E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Lump on penile shaft and curvature of the erect penis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Male diseases of the urinary and reproductive systems [C12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10034765 |
E.1.2 | Term | Peyronie's disease |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This study is a Phase 3, open-label study to evaluate the safety and efficacy of AA4500 0.58 mg in subjects with Peyronie’s disease.
Primary endpoint analyses are the following:
• Change from baseline in the Peyronie’s disease bother domain
• Percent improvement from baseline in penile curvature
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E.2.2 | Secondary objectives of the trial |
Secondary endpoint analyses are:
• Change from baseline in the severity of Peyronie’s disease physical and psychological symptoms
• Change in the penile pain domain of the PDQ in subjects with penile pain score of at least 4 at baseline
• A responder analysis based on subject global assessment
• Change in the overall satisfaction domain of the IIEF
• Change in penile plaque consistency
• Change in penile length
Safety will be assessed through the recording of adverse events, vital signs, change in the erectile function domain of the IIEF, and clinical laboratory testing.
Immunogenicity will be assessed through the determination of anti-AUX-I and anti-AUX-II antibody levels and neutralizing potential of antibodies to AUX-I and AUX-II.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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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E.4 | Principal exclusion criteria |
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. 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint analyses are the following:
• Change from baseline in the Peyronie’s disease bother domain
• Percent improvement from baseline in penile curvature
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary time point for analyses will be Day 252 (nominal week 36) |
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E.5.2 | Secondary end point(s) |
Secondary endpoint analyses are:
• Change from baseline in the severity of Peyronie's disease physical and
psychological symptoms
• Change in the penile pain domain of the PDQ in subjects with penile
pain score of at least 4 at baseline
• A responder analysis based on subject global assessment
• Change in the overall satisfaction domain of the IIEF
• Change in penile plaque consistency
• Change in penile length |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The primary time point for analyses will be Day 252 (nominal week 36). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
New Zealand |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study is when the last subject completes the Day 252 (nominal week 36) follow-up visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 16 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 19 |
E.8.9.2 | In all countries concerned by the trial days | 0 |