Dose Escalation Study With QLT0074 for Benign Prostatic Hyperplasia
Dose Escalation Study With QLT0074 for Benign Prostatic Hyperplasia
The primary objective of this study is to assess the safety and tolerance of transurethral
 photodynamic therapy (PDT) with QLT0074.

 Secondary objectives are:

 1. To determine if transurethral PDT with QLT0074 has a therapeutic effect on benign
 prostatic hyperplasia (BPH), evaluated by the American Urological Association Symptom
 Index (AUA SI), urinary flow rate (Qmax), and post-void residual volume (PVR).

 2. To determine the extent of systemic exposure to QLT0074 following transurethral
 intraprostatic injection.

 3. To select up to two transurethral PDT drug-light regimens for further clinical
 development.
This will be a multicenter, uncontrolled, dose escalation, exploratory study in subjects with
 symptomatic BPH. Six study centers are planned.

 Each subject will receive a fixed dose of QLT0074 (0.4 mg) injected transurethrally into the
 prostate followed by transurethral light application to activate the drug. Five light dose
 cohorts will be investigated sequentially (25, 50, 80, 120, and 150 J/cm2), with 3 subjects
 in the first cohort and 6 subjects in cohorts 2-5 for a total of 27 subjects. The follow-up
 period for each subject is 180 days. There will be a minimum 30-day interval between
 treatment of the last subject in one cohort (Day 0) and treatment of the first subject in the
 next cohort to monitor predefined toxicities and ensure safety and tolerance in subjects of
 the previous cohort.

 A Safety Monitoring Committee will evaluate toxicity related to PDT effects, and approve
 escalation of the light dose for each cohort. The light dose will not be escalated if any of
 the following predefined toxicity criteria occur and are judged to be related to a PDT effect
 by the Safety Monitoring Committee:

 1. 1 or more subjects in the cohort experience macroscopic urinary bleeding not resolved by
 Day 14, or

 2. 2 or more subjects in the cohort experience intolerable urinary pain not controlled with
 over-the-counter medication by Day 14, or

 3. 1 or more subjects in the cohort experience any other clinically significant urological
 adverse event, as judged by the Investigator and confirmed by the Safety Monitoring
 Committee.

 In addition to the above events, the Safety Monitoring Committee will evaluate the incidence,
 timing, severity, and frequency of other adverse events and serious adverse events to assess
 the safety of transurethral PDT and the treatment procedures (such as the use of the
 cystoscope, InjectTx device, treatment balloon-catheter, etc).

 To prevent treating subjects with a light dose greater than that which already provides
 substantial clinical benefit, the Safety Monitoring Committee will review preliminary
 efficacy data (AUA SI scores and Qmax values) after all subjects in a cohort (for each of the
 first 4 cohorts) have completed the Day 90 visit. Further enrollment will be curtailed if
 more than 75% of subjects in a cohort experience both of the following efficacy stopping
 criteria by Day 90:

 1. greater or equal to 75% reduction in the AUA SI score and,

 2. greater or equal to 100% increase in Qmax.
-  Twenty-seven men with symptomatic BPH despite adequate drug therapy and who are
 candidates for surgical or minimally invasive treatment will be enrolled in the study.

 -  Subjects must have an AUA SI >13, Qmax between 5 and 15 mL/sec, and a urethral
 treatment length between 30 and 65 mm (defined as the length of the urethra between
 the bladder neck and the edge of the verumontanum distal to the bladder).