Trial Outcomes & Findings for Study of AA4500 in the Treatment of Peyronie's Disease (NCT NCT01221623)
NCT ID: NCT01221623
Last Updated: 2017-10-05
Results Overview
A negative value in the percentage change from baseline in penile curvature deformity (angle measured in degrees) indicates less curvature.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
418 participants
Primary outcome timeframe
Baseline and Week 52
Results posted on
2017-10-05
Participant Flow
Includes all subjects who were randomized and received at least 1 dose of study drug; subjects who were randomized but not treated were excluded from the population.
Participant milestones
| Measure |
AA4500
collagenase clostridium histolyticum
AA4500: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
Placebo
Placebo
Placebo: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
|---|---|---|
|
Overall Study
STARTED
|
274
|
141
|
|
Overall Study
COMPLETED
|
236
|
127
|
|
Overall Study
NOT COMPLETED
|
38
|
14
|
Reasons for withdrawal
| Measure |
AA4500
collagenase clostridium histolyticum
AA4500: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
Placebo
Placebo
Placebo: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
19
|
8
|
|
Overall Study
Lost to Follow-up
|
7
|
1
|
|
Overall Study
Adverse Event
|
6
|
3
|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Other
|
5
|
2
|
Baseline Characteristics
Study of AA4500 in the Treatment of Peyronie's Disease
Baseline characteristics by cohort
| Measure |
AA4500
n=274 Participants
collagenase clostridium histolyticum
AA4500: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
Placebo
n=141 Participants
Placebo
Placebo: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
Total
n=415 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
225 Participants
n=5 Participants
|
112 Participants
n=7 Participants
|
337 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
49 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
78 Participants
n=5 Participants
|
|
Age, Continuous
|
57.3 years
STANDARD_DEVIATION 8.77 • n=5 Participants
|
57.6 years
STANDARD_DEVIATION 7.52 • n=7 Participants
|
57.4 years
STANDARD_DEVIATION 8.36 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
274 Participants
n=5 Participants
|
141 Participants
n=7 Participants
|
415 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
234 participants
n=5 Participants
|
124 participants
n=7 Participants
|
358 participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
40 participants
n=5 Participants
|
17 participants
n=7 Participants
|
57 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 52Population: Efficacy is based on the modified intent-to-treat (mITT) population.
A negative value in the percentage change from baseline in penile curvature deformity (angle measured in degrees) indicates less curvature.
Outcome measures
| Measure |
AA4500
n=202 Participants
collagenase clostridium histolyticum
AA4500: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
Placebo
n=107 Participants
Placebo
Placebo: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
|---|---|---|
|
Percentage Change From Baseline in Penile Curvature
|
-30.5 percentage of curvature change
Standard Deviation 27.7
|
-15.2 percentage of curvature change
Standard Deviation 28.6
|
PRIMARY outcome
Timeframe: Baseline and Week 52Population: Efficacy is based on the mITT population.
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.
Outcome measures
| Measure |
AA4500
n=202 Participants
collagenase clostridium histolyticum
AA4500: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
Placebo
n=107 Participants
Placebo
Placebo: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
|---|---|---|
|
Change From Baseline in the Peyronie's Disease Bother Domain of the Peyronie's Disease Questionnaire (PDQ)
|
-2.4 units on a scale
Standard Deviation 3.62
|
-1.6 units on a scale
Standard Deviation 3.52
|
SECONDARY outcome
Timeframe: Week 52Population: Efficacy is based on the mITT population.
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 indicated a responder.
Outcome measures
| Measure |
AA4500
n=202 Participants
collagenase clostridium histolyticum
AA4500: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
Placebo
n=107 Participants
Placebo
Placebo: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
|---|---|---|
|
A Responder Analysis Based on Subject Overall Global Assessment
Responder Status - Yes
|
112 participants
|
32 participants
|
|
A Responder Analysis Based on Subject Overall Global Assessment
Responder Status - No
|
90 participants
|
75 participants
|
SECONDARY outcome
Timeframe: Baseline and Week 52Population: Efficacy is based on the mITT population.
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.
Outcome measures
| Measure |
AA4500
n=202 Participants
collagenase clostridium histolyticum
AA4500: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
Placebo
n=107 Participants
Placebo
Placebo: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
|---|---|---|
|
Change From Baseline in the Severity of Peyronie's Disease Symptoms Domain of the PDQ
|
-2.6 units on a scale
Standard Deviation 4.83
|
-1.0 units on a scale
Standard Deviation 4.78
|
SECONDARY outcome
Timeframe: Baseline and Week 52Population: Efficacy is based on the mITT population.
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.
Outcome measures
| Measure |
AA4500
n=202 Participants
collagenase clostridium histolyticum
AA4500: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
Placebo
n=107 Participants
Placebo
Placebo: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
|---|---|---|
|
Change in the Overall Satisfaction Domain of the International Index of Erectile Function (IIEF)
|
1.0 units on a scale
Standard Deviation 2.33
|
0.3 units on a scale
Standard Deviation 2.35
|
SECONDARY outcome
Timeframe: Baseline and Week 52Population: Efficacy is based on the mITT population.
Penile plaque consistency score range 1 (non-palpable) to 5 (hard). A decrease in the change from baseline score in penile plaque consistency is indicated by a negative number.
Outcome measures
| Measure |
AA4500
n=202 Participants
collagenase clostridium histolyticum
AA4500: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
Placebo
n=107 Participants
Placebo
Placebo: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
|---|---|---|
|
Change From Baseline in Penile Plaque Consistency
|
-0.8 units on a scale
Standard Deviation 0.97
|
-0.4 units on a scale
Standard Deviation 0.86
|
SECONDARY outcome
Timeframe: Baseline and Week 52Population: Efficacy is based on the mITT population.
