Clinical trial NCT05471648: A Pharmacokinetic Study Comparing EG1206A and Perjeta (Pertzumab) in Healthy Male Volunteers
Official title: Phase 1, Double-Blind, Randomized, Parallel-Group, Single-Dose, 3-Arm, Comparative Pharmacokinetic Trial of EirGenix' Pertuzumab and Perjeta® (Pertuzumab) Sourced From US and EU Administered to Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Keywords: HER2 positive
early stage breast cancer
metastatic breast cancer
combination therapy
inhibiting MAP Kinase
P13K/Akt
Lead sponsor: EirGenix, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Sacura GmbH
First posted: 2022-07-25
Enrollment: 135
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1, Double-Blind, Randomized, Parallel-Group, Single-Dose, 3-Arm, Comparative Pharmacokinetic Trial of EirGenix' Pertuzumab and Perjeta® (Pertuzumab) sourced from US and EU Administered to Healthy Male Volunteers
Primary purpose: TREATMENT

Brief summary: This trial is a single-center, single-dose, double-blind, parallel-group, randomized, 3-arm PK trial in healthy male volunteers comparing a biosimilar pertuzumab (EG1206A) to a single intravenous (i.v.) infusion to both European Union (EU) and United States of America (US) reference products.

Detailed description: This trial is part of a clinical development program developing a biosimilar pertuzumab, comparing the PK, safety and tolerability and immunogenicity of pertuzumab after a single intravenous (i.v.) infusion.

It assess the bioequivalence, PK characteristics, safety and tolerability as well as the immunogenicity of a test preparation containing 420 mg pertuzumab (EG1206A EirGenix Pertuzumab) as compared to marketed reference (EU and US) after a single dose i.v. infusion over 60 minutes in fasted state.

Eligibility criteria: Inclusion Criteria:

* aged 18 to 55 years
* overtly healthy as determined by medical evaluation
* Body weight of at least 50 kg and not higher than 105 kg at screening
* BMI above/equal to 18.0 and below/equal to 30.0 kg/m2 at screening
* Male
* Agrees to the following during the treatment period and until 3 months after administration:
* Be and remain abstinent from heterosexual intercourse OR agree to use a male condom and female partners of childbearing potential must use an additional highly effective contraceptive method
* Abstain from donating sperm.
* Signed informed consent
* Valid COVID-19 immunization status as per current regulations

Exclusion Criteria:

* History or evidence of any clinically relevant disease, as judged by the investigator
* Any medical disorder, condition, or history of such that would impair the participant's ability to participate or complete this trial in the opinion of the investigator
* Pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination, and effects of the IMP will not be normal
* Known or suspected hypersensitivity to the IMPs (active substances, or excipients of the preparations)
* Known severe allergies e.g., allergies to more than 3 allergens
* Relevant diseases within the last 4 weeks before IMP administration
* Febrile illness within 2 weeks before IMP administration.
* History of known or suspected malignant tumors
* Known or suspected disorder of the liver
* Use of systemic/topical medicines/substances which oppose the trial objectives, or which might influence them within 4 weeks before IMP administration
* Regular use of therapeutic or recreational drugs or supplements
* Use of any herbal products or St. John's wort from 4 weeks before IMP administration
* Prior treatment with pertuzumab
* Smoking
* History of alcohol or drug abuse
* Regular daily consumption of more than 500 mL of usual beer or the equivalent quantity of approximately 20 g of alcohol in another form
* Intake of alcohol containing food and beverages from 48 h prior to admission to the ward
* Regular daily consumption of more than 1 L of methylxanthine-containing beverages
* Excluded physical therapies that might alter the PK or safety results of the trial from 7 days before IMP administration until follow-up
* Strenuous physical exercise or sauna visit with 72 h before admission to the ward
* Donation of more than 100 mL of whole blood or plasma within 4 weeks or approximately 500 mL whole blood within 3 months before IMP administration
* Plasmapheresis within 3 months before IMP administration
* Previous or concomitant participation in another clinical trial with IMP(s)
* Clinically relevant findings in the ECG
* LVEF below 55%
* Systolic blood pressure below 100 mmHg or above 140 mmHg
* Diastolic blood pressure below 50 mmHg or above 90 mmHg
* Heart rate below 50 beats/ min or above 90 beats/min
* Clinically relevant findings in the physical examination that may affect the objectives of the trial, or the safety of the participant
* Poor venous access
* Clinically relevant deviations of the screened safety laboratory parameters
* Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase, or total bilirubin above 1.2 upper limit of normal
* Thyroid disorders as evidenced by assessment of thyroid stimulating hormone (TSH) level outside the normal reference range
* Positive results for hepatitis B virus surface antigen, hepatitis C virus antibodies, human immune deficiency virus antibodies, and human immune deficiency virus antigen
* Positive urine drug test
* Positive alcohol test
* Positive cotinine test
* Any criteria which, in the opinion of the investigator, preclude participation for scientific reasons, for reasons of compliance, or for reasons of the participant's safety
* Close affiliation with the investigational site
* Vulnerable participants who are e.g., institutionalized due to regulatory or juridical order dependent on sponsor, site, or investigator or not able to consent, respectively.
* History of COVID-19 within 2 months prior to screening
* Long COVID-19 syndrome or other clinically relevant COVID-19 related symptoms or sequelae
* Positive SARS-CoV-2 viral ribonucleic acid (RNA) test at admission
* No SARS-CoV-2 vaccinations should be booked within 14 days before IMP administration and until last trial visit.

Primary outcomes:
measure: AUC0-inf of pertuzumab
timeFrame: Pre-dose to day 91, 21 timepoints
Secondary outcomes:
measure: Cmax
timeFrame: Pre-dose to day 91, 21 timepoints
measure: tmax
timeFrame: Pre-dose to day 91, 21 timepoints
measure: t1/2
timeFrame: Pre-dose to day 91, 21 timepoints
measure: Drug clearance (CL)
timeFrame: Pre-dose to day 91, 21 timepoints
measure: Volume of distribution (Vd)
timeFrame: Pre-dose to day 91, 21 timepoints
measure: AUC0-last of pertuzumab
timeFrame: Pre-dose to day 91, 21 timepoints
measure: Frequency of treatment-emergent adverse events (AEs)
timeFrame: Day 1 to day 91
measure: Immunogenicity: Anti-drug antibodies (ADA) and neutralizing antibodies (NAb)
timeFrame: Pre-dose to day 91, 7 timepoints
Other outcomes:
measure: Local tolerability at infusion site
timeFrame: Day 1 to day 15, 14 timepoints
measure: Vital sign - blood pressure
timeFrame: Day 1 to day 91, 8 timepoints
measure: Vital sign - pulse rate
timeFrame: Day 1 to day 91, 8 timepoints
measure: Physical examination
timeFrame: Day -1 to day 91, 5 timepoints
measure: Electrocardiogram (ECG) measurements
timeFrame: Day 1 to day 91, 7 timepoints
Locations:
city: Berlin
country: Germany
facility: CRS Clinical Research Services Berlin GmbH
Study officials:
affiliation: CRS Clinical Research Services Berlin GmbH
name: Matthias Berse, Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: