Efficacy of a Novel Collagenase Clostridium Histolyticum Protocol for Peyronie's Disease Among Prior Non-responders: A Randomized, Controlled, Single-Blinded Study
Phase: PHASE4
Conditions: Peyronie's Disease
Sponsor: Charitable Union for the Research and Education of Peyronie's Disease

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Efficacy of a Novel Collagenase Clostridium Histolyticum Protocol for 
Peyronie’s Disease Among Prior Non-responders: A Randomized, Controlled, 
Single-Blinded Study 
 
 
Principal Investigator 
 
[Study Coordinators] 
Landon Trost, MD 
 
Holli Burgon 
Benjamin Green 
 
Funding Sponsor: 
 
Endo Pharmaceuticals 
Protocol Number: (IRBe) 
CUREPD103 
 
 
 
 
 
Initial version: June 5, 2021 Version (1.0)  
 
 

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Table of Contents 
STUDY SUMMARY ...................................................................................................................................................5 
1 
INTRODUCTION ..............................................................................................................................................6 
1.1 
BACKGROUND AND CLINICAL NEED FOR THE CURRENT STUDY ................................................................. 6 
1.2 
INVESTIGATIONAL TREATMENTS ................................................................................................................ 6 
1.3 
PRELIMINARY DATA ................................................................................................................................... 7 
1.4 
STUDY RATIONALE AND RISK ANALYSIS (RISKS TO BENEFITS RATIO) ...................................................... 8 
1.4.1 
Study Rationale .......................................................................................................................................8 
1.5 
ANTICIPATED DURATION OF THE CLINICAL INVESTIGATION ...................................................................... 8 
2 
STUDY ENDPOINTS .........................................................................................................................................8 
2.1 
PRIMARY ENDPOINTS ................................................................................................................................. 8 
2.2 
SECONDARY OUTCOMES ............................................................................................................................ 8 
3 
STUDY DESIGN ................................................................................................................................................9 
3.1 
SUBJECT SELECTION ................................................................................................................................... 9 
3.1.1 
Inclusion Criteria ....................................................................................................................................9 
3.1.2 
Exclusion Criteria ...................................................................................................................................9 
3.2 
SETTING AND INVESTIGATOR ..................................................................................................................... 9 
3.3 
RECRUITMENT ............................................................................................................................................ 9 
3.4 
CONSENT AND ENROLLMENT ....................................................................................................................10 
3.5 
STUDY SCHEMA .........................................................................................................................................10 
3.6 
RANDOMIZATION PROTOCOL.....................................................................................................................11 
4 
STUDY PROCEDURES .................................................................................................................................. 11 
4.1 
SCREENING ASSESSMENTS ........................................................................................................................11 
4.2 
ASSESSMENTS ...........................................................................................................................................11 
5 
STATISTICAL PLAN ..................................................................................................................................... 12 
5.1 
DATA HANDLING.......................................................................................................................................12 
5.2 
STATISTICAL ANALYSIS ............................................................................................................................12 
6 
SAFETY AND ADVERSE EVENTS ................................................................................................................ 13 
6.1 
ADVERSE EVENT REPORTING PERIOD .......................................................................................................13 
6.2 
PREEXISTING CONDITION ..........................................................................................................................14 
6.3 
POST-STUDY ADVERSE EVENT ..................................................................................................................14 
6.4 
HOSPITALIZATION, PROLONGED HOSPITALIZATION OR SURGERY .............................................................14 
6.5 
RECORDING OF ADVERSE EVENTS .............................................................................................................14 
6.6 
REPORTING OF SERIOUS ADVERSE EVENTS AND UNANTICIPATED PROBLEMS ..........................................15 
6.6.1 
Sponsor-investigator Reporting: Notifying the Western IRB ..................................................................... 15 
6.6.2 
Stopping Rules ..................................................................................................................................... 15 
6.6.3 
Medical Monitoring .............................................................................................................................. 15 
7 
DATA HANDLING AND RECORD KEEPING .............................................................................................. 16 
7.1 
CONFIDENTIALITY .....................................................................................................................................16 
7.2 
SOURCE DOCUMENTS ................................................................................................................................16 
7.3 
RECORDS RETENTION ................................................................................................................................16 
8 
STUDY FINANCES ......................................................................................................................................... 16 
8.1 
FUNDING SOURCE ......................................................................................................................................16 
8.2 
CONFLICT OF INTEREST .............................................................................................................................16 
8.3 
SUBJECT STIPENDS OR PAYMENTS .............................................................................................................17 
8.4 
REGULATORY INFORMATION .....................................................................................................................17 

