A Study in Healthy Male Subjects to Investigate the Comparability of Pharmacokinetics of the Fixed-Dose Combination of Pertuzumab and Trastuzumab Administered Subcutaneously Using a Handheld Syringe or Using the On-Body Delivery System

Study Overview
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Brief Summary
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This is a randomized, open-label, 2-arm, parallel-group, single-dose, multi-center study in healthy male subjects to investigate the comparability of the pharmacokinetics of the fixed-dose combination of pertuzumab and trastuzumab administered subcutaneously using the proprietary on-body delivery system or a handheld syringe with hypodermic needle.

Official Title
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A Randomized, Open-Label, 2-Arm, Parallel Group, Single Dose, Multi-Centre Study in Healthy Male Subjects to Investigate the Comparability of Pharmacokinetics of the Fixed-Dose Combination of Pertuzumab and Trastuzumab Administered Subcutaneously Using a Handheld Syringe or Using the On-Body Delivery System

Conditions
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Healthy Male Subjects

Intervention / Treatment
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* Drug: Fixed-Dose Combination of Pertuzumab and Trastuzumab SC (PH FDC SC)
* Device: Handheld Syringe with Hypodermic Needle
* Device: On-Body Delivery System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects age 18-45 years at time of signing Informed Consent Form Ability to comply with the study protocol Agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, during the treatment period and for 7 months after the dose of PH FDC SC A body mass index (BMI) between 18 and 32 kilograms per metre squared (kg/m2), inclusive Intact normal skin without potentially obscuring tattoos, pigmentation, or lesions in the area for intended injection on the thighs Baseline LVEF≥55% measured by echocardiogram (ECHO) No history of hypersensitivity or confirmed, clinically significant and clinically relevant allergic reactions, either spontaneously or following any drug administration No history of any clinically significant and clinically relevant cardiac condition No history of previous anticancer treatments including pertuzumab, trastuzumab, anthracyclines, or any cardiotoxic drugs No apparent family history of clinically significant and clinically relevant hypersensitivity, allergy, and severe cardiac diseases No contraindications from detailed medical and surgical history and physical examinations No previous enrollment in this study protocol and no concurrent enrollment in any other study protocol Exclusion Criteria: Positive urine test for drugs of abuse as per local standard (for alcohol abuse, positive breath test is also acceptable) Positive test result for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) 1 or 2, showing: History of exposure to HBV, HCV, or HIV; or Active viral hepatitis infection (HBV or HCV) or HIV infection Systolic blood pressure ≥140 millimetres of mercury (mmHg) or <90 mmHg, or diastolic blood pressure >90 mmHg or <50 mmHg Use of prohibited medications including non-prescription medications, nutraceuticals, nutritional supplements or any herbal remedies taken within 10 days or 5 times the elimination half-life (whichever is longer) prior to randomization into the study Concomitant subcutaneous, intravenous, or any parenteral drugs within 90 days prior to screening Participation in an investigational drug or device study within 90 days or five times the elimination half-life (whichever is longer) prior to screening Donation of blood over 500 millilitres (mL) within 3 months prior to enrollment Known severe hypersensitivity to plaster, medical adhesive tapes, or bandages Known allergy to murine proteins, hyaluronidase, bee, or vespid venom, or any other ingredient in the formulation of rHuPH20 (Hylenex® recombinant [hyaluronidase human injection]) or any other ingredients and excipients in the formulation of PH FDC SC Clinically significant abnormalities in laboratory test results (including hepatic and renal panels, CBC, chemistry panel, and urinalysis) Clinically relevant electrocardiogram abnormalities at screening or Day -1 History of any cardiac condition Lower extremity edema or pathology (e.g., cellulitis, lymphatic disorder or prior surgery, pre-existing pain syndrome, previous lymph node dissection etc.) that could interfere with any protocol-specified outcome assessment Any history of clinically significant and clinically relevant allergies, oncologic, psychiatric, gastrointestinal, renal, hepatic, cardiovascular or pulmonary disease Concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in this study Any clinically relevant history of systemic disease (e.g., malignancy, diabetes mellitus, gastrointestinal, renal, hepatic, cardiovascular, rheumatological, or pulmonary disease) History of breast cancer or treatment for breast cancer Current chronic daily treatment (continuous for >3 months) with corticosteroids (dose ≥10 mg/day methylprednisolone), excluding inhaled corticosteroids Receipt of intravenous antibiotics for infection within 7 days prior to enrollment into the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1: PH FDC SC Administered Using a Handheld Syringe with Hypodermic Needle<br> | Drug: Fixed-Dose Combination of Pertuzumab and Trastuzumab SC (PH FDC SC)<br>* A single dose of PH FDC SC (600 mg pertuzumab/600 mg trastuzumab) will be administered by a healthcare professional subcutaneously (SC) into the anterior thigh, using either a handheld syringe with hypodermic needle (Arm 1) or the on-body delivery system (Arm 2).