MDPK67b in Patients With Prostate Cancer

Open-label Phase Ib Study of Preoperative Treatment With the KLK Inhibitor MDPK67b in Patients With Untreated Prostate Cancer

Administration of MDPK67b to assess its Tolerability and Safety profile in prostate cancer patients, and to assess histo-pathological and molecular changes in prostate tumor tissue samples.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: MDPK67b

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Christoph Kündig; Phone Number: +41 21 566 14 11; Email: christoph.kundig@med-discovery.com

Study Locations

• Switzerland
  • Zürich, Switzerland, 8091
    • Recruiting
    • Klinik für Urologie, UniversitätSpital Zürich (USZ)
    • Contact: Daniel Eberli, Prof.; Phone Number: +41 44 255 9619; Email: daniel.eberli@usz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Subject screening criteria

1. Patients aged 18 years or older.
2. Patients who have untreated suspected PCa or PCa under active surveillance (AS) with progression/upgrading.
3. Patients who signed a written screening phase ICF.

Subject non-screening criteria

1. Patients who have an uncontrolled disease that would unduly increase the risk of toxicity or limit compliance with study requirements in the opinion of the Investigator; including but not limited to: ongoing or active symptomatic infection, uncontrolled diabetes mellitus, diseases of the coagulation system, unstable or uncompensated cardiac, hepatic, renal, respiratory, or psychiatric disease.
2. Patients who required a significant change in their concomitant medications during the week prior to screening visit, or who will likely need to have a change in their concomitant medications during the study. This includes any medication other than those required for PCa diagnosis or for RPE.
3. Patients who have received prior radiotherapy to the prostate.
4. Patients who have had prior exposure to MDPK67b.
5. Patients who have participated in another clinical trial within 3 months prior to screening visit, except if in the opinion of the investigator the type of trial does not interfere in any way with the present trial (eg. non-interventional observational trial). In case of doubt, the sponsor's prior approval must be obtained and the decision to include such a patient will be documented in detail.

Non-screening criteria are exclusion criteria for the screening phase.

For the patients not participating in the screening phase (ie patients with previously established PCa diagnosis), all the criteria above shall be checked prior to enrolment in the treatment phase. However, these patients do not have to sign a screening ICF (screening criterion n°3 is not applicable), and for non-screening criterion n°5, the 3-month wash-out period is prior to the inclusion visit in the treatment phase.

Subject inclusion criteria

1. Patients who still meet all the eligibility criteria checked at screening visit.
2. Patients who have untreated PCa with a Gleason score of 7 (preferably) or higher, with local disease or with metastatic disease (if metastatic, no visceral metastases, no more than five bone or lymph node metastases), and are scheduled to undergo RPE about 3 weeks later.
3. Patients with an expected minimal survival time of 12 months.

4. Patients who have an acceptable organ and marrow function as assessed at the inclusion visit and defined as follows:

   1. Absolute neutrophil count ≥ 1.5 × 109/L.
   2. Platelets ≥ 100 × 109/L.
   3. Hemoglobin ≥ 9 g/dL.
   4. Total bilirubin ≤ 1.5 × ULN, unless the patient has known Gilbert's syndrome.
   5. Aspartate amino transferase (AST) and alanine amino transferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN in presence of liver metastasis.
   6. Serum creatinine ≤ 2.0 × ULN, or GFR ≥ 30 mL/min by Cockcroft-Gault.
   7. INR <1.5, aPTT < 60 s
5. Patients with an ECOG performance status ≤ 1.
6. Patients who agree to refrain to donate sperm for the duration of the study.
7. Patients who signed a written treatment phase ICF.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dose; Five patients will be included into the 24 mg dose level. In case of dose limiting toxicity (DLT) in at least one patient, 5 additional patients will be enrolled in the 24 mg dose level. If the treatment is well tolerated, i.e. no DLT is encountered, the dose of MDPK67b is escalated to 48 mg on a second cohort of 5 patients. In case of DLT in at least one patient at the 48 mg dose level, the 24 mg dose level of MDPK67b is expanded from 5 to 10 patients, or declared the maximum tolerated dose (MTD) if already expanded to 10 patients.

Drug: MDPK67b; 24 mg or 48 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability and Safety	Number of subjects with changes in blood pressure	Day 1
Tolerability and Safety	Number of subjects with changes in blood pressure	Day 8
Tolerability and Safety	Number of subjects with changes in blood pressure	Day 15
Tolerability and Safety	Number of subjects with changes in blood pressure	Day 20-25
Tolerability and Safety	Body temperature	Day 1
Tolerability and Safety	Number of subjects with changes in body temperature	Day 8
Tolerability and Safety	Number of subjects with changes in body temperature	Day 15
Tolerability and Safety	Number of subjects with changes in body temperature	Day 20-25
Tolerability and Safety	Number of subjects with changes in respiration rate	Day 1
Tolerability and Safety	Number of subjects with changes in respiration rate	Day 8
Tolerability and Safety	Number of subjects with changes in respiration rate	Day 15
Tolerability and Safety	Number of subjects with changes in respiration rate	Day 20-25
Tolerability and Safety	Number of subjects with changes in weight	Day 1
Tolerability and Safety	Number of subjects with changes in weight	Day 8
Tolerability and Safety	Number of subjects with changes in weight	Day 15
Tolerability and Safety	Number of subjects with changes in weight	Day 20-25
Tolerability and Safety	Number of subjects with changes in QTc on ECG	Day 1
Tolerability and Safety	Number of subjects with changes in QTc on ECG	Day 8
Tolerability and Safety	Number of subjects with changes in QTc on ECG	Day 15
Tolerability and Safety	Number of subjects with changes in QTc on ECG	Day 20-25
Tolerability and Safety	Number of subjects with changes in heart rate on ECG	Day 1
Tolerability and Safety	Number of subjects with changes in heart rate on ECG	Day 8
Tolerability and Safety	Number of subjects with changes in heart rate on ECG	Day 15
Tolerability and Safety	Number of subjects with changes in heart rate on ECG	Day 20-25
Tolerability and Safety	Number of subjects with changes in hematology safety parameters: haemoglobin, haematocrit, RBC, MCH, MCV, WBC differential count (absolute and relative count), platelet count, INR, aPTT, Thrombin time and fibrinogen	Day 8
Tolerability and Safety	Number of subjects with changes in hematology safety parameters: haemoglobin, haematocrit, RBC, MCH, MCV, WBC differential count (absolute and relative count), platelet count, INR, aPTT, Thrombin time and fibrinogen	Day 15
Tolerability and Safety	Number of subjects with changes in hematology safety parameters: haemoglobin, haematocrit, RBC, MCH, MCV, WBC differential count (absolute and relative count), platelet count, INR, aPTT, Thrombin time and fibrinogen	Day 20-25
Tolerability and Safety	Number of subjects with changes in blood chemistry safety parameters: fasting glucose, total protein, creatinine, urea, sodium, potassium, calcium, uric acid, AST, ALT, CPK, AlkP, LDH, total bilirubin, PSA	Day 8
Tolerability and Safety	Number of subjects with changes in blood chemistry safety parameters: fasting glucose, total protein, creatinine, urea, sodium, potassium, calcium, uric acid, AST, ALT, CPK, AlkP, LDH, total bilirubin, PSA	Day 15
Tolerability and Safety	Number of subjects with changes in blood chemistry safety parameters: fasting glucose, total protein, creatinine, urea, sodium, potassium, calcium, uric acid, AST, ALT, CPK, AlkP, LDH, total bilirubin, PSA	Day 20-25
Tolerability and Safety	Number of subjects with changes in urine safety parameters: pH, ketones, protein, glucose, blood, leukocytes, urobilinogen, bilirubin	Day 8
Tolerability and Safety	Number of subjects with changes in urine safety parameters: pH, ketones, protein, glucose, blood, leukocytes, urobilinogen, bilirubin	Day 15
Tolerability and Safety	Number of subjects with changes in urine safety parameters: pH, ketones, protein, glucose, blood, leukocytes, urobilinogen, bilirubin	Day 20-25
Tolerability and Safety	Number of subjects with changes in physical examination	Day 1
Tolerability and Safety	Number of subjects with changes in physical examination	Day 8
Tolerability and Safety	Number of subjects with changes in physical examination	Day 15
Tolerability and Safety	Number of subjects with changes in physical examination	Day 20-25
Tolerability and Safety	Adverse events	Day 1
Tolerability and Safety	Adverse events	Day 8
Tolerability and Safety	Adverse events	Day 15
Tolerability and Safety	Adverse events	Day 20-25
Tolerability and Safety	Local tolerance using the 5-point Draize scale (0: no irritation to 5: Frank vein thrombosis in addition to grade 4 signs and symptoms)	Day 1
Tolerability and Safety	Local tolerance using the 5-point Draize scale (0: no irritation to 5: Frank vein thrombosis in addition to grade 4 signs and symptoms)	Day 8
Tolerability and Safety	Local tolerance using the 5-point Draize scale (0: no irritation to 5: Frank vein thrombosis in addition to grade 4 signs and symptoms)	Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histo-pathological and molecular changes in prostate tumor tissue samples	Androgen receptor expression	Screening (Diagnostic biopsy)
Histo-pathological and molecular changes in prostate tumor tissue samples	Androgen receptor expression	Day 16/17 (Radical prostatectomy sample)
Histo-pathological and molecular changes in prostate tumor tissue samples	Extent of proliferation using Ki67	Screening (Diagnostic biopsy)
Histo-pathological and molecular changes in prostate tumor tissue samples	Extent of proliferation using Ki67	Day 16/17 (Radical prostatectomy sample)
Histo-pathological and molecular changes in prostate tumor tissue samples	Extent of inflammation using leukocyte markers	Screening (Diagnostic biopsy)
Histo-pathological and molecular changes in prostate tumor tissue samples	Extent of inflammation using leukocyte markers	Day 16/17 (Radical prostatectomy sample)
Histo-pathological and molecular changes in prostate tumor tissue samples	Expression of KLK2, KLK4, and KLK14 using immunohistochemistry	Screening (Diagnostic biopsy)
Histo-pathological and molecular changes in prostate tumor tissue samples	Expression of KLK2, KLK4, and KLK14 using immunohistochemistry	Day 16/17 (Radical prostatectomy sample)
Histo-pathological and molecular changes in prostate tumor tissue samples	Treatment induced change in RNA transcriptome assessed by RNA sequencing	Screening (Diagnostic biopsy)
Histo-pathological and molecular changes in prostate tumor tissue samples	Treatment induced change in RNA transcriptome assessed by RNA sequencing	Day 16/17 (Radical prostatectomy sample)

Collaborators and Investigators

• Sponsor: Med Discovery SA
• Collaborators: Soladis; Camara and Partners Sàrl
• Investigators: Principal Investigator: Daniel Eberli, Prof., Klinik für Urologie, UniversitätSpital Zürich (USZ)

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2021
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: July 7, 2022
• First Submitted That Met QC Criteria: October 11, 2022
• First Posted (Actual): October 14, 2022

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: prostate cancer; radical prostatectomy; Gleason score 7 or higher
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: MDPK67b-2002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No