Prospective, randomized, double-blind, vehicle controlled, multicenter phase IIb clinical trial of the pore forming protein PRX302 for targeted treatment of symptomatic benign prostatic hyperplasia

Mostafa M. Elhilali, Peter Pommerville, Richard C. Yocum, Rosemina Merchant, Claus Roehrborn, Samuel R. Denmeade

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Purpose: We conducted a safety and efficacy evaluation of intraprostatic injection of PRX302, a modified pore forming protein (proaerolysin) activated by prostate specific antigen, as a highly targeted, localized approach to treat lower urinary tract symptoms due to benign prostatic hyperplasia. Materials and Methods: A total of 92 patients with I-PSS (International Prostate Symptom Score) 15 or greater, peak urine flow 12 ml or less per second and prostate volume 30 to 100 ml were randomized 2:1 to a single ultrasound guided intraprostatic injection of PRX302 vs vehicle (placebo) in this phase IIb double-blind study. Injection was 20% of prostate volume and 0.6 μg PRX302 per gm prostate. Peak urine flow was determined by a blinded reviewer. Benign prostatic hyperplasia medications were prohibited. The primary data set of efficacy evaluable patients (73) was analyzed using last observation carried forward. Results: PRX302 treatment resulted in an approximate 9-point reduction in I-PSS and 3 ml per second increase in peak urine flow that were statistically significant changes from baseline compared to vehicle. Efficacy was sustained for 12 months. Early withdrawal for other benign prostatic hyperplasia treatment was more common for patients in the vehicle group. Relative to vehicle, PRX302 apparent toxicity was mild, transient, and limited to local discomfort/pain and irritative urinary symptoms occurring in the first few days, with no effect on erectile function. Conclusions: A single administration of PRX302 as a short, outpatient based procedure was well tolerated in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. PRX302 produced clinically meaningful and statistically significant improvement in patient subjective (I-PSS) and quantitative objective (peak urine flow) measures sustained for 12 months. The side effect profile is favorable with most effects attributed to the injection itself and not related to drug toxicity.

Original languageEnglish (US)
Pages (from-to)1421-1426
Number of pages6
JournalJournal of Urology
Volume189
Issue number4
DOIs
StatePublished - Apr 2013

Fingerprint

Porins
Prostatic Hyperplasia
Prostate
Clinical Trials
Urine
Lower Urinary Tract Symptoms
Injections
Therapeutics
Prostate-Specific Antigen
PRX302
Drug-Related Side Effects and Adverse Reactions
Double-Blind Method
Outpatients
Placebos
Observation
Safety
Pain

Keywords

  • aerolysin
  • lower urinary tract symptoms
  • prostatic hyperplasia
  • PRX302

ASJC Scopus subject areas

  • Urology

Cite this

Prospective, randomized, double-blind, vehicle controlled, multicenter phase IIb clinical trial of the pore forming protein PRX302 for targeted treatment of symptomatic benign prostatic hyperplasia. / Elhilali, Mostafa M.; Pommerville, Peter; Yocum, Richard C.; Merchant, Rosemina; Roehrborn, Claus; Denmeade, Samuel R.

In: Journal of Urology, Vol. 189, No. 4, 04.2013, p. 1421-1426.

Research output: Contribution to journalArticle

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abstract = "Purpose: We conducted a safety and efficacy evaluation of intraprostatic injection of PRX302, a modified pore forming protein (proaerolysin) activated by prostate specific antigen, as a highly targeted, localized approach to treat lower urinary tract symptoms due to benign prostatic hyperplasia. Materials and Methods: A total of 92 patients with I-PSS (International Prostate Symptom Score) 15 or greater, peak urine flow 12 ml or less per second and prostate volume 30 to 100 ml were randomized 2:1 to a single ultrasound guided intraprostatic injection of PRX302 vs vehicle (placebo) in this phase IIb double-blind study. Injection was 20{\%} of prostate volume and 0.6 μg PRX302 per gm prostate. Peak urine flow was determined by a blinded reviewer. Benign prostatic hyperplasia medications were prohibited. The primary data set of efficacy evaluable patients (73) was analyzed using last observation carried forward. Results: PRX302 treatment resulted in an approximate 9-point reduction in I-PSS and 3 ml per second increase in peak urine flow that were statistically significant changes from baseline compared to vehicle. Efficacy was sustained for 12 months. Early withdrawal for other benign prostatic hyperplasia treatment was more common for patients in the vehicle group. Relative to vehicle, PRX302 apparent toxicity was mild, transient, and limited to local discomfort/pain and irritative urinary symptoms occurring in the first few days, with no effect on erectile function. Conclusions: A single administration of PRX302 as a short, outpatient based procedure was well tolerated in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. PRX302 produced clinically meaningful and statistically significant improvement in patient subjective (I-PSS) and quantitative objective (peak urine flow) measures sustained for 12 months. The side effect profile is favorable with most effects attributed to the injection itself and not related to drug toxicity.",
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