; total score range 0 to 16. A decrease in the change from baseline total score in the Peyronie's disease bother domain of the PDQ is indicated by a negative number.

  Baseline and Week 52

Secondary Outcomes (7)

• A Responder Analysis Based on Subject Overall Global Assessment

  Week 52

• Change From Baseline in the Severity of Peyronie's Disease Symptoms Domain of the PDQ

  Baseline and Week 52

• Change in the Overall Satisfaction Domain of the International Index of Erectile Function (IIEF)

  Baseline and Week 52

• Change From Baseline in Penile Plaque Consistency

  Baseline and Week 52

• Change From Baseline in Penile Length

  Baseline and Week 52

Study Arms (2)

AA4500

EXPERIMENTAL

collagenase clostridium histolyticum

Biological: AA4500

Placebo

PLACEBO COMPARATOR

Placebo

Biological: Placebo

Interventions

AA4500 BIOLOGICAL

2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.

Also known as: XIAFLEX

AA4500

Placebo BIOLOGICAL

2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be a male and be ≥ 18 years of age
• Be in a stable relationship with a female partner/spouse for at least 3 months before screening and be willing to have vaginal intercourse with that partner/spouse
• Have symptom(s) of Peyronie's disease for at least 12 months before the first dose of study drug and have evidence of stable disease as determined by the investigator
• Have penile curvature of at least 30° in the dorsal, lateral, or dorsal/lateral plane at screening. It must be possible to delineate the single plane of maximal curvature for evaluation during the study
• Be judged to be in good health, based upon the results of a medical history, physical examination, and laboratory profile
• Voluntarily sign and date an informed consent agreement approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC). The subject must also sign an authorization form to allow disclosure of his protected health information (PHI). The PHI authorization form and informed consent form may be an integrated form or may be separate forms depending on the institution
• Be able to read, complete, and understand the various rating instruments in English

You may not qualify if:

• Has a penile curvature of less than 30° or greater than 90° at the screening visit
• Has any of the following conditions:
• Chordee in the presence or absence of hypospadias
• Thrombosis of the dorsal penile artery and/or vein
• Infiltration by a benign or malignant mass resulting in penile curvature
• Infiltration by an infectious agent, such as lymphogranuloma venereum
• Ventral curvature from any cause
• Presence of an active sexually transmitted disease
• Known active hepatitis B or C
• Known immune deficiency disease or be positive for human immunodeficiency virus (HIV)
• Has previously undergone surgery for Peyronie's disease
• Fails to have an erection which in the opinion of the investigator is sufficient to accurately measure the subject's penile deformity after administration of prostaglandin E1 (PGE1) or trimix
• Has an isolated hourglass deformity of the penis
• Has the plaque causing curvature of the penis located proximal to the base of the penis, so that the injection of the local anesthetic would interfere with the injection of AA4500 into the plaque
• Has previously received alternative medical therapies for Peyronie's disease administered by the intralesional route (including, but not limited to, steroids, verapamil, and the naturally occurring low molecular weight protein, interferon-α2b) within 3 months before the first dose of study drug or plans to use any of these medical therapies at any time during the study

Sponsors & Collaborators

• Endo Pharmaceuticals: lead

Study Sites (34)

Costal Clinical Research, Inc.

Mobile, Alabama, 36608, United States

Location

Alaska Clinical Research Center, LLC

Anchorage, Alaska, 99508, United States

Location

Connect Clinical Research Center (CCRC)

Phoenix, Arizona, 85048, United States

Location

So. Orange County Medical Research Center

Laguna Hills, California, 92653, United States

Location

The Urology Center of Colorado

Denver, Colorado, 80211, United States

Location

Connecticut Clinical Resarch Center, LLC

Middlebury, Connecticut, 06762, United States

Location

South Florida Medical Research

Aventura, Florida, 33180, United States

Location

Winter Park Urology Associates

Orlando, Florida, 32803, United States

Location

Idaho Urologic Institute

Meridian, Idaho, 83642, United States

Location

Northeast Indiana Research, LLC

Fort Wayne, Indiana, 46825, United States

Location

Metropolitan Urology, P.S.C.

Jeffersonville, Indiana, 47130, United States

Location

Kansas City Urology Care, P.A. Research Department

Overland Park, Kansas, 66211, United States

Location

Tulane University Health Sciences Center Dept. of Urology

New Orleans, Louisiana, 70112, United States

Location

Regional Urology L.L.C.

Shreveport, Louisiana, 71106, United States

Location

Chesapeake Urology Research Assoc.

Glen Burnie, Maryland, 21061, United States

Location

Chesapeake Urology Research Assoc., PA

Towson, Maryland, 21204, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Cooper Health System

Camden, New Jersey, 08103, United States

Location

AdvanceMed Research

Lawrenceville, New Jersey, 08648, United States

Location

The Capital Region Medical Research Foundation @ the Urological Institute of Northeastern New York

Albany, New York, 12208, United States

Location

Bruce R. Gilbert, MD, PhD, PC

Great Neck, New York, 11021, United States

Location

University Urology Associates

New York, New York, 10016, United States

Location

Michael A. Werner, MD, PC

Purchase, New York, 10577, United States

Location

Universitiy of North Carolina School of Medicine Div. of Urology

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center Division of Urologic Surgery

Durham, North Carolina, 27710, United States

Location

The Miriam Hospital

Providence, Rhode Island, 02906, United States

Location

Research Across America

Carrollton, Texas, 75010, United States

Location

Urology Clinics of North Texas, PA

Dallas, Texas, 75231, United States

Location

Urology San Antonio Research, PA

San Antonio, Texas, 78229, United States

Location

Urology Sydney

Kogarah, New South Wales, NSW 2217, Australia

Location

Health Pac Medical Centre

Sydney, New South Wales, NSW 2000, Australia

Location

AusTrials Pty Limited

Brisbane, Queensland, QLD 4000, Australia

Location

Bayside Urology

Mentone, Victoria, VIC 3193, Australia

Location

Keogh Institute for Medical Research

Nedlands, Western Australia, WA 6009, Australia

Location

Related Publications (1)

• Hellstrom WJ, Feldman RA, Coyne KS, Kaufman GJ, Smith TM, Tursi JP, Rosen RC. Self-report and Clinical Response to Peyronie's Disease Treatment: Peyronie's Disease Questionnaire Results From 2 Large Double-Blind, Randomized, Placebo-Controlled Phase 3 Studies. Urology. 2015 Aug;86(2):291-8. doi: 10.1016/j.urology.2015.04.047. Epub 2015 Jul 18.

  PMID: 26199168 DERIVED

MeSH Terms

Conditions

Penile Induration

Interventions

Microbial Collagenase

Condition Hierarchy (Ancestors)

Penile Diseases; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Collagenases; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases

Results Point of Contact

• Title: Clinical Trial Coordinator
• Organization: Endo Pharmaceuticals, Inc.

clinicalsite.inquiries@endo.com

Study Officials

• Gregory Kaufman, MD

  Auxilium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2010
• First Posted: October 15, 2010
• Study Start: October 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: October 5, 2017
• Results First Posted: April 7, 2015

Record last verified: 2017-09

Locations

US (29); AU (5)