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9 
REFERENCES ................................................................................................................................................ 17 
 
 
 
 
 
 

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LIST OF ABBREVIATIONS 
 
AE 
Adverse Event/Adverse Experience 
CCH 
HIPAA 
Collagenase clostridium histolyticum 
Health Insurance Portability and Accountability Act 
IIEF 
PDE5s 
PTT 
PD 
International Index of Erectile Function 
Phosphodiesterase-5 inhibitors 
Penile traction therapy 
Peyronie’s Disease 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Summary 
Title 
Efficacy of a Novel Collagenase Clostridium Histolyticum Protocol for 
Peyronie’s Disease Among Prior Non-responders: A Randomized, 
Controlled, Single-blinded Study 
IRB Protocol 
Number 
20213914 
Methodology 
Prospective, randomized, controlled, single-blinded 
Overall Study 
Duration 
2 years 
Subject Participation 
Duration 
1 year 
Objectives 
Compare key clinical outcomes between controls and men treated 
with a novel CCH protocol among men previously unresponsive to 
CCH administration.   
Number of Subjects 
40 
Diagnosis and Main 
Inclusion Criteria 
Men >18 years of age with Peyronie’s Disease, current curvature of 
30 degrees or more, prior treatment with 6-8 injections of CCH, and 
prior minimal (<20% and/or <10 degrees) responsiveness to CCH 
administration.  
Randomization 
Patients will be randomized 1:3 to control (no treatment) or CCH (up 
to 8 injections).  Patients in the control arm will subsequently be 
crossed over to CCH treatment after 6 months.  Randomization tables 
will be created and pre-stratified based on baseline penile curvature. 
Follow-up Period 
and Assessments 
Men will have objective assessments of curvature and length and 
standardized and non-standardized questionnaires obtained at various 
time points (baseline, 6-weeks following completion of CCH, and at 
the end of the no treatment phase).     
Statistical 
Methodology 
Stratification of subjects prior to randomization to assure an equal 
representation based on baseline penile curvature (30-44, 45-59, 60-
74, 75-89, 90 or above).  Statistical comparisons between groups and 
to baseline will be made of responses to subjective questionnaires and 
objective measures.   
Plan for Publication 
It is anticipated that the primary study will be published following 
accumulation of data out to 1 year.  Pending novelty of findings, 
additional studies may also be published if felt to be warranted 
(subset analyses).   
 
 
 
 
 

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1 Introduction 
 
This document is a protocol for a randomized, controlled, single-blinded clinical trial.  This study will 
be carried out in accordance with the procedures described in this protocol, applicable United States 
government regulations and Western International Review Board policies and procedures.  
 
1.1 
Background and Clinical Need for the Current Study 
 
Collagenase Clostridium histolyticum (CCH) is the first FDA approved medication for the treatment of 
Peyronie’s Disease and demonstrated significant improvements in penile curvature and bother in two 
phase III trials.1  Results specifically demonstrated a mean 34%, or 17-degree improvement in curvature.  
Post-FDA release, multiple series, including the investigators’ own data have confirmed similar 
findings, including among men with ventral curvatures and calcification.2-8   
 
Beginning approximately 3 years ago, the investigators’ team sought to achieve further improvements 
with CCH through the addition of more aggressive modeling therapies.  Results from a comparison of 
CCH alone vs CCH and traction with RestoreX demonstrated a mean 33.8 degree (49%) curvature 
improvement with combined therapy compared to 19-20 degrees (30-31%) with CCH alone or CCH and 
other traction devices).9  These results currently represent the greatest improvements with CCH in 
published literature and further build upon phase IIb results which demonstrated that mechanical traction 
(via manual modeling in the phase IIb trial) represents a critical factor in achieving improvements with 
CCH.10   
 
The investigators’ team additionally published a survey of men who had experienced suspected penile 
fractures with CCH and demonstrated greater curvature improvements without any loss / worsening of 
erectile function.11  This critical study highlighted that conservative management of suspected fractures 
should not only be considered a standard of care in managing suspected fractures, but also that these 
men achieved better final outcomes (again highlighting the importance of the combination of 
mechanical curvature correction in addition to CCH management).   
 
Based on the above findings, the investigators’ team began performing a more aggressive manual 
modeling protocol.  This novel protocol included several notable innovations: dilution of the 0.9 mg of 
CCH in 0.7 ml of diluent, injection to the erect penis to assure accurate injection, repeat curvature 
assessments with each series (due to changing of the point of maximal curvature), incorporation of 
RestoreX traction therapy post injection, and ‘aggressive’ manual modeling (equivalent of 10-15 lbs of 
force) to achieve curvature correction.  Preliminary (unpublished – abstract submitted to SMSNA 2021) 
results from these men demonstrated a median ~60% curvature improvement.  Importantly, several of 
the patients had previously undergone 8 CCH injections with outside providers and were able to 
similarly achieve a median 60% improvement with the investigators’ injection / modeling protocol.   
 
1.2 
Investigational Treatments 
 
The current study would randomize men 1:3 into one of two treatment cohorts: 1. Observation followed 
by CCH or 2. CCH followed by observation.  This study design offers the benefits of a randomized, 

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controlled trial (highest level of evidence), while also providing data for a second set of publications 
evaluating the cross-over to treatment phase (for controls).  RCTs are particularly important in PD, 
where the disease changes over time in a percentage of men as a function of its natural history.  This 
would also allow blinding of measurements using photographs (single-blinded assessments), which 
provides further study rigor.  See Figure 1 for overall study schema.   
 
1. No treatment (control) followed by CCH.  Men in this cohort would undergo baseline 
assessments followed by no treatment for 6 months and then repeat assessments.  Men would 
then cross-over to CCH treatment and undergo up to 8 injections (or until curvature is <15 
degrees).  Interval assessments would be performed with the 1st injection of each series, and final 
assessments would then be performed 6 weeks following the final injection. 
2. CCH followed by no treatment.  Men in this cohort would undergo baseline assessments 
followed by up to 8 injections of CCH (or until curvature is <15 degrees).  Interval assessments 
would be performed with the 1st injection of each series and 6 weeks following completion of 
treatment.  Men then would not undergo any additional treatments for 6 months, after which final 
assessments would then performed.   
 
During CCH administration, several key differences from the IMPRESS protocols would be performed.  
Please note that each of these changes have been slowly implemented in the investigators’ practice over 
time to improve overall efficacy of therapy: 
 
 
IMPRESS Protocol 
Current Study Protocol 
Amount administered 
0.58 mg 
0.9 mg 
Suspension volume 
0.37 ml 
0.7 ml 
Method of injection 
Into plaque 
To point of maximal curvature 
in the tunica, as determined with 
an erection at the first injection 
of each series 
Administration schedule 
1-3 days apart 
1 day apart 
Mechanical device traction 
None 
RestoreX 30-60 min daily until 
6 weeks after final injection 
Office modeling 
Performed 1-3 days after initial 
injections (defined as “firm” 
10-15 lbs of force performed at 
the time of 2nd injection 
Home modeling 
3x daily modeling performed, 
gentle attempts at straightening 
erection 
10-15 lbs of force performed at 
least one daily; straightening 
during erection 
Penile wrapping 
No comments 
Mandatory x 5 days after 2nd 
injection of each series 
 
1.3 
Preliminary Data 
 
Please refer to the introductory section for a more complete description of preliminary data.  The 
investigators’ team has been implementing the above, novel techniques in a step-wise fashion over time.  
Data from men who have been treated since Jan 2020 demonstrates a median improvement of ~60% 
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previously undergone prior CCH injections with other providers.  These findings suggest a proof of 
concept for the novel approach and would represent the largest improvement in curvature ever achieved 
with CCH.  Findings would also benefit Endo Pharmaceutical, as it would provide proof of concept data 
that additional series of CCH may be merited in many cases of men with PD.   
 
