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

Sponsor

EirGenix, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05471648

Collaborator

Sacura GmbH (Other)

135

Enrollment

Location

Arms

12.5

Anticipated Duration (Months)

10.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	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	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

135 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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 VolunteersPhase 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

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 16, 2022

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

AUC0-inf of pertuzumab [Pre-dose to day 91, 21 timepoints]
Area under the plasma concentration-time curve, from time 0 h extrapolated to infinity

Secondary Outcome Measures

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

Other Outcome Measures

Local tolerability at infusion site [Day 1 to day 15, 14 timepoints]
Assessment at the injection site by visual inspection of local reactions at and around the injection site
Vital sign - blood pressure [Day 1 to day 91, 8 timepoints]
Blood pressure (systolic and diastolic) will be measured after the participant had rested at least 5 min rest in supine position
Vital sign - pulse rate [Day 1 to day 91, 8 timepoints]
Pulse rate will be measured after the participant had rested at least 5 min rest in supine position
Physical examination [Day -1 to day 91, 5 timepoints]
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.
Electrocardiogram (ECG) measurements [Day 1 to day 91, 7 timepoints]
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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.