Study of AA4500 in the Treatment of Peyronie's Disease

NCT ID: NCT01221623

Last Updated: 2017-10-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 418 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2012-03-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

AA4500

collagenase clostridium histolyticum

Group Type: EXPERIMENTAL

AA4500

Intervention Type: 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

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Other Intervention Names

XIAFLEX

Eligibility Criteria

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 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

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 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 (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 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 -

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Endo Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gregory Kaufman, MD

Role: STUDY_DIRECTOR

Auxilium Pharmaceuticals, Inc.

Locations

Costal Clinical Research, Inc.

Mobile, Alabama, United States

Alaska Clinical Research Center, LLC

Anchorage, Alaska, United States

Connect Clinical Research Center (CCRC)

Phoenix, Arizona, United States

So. Orange County Medical Research Center

Laguna Hills, California, United States

The Urology Center of Colorado

Denver, Colorado, United States

Connecticut Clinical Resarch Center, LLC

Middlebury, Connecticut, United States

South Florida Medical Research

Aventura, Florida, United States

Winter Park Urology Associates

Orlando, Florida, United States

Idaho Urologic Institute

Meridian, Idaho, United States

Northeast Indiana Research, LLC

Fort Wayne, Indiana, United States

Metropolitan Urology, P.S.C.

Jeffersonville, Indiana, United States

Kansas City Urology Care, P.A. Research Department

Overland Park, Kansas, United States

Tulane University Health Sciences Center Dept. of Urology

New Orleans, Louisiana, United States

Regional Urology L.L.C.

Shreveport, Louisiana, United States

Chesapeake Urology Research Assoc.

Glen Burnie, Maryland, United States

Chesapeake Urology Research Assoc., PA

Towson, Maryland, United States

University of Michigan

Ann Arbor, Michigan, United States

Cooper Health System

Camden, New Jersey, United States

AdvanceMed Research

Lawrenceville, New Jersey, United States

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

Albany, New York, United States

Bruce R. Gilbert, MD, PhD, PC

Great Neck, New York, United States

University Urology Associates

New York, New York, United States

Michael A. Werner, MD, PC

Purchase, New York, United States

Universitiy of North Carolina School of Medicine Div. of Urology

Chapel Hill, North Carolina, United States

Duke University Medical Center Division of Urologic Surgery

Durham, North Carolina, United States

The Miriam Hospital

Providence, Rhode Island, United States

Research Across America

Carrollton, Texas, United States

Urology Clinics of North Texas, PA

Dallas, Texas, United States

Urology San Antonio Research, PA

San Antonio, Texas, United States

Urology Sydney

Kogarah, New South Wales, Australia

Health Pac Medical Centre

Sydney, New South Wales, Australia

AusTrials Pty Limited

Brisbane, Queensland, Australia

Bayside Urology

Mentone, Victoria, Australia

Keogh Institute for Medical Research

Nedlands, Western Australia, Australia

Countries

United States; Australia

References

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.

Reference Type: DERIVED

PMID: 26199168 (View on PubMed)

Other Identifiers

AUX-CC-804

Identifier Type: -

Identifier Source: org_study_id