1.4 
Study Rationale and Risk Analysis (Risks to Benefits Ratio) 
1.4.1 Study Rationale 
 
As noted previously, the investigators’ team had previously performed a survey of men who experience 
suspected fractures with CCH and showed greater curvature correction without worsening of erectile 
function.11  More recent preliminary data from the investigators’ prospective cohort also demonstrated 
significantly improvement outcomes with the protocol described above without any worsening of 
complications compared to historical series (SMSNA abstract 2021).  These findings suggest data 
sufficient to perform a more rigorous study evaluating the use of CCH with this modified protocol.   
 
1.5 
Anticipated Duration of the Clinical Investigation 
 
The overall study will be scheduled for approximately 1 year.  Depending on the duration of CCH 
administration, this time period may fluctuate by several months.     
 
2 Study Endpoints 
 
2.1 
Primary Endpoints 
 
1. Compare penile curvature between control and treatment groups at 6 months 
2. Compare PDQ outcomes between control and treatment groups at 6 months 
 
2.2 
Secondary Outcomes 
 
1. Compare IIEF outcomes between control and treatment groups at 6 months 
2. Compare penile curvature changes in control men at baseline and 12 months (i.e. prior to and 
following cross-over to CCH) 
3. Compare penile length changes in control men at baseline and 12 months (i.e. prior to and 
following cross-over to CCH) 
4. Compare PDQ changes in control men at baseline and 12 months (i.e. prior to and following 
cross-over to CCH) 
5. Compare IIEF changes in control men at baseline and 12 months (i.e. prior to and following 
cross-over to CCH) 
6. Compare penile length changes between control and treatment groups at 6 months 
7. Report adverse events at 6 and 12-month time points 

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8. Report changes in penile curvature between 6 and 12-month assessments for CCH men 
 
3 Study Design 
 
3.1 
Subject Selection 
3.1.1 Inclusion Criteria 
 
• Men with PD 
• >18 years old 
• Curvature ≥30 degrees 
• Previously completed 6-8 CCH injections 
• Prior minimal (<20% and/or <10 degrees) responsiveness to CCH administration 
• Prior CCH injections must have been performed without use of a Restorex traction device and 
used the IMPRESS protocol 
• Ability to achieve an erection satisfactory for intercourse with or without PDE5 inhibitors 
• The patient exhibits a palpable plaque consistent with Peyronie’s Disease 
3.1.2 Exclusion Criteria 
 
• Prior surgical treatment on the penis (other than circumcision) 
• Any contraindications to CCH – as determined by the PI 
• Inability to complete 8 additional CCH injections 
• Severe plaque calcification (i.e. >1 cm shadowing) 
 
3.2 
Setting and Investigator 
 
The current study will be conducted by CURE PD, a charity established to conduct studies in men with 
PD.  All treatments will be performed at the Male Fertility and Peyronie’s Clinic in Orem, UT by Dr. 
Landon Trost.   
 
Dr. Landon Trost is the former head of male infertility and Andrology at the Mayo Clinic in Rochester, 
MN, and he has previously completed several investigator-initiated randomized, controlled trials.  
 
3.3 
Recruitment  
 
Men who are seen in the Male Fertility and Peyronie’s Clinic for Peyronie’s Disease and who have prior 
histories of CCH administration with minimal / no improvements will be offered entry into the trial at 
the time of their clinical visit.  Additional recruitment will be performed by contacting other PD 
providers around the country and through advertising in common PD forums.   
 
 

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3.4 
Consent and Enrollment 
 
Patients attending the Male Fertility and Peyronie’s Clinic or noting interest via email will receive a 
description of the study. Those interested in participating, will be given the opportunity to meet with the 
study coordinator to further review study details and formal consent.  
 
Patients that would like additional time to consider their participation will be given another opportunity 
to meet with the study coordinator at a later time.   If the patient expresses interest in participating at any 
time, a formal consent will be reviewed.  
 
At enrollment, all participants will be assigned a study identifier, with a master list maintained in a 
password protected database linking the patient to the identifier. A total of up to 40 patients will be 
enrolled to achieve outcomes of at least 30 men (total study power 40 given that each participant will 
serve as a control as well as treatment comparator).   
 
