A Study of AA4500 in Men With Peyronie's Disease

A Phase 3, Open-label 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, open-label study of the safety and efficacy of AA4500 0.58 mg in subjects with Peyronie's disease. Subjects will be screened for study eligibility within 21 days before the initial injection of study drug in the first treatment cycle.

After up to four treatment cycles, each subject will be followed for additional safety and efficacy assessments on Days 168 (± 7 days) and 252 (± 7 days) (nominal weeks 24 and 36).

After the final injection of each treatment cycle, the investigator will model the plaque in an attempt to stretch or elongate the plaque. If the subject's penile curvature is reduced to <15° 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.

Approximately 300 subjects will be enrolled.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 348
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, DK-9100
    • Aarhus Universitiy Hospital, Aalborg Sygehus
  • Frederiksberg, Denmark, DK-2000
    • Frederiksberg Hospital
  • Frederikssund, Denmark, DK-3600
    • Frederikssunds Hospital
  • Gentofte, Denmark, DK-2820
    • Klinik for seksuelle dysfunktioner
• France
  • Lyon, France, F-69 437
    • Centre Hospitalier Edouar Herriot
  • Saint Genis Laval, France, F-69230
    • Hopital Henri Gabrielle
• Germany
  • Freiburg, Germany, DE-79106
    • Universitätsklinikum Freiburg, Abteilung Urologie
  • Hamburg, Germany, DE-20354
    • Private Practice of Urology/Andrology
  • Marburg, Germany, DE-35039
    • Uro-Onkologische Praxis Dr. von Keitz
  • Reutlingen, Germany, DE-72764
    • Urologische Gemeinschaftspraxis Reutlingen
  • Tubingen, Germany, DE-72096
    • Universitatsklinikum Tubingen
• Italy
  • Naples, Italy, I-80131
    • University of Naples "Federico II"
  • Rome, Italy, I-00133
    • Universitiy Tor Vergatat of Rome
• New Zealand
  • Auckland
    • Takapuna, Auckland, New Zealand, 0622
      • Waitemata Urology Research North Shore Hospital
  • Bay of Plenty
    • Tauranga, Bay of Plenty, New Zealand, 3140
      • Tauranga Urology Research Ltd.
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8011
      • Primorus Clinical Trials Ltd.
    • Christchurch, Canterbury, New Zealand, 8014
      • CURT Medical Trials Trust Board Inc.
  • Northland
    • Whangarei, Northland, New Zealand, 0112
      • Cardinal Points Research Ltd.
  • Wellington
    • Wellington South, Wellington, New Zealand, 6021
      • Wellington Urology Associates
• Spain
  • Barcelona, Spain, ES-08036
    • Hospital Clinic de Barcelona
  • Madrid, Spain, ES-28043
    • Hospital la Zarzuela
• Sweden
  • Goteborg, Sweden, SE-405 45
    • Specialistmottagningen i urologi
  • Karlshamn, Sweden, SE-374 35
    • Carlshamns Specialistklinik
  • Uppsala, Sweden, SE-751 85
    • Akademiska Sjukhuse
• United Kingdom
  • London, United Kingdom, W1G 6BJ
    • St. Peter's Andrology Centre
  • Sunderland, United Kingdom, SR4 &TP
    • Sunderland Royal Hospital
• United States
  • California
    • Burbank, California, United States, 91505
      • Urology Associates Medical Group
  • Connecticut
    • Middlebury, Connecticut, United States, 06762
      • Connecticut Clinical Research Center, LLC
    • New Haven, Connecticut, United States, 06511
      • The Urology Center, P.C.
  • Florida
    • Aventura, Florida, United States, 33180
      • South Florida Medical Research
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Urology Specialists, S.C.
  • Indiana
    • Fort Wayne, Indiana, United States, 46825
      • Northeast Indiana Research, LLC
    • Jeffersonville, Indiana, United States, 47130
      • Metropolitan Urology, P.S.C.
  • New York
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center, Division of Urology
    • New York, New York, United States, 10016
      • University Urology Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • Tristate Urologic Services PSC, Inc./ dba TUG Research
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • Urologic Consultants of SE PA
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Urology of Virginia-Sentara Medical Group
    • Richmond, Virginia, United States, 23235
      • Virginia 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:

No subject should be enrolled until all eligibility criteria have been satisfied. Subjects who receive placebo in a previous Auxilium-sponsored study may enroll in this study provided they continue to meet the eligibility requirements. To qualify for the study a subject must:

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 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
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 or the appropriate local language for the country in which the study is being performed.

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Exclusion Criteria:

A subject will be excluded from study participation if he:

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 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)
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 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 (penile ultrasound only in EU countries). 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 the 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, except for subjects who receive one treatment cycle of AA4500 in Study AUX-CC-805
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 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, except for subjects who receive one treatment cycle of AA4500 in Study AUX-CC-805
23. Has, at any time, received AA4500 for the treatment of Peyronie's disease, except for subjects who receive one treatment cycle of AA4500 in Study AUX-CC-805

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AA4500; collagenase clostridium histolyticum	Biological: AA4500; 2 injections separated by at least 24 hours but not more than 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles (ie, total of up to 8 injections per subject); 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 36
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 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Severity of Peyronie's Disease Symptoms Domain of the PDQ	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 36
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 36
A Responder Analysis Based on Subject Overall Global Assessment	Subject overall global assessment of Peyronie's disease score range -3 (much worse) to 3 (much improved). A score of 1 (improved in a small but important way), 2 (moderately improved), or 3 indicate a responder.	Week 36
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 36
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 in penile plaque consistency is indicated by a negative number.	Baseline and Week 36
A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score	A composite responder is indicated by; a percent reduction from baseline in penile curvature greater than or equal to the threshold, and; a reduction from baseline in Peyronie's disease bother score greater than or equal to the threshold, or change in the overall sexual activity within the last 3 months to having vaginal intercourse from no vaginal intercourse at screening.	Week 36
Change From Baseline in Penile Length	A negative value represents a reduction in measurement from baseline.	Baseline and Week 36

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Levine LA, Cuzin B, Mark S, Gelbard MK, Jones NA, Liu G, Kaufman GJ, Tursi JP, Ralph DJ. Clinical safety and effectiveness of collagenase clostridium histolyticum injection in patients with Peyronie's disease: a phase 3 open-label study. J Sex Med. 2015 Jan;12(1):248-58. doi: 10.1111/jsm.12731. Epub 2014 Nov 12.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: November 17, 2010
• First Submitted That Met QC Criteria: November 17, 2010
• First Posted (Estimate): November 18, 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 plaque, penile curvature
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Penile Diseases; Penile Induration
• Other Study ID Numbers: AUX-CC-802