Study of Teverelix DP on Prostate Volume, Urinary Function and Clinical Outcomes Following Acute Urinary Retention

Официальное название

A Randomized, Double-Blind, Placebo-Controlled, Multi-centre Study to Evaluate the Effects of Teverelix DP, a GnRH Antagonist, on Prostate Volume, Urinary Function and Clinical Outcomes in Men Following a First Episode of Acute Urinary Retention (AUR)

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Teverelix DP
  Single dose at Day 1 of 90 mg injection IM
• Препарат Teverelix DP Placebo
  Single dose at Day 1 of 90 mg injection IM
• Препарат Teverelix DP
  Single dose at Day 1 of 120 mg injection SC
• Препарат Teverelix DP Placebo
  Single dose at Day 1 of 120 mg injection SC

Первичные конечные точки

• Percent Change from Baseline in Total Prostate Volume (TPV) at Week 12 [Срок оценки: Change from baseline to Week 12]

Вторичные конечные точки (11)

• To assess the AUR clinical benefit rate of Teverelix DP after a single dose [Срок оценки: From dosing to week 52]
• Evaluate the durability of prostate volume reduction following a single dose of Teverelix DP [Срок оценки: Change from baseline to week 52]
• Change from baseline in post-void residual volume (PVR) (mL), assessed by ultrasound. [Срок оценки: Change from baseline to week 28]
• Change from baseline in maximum urinary flow rate (Qmax) (mL/sec), using Uroflowmetry. [Срок оценки: Change from baseline to week 28]
• Explore the correlation between change prostate volume and change in post-void residual volume (PVR) (mL) [Срок оценки: Change from baseline to week 28]
• Explore the correlation between change prostate volume and change in maximum urinary flow rate (Qmax) (mL/sec) [Срок оценки: 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) [Срок оценки: 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. [Срок оценки: 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). [Срок оценки: From Day 1 through study completion (an average of 1 year)]
• To assess progression of BPH-related symptoms. [Срок оценки: 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. [Срок оценки: From Day 1 through study completion (an average of 1 year)]

Критерии участия

Критерии включения

• Male aged 45 years or older
• Having given his written consent
• Successful TWOC as defined by successful voiding with a minimum residual volume
• Having had a first episode of spontaneous acute urinary retention within 6 days of study screening visit.
• Prostate volume >40 g (assessed by TRUS)
• Patients may initiate or continue alpha-blocker therapy at or before randomization. The same agent and dose should be continued throughout the treatment period where possible
• Agrees to practice contraception during the entire study treatment period and for 3 months after the last dose of IMP is administered:

• Either by using double barrier contraception and in compliance with local guidelines,
• or, is truly sexually abstinent, when this is in line with the preferred and usual lifestyle of the patient

i. Note: Periodic abstinence \[e.g. calendar, ovulation, symptothermal, postovulation methods for the female partner with childbearing potential\] and withdrawal are not acceptable methods of contraception.

• Must be treatment naïve to GnRH analogues

Критерии исключения

• Participated in another investigational study within 3 months before recruitment
• AUR due to i.e. postoperative retention following major abdominal/pelvis/spinal surgery
• Neurological related AUR
• Contraindication to the use of alpha blockers
• Previous prostate or urethral surgery
• Previous histological or clinical diagnosis of prostate cancer
• Any unstable co-existing medical condition
• Has abnormal screening and/or baseline laboratory values that suggest a clinically significant underlying disease, or the following laboratory values:

• Liver function test (aspartate aminotransferase \[ASAT/SGOT\], alanine aminotransferase \[ALAT/SGPT\]), exceeding >2X the upper limit of the normal (ULN) range
• Total bilirubin exceeding >1.5X the upper limit of the normal (ULN) range
• An estimated glomerular filtration rate (eGFR) < 30 mL/min, based on creatinine clearance calculation by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation normalised to an average surface area of 1.73m2, at the screening visit.
• Has congenital long QT syndrome or ECG abnormalities at screening of:

• Q-wave infarction, unless identified ≥6 months before screening
• Fridericia corrected QT interval (QTcF interval) >480 msec. If QTcF is prolonged in a patient with a pacemaker, the patient may be enrolled in the study upon discussion with the project clinician
• If the QTcF interval is 450-480 msec, inclusive, in a patient with current use of medications with known effects on QT interval, the patient may be enrolled in the study following discussion with the Medical Lead

Note: Cardiac arrhythmia grading:

• Bradyarrhythmias (HR <60/min)
• Tachyarrhythmias (HR >100/min
• Supraventricular arrhythmias - arrhythmias that originate in the sinoatrial node, atrial myocardium or atrioventricular node (regular QRS complex)
• Ventricular arrhythmias - arrhythmias that originate below the atrioventricular node (wide QRS complex)
• History or current evidence of alcohol or drug abuse within the last 12 months
• Prostate Specific Antigen (PSA) greater than 20ng/ml
• Use of suprapubic catheterization after failed urethral catheterization
• Neurogenic bladder dysfunction, confirmed or suspected, irrespective of etiology
• Isolated bladder neck disease
• Acute or chronic prostatitis
• Confirmed or suspected urethral stricture
• Known bladder stones
• Use of the following medications prior to and during study participation:

• Any other IMP (within 3 months of enrolment)
• Herbal medications known to have anti-androgenic effects (e.g. red reishi, licorice, white peony, green tea, spearmint, black cohosh, chaste tree, saw palmetto, etc) (within 3 months of enrolment)
• Anti-androgen therapy (within 3 months of enrolment)
• T replacement therapy (within 3 months of enrolment)
• 5α-reductase inhibitor treatment etc. (within 25 weeks prior to screening: dutasteride; within 12 weeks prior to screening: finasteride (and others))
• Bethanechol chloride
• Any other medication or herbal product that may affect hormone levels and might, therefore, confound interpretation of the study results (e.g. St. John's wort) (within 3 months of enrolment)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07733934 · ANT-2111-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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