Study of AA4500 in the Treatment of Peyronie's Disease

A Phase 3, Double-blind, Randomized, Placebo-controlled Study of the Safety and Effectiveness of AA4500 Administered Twice Per Treatment Cycle for up to Four Treatment Cycles (2 x 4) in Men With Peyronie's Disease

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 400 (267 AA4500 and 133 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 deformity (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 further treatment is not clinically indicated, 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.

Study Overview

• Status: Completed
• Conditions: Peyronie's Disease
• Intervention / Treatment: Biological: AA4500; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 418
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St. Leonards, New South Wales, Australia, NSW 2065
      • Australian Centre for Sexual Health
    • Westmead, New South Wales, Australia, NSW 2145
      • Western Urology
  • Queensland
    • Kipparing, Queensland, Australia, QLD 4019
      • Austrials
  • South Australia
    • Daws Park, South Australia, Australia, SA 5041
      • Repatriation General Hospital
  • Victoria
    • Malvern, Victoria, Australia, VIC 3144
      • Australian Urology Associates Pty Ltd
• United States
  • Alabama
    • Homewood, Alabama, United States, 35209
      • Urology Centers of Alabama, PC
  • Arizona
    • Phoenix, Arizona, United States, 85050
      • HOPE Research Institute, LLC
  • California
    • Burbank, California, United States, 91505
      • Urology Associates Medical Group
    • Newport Beach, California, United States, 92660
      • California Professional Research
    • San Diego, California, United States, 92120
      • San Diego Sexual Medicine
  • Connecticut
    • New Britain, Connecticut, United States, 06052
      • Grove Hill Clinical Research, Grove Hill Medical Center
    • New Haven, Connecticut, United States, 06511
      • The Urology Center, PC
  • Florida
    • Celebration, Florida, United States, 34747
      • DCT-Celebration, LLC dba Discovery Clinical Trials
    • Wellington, Florida, United States, 33414
      • Palm Beach Urology Associates
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Southeastern Medical Research Institute
  • Illinois
    • Downers Grove, Illinois, United States, 60515
      • DuPage Medical Group
  • Indiana
    • Avon, Indiana, United States, 46123
      • Urology of Indiana LLC
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
    • Baltimore, Maryland, United States, 21204
      • Chesapeake Urology Research Associates
  • Massachusetts
    • Brookline, Massachusetts, United States, 02445
      • Mens Health Boston
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic at Rochester, Dept. of Urology
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Center for Reproductive Medicine
  • New York
    • Brooklyn, New York, United States, 11235
      • Division of Urology at Maimonides Medical Center
  • North Carolina
    • Greensboro, North Carolina, United States, 27403
      • Alliance Urology Specialists, PA
    • Raleigh, North Carolina, United States, 27607
      • Wake Urological Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • Tristate Urologic Services PSC Inc. dba TUG Research
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Urology Health Specialists,LLC
    • Lancaster, Pennsylvania, United States, 17604
      • Urological Associates of Lancaster
  • Tennessee
    • Clarksville, Tennessee, United States, 37043
      • Alpha Clinical Research, LLC
  • Texas
    • Arlington, Texas, United States, 76017
      • Urology Associates of North Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine, Department of Urology
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Salt Lake Research, PLLC
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Urology of Virginia - Sentara Medical Group
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin, Department of Urology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Be a male and be ≥ 18 years of age
2. 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
3. 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
4. Have curvature deformity 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
5. Be judged to be in good health, based upon the results of a medical history, physical examination, and laboratory profile
6. 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
7. Be able to read, complete and understand the various rating instruments in English