3.5 
Study Schema 
 
Patients meeting criteria who have consented will be randomized to either control or CCH x 6 months, 
followed by a cross-over phase where controls will receive CCH.  See Figure 1 for full study schema.    
 
1. Control.  Men in this cohort would undergo baseline assessments followed by no treatment for 6 
months and then repeat assessments.  Men would then cross-over to the CCH treatment phase 
and undergo up to 8 injections (or until curvature is <15 degrees, whichever comes first).  Final 
assessments would then be performed 6 weeks following the final injection. 
2. CCH followed by observation.  Men in this cohort would undergo baseline assessments followed 
by up to 8 injections of CCH (or until curvature is <15 degrees).  Assessments would then be 
performed 6 weeks after completion of treatment.  Men then would not undergo any additional 
treatments for 6 months, after which they would have final assessments performed.     
 
The following table provides an overview of the objective and subjective questionnaire administration: 
 
 
Baseline 
1st CCH of each 
series 
6-weeks after 
CCH completed 
End of no 
treatment phase 
Baseline disease 
specific 
questionnaire 
X 
 
 
 
Baseline 
subjective 
questionnaire 
X 
 
 
 
IIEF 
X 
X 
X 
X 
PDQ 
X 
X 
X 
X 
1st injection 
Xiaflex 
questionnaire 
 
X 
X 
 

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Post Xiaflex 
subjective 
questionnaire 
 
 
X 
 
Post no treatment 
subjective 
questionnaire 
 
 
 
X 
Length 
measurement 
X 
X 
X 
X 
Curve 
measurement 
X 
X 
X 
X 
Penile ultrasound 
X 
 
 
 
 
 
3.6 
Randomization Protocol 
 
Following enrollment and completion of the consent, a length and curvature assessment will be 
performed as well as baseline questionnaires.  Men will then be randomized based on a previously 
created randomization table that takes into account baseline curvatures (see attached Randomization 
Table).  Groupings are divided based on initial curvature of 30-44, 45-59, 60-74, 75-89, 90 or above to 
assure equal representation in each study arm.  Men will then undergo treatment as noted above. 
 
4 Study Procedures 
 
4.1 
Screening Assessments 
 
• 
Potential patient questioned to assure that they meet all inclusion / exclusion criteria 
• 
Participant consented 
 
4.2 
Assessments 
 
• Please refer to the table schema above (Section 3.5) for details as to timing of questionnaire 
administration.   
• Objective measurements 
o Penile length obtained (pubic symphysis to corona and tip) – obtained by two separate 
providers with experience in PD therapies 
o Erection induced with alprostadil (dose to be determined by PI, with a goal to achieve a 
penetration-quality erection).   
o Curvature assessed in two planes as well as with photography (obtained in two planes) 
o Penile ultrasound performed to evaluate for plaque calcification.  Plaques classified as 
none, mild (stippling), moderate (shadowing), and severe (>1 cm). 
• Questionnaires 

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o Baseline disease specific questionnaire 
o Baseline subjective questionnaire 
o IIEF-15 
o PDQ 
o 1st injection Xiaflex questionnaire 
o Post Xiaflex subjective questionnaire 
o Post no treatment subjective questionnaire 
o Adverse events (completed by study personnel only – not completed by study subjects) 
 
5 Statistical Plan 
5.1 
Data Handling 
 
All data will be recorded either by the patient themselves or by the provider directly onto printed forms.  
Information will remain de-identified throughout the remainder of the study period and will remain on 
password protected, CURE PD servers.   
 
After completion of the study, de-identified information will be shared with individuals associated with 
Endo Pharmaceuticals who may assist with portions of the data analysis and/or manuscript drafting if 
desired.  No identifiable information will be sent.   
 
5.2 
Statistical Analysis 
 
The current study is considered exploratory in nature.  Analyses will be performed using comparisons 
within and between patient cohorts.  All captured data will be utilized as a point of comparison based on 
accepted standards (e.g. IIEF subdomains, PDQ subdomains, etc.).  All data will be analyzed to 
determine if it is normative / non-normative and will be described and compared appropriately (mean, 
SD versus median, IQR).  
 
