TRIUMPH - 1 TRansperineal Intraprostatic Injection of PRX302 Under Ultrasound Guidance for Management of Prostatic Hyperplasia

• Compare efficacy of PRX302 as assessed by changes from baseline in QoL, Qmax, and PVR at 3, 6, 12 and 24 months and prostate volume at 3 and 6 months, when compared to placebo [ Time Frame: 3, 6, 12 and 24 months post treatment ] [ Designated as safety issue: No ]
• Parameters for assessment of safety and tolerability of PRX302 will include adverse events, including Serious Adverse Events(SAEs), physical exam, vital signs, ECG, clinical lab tests, and the International index for erectile function (IIEF) [ Time Frame: 12 months post treatment ] [ Designated as safety issue: Yes ]

• To compare efficacy of PRX302 as assessed by a change from baseline in Quality of Life, maximum urine flow rate (Qmax), and Post-void residual urine volume (PVR), at 3, 6 and 12 months when compared to placebo [ Time Frame: 3, 6 and 12 months post treatment ] [ Designated as safety issue: No ]
• Parameters for assessment of safety and tolerability of PRX302 will include adverse events, including Serious Adverse Events(SAEs), physical exam, vital signs, ECG, clinical lab tests, and the International index for erectile function (IIEF) [ Time Frame: 12 months post treatment ] [ Designated as safety issue: Yes ]

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).

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.

• Experimental: Active Drug
  Intervention: Drug: PRX302
• Placebo Comparator: Placebo
  Intervention: Drug: PRX302

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. 5.2

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.