Clinical trial NCT01221623: Study of AA4500 in the Treatment of Peyronie's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Peyronie's Disease
Keywords: Peyronie's Disease
penile plaque
penile curvature
Lead sponsor: Endo Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2010-10-15
Enrollment: 418
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 -

Primary outcomes:
measure: Percentage Change From Baseline in Penile Curvature
timeFrame: Baseline and Week 52
measure: Change From Baseline in the Peyronie's Disease Bother Domain of the Peyronie's Disease Questionnaire (PDQ)
timeFrame: Baseline and Week 52
Secondary outcomes:
measure: A Responder Analysis Based on Subject Overall Global Assessment
timeFrame: Week 52
measure: Change From Baseline in the Severity of Peyronie's Disease Symptoms Domain of the PDQ
timeFrame: Baseline and Week 52
measure: Change in the Overall Satisfaction Domain of the International Index of Erectile Function (IIEF)
timeFrame: Baseline and Week 52
measure: Change From Baseline in Penile Plaque Consistency
timeFrame: Baseline and Week 52
measure: Change From Baseline in Penile Length
timeFrame: Baseline and Week 52
measure: Change From Baseline in the Penile Pain Domain of the PDQ in Subjects With Baseline Penile Pain Score ≥4
timeFrame: Baseline and Week 52
measure: A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score
timeFrame: Week 52
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Costal Clinical Research, Inc.
state: Alabama
city: Anchorage
country: United States
facility: Alaska Clinical Research Center, LLC
state: Alaska
city: Phoenix
country: United States
facility: Connect Clinical Research Center (CCRC)
state: Arizona
city: Laguna Hills
country: United States
facility: So. Orange County Medical Research Center
state: California
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: Middlebury
country: United States
facility: Connecticut Clinical Resarch Center, LLC
state: Connecticut
city: Aventura
country: United States
facility: South Florida Medical Research
state: Florida
city: Orlando
country: United States
facility: Winter Park Urology Associates
state: Florida
city: Meridian
country: United States
facility: Idaho Urologic Institute
state: Idaho
city: Fort Wayne
country: United States
facility: Northeast Indiana Research, LLC
state: Indiana
city: Jeffersonville
country: United States
facility: Metropolitan Urology, P.S.C.
state: Indiana
city: Overland Park
country: United States
facility: Kansas City Urology Care, P.A. Research Department
state: Kansas
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center Dept. of Urology
state: Louisiana
city: Shreveport
country: United States
facility: Regional Urology L.L.C.
state: Louisiana
city: Glen Burnie
country: United States
facility: Chesapeake Urology Research Assoc.
state: Maryland
city: Towson
country: United States
facility: Chesapeake Urology Research Assoc., PA
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Camden
country: United States
facility: Cooper Health System
state: New Jersey
city: Lawrenceville
country: United States
facility: AdvanceMed Research
state: New Jersey
city: Albany
country: United States
facility: The Capital Region Medical Research Foundation @ the Urological Institute of Northeastern New York
state: New York
city: Great Neck
country: United States
facility: Bruce R. Gilbert, MD, PhD, PC
state: New York
city: New York
country: United States
facility: University Urology Associates
state: New York
city: Purchase
country: United States
facility: Michael A. Werner, MD, PC
state: New York
city: Chapel Hill
country: United States
facility: Universitiy of North Carolina School of Medicine Div. of Urology
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center Division of Urologic Surgery
state: North Carolina
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Carrollton
country: United States
facility: Research Across America
state: Texas
city: Dallas
country: United States
facility: Urology Clinics of North Texas, PA
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio Research, PA
state: Texas
city: Kogarah
country: Australia
facility: Urology Sydney
state: New South Wales
city: Sydney
country: Australia
facility: Health Pac Medical Centre
state: New South Wales
city: Brisbane
country: Australia
facility: AusTrials Pty Limited
state: Queensland
city: Mentone
country: Australia
facility: Bayside Urology
state: Victoria
city: Nedlands
country: Australia
facility: Keogh Institute for Medical Research
state: Western Australia
Study officials:
affiliation: Auxilium Pharmaceuticals, Inc.
name: Gregory Kaufman, MD
role: STUDY_DIRECTOR
References:
citation: 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.