Patients with partial missing data will have all available data included for analysis, with no attempts 
made to statistically replace missing variables.  All data will be analyzed using an intent-to-treat 
analysis.   
 
Adverse events will be reported as a total as well as compared between cohorts.   
 
A power analysis was performed using historical data from another one of the investigators’ RCTs to 
determine the standard deviation for control men between two sequential assessments.  Results of 
absolute curvature improvements demonstrated a standard deviation of 16 degrees or 27% relative 
improvement.  Using a 0.05 alpha threshold, power of 80%, and expected cohort size of 30 (assuming 
30 with 6-month data) this would allow us to distinguish differences over 17 degrees or 29%.  Given the 
investigators’ current improvements of 60% with the investigators’ preliminary data, we would expect 
this study to have sufficient power to demonstrate a clinically and statistically significant finding.   
 

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6 Safety and Adverse Events 
 
Definition of Adverse Event 
 
Unanticipated Problems Involving Risk to Subjects or Others (UPIRTSO) - any unanticipated problem 
or adverse event that meets the following three criteria:  
 
Serious: Serious problems or events that results in significant harm, (which may be physical, 
psychological, financial, social, economic, or legal) or increased risk for the subject or others (including 
individuals who are not research subjects). These include: (1) death; (2) life threatening adverse 
experience; (3) hospitalization - inpatient, new, or prolonged; (4) disability/incapacity - persistent or 
significant; (5) breach of confidentiality and (6) other problems, events, or new information (i.e. 
publications, interim findings, product labeling change) that in the opinion of the local investigator may 
adversely affect the rights, safety, or welfare of the subjects or others, or substantially compromise the 
research data, AND 
 
Unanticipated: (i.e. unexpected) problems or events are those that are not already described as potential 
risks in the protocol, consent document, or not part of an underlying disease. A problem or event is 
"unanticipated" when it was unforeseeable at the time of its occurrence. A problem or event is 
"unanticipated" when it occurs at an increased frequency or at an increased severity than expected, AND 
 
Related: A problem or event is "related" if it is possibly related to the research procedures. 
 
Adverse Event - an untoward or undesirable experience associated with the use of a medical product (i.e. 
drug, device, biologic) in a patient or research subject. 
 
Serious Adverse Event - adverse events are classified as serious or non-serious.  Serious 
problems/events can be well defined and include: 
 
• 
Death 
• 
Life threatening adverse experience 
• 
Hospitalization 
• 
Inpatient, new, or prolonged; disability/incapacity 
• 
And/or per protocol may be problems/events that in the opinion of the sponsor-investigator may 
have adversely affected the rights, safety, or welfare of the subjects or others, or substantially 
compromised the research data. 
 
All AEs that do not meet any of the criteria for serious, should be regarded as non-serious AEs.  
 
6.1 
Adverse Event Reporting Period 
 
For the current study, the treatment follow-up period is defined as 6 weeks following the last 
administration of study treatment (for new symptoms).   

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6.2 
Preexisting Condition 
 
A preexisting condition is one that is present at the start of the study.  A preexisting condition should be 
recorded as an adverse event if the frequency, intensity, or the character of the condition worsens during 
the study period. 
 
At screening, any clinically significant abnormality should be recorded as a preexisting condition.  At 
the end of the study, any new clinically significant findings/abnormalities that meet the definition of an 
adverse event must also be recorded and documented as an adverse event.  
 
6.3 
Post-study Adverse Event 
 
All unresolved AEs will be followed by the study team until the events are resolved, the subject is lost to 
follow-up, or the AE is otherwise explained.  A review of AEs which the subject or subject’s physician 
believe might reasonably be related to participation in the study will be performed up to 12 months 
following treatment.   
 
6.4 
Hospitalization, Prolonged Hospitalization or Surgery 
 
Any AE related to the study intervention that results in hospitalization or surgery should be documented 
and reported as a serious AE.   
 
