Transperineal Intraprostatic Injection of PRX302 Under Ultrasound Guidance for Management of Prostatic Hyperplasia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether PRX302 is safe and effective in the treatment of moderate to severe Benign Prostatic Hyperplasia (BPH).

Detailed Description
-----------------
This is a randomized, double-blinded, placebo-controlled study of transperineal intraprostatic injection of PRX302 under sonographic guidance. Subjects will be randomly assigned to the two treatment groups in a ratio of 2:1 between PRX302 and Placebo, stratified by prostate size and baseline IPSS.

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled Phase II Study of Transperineal Intraprostatic Injection of PRX302 for the Treatment of Benign Prostatic Hyperplasia

Conditions
-----------------
Benign Prostatic Hyperplasia

Intervention / Treatment
-----------------
* Drug: PRX302
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males aged 40 to 80 years; Lower urinary tract symptoms (LUTS), such as frequency, nocturia, urgency, weak urine stream, hesitancy, intermittency or post-void dribbling attributable to BPH for at least 6 months prior to dosing; Untreated, intolerant or refractory to α-blockers; should not have received the medication for at least 2 weeks prior to screening and 4 weeks prior to dosing; Subjects with PSA values 4 - 10 ng/mL should be assessed or medical records checked (e.g. biopsy report) to rule out the presence of prostate cancer; Untreated, intolerant or intolerant to 5-α reductase inhibitors AND must be off medication for at least 6 months prior to dosing; IPSS of 15 or higher; Prostate volume at screening estimated at 30 to 100 mL as determined by TRUS; Provided written Informed Consent for participation in the study. Exclusion Criteria: Maximum urine flow rate (Qmax) of greater than 12 mL/sec; Inability to void at least 150 mL of urine; Post voiding residual urine volume (PVR) of greater than 200 mL; Subjects unable to stand to void; Subjects with acute or chronic bacterial prostatitis; Using drugs (e.g. estrogen, androgen) that can produce androgen depression or anabolic steroids; Penile prosthesis or artificial urinary sphincter; Presence of prostatic cyst larger than 1 cm in diameter; Unwilling to use condoms for 3 weeks post-treatment to prevent pregnancy and to avoid semen contact with partner(s); Urethral stricture disease; Bladder neck abnormalities/strictures; Significant median lobe hyperplasia that contributes to outflow obstruction; Confirmed or suspected neurogenic bladder dysfunction; Systemic neurological disorders that may affect voiding function; Previous pelvic surgery, trauma or radiation; Active genitourinary infection within 7 days before screening; Significant renal dysfunction (as evidenced by a serum creatinine > 1.6 mg/dL on the screening laboratory evaluation); Abnormal liver function as evidenced by any of the following abnormal laboratory values being greater than 1.5 upper limit of normal (ULN) at screening: alkaline phosphatase (ALP); total bilirubin; alanine transferase (ALT); and/or aspartate aminotransferase (AST); Abnormal Prothrombin Time (PT > 13 sec) / International Normalized Ratio (INR > 1.2); Severe cardiovascular or hepatic disease (American Society of Anesthesiologists [ASA] > 3); Presence of suspected or confirmed malignancy other than non-melanomatous, cutaneous malignancies which have undergone curative interventions; Receiving anticoagulants (Subjects receiving anticoagulants may be enrolled after discontinuation of anticoagulant therapy and return of INR level to within normal limits (INR < 1.2) before dosing day. Subjects receiving platelet inhibitors (including garlic) must be off the inhibitors for at least 6 days or more. Subjects unable to discontinue anticoagulant therapy may not be enrolled in this study); Subjects who have received any treatment for BPH other than α-blockers, 5-α reductase inhibitors or phytotherapy; Subjects taking α-blockers and phytotherapy within 2 weeks of screening and 4 weeks of dosing; Subjects receiving 5-α reductase inhibitors within 6 months of dosing; Subjects taking part in other experimental programs prior to the start of the study or during the study period; Any medical, psychological or other condition or medical history of the subject that, in the opinion of the Investigator or the Sponsor's Medical Monitor, unduly increases the risk of subject's participation or that would unnecessarily confound the data to be collected in this study; Unable or unwilling to comply with the requirements of the protocol.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Drug<br>PRX302 | Drug: PRX302<br>* PRX302 will be administered at a volume equivalent to 20% of the prostate volume and at a fixed concentration. Treatment will be administered through 1 injection into the transition zone of each lobe of the prostate. A minimum of 2 deposits will be made in the transition zone into each of the right and left lobes of the prostate, with a minimum of 1.0 mL per deposit.<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* PRX302 will be administered at a volume equivalent to 20% of the prostate volume and at a fixed concentration. Treatment will be administered through 1 injection into the transition zone of each lobe of the prostate. A minimum of 2 deposits will be made in the transition zone into each of the right and left lobes of the prostate, with a minimum of 1.0 mL per deposit.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in International Prostate Symptom Scale (IPSS) of Lower Urinary Tract Symptoms From Baseline to 3 Months (Total Score at 3 Months Minus Total Score at Baseline) | Total of 7 questions regarding lower urinary tract symptoms, with each question scored on a range of 0 (not at all) to 5 (almost always have the symptom). The total score is the summation of all 7 questions, and therefore has a possible range of 0 to 35. | 3 months post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Maximum Urinary Flow Rate (Qmax) From Baseline to 3 Months (Qmax at 3 Months Minus Qmax at Baseline) | A printout of uroflowmetry was provided to a central, blinded, independent reviewer for determination of the Qmax values to be used for evaluation of efficacy. The central, independent, blinded reviewer determined the Qmax from over-reads of the uroflowmetry printouts, applying the 2-second rule to reduce variability and increase the accuracy. | 3 months after treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Benign Prostatic Hyperplasia, BPH, Enlarged Prostate