A negative value represents a reduction in measurement from baseline.
Outcome measures
| Measure |
AA4500
n=202 Participants
collagenase clostridium histolyticum
AA4500: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
Placebo
n=107 Participants
Placebo
Placebo: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
|---|---|---|
|
Change From Baseline in Penile Length
|
0.5 centimeters
Standard Deviation 1.34
|
0.2 centimeters
Standard Deviation 1.49
|
SECONDARY outcome
Timeframe: Baseline and Week 52Population: Efficacy is based on the mITT population; this population only includes those subjects in the mITT population with a baseline penile pain score of 4 or greater.
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.
Outcome measures
| Measure |
AA4500
n=87 Participants
collagenase clostridium histolyticum
AA4500: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
Placebo
n=51 Participants
Placebo
Placebo: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
|---|---|---|
|
Change From Baseline in the Penile Pain Domain of the PDQ in Subjects With Baseline Penile Pain Score ≥4
|
-3.8 units on a scale
Standard Deviation 5.93
|
-4.5 units on a scale
Standard Deviation 5.39
|
SECONDARY outcome
Timeframe: Week 52Population: Composite responder analysis is based on the ITT population.
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.
Outcome measures
| Measure |
AA4500
n=274 Participants
collagenase clostridium histolyticum
AA4500: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
Placebo
n=141 Participants
Placebo
Placebo: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
|---|---|---|
|
A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score
Responder - Yes
|
105 participants
|
41 participants
|
|
A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score
Responder - No
|
143 participants
|
93 participants
|
|
A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score
Responder - Missing
|
26 participants
|
7 participants
|
Adverse Events
AA4500
Serious events: 12 serious events
Other events: 237 other events
Deaths: 0 deaths
Placebo
Serious events: 4 serious events
Other events: 51 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AA4500
n=274 participants at risk
collagenase clostridium histolyticum
AA4500: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
Placebo
n=141 participants at risk
Placebo
Placebo: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
|---|---|---|
|
Cardiac disorders
Hypertrophic cardiomyopathy
|
0.36%
1/274 • Number of events 1
|
0.00%
0/141
|
|
Infections and infestations
Bacteraemia
|
0.36%
1/274 • Number of events 1
|
0.00%
0/141
|
|
Cardiac disorders
Atrial fibrillation
|
0.73%
2/274 • Number of events 2
|
0.00%
0/141
|
|
Injury, poisoning and procedural complications
Joint injury
|
0.36%
1/274 • Number of events 1
|
0.00%
0/141
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.36%
1/274 • Number of events 1
|
0.00%
0/141
|
|
Nervous system disorders
Syncope
|
0.36%
1/274 • Number of events 1
|
0.00%
0/141
|
|
Reproductive system and breast disorders
Penile haematoma
|
0.36%
1/274 • Number of events 1
|
0.00%
0/141
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.36%
1/274 • Number of events 1
|
0.00%
0/141
|
|
Injury, poisoning and procedural complications
Fracture of penis
|
0.73%
2/274 • Number of events 2
|
0.00%
0/141
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer metastatic
|
0.36%
1/274 • Number of events 1
|
0.00%
0/141
|
|
Infections and infestations
Appendicitis
|
0.00%
0/274
|
0.71%
1/141 • Number of events 1
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/274
|
0.71%
1/141 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/274
|
0.71%
1/141 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/274
|
0.71%
1/141 • Number of events 1
|
Other adverse events
| Measure |
AA4500
n=274 participants at risk
collagenase clostridium histolyticum
AA4500: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
Placebo
n=141 participants at risk
Placebo
Placebo: 2 injections separated by at least 24 hours but not more than 72 hours. At least 24 hours but not more than 72 hours after the 2nd injection of the treatment cycle, the investigator will model the plaque (ie, gradual, gentle stretching of the flaccid penis in the direction opposite to the curvature). Treatment may be repeated after 42 days (± 5 days) for up to 4 treatment cycles.
|
|---|---|---|
|
Reproductive system and breast disorders
Penile haematoma
|
60.2%
165/274 • Number of events 413
|
15.6%
22/141 • Number of events 29
|
|
Reproductive system and breast disorders
Penile pain
|
35.0%
96/274 • Number of events 212
|
5.7%
8/141 • Number of events 10
|
|
Reproductive system and breast disorders
Penile swelling
|
34.7%
95/274 • Number of events 170
|
1.4%
2/141 • Number of events 2
|
|
General disorders
Injection site haematoma
|
22.3%
61/274 • Number of events 85
|
11.3%
16/141 • Number of events 20
|
|
Reproductive system and breast disorders
Penile haemorrhage
|
15.7%
43/274 • Number of events 68
|
0.71%
1/141 • Number of events 1
|
|
General disorders
Injection site pain
|
15.0%
41/274 • Number of events 59
|
2.8%
4/141 • Number of events 4
|
|
Reproductive system and breast disorders
Penile oedema
|
14.6%
40/274 • Number of events 87
|
0.00%
0/141
|
|
General disorders
Injection site swelling
|
12.8%
35/274 • Number of events 54
|
1.4%
2/141 • Number of events 2
|
|
Injury, poisoning and procedural complications
Contusion
|
9.9%
27/274 • Number of events 40
|
0.71%
1/141 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Blood blister
|
6.2%
17/274 • Number of events 20
|
0.00%
0/141
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.3%
9/274 • Number of events 11
|
5.0%
7/141 • Number of events 9
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER