A Study of AA4500 in Men With Peyronie's Disease
Condition: Peyronie's Disease
MeSH terms: Penile Induration
Intervention: AA4500
Intervention description: 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)
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 348.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Peyronie's Disease, penile plaque, penile curvature

Summary:

      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.
    

Eligibility criteria:

        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.

             -

        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