Exclusion criteria

1. Has a penile curvature of less than 30° or greater than 90° at the screening visit

2. 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 curvature deformity
   • 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)
3. Has previously undergone surgery for Peyronie's disease
4. 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
5. Has a calcified plaque as evident by appropriate radiographic evaluation, penile x-ray or penile ultrasound that would prevent proper injection of study medication. Non-contiguous stippling of calcium is acceptable for inclusion provided the calcium deposit does not interfere with the injection of AA4500 into the plaque
6. Has an isolated hourglass deformity of the penis
7. 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
8. 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
9. Has received alternative medical therapies for Peyronie's disease administered by the oral (including, but not limited to, vitamin E [> 500 U], potassium aminobenzoate [Potaba], tamoxifen, colchicine, pentoxifylline, over-the-counter erectile dysfunction medications, or steroidal anti-inflammatory drugs) or topical routes (including, but not limited to, verapamil applied as a cream) 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
10. Has had extracorporeal shock wave therapy (ESWT) for correction of Peyronie's disease within the 6-month period before screening or plans to have ESWT at any time during the study
11. Has used any mechanical type device for correction of Peyronie's disease within the 2-week period before screening or plans to use any these devices at any time during the study
12. Has used a mechanical device to induce a passive erection within the 2-week period before screening or plans to use any of these devices at any time during the study
13. Has significant erectile dysfunction that has failed to respond to oral treatment with phosphodiesterase type 5 (PDE5) inhibitors
14. Has a penile Duplex Doppler ultrasound evaluation at screening that shows compromised penile hemodynamics that in the opinion of the investigator is clinically significant
15. Has uncontrolled hypertension, as determined by the investigator
16. Has a known recent history of stroke, bleeding, or other significant medical condition, which in the investigator's opinion would make the subject unsuitable for enrollment in the study
17. Is unwilling or unable to cooperate with the requirements of the study including completion of all scheduled study visits
18. Has received an investigational drug or treatment within 30 days before the first dose of study drug
19. Has a known systemic allergy to collagenase or any other excipient of AA4500
20. Has a known allergy to any concomitant medication required as per the protocol
21. Has received anticoagulant medication (except for ≤ 165 mg aspirin daily or ≤ 800 mg of over-the-counter non-steroidal anti-inflammatory drugs [NSAIDS] daily) during the 7 days before each dose of study drug
22. Has received any collagenase treatments within 30 days of the first dose of study drug

23. Has, at any time, received AA4500 for the treatment of Peyronie's disease

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Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; placebo	Biological: Placebo; 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.
Experimental: AA4500; collagenase clostridium histolyticum	Biological: AA4500; 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.; Other Names: XIAFLEX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
A Responder Analysis Based on Subject Overall Global Assessment of Peyronie's Disease	A responder was defined as a subject who recorded his Peyronie's disease had either improved in a small but important way, moderately improved, or much improved in overall global assessment question.	Week 52
Change From Baseline in the Severity of Peyronie's Disease Physical and Psychological Symptoms	Peyronie's disease symptoms (physical and psychological) severity score range 0 (none) to 4 (very severe) on 6 questions; total score range 0 to 24. A decrease in the change from baseline total score in the Peyronie's disease symptoms domain of the PDQ is indicated by a negative number.	Baseline and Week 52
Change in the Overall Satisfaction Domain of the International Index of Erectile Function (IIEF)	Overall satisfaction domain of the IIEF score range 0 to 5 on 2 questions where higher scores indicate improved function or satisfaction; total score range 0 to 10.	Baseline and Week 52
Change From Baseline in Penile Plaque Consistency	Penile plaque consistency score range 1 (non-palpable) to 5 (hard). A decrease in the change from baseline score in penile plaque consistency is indicated by a negative number.	Baseline and Week 52
Change From Baseline in Penile Length	A negative value represents a reduction in measurement from baseline.	Baseline and Week 52
Change From Baseline in the Penile Pain Domain of the PDQ in Subjects With Baseline Penile Pain Score ≥4	Penile pain scale range 0 (no pain) to 10 (extreme pain) on 3 questions; total score range 0 to 30. A decrease in the change from baseline total score in the penile pain domain of the PDQ is indicated by a negative number. Subjects were required to have a penile pain score of 4 or greater at baseline.	Baseline and Week 52
Composite Responder Based on Change in Curvature Deformity and Change in Peyronie's Disease Bother Score	A responder was defined as a subject who satisfied the following 2 criteria at that visit: a) percent reduction from baseline in curvature deformity was ≥20% and b) reduction from baseline in PDQ Peyronie's disease bother score was ≥1, or had a change from reporting no sexual activity at screening to reporting sexual activity.	Week 52

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals
• Investigators: Study Director: Gregory J. Kaufman, MD, Auxilium Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: October 8, 2010
• First Submitted That Met QC Criteria: October 14, 2010
• First Posted (Estimate): October 15, 2010

Study Record Updates

• Last Update Posted (Actual): October 5, 2017
• Last Update Submitted That Met QC Criteria: September 7, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Peyronie's Disease; penile curvature; penile plaque
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Penile Diseases; Penile Induration
• Other Study ID Numbers: AUX-CC-803