We have completed nine clinical trials of topsalysin (PRX302) – including a Phase 2b trial for the treatment of localized prostate cancer (PRX302-2-08) and a Phase 3 trial for the treatment of the lower urinary tract symptoms of BPH (PRX302-3-01). In December 2018, we reported safety and biopsy findings from our Phase 2b clinical trial for the treatment of clinically significant localized prostate cancer following a single administration of topsalysin. A single administration of topsalysin continues to appear to be safe and well-tolerated and demonstrated an ability to ablate prostate cancer tumor cells with 10/37 patients (27%) demonstrating a clinical response of which 6 were complete ablations. See additional details about this study below. In the PLUS-1 study, PRX302 demonstrated a favorable safety profile, with no evidence of any treatment related sexual or cardiovascular side effects. The Phase 3 trial achieved its primary endpoint — a single treatment with topsalysin demonstrated a statistically significant improvement in BPH symptoms over a 12 month period.
On June 19, 2019, the we announced that we have received formal scientific advice from the European Medicines Agency (EMA) regarding a proposed design of a Phase 3 clinical trial to evaluate the potential of topsalysin as a targeted focal therapy to treat patients with intermediate risk localized prostate cancer.
The Phase 3 study design, agreed upon by the EMA, will enroll patients with a confirmed diagnosis of intermediate risk disease. Approximately 700 men who meet the eligibility criteria will be equally randomized to receive a single administration of either topsalysin or placebo. The primary endpoint for the study will be the proportion of patients at 12 months who have failed treatment, defined as histological progression of disease resulting in the need for alternative intervention, per an independent central adjudication panel.
The initiation of this clinical trial is dependent upon obtaining additional financing and/or entering into partnering or other strategic transactions.
Completed Clinical Trials
Localized Prostate Cancer
We have completed four clinical trials of PRX302 – including a Phase 2b trial for the treatment of localized prostate cancer (PRX302-2-08). Learn more about our completed clinical development in Localized Prostate Cancer and their trial designs below:
In March 2017, we initiated a second Phase 2 clinical trial to confirm the dose and optimize the delivery of topsalysin for the treatment of clinically significant localized prostate cancer. This study utilizes previously obtained MRI images of each patient’s prostate mapped to real time 3D ultrasound to target the delivery of topsalysin directly into and around a pre-identified clinically significant tumor. The primary objective of the study is safety and tolerability of an injection of topsalysin and the key efficacy variable is focal ablation of a clinically significant lesion on biopsy after six months.
We have reported safety and biopsy findings from our Phase 2b clinical trial following a single administration of topsalysin. A single administration of topsalysin continues to be safe and well-tolerated and demonstrated an ability to ablate prostate cancer tumor cells with 10/37 patients (27%) demonstrating a clinical response of which 6 were complete ablations.
The Phase 2b prostate cancer clinical trial represents the first trial designed to allow qualified patients to receive a second administration of topsalysin six months after initial treatment. On December 17, 2018 we announced top-line safety and biopsy results from the ten patients who received a second administration of study drug, which appeared to be safe and generally well-tolerated. Additional benefit was not observed on targeted biopsy six months after re-treatment with a second administration of topsalysin. The decision to include a second administration of topsalysin in any future clinical studies is under review by the Company.
A total of 18 patients with localized low to intermediate risk prostate cancer were enrolled in the Phase 2a proof of concept clinical 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 60 percent of patients (11/18 patients) six months after treatment in a patient population with pre-identified, clinically significant prostate cancer.
All 18 patients enrolled completed the study. Biopsy data at six months following treatment showed that:
- Two patients experienced complete ablation of their targeted tumor with no evidence of any tumor remaining at six months;
- Nine patients experienced a partial response, defined as either a reduction in the maximum cancer core length or a reduction in Gleason pattern; and
- Seven patients had no response to treatment.
See additional details of the results of this study here.
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.
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.
We have completed five clinical trials of PRX302 for the treatment of the lower urinary tract symptoms of BPH – including a Phase 3 trial l for the treatment of the lower urinary tract symptoms of BPH. Learn more about our completed clinical development in BPH and their trial designs below:
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.
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). Learn More »
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.
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.