We have completed eight clinical trials of PRX302 – including a Phase 3 trial l for the treatment of the lower urinary tract symptoms of BPH and a Phase 2a trial for the treatment of localized prostate cancer (PRX302-2-7 PCa). The Phase 3 trial, called PLUS-1, achieved its primary endpoint — a single treatment with PRX302 (topsalysin) demonstrated a statistically significant improvement in BPH symptoms over a 12 month period. In the PLUS-1 study, PRX302 also demonstrated a favorable safety profile, with no evidence of any treatment related sexual or cardiovascular side effects. In our completed PRX302-2-7 PCA trial, the one-time administration of topsalysin was well tolerated with no serious adverse events and no new safety signals being reported. Topsalysin demonstrated an ability to ablate tumor cells in 50 percent (9/18 patients) six months after treatment in a patient population with pre-identified, clinically significant prostate cancer. The results support advancing topsalysin for the treatment of localized prostate cancer into another Phase 2 study to confirm dose and optimize delivery.
The Phase 2a proof of concept study is a single center, open-label study that will enroll approximately 20 patients. Previously-obtained multi-parametric magnetic resonance imaging (mpMRI) of tumor lesions in each patient’s prostate, mapped to real-time three-dimensional transrectal ultrasound (TRUS), will be used in the study to guide the injection of PRX302 to treat a single, histological-proven, clinically significant lesion area in each patient’s prostate. Although the primary objective of the study is safety and tolerability, the key efficacy variable is the change in the treated clinically significant lesion on biopsy after 6 months.
Completed Clinical Development
(pts treated with PRX302
|PRX302-2-7 PCa||IIa Completed (approximately 18 patients)||Open label, Phase 2a study, evaluating the safety and tolerability of targeted intraprostatic administration of PRX302 to treat men with histologically proven, clinically significant, localized, low to intermediate risk prostate cancer|
|III Completed (479 patients)||Prospective, randomized, double-blind, placebo-controlled, transrectal treatment of PRX302, which will utilize the IPSS outcome measure evaluated at 12 months as the primary endpoint|
|IIb (61 pts)||Randomized, double-blind, placebo-controlled, transperineal treatment of PRX302|
|PRX302-2-06 BPH||I/II (32 pts)||Randomized dose escalation, multicenter trial of a single transrectal intraprostatic treatment of PRX302|
Phase 2a BPH
|IIa (18 pts)||Open-label, safety, volume escalation clinical trial of a single transperineal treatment of PRX302|
|I (15 pts)||Open-label, safety, dose escalation clinical trial of a signal transperineal intraprostatic treatment of PRX302|
|PRX302 PCa||I (24 pts)||Open-label, safety and tolerability, dose escalation trial of PRX302 in patients with biopsy-proven, locally-recurrent prostate cancer|
|PRX302 PCa||II (6 pts)||Open-label clinical trial in locally-recurrent prostate cancer|
PLUS-1 phase III trial
A Phase 3 “PLUS-1” trial evaluating PRX302 as a treatment for lower urinary tract symptoms of benign prostatic hyperplasia (BPH, enlarged prostate) met its primary endpoint. PRX302 demonstrated a statistically significant improvement in International Prostate Symptom Score (IPSS) total score from baseline over 12 months compared to the vehicle-only control group (7.60 vs. 6.58 point overall improvement; p = 0.043), the primary endpoint of the study. PRX302 continues to demonstrate a favorable safety profile, with no evidence of any treatment related sexual or cardiovascular side effects. Additional details were announced here.
TRIUMPH Phase IIb trial (PRX 302-2-03)
A multi-center, double blinded, placebo controlled Phase IIb study (TRIUMPH) of PRX302 in men with moderate to severe BPH met its primary endpoint demonstrating a statistically significant improvement in IPSS from baseline when compared to placebo at 3 months post-treatment. In the study, patients treated with PRX302 showed an improvement of 9.1 points from baseline versus an improvement in IPSS of 5.8 points from baseline in patients receiving placebo (p<0.05) A clinically meaningful improvement was maintained throughout the 12 months (Elihilali, M. et al J Urol. 2013 Apr189 (4) : 1421-6).
PRX302-2-06 Phase I/II trial
A double-blind, multi-center, placebo controlled Phase IIa study in 40 patients with moderate to severe BPH. Patients were randomized to PRX302 or placebo within one of four dose cohorts in this transrectal study. The primary endpoint of the study was to evaluate the 3-month safety and tolerability of escalating doses of PRX302. The side effect profile in this Transrectal clinical trial was consistent with the side effects reported in the previous, transperineal PRX302 clinical trials, indicating that PRX302 injection by the Transrectal route was well tolerated, and was comparable to the transperineal route.
PRX302-2-01 Phase I and PRX302-2-02 Phase II
The transperineal administration of PRX302 was well tolerated in these open label and dose-escalation and volume studies, and, IPSS scores improved significantly for up to 12 months after treatment. The dose escalation of 14-fold was well tolerated and the Maximum Tolerated Dose was not reached. No drug-related adverse events Grade 3 or higher were observed. Results supported further development of PRX302.
Phase 1 Open-Label Clinical Trial in Prostate Cancer
In May 2008, we completed a multicenter, open-label, dose-escalation Phase 1 clinical trial of PRX302 in 24 patients in the United States with biopsy-proven, locally-recurrent prostate cancer that, following radiation therapy, showed signs of disease progression evidenced by rising levels of PSA. Elevated and rising levels of PSA can be a sign of the presence or progression of prostate cancer. The primary clinical endpoint of this clinical trial was to examine the safety and tolerability of PRX302 with therapeutic activity as the secondary clinical endpoint. Clinical trial results demonstrated that PRX302 was well-tolerated and showed early signs of therapeutic activity following a single intraprostatic treatment.
No PRX302 treatment-related serious adverse events were reported and the treatment-related adverse effects that were reported were mild and were primarily associated with the injection procedure.
Phase 2 Open-Label Clinical Trial in Prostate Cancer
In September 2009, we completed a Phase 2 clinical trial of PRX302 in six patients with biopsy-proven, locally-recurrent prostate cancer that, following radiation therapy, showed signs of disease progression evidenced by rising levels of PSA. Therapeutic activity in the form of overall decreases in PSA levels and in the number of adenocarcinoma-positive biopsy cores following PRX302 treatment was observed in two of six patients.