Evaluation of Teverelix DP, a GnRH Antagonist, in Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety for Advanced Prostate Cancer Patients

Trial ID: 2023-509255-14-01
Protocol: ANT-1111-05
Sponsor: Antev Nordic AB

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Diseases & Conditions

Prostate cancer

Objectives

The primary objective of this study is to evaluate the **efficacy** of a dosing regimen of teverelix DP in achieving and maintaining a castration rate in participants with advanced prostate cancer. This is defined by the cumulative probability of testosterone suppression to less than 0.5 ng/mL by Day 29 and sustaining this level to Day 155, with the lower bound of the 95% confidence interval being greater than 90%. This objective is clinically relevant as it aims to ensure effective testosterone suppression, which is crucial in the management of advanced prostate cancer.

Secondary objectives include evaluating the ability of the dosing regimen to achieve and sustain a profound castration rate, defined as the cumulative probability of testosterone suppression to less than 0.2 ng/mL, from Day 29 to Day 155. This further assessment of testosterone suppression levels provides additional insights into the potential therapeutic benefits of teverelix DP in managing advanced prostate cancer.

Participants

The clinical trial focuses on evaluating the efficacy of a dosing regimen of teverelix DP in patients with **advanced prostate cancer**. The study population consists exclusively of male participants, aged 18 to 85 years, who have histologically proven advanced adenocarcinoma of the prostate, either metastatic or non-metastatic, and are suitable for androgen deprivation therapy. Participants are treatment-naïve for GnRH analogues. The trial does not include female subjects or vulnerable populations. The sponsor has not provided information regarding the total number of participants. The selection criteria emphasize the inclusion of individuals who are hormone-sensitive and in a non-curative stage of the disease. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

Plans and Procedures

The clinical trial is designed as a **Phase 2, open-label, single-arm, multicentre study** to investigate the pharmacokinetics, pharmacodynamics, efficacy, and safety of **Teverelix DP**, a gonadotropin-releasing hormone (GnRH) antagonist, in participants with advanced prostate cancer. The primary objective is to evaluate the efficacy of a dosing regimen of Teverelix DP in achieving and maintaining a castration rate, defined as the cumulative probability of testosterone suppression to less than 0.5 ng/mL, with the lower bound of the 95% confidence interval being greater than 90% by Day 29 and sustained to Day 155. The trial is expected to commence recruitment on April 1, 2025, and conclude by October 31, 2026.

Participants will be involved in the study for a maximum treatment period of 22 weeks. The study will include an initial screening visit to confirm eligibility based on criteria such as being male, aged 18 years or older, with histologically proven advanced adenocarcinoma of the prostate suitable for androgen deprivation therapy, and treatment-naïve for GnRH analogues. Following the screening, participants will receive Teverelix DP via **parenteral** administration in the form of a solution for injection. The maximum daily dose is set at 10.5 mg, with a total dose not exceeding 1620 mg over the treatment period.

Study visits will be scheduled to monitor the participants' response to the treatment, including follow-up visits to assess testosterone levels and other safety parameters. The primary endpoint is the sustained castration rate, defined as the cumulative probability of achieving testosterone suppression to castrate levels of ≤ 0.5 ng/mL from Study Day 29 through Study Day 155. Secondary endpoints include the sustained castration rate with testosterone suppression to ≤ 0.2 ng/mL within the same timeframe. Participants may be withdrawn from the study if they experience adverse events that compromise their safety or if they fail to adhere to the study protocol. The trial is not categorized as low intervention, and it does not involve a pediatric formulation or orphan drug designation.

Treatment

The clinical trial involves the administration of **Teverelix TFA**, an experimental medication developed by ANTEV LIMITED. Teverelix TFA is a **gonadotropin-releasing hormone (GnRH) antagonist** formulated as a **solution for injection**. The active substance in this medication is **teverelix**, a synthetic peptide classified under the origin of "Protein - Other." The pharmaceutical form is specifically designed for **parenteral administration**. The dosing regimen for Teverelix TFA involves a maximum daily dose of 10.5 mg, with a total maximum dose of 1620 mg over a treatment period of 22 days. The primary objective of the trial is to evaluate the efficacy of Teverelix TFA in achieving and maintaining testosterone suppression to below 0.5 ng/mL in participants with advanced prostate cancer.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is structured as a Phase 2, open-label, single-arm, multicentre study, focusing on the pharmacokinetics, pharmacodynamics, efficacy, and safety of Teverelix DP. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The study aims to sustain the castration rate with a cumulative probability of testosterone suppression, with the lower bound of the 95% confidence interval being greater than 90% by Day 155.

Efficacy

The efficacy of the clinical trial will be assessed by evaluating the ability of **Teverelix DP**, a Gonadotropin-releasing Hormone (GnRH) antagonist, to achieve and maintain testosterone suppression in participants with advanced prostate cancer. The primary endpoint for efficacy is defined as the sustained **castration rate**, which is the cumulative probability of achieving testosterone suppression to castrate levels of ≤ 0.5 ng/mL (1.7 nmol/L) from Study Day 29 through Study Day 155. This will be measured by assessing testosterone levels at specified timepoints during the study period.

Secondary endpoints include the sustained castration rate defined as the cumulative probability of testosterone suppression to ≤ 0.2 ng/mL (0.7 nmol/L) while on study treatment from Study Day 29 through Study Day 155. The efficacy parameters will be collected and analyzed using validated laboratory tests to ensure accuracy and reliability of the data. The study aims to determine the effectiveness of the dosing regimen of Teverelix DP in achieving the desired testosterone suppression levels, with the lower bound of the 95% confidence interval being greater than 90% by Day 29 and sustained through Day 155.

Inclusion and Exclusion Criteria

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

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Exclusion Criteria

Has abnormal screening and/or baseline laboratory values that suggest a clinically significant underlying disease, or the following laboratory values: o Liver function test (aspartate aminotransferase [ASAT/SGOT], alanine aminotransferase [ALAT/SGPT]), exceeding >2X the ULN range o Total bilirubin exceeding >1.5X the ULN range o Creatinine twice the ULN range o Uncontrolled diabetes (HbA1c >7.5%) or previously undiagnosed diabetes mellitus with HbA1c >6.5% o 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 enrollment)
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:-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 enrollment)
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 patient may be enrolled in the study following discussion with the Medical Lead
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