Breast Cancer
Conditions
Keywords
HER2 positive, early stage breast cancer, metastatic breast cancer, combination therapy, inhibiting MAP Kinase, P13K/Akt
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.
Interventions
DRUG420 mg EG1206A EirGenix Pertuzumab in 14 mL Injection
Healthy volunteers receive pertuzumab (EG1206A, 420 mg, single dose)
DRUGPerjeta (EU origin) 420 mg in 14 mL Injection
Healthy volunteers receive pertuzumab (Perjeta (EU origin) 420 mg, single dose)
DRUGPerjeta (US origin) 420 mg in 14 mL Injection
Healthy volunteers receive pertuzumab (Perjeta (US origin), 420 mg, single dose)
Sponsors
Sacura GmbH
EirGenix, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 |
Countries
Germany
Outcome results
None listed