A Pharmacokinetic Study Comparing EG1206A and Perjeta (Pertzumab) in Healthy Male Volunteers

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: 420 mg EG1206A EirGenix Pertuzumab in 14 mL Injection; Drug: Perjeta (EU origin) 420 mg in 14 mL Injection; Drug: Perjeta (US origin) 420 mg in 14 mL Injection

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.

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • CRS Clinical Research Services Berlin GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 420 mg EirGenix Pertuzumab; EirGenix Pertuzumab given intravenous with an infusion bag as a single dose of 420 mg over 60min.	Drug: 420 mg EG1206A EirGenix Pertuzumab in 14 mL Injection; Healthy volunteers receive pertuzumab (EG1206A, 420 mg, single dose); Other Names: Pertuzumab
Active Comparator: 420 mg Pertuzumab Perjeta EU Origin; EU Pertuzumab given intravenous with an infusion bag as a single dose of 420 mg over 60min.	Drug: Perjeta (EU origin) 420 mg in 14 mL Injection; Healthy volunteers receive pertuzumab (Perjeta (EU origin) 420 mg, single dose); Other Names: Pertuzumab
Active Comparator: 420 mg Pertuzumab Perjeta US Origin; US Pertuzumab given intravenous with an infusion bag as a single dose of 420 mg over 60min.	Drug: Perjeta (US origin) 420 mg in 14 mL Injection; Healthy volunteers receive pertuzumab (Perjeta (US origin), 420 mg, single dose); Other Names: Pertuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-inf of pertuzumab	Area under the plasma concentration-time curve, from time 0 h extrapolated to infinity	Pre-dose to day 91, 21 timepoints

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Peak plasma concentration of a pertuzumab after administration	Pre-dose to day 91, 21 timepoints
tmax	Time to reach peak plasma concentration of pertuzumab after administration	Pre-dose to day 91, 21 timepoints
t1/2	Terminal elimination half-life	Pre-dose to day 91, 21 timepoints
Drug clearance (CL)	Total clearance	Pre-dose to day 91, 21 timepoints
Volume of distribution (Vd)	The apparent volume in which pertuzumab is distributed	Pre-dose to day 91, 21 timepoints
AUC0-last of pertuzumab	Area under the plasma concentration-time curve, from time 0 h to last measured timepoint	Pre-dose to day 91, 21 timepoints
Frequency of treatment-emergent adverse events (AEs)		Day 1 to day 91
Immunogenicity: Anti-drug antibodies (ADA) and neutralizing antibodies (NAb)	Analysis of anti-drug antibodies (ADA) and neutralizing antibodies (NAb; only assessed following confirmed positive ADA results)	Pre-dose to day 91, 7 timepoints

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local tolerability at infusion site	Assessment at the injection site by visual inspection of local reactions at and around the injection site	Day 1 to day 15, 14 timepoints
Vital sign - blood pressure	Blood pressure (systolic and diastolic) will be measured after the participant had rested at least 5 min rest in supine position	Day 1 to day 91, 8 timepoints
Vital sign - pulse rate	Pulse rate will be measured after the participant had rested at least 5 min rest in supine position	Day 1 to day 91, 8 timepoints
Physical examination	Physical examination (by means of inspection, palpation, auscultation) includes general condition/psyche, skin, lymph nodes, head (including eyes, ears, mouth), thyroid gland, and throat, lungs, heart, abdomen, musculoskeletal system, neurological system, and vascular system.	Day -1 to day 91, 5 timepoints
Electrocardiogram (ECG) measurements	A standard 12-lead ECG will be recorded after at least 5 min rest in supine position calculating heart rate (HR), PR/PQ interval, QRS interval, QT interval (uncorrected), QT interval according to Bazett's formula (QTcB)	Day 1 to day 91, 7 timepoints

Collaborators and Investigators

• Sponsor: EirGenix, Inc.
• Collaborators: Sacura GmbH
• Investigators: Principal Investigator: Matthias Berse, Dr. med., CRS Clinical Research Services Berlin GmbH

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2022
• Primary Completion (Actual): January 24, 2023
• Study Completion (Actual): January 24, 2023

Study Registration Dates

• First Submitted: July 8, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (Actual): July 25, 2022

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 24, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: combination therapy; HER2 positive; metastatic breast cancer; early stage breast cancer; inhibiting MAP Kinase; P13K/Akt
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pertuzumab
• Other Study ID Numbers: EGC101; 2021-006769-40 (EudraCT Number)

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes