A Study Investigating the Pharmacokinetics, Pharmacodynamics, Efficacy and Safety of Teverelix DP, a Gonadotropin-releasing Hormone (GnRH) Antagonist, in Patients With Advanced Prostate Cancer

A Phase 2, Open-Label, Single-Arm, Multicentre Study Investigating the Pharmacokinetics, Pharmacodynamics, Efficacy and Safety of Teverelix DP, a Gonadotropin-releasing Hormone (GnRH) Antagonist, in Patients With Advanced Prostate Cancer

The purpose of this clinical trial is to test the effectiveness of a dosing regimen of Teverelix DP castration rate defined as the cumulative probability of testosterone suppression to < 0.5 ng/mL with the lower bound of the 95% confidence interval (CI) being > 90% to meet the evaluation criteria for efficacy.

The main question it aims to answer is:

•Is the dosing regimen of Teverelix DP in this study effective at achieving the required testosterone suppression to castrate levels.

Participants will

• Receive a single loading dose consisting of 3 injections of teverelix DP (180 mg IM + 2x 180 mg SC) on Day 1.
• Receive a maintenance dose consisting of 2 injections (2X 180 mg SC) from week 4 (Day 29) and every 6 weeks up to Week 16 (Day 113).
• The first 30 enrolled participants will have 24-hour continuous Holter monitoring performed and 24-hour PK samples will be drawn.

The results of this study are intended to support dose selection and provide supportive safety and PK/PD data to enable advancement into a subsequent Phase 3 clinical study in patients with advanced prostate cancer who are at high cardiovascular risk.

Inclusion Criteria:

• Is male, aged ≤85 years (≥18 years) at the beginning of the treatment period (Day 1)

• Has histologically proven advanced adenocarcinoma of the prostate (metastatic or non metastatic, hormone-sensitive, non-curative), suitable for androgen deprivation therapy

• Is treatment naïve for GnRH analogues

• 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,
  • or, is truly sexually abstinent, when this is in line with the preferred and usual lifestyle of the patient

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.

• Has provided written (personally signed and dated) informed consent before completing any study-related procedure, which means any assessment or evaluation that would not have formed a part of his normal medical care

Exclusion Criteria:

• 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 ULN range
  • Total bilirubin exceeding >1.5X the ULN range
  • Creatinine twice the ULN range
  • Uncontrolled diabetes (HbA1c >7.5%) or previously undiagnosed diabetes mellitus with HbA1c >6.5%
  • An estimated glomerular filtration rate (eGFR) < 30 mL/min, based on creatinine clearance calculation by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation normalized to an average surface area of 1.73m2, at the screening visit.

• Has any contraindication to the use of teverelix DP

• Has a life expectancy of less than 1 year

• Has T levels <1.5 ng/mL at screening

• Has a medical history of bilateral orchidectomy

• Any other IMP (within 3 months of enrolment)

• GnRH analogues (subjects must be treatment naïve to GnRH analogues)

• Using any of the following prohibited treatments:

  • Within 25 weeks prior to screening: dutasteride
  • Within 12 weeks prior to screening: finasteride and others

• Current use of any of the following:

  o Anti-androgen therapy, including T replacement therapy and 5α-reductase inhibitor treatment etc. within 3 months of enrolment (Spironolactone is a permitted concomitant treatment)

• 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, red reishi, licorice, white peony, green tea, spearmint, black cohosh, chaste tree, saw palmetto, etc) (within 3 months of enrolment)

• Has neurological disease, psychiatric disease, drug or alcohol abuse, which could interfere with the patient's proper compliance

• Has a history of myocardial infarction, unstable symptomatic ischaemic heart disease, any ongoing cardiac arrhythmias of grade >2 (chronic stable atrial fibrillation on stable anticoagulant therapy is allowed), thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other significant cardiac condition (e.g. pericardial effusion, restrictive cardiomyopathy) within the 6 months prior to screening

• 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 patien 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)

• Has known or suspected severe renal impairment

• Has a medical history of diagnosis of, or treatment for, another malignancy within the 2 years prior to administration of the first dose of IMP, or previous diagnosis of another malignancy with evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection

• Is currently using Class IA (e.g. quinidine, procainamide) or Class III (e.g. amiodarone, sotalol) antiarrhythmic medications

• Has uncontrolled hypertension despite appropriate medical therapy (sitting blood pressure [BP] of >180 millimetres of mercury [mmHg] systolic and >95 mmHg diastolic at 2 separate measurements taken no more than 60 minutes apart during the screening visit). Patients with isolated systolic BP measurements >180 mmHg may be rescreened. Patients with isolated systolic BP measurements 141 to 180 mmHg or isolated diastolic BP measurements ≥95 mmHg, although eligible, should be referred for further management of hypertension if indicated

• Has known, previously diagnosed HIV infection, active chronic hepatitis B or C, life-threatening illness unrelated to prostate cancer, or any serious medical condition that could, in the investigator's opinion, potentially interfere with participation in this study. Specific screening for chronic viral illness is at the discretion of the site and/or local Institutional Review Board (IRB)

• Has been exposed to another investigational drug within the 3 months prior to screening

• Has anticipated non-availability for study visits/procedure

• Plans to undergo surgery during the study period

• Known presence of hepatic metastases