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
Condition: Peyronie's Disease
MeSH terms: Penile Induration
Intervention: AA4500
Intervention description: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 189.0
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. 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.
    

Eligibility criteria:

        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:

          1. 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

          2. Be judged to be in good health, based upon the results of a medical history, physical
             examination,and laboratory profile

          3. Have participated in Study AUX-CC-803 or Study AUX-CC-804, received placebo in that
             study,and completed that study

          4. 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

          5. 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:

          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 or another suitable injectable pharmacologic stimulant
             according to the standard practice at the investigator's institution

          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, 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

         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. 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

         18. Has a known systemic allergy to collagenase or any other excipient of AA4500

         19. Has a known allergy to any concomitant medication required as per the protocol

         20. Has received anticoagulant medication (except for ≤ 150 mg aspirin daily) during the 7
             days before each dose of study drug

         21. Has received any collagenase treatments within 30 days of the first dose of study drug

         22. Has, at any time, received AA4500 for the treatment of Peyronie's disease

         23. Is unwilling or unable to cooperate with the requirements of the study including
             completion of all scheduled study visits