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported as an adverse 
event in the following circumstances:  
• 
Hospitalization or prolonged hospitalization for diagnostic or elective surgical procedures for a 
preexisting condition.  Surgery should not be reported as an outcome of an adverse event if the purpose 
of the surgery was elective or diagnostic and the outcome was uneventful. 
 
6.5 
Recording of Adverse Events 
 
The study team will seek information on adverse events by specific questioning between baseline and 
the follow-up visits.  Information on all adverse events will be recorded immediately in the adverse 
event section of the specific questionnaire as well as in an adverse event form. 
 
All adverse events occurring during the study period will be recorded.  The clinical course will be 
followed until resolution, stabilization, or until it has been ultimately determined that the study treatment 
or participation is not the probable cause.  Serious adverse events that are still ongoing at the end of the 
study period will be followed up, to determine the final outcome.  Any serious adverse event that occurs 
after the study period and is considered to be at least possibly related to the study treatment or study 
participation will be recorded and reported immediately. 
 

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6.6 
Reporting of Serious Adverse Events and Unanticipated Problems 
 
When an adverse event has been identified, the study team will take appropriate action necessary to 
protect the study participant and then complete the Adverse Event Form.  The sponsor-investigator will 
evaluate the event and determine the necessary follow-up and reporting required. 
 
6.6.1 Sponsor-investigator Reporting: Notifying the Western IRB 
 
An adverse event form will be completed for any serious adverse event.  This will be reported to the 
Western IRB in a de-identified manner.   
 
The study team will report to the Western IRB any UPIRTSOs and Non-UPIRTSOs. 
 
Information collected on the adverse event form (and entered into the research database)  
• 
Subject’s ID 
• 
Description of adverse event 
• 
The date the adverse event occurred and resolved (if applicable) 
• 
Intensity 
• 
Outcome 
• 
Action taken to address 
• 
Relationship to study 
• 
Impact on study withdrawal 
• 
Classification as serious or not 
 
The sponsor-investigator will review all adverse event reports to determine if specific reports need to be 
made to the IRB.  The sponsor-investigator will sign and date the adverse event report when it is 
reviewed.  For this protocol, only directly related SAEs/UPIRTSOs will be reported to the IRB. 
 
6.6.2 Stopping Rules 
 
Any serious adverse event which is determined to reasonably be related to the study treatment by the 
sponsor-investigator will result in immediate discontinuation of the therapy.  If 5 patients develop 
serious adverse events, the study will be halted with re-review required by the Western IRB prior to 
consideration of study resumption.   
 
6.6.3 Medical Monitoring 
 
Medical monitoring of serious adverse events will be performed by the study investigator on a monthly-
basis if serious adverse events have been reported.   
 
 

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7 Data Handling and Record Keeping 
7.1 
Confidentiality 
Information about study subjects will be kept confidential and managed according to the requirements of 
the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  Those regulations require a 
signed subject authorization informing the subject of the following: 
• What protected health information (PHI) will be collected from subjects in this study 
• Who will have access to that information and why 
• Who will use or disclose that information 
• The rights of a research subject to revoke their authorization for use of their PHI. 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, 
retains the ability to use all information collected prior to the revocation of subject authorization.  For 
subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain 
permission to collect at least vital status (long term survival status that the subject is alive) at the end of 
their scheduled study period. 
7.2 
Source Documents 
 
Source data comprise all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial.  Source data are 
contained in source documents.  Examples of these original documents, and data records include: 
hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation 
checklists, pharmacy dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate and complete, microfiches, photographic 
negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the 
laboratories, and at medico-technical departments involved in the clinical trial. When applicable, 
information recorded on the CRF shall match the Source Data recorded on the Source Documents. 
 
7.3 
Records Retention 
 
The sponsor-investigator will maintain records and essential documents related to the conduct of the 
study.  These will include subject case histories and regulatory documents. 
 
The sponsor-investigator will retain the specified records and reports during the study and for a period of 
2 years after the investigation is terminated or completed. 
 
