This randomized, double-blind, placebo-controlled Phase 2 study is evaluating Teverelix DP in men following a first episode of acute urinary retention (AUR) associated with benign prostatic hyperplasia (BPH), a population at risk of recurrent urinary retention and subsequent surgical or minimally invasive intervention. The study is designed to evaluate the effects of Teverelix DP on total prostate volume and urinary function and to prospectively evaluate clinically meaningful outcomes including recurrent AUR, BPH-related surgical or minimally invasive intervention, protocol-defined treatment failure and clinical benefit. Participants will be randomized to one of four treatment groups evaluating two active Teverelix DP regimens: 90 mg administered intramuscularly (IM) and 120 mg administered subcutaneously (SC) and their respective matched placebo controls. The primary endpoint is percent change from baseline in total prostate volume (TPV) at Week 12. Participants will continue to be evaluated during the 28-week treatment period for urinary function and prospectively defined clinical outcomes, including recurrent AUR, BPH-related intervention, treatment failure and clinical benefit, and will be followed through Week 52 for protocol-defined longer-term assessments and safety follow-up. The study is designed to characterize biological activity, urinary function, clinical outcomes, safety and the relative treatment effects of the two Teverelix DP regimens to inform dose and route selection and subsequent clinical development.
An interim analysis of the primary endpoint will be conducted after at least 50% of patients have completed their 12-week visit. The interim analysis may also be used to inform future development strategy for Teverelix DP. Should the interim data demonstrate supportive safety and pharmacodynamic trends, the Sponsor may consider expansion of the clinical development program into a confirmatory Phase 3 trial.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
126
Single dose at Day 1 of 90 mg injection IM
Single dose at Day 1 of 90 mg injection IM
Single dose at Day 1 of 120 mg injection SC
Single dose at Day 1 of 120 mg injection SC
Percent Change from Baseline in Total Prostate Volume (TPV) at Week 12
Percent change from baseline in total prostate volume as assessed by transrectal ultrasound.
Time frame: Change from baseline to Week 12
To assess the AUR clinical benefit rate of Teverelix DP after a single dose
The proportion of patients meeting all of the following criteria during the 28-week treatment period and the 52-week observation period: * No relapse of AUR; * No need or indication for surgical intervention; and * No occurrence of treatment failure (PVR \>300 mL with Qmax \<10 mL/sec).
Time frame: From dosing to week 52
Evaluate the durability of prostate volume reduction following a single dose of Teverelix DP
Percent change in total prostate volume
Time frame: Change from baseline to week 52
Change from baseline in post-void residual volume (PVR) (mL), assessed by ultrasound.
Time frame: Change from baseline to week 28
Change from baseline in maximum urinary flow rate (Qmax) (mL/sec), using Uroflowmetry.
Time frame: Change from baseline to week 28
Explore the correlation between change prostate volume and change in post-void residual volume (PVR) (mL)
Time frame: Change from baseline to week 28
Explore the correlation between change prostate volume and change in maximum urinary flow rate (Qmax) (mL/sec)
Time frame: Change from baseline to week 28
Incidence of AUR recurrence according to Teverelix dose (90 mg vs 120 mg) and route of administration (IM vs SC)
Identifying the optimal dosing regimen and route of administration from the following; 90 mg or 120 mg of Teverelix DP and intramuscular (IM) or subcutaneous (SC).
Time frame: From Day 1 through study completion (an average of 1 year)
To assess time to Post-void residual (PVR) >60% of total bladder volume, measured by ultrasound.
PVR volume measurements will be taken at various timepoints in the study to assess the time taken for PVR \>60% of total bladder volume
Time frame: From Day 1 through study completion (an average of 1 year)
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of Teverelix DP in men with AUR secondary to benign prostatic hyperplasia (BPH).
Safety and tolerability will be evaluated by the incidence, nature, severity, and relationship to study treatment of adverse events (AEs) and serious adverse events (SAEs), together with assessments of clinical laboratory parameters, vital signs, physical examinations, electrocardiograms (ECGs), concomitant medications, and any clinically significant findings observed throughout the study.
Time frame: From Day 1 through study completion (an average of 1 year)
To assess progression of BPH-related symptoms.
The International Prostate Symptom Score (IPSS) will be used to assess progression of BPH-related symptoms. The total IPSS score is calculated by summing the scores from all seven questions, giving a range of 0 to 35. Change in IPSS score will be reviewed. Lower scores indicate fewer or less severe urinary symptoms, and higher scores indicate more severe urinary symptoms.
Time frame: Change from Day 1 through study completion (an average of 1 year)
To assess the incidence of BPH-related minimally invasive procedures or surgeries. Procedure/surgery review will completed at visits throughout the study.
Time frame: From Day 1 through study completion (an average of 1 year)
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