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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 418
- 试验地点
- 68
- 主要终点
- Change From Baseline in the Peyronie's Disease Bother Domain of the Peyronie's Disease Questionnaire (PDQ)
研究概览
简要总结
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 400 (267 AA4500 and 133 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 deformity (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 further treatment is not clinically indicated, 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Be a male and be ≥ 18 years of age
- •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
- •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
- •Have curvature deformity 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
- •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
排除标准
- •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 curvature deformity
- •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 (PGE1) or trimix
- •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, 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
- •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
- •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
- •Is unwilling or unable to cooperate with the requirements of the study including completion of all scheduled study visits
- •Has received an investigational drug or treatment within 30 days before the first dose of study drug
- •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 ≤ 165 mg aspirin daily or ≤ 800 mg of over-the-counter non-steroidal anti-inflammatory drugs [NSAIDS] 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
研究组 & 干预措施
Placebo
placebo
干预措施: Placebo (Biological)
AA4500
collagenase clostridium histolyticum
干预措施: AA4500 (Biological)
结局指标
主要结局
Change From Baseline in the Peyronie's Disease Bother Domain of the Peyronie's Disease Questionnaire (PDQ)
时间窗: Baseline and Week 52
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.
Percentage Change From Baseline in Penile Curvature
时间窗: Baseline and Week 52
A negative value in the percentage change from baseline in penile curvature deformity (angle measured in degrees) indicates less curvature.
次要结局
- Change From Baseline in the Penile Pain Domain of the PDQ in Subjects With Baseline Penile Pain Score ≥4(Baseline and Week 52)
- A Responder Analysis Based on Subject Overall Global Assessment of Peyronie's Disease(Week 52)
- Change in the Overall Satisfaction Domain of the International Index of Erectile Function (IIEF)(Baseline and Week 52)
- Change From Baseline in Penile Length(Baseline and Week 52)
- Composite Responder Based on Change in Curvature Deformity and Change in Peyronie's Disease Bother Score(Week 52)
- Change From Baseline in the Severity of Peyronie's Disease Physical and Psychological Symptoms(Baseline and Week 52)
- Change From Baseline in Penile Plaque Consistency(Baseline and Week 52)