8 Study Finances 
8.1 
Funding Source 
 
This study is funded by Endo Pharmaceuticals.  
8.2 
Conflict of Interest 
 

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Dr. Landon Trost is the inventor and developer of the RestoreX® device.  His conflict has previously 
been reviewed with the Mayo Clinic Conflict of Interest Review Board, and following review, it has 
been determined that Dr. Trost is able to conduct clinical studies as a Primary Investigator (IRB17-
001283).   
8.3 
Subject Stipends or Payments 
 
Subjects will receive payment for their participation, including stipends for travel, and all treatments 
provided at no cost.    
 
8.4 
Regulatory Information 
 
CCH is an FDA approved therapy for the treatment of PD.  The current FDA label includes an 
indication for men with PD who have a palpable plaque and at least 30 degrees of curvature at the 
beginning of therapy.  These indications are consistent with the current protocol (i.e. no new indications 
would be sought).   
 
PathRight Medical has registered the RestoreX® device with the FDA as a Class I device, similar to 
limb orthotics (see Attachment – RCRI Position Paper).  The device is available without a prescription 
and may be purchased by the general public.  As such, clinical studies are not required prior to its 
routine use, and the current studies are being done as an investigator-initiated project to determine its 
potential role in length of penile prosthesis inserted.   
 
 
 
9 References 
 
  
[1] 
Gelbard M, Goldstein I, Hellstrom WJ, et al. Clinical efficacy, safety and tolerability of collagenase 
clostridium histolyticum for the treatment of peyronie disease in 2 large double-blind, randomized, placebo 
controlled phase 3 studies. The Journal of urology. 2013;190: 199-207. 
[2] 
Alom M, Meng Y, Sharma KL, Savage J, Kohler T, Trost L. Safety and Efficacy of Collagenase 
Clostridium Histolyticum in Peyronie's Disease Men With Ventral Curvatures. Urology. 2019;129: 119-25. 
[3] 
Wymer K, Ziegelmann M, Savage J, Kohler T, Trost L. Plaque calcification: An important predictor of 
collagenase clostridium histolyticum treatment outcomes for men with Peyronie's Disease. Urology. 2018. 
[4] 
Ziegelmann MJ, Viers BR, McAlvany KL, Bailey GC, Savage JB, Trost LW. Restoration of Penile Function 
and Patient Satisfaction with Intralesional Collagenase Clostridium Histolyticum Injection for Peyronie's Disease. 
The Journal of urology. 2016;195: 1051-6. 
[5] 
Ziegelmann MJ, Viers BR, Montgomery BD, Westerman ME, Savage JB, Trost LW. Self-reported Clinical 
Meaningfulness Early in the Treatment Course Predicts Objective Outcomes in Men Undergoing Collagenase 
Clostridium histolyticum Injections for Peyronie Disease. Urology. 2017;106: 107-12. 
[6] 
Capece M, Cocci A, Russo G, et al. Collagenase clostridium histolyticum for the treatment of Peyronie's 
disease: a prospective Italian multicentric study. Andrology. 2018;6: 564-67. 
[7] 
Nguyen HMT, Anaissie J, DeLay KJ, Yafi FA, Sikka SC, Hellstrom WJG. Safety and Efficacy of 
Collagenase Clostridium histolyticum in the Treatment of Acute-Phase Peyronie's Disease. The journal of sexual 
medicine. 2017;14: 1220-25. 

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[8] 
Yang KK, Bennett N. Peyronie's Disease and Injectable Collagenase Clostridium histolyticum: Safety, 
Efficacy, and Improvements in Subjective Symptoms. Urology. 2016;94: 143-7. 
[9] 
Alom M, Sharma KL, Toussi A, Kohler T, Trost L. Efficacy of Combined Collagenase Clostridium 
histolyticum and RestoreX Penile Traction Therapy in Men with Peyronie's Disease. The journal of sexual 
medicine. 2019;16: 891-900. 
[10] 
Gelbard M, Lipshultz LI, Tursi J, Smith T, Kaufman G, Levine LA. Phase 2b study of the clinical efficacy 
and safety of collagenase Clostridium histolyticum in patients with Peyronie disease. The Journal of urology. 
2012;187: 2268-74. 
[11] 
Sharma KL, Bole R, Yang D, et al. Conservative management of suspected fractures in men undergoing 
collagenase clostridium histolyticum for Peyronie's Disease is not associated with worsening of erectile function. 
International journal of impotence research. 2020.