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

Study Overview
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Brief Summary
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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. Enrollment will include all subjects who meet the eligibility criteria and who received placebo and completed one of the Auxilium-sponsored studies AUX-CC-803 or AUX-CC-804.

Detailed Description
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After the final injection of each treatment cycle, the investigator or qualified designee (ie, qualified by license, education, and training to perform the study procedure according to local, state, and country requirements) 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. Following the maximum of 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).

Official Title
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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

Conditions
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Peyronie's Disease

Intervention / Treatment
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* Biological: AA4500


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No subject should be enrolled until all eligibility criteria have been satisfied. Subjects who completed their participation in Auxilium-sponsored studies AUX-CC-803 or AUX-CC-804 and received placebo in that study may enroll in this study provided they continue to meet the eligibility requirements. To qualify for the study a subject must: 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 Have participated in Study AUX-CC-803 or Study AUX-CC-804, received placebo in that study,and completed that study 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. Exclusion Criteria: A subject will be excluded from study participation if he: 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 or trimix or another suitable injectable pharmacologic stimulant according to the standard practice at the investigator's institution 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 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 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, and pentoxifylline, ,) 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 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 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 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 Has significant erectile dysfunction that has failed to respond to oral treatment with phosphodiesterase type 5 (PDE5) inhibitors Has a penile Duplex Doppler ultrasound evaluation at screening that shows compromised penile hemodynamics that in the opinion of the investigator is clinically significant Has uncontrolled hypertension, as determined by the investigator 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 Has received an investigational drug or treatment within 30 days before the first dose of study drug, except for placebo in Studies AUX-CC-803 or AUX-CC-804 Has a known systemic allergy to collagenase or any other excipient of AA4500 Has a known allergy to any concomitant medication required as per the protocol Has received anticoagulant medication (except for ≤ 150 mg aspirin daily) during the 7 days before each dose of study drug Has received any collagenase treatments within 30 days of the first dose of study drug Has, at any time, received AA4500 for the treatment of Peyronie's disease Is unwilling or unable to cooperate with the requirements of the study including completion of all scheduled study visits

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AA4500<br>collagenase clostridium histolyticum | Biological: AA4500<br>* 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles<br>* Other names: Xiapex;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peyronie's disease, penile plaque, penile curvature