<br>* Other names: RG6264;Device: Handheld Syringe with Hypodermic Needle<br>* A single 10-mL dose of PH FDC SC will be administered as a subcutaneous (SC) injection using a handheld manual syringe.<br>|
| Experimental: Arm 2: PH FDC SC Administered Using the On-Body Delivery System<br> | Drug: Fixed-Dose Combination of Pertuzumab and Trastuzumab SC (PH FDC SC)<br>* A single dose of PH FDC SC (600 mg pertuzumab/600 mg trastuzumab) will be administered by a healthcare professional subcutaneously (SC) into the anterior thigh, using either a handheld syringe with hypodermic needle (Arm 1) or the on-body delivery system (Arm 2).<br>* Other names: RG6264;Device: On-Body Delivery System<br>* A single 10-mL dose of PH FDC SC will be administered as a subcutaneous (SC) injection using the on-body delivery system.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Time-Concentration Curve from the Start of Dosing to 63 Days (AUC0-62) of Serum Pertuzumab |  | Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63 | 
| Area Under the Time-Concentration Curve from the Start of Dosing to 63 Days (AUC0-62) of Serum Trastuzumab |  | Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63 | 
| Maximum Serum Concentration (Cmax) of Pertuzumab |  | Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63 | 
| Maximum Serum Concentration (Cmax) of Trastuzumab |  | Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observed Serum Concentration of Pertuzumab on Day 22 |  | Day 22 | 
| Observed Serum Concentration of Trastuzumab on Day 22 |  | Day 22 | 
| Observed Serum Concentration of Pertuzumab on Day 63 |  | Day 63 | 
| Observed Serum Concentration of Trastuzumab on Day 63 |  | Day 63 | 
| Area Under the Time-Concentration Curve from the Start of Dosing Extrapolated to Infinity (AUC0-∞) of Serum Pertuzumab |  | Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63 | 
| Area Under the Time-Concentration Curve from the Start of Dosing Extrapolated to Infinity (AUC0-∞) of Serum Trastuzumab |  | Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63 | 
| Observed Time to Maximum Serum Concentration (tmax) of Pertuzumab |  | Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63 | 
| Observed Time to Maximum Serum Concentration (tmax) of Trastuzumab |  | Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63 | 
| Terminal Elimination Half-Life (t1/2) of Pertuzumab |  | Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63 | 
| Terminal Elimination Half-Life (t1/2) of Trastuzumab |  | Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63 | 
| Apparent Drug Clearance (CL/F) of Pertuzumab |  | Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63 | 
| Apparent Drug Clearance (CL/F) of Trastuzumab |  | Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63 | 
| Apparent Volume of Distribution (Vd/F) of Pertuzumab |  | Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63 | 
| Apparent Volume of Distribution (Vd/F) of Trastuzumab |  | Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63 | 
| Summary of the Number of Participants with at Least One Adverse Event, with Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) |  | From informed consent until safety follow-up visit (up to 7 months) | 
| Change from Baseline Left Ventricular Ejection Fraction (LVEF) Over Time |  | Baseline, once between Days 20 and 35, and once between Days 56 and 63 | 
| Change from Baseline Respiratory Rate Over Time |  | Baseline, Days 1, 2, 7, 22, and 63 | 
| Change from Baseline Pulse Rate Over Time |  | Baseline, Days 1, 2, 7, 22, and 63 | 
| Change from Baseline Body Temperature Over Time |  | Baseline, Days 1 and 63 | 
| Change from Baseline Systolic Blood Pressure Over Time |  | Baseline, Days 1, 2, 7, 22, and 63 | 
| Change from Baseline Diastolic Blood Pressure Over Time |  | Baseline, Days 1, 2, 7, 22, and 63 | 
| Change from Baseline Electrocardiogram PR Interval Over Time |  | Baseline, Days 1, 2, 7, 22, and 63 | 
| Change from Baseline Electrocardiogram QRS Interval Over Time |  | Baseline, Days 1, 2, 7, 22, and 63 | 
| Change from Baseline Electrocardiogram Uncorrected QT Interval Over Time |  | Baseline, Days 1, 2, 7, 22, and 63 | 
| Number of Participants with Abnormal Clinical Laboratory Test Results as a Shift from Baseline to the Maximum Post-Baseline Severity Grade |  | From Baseline until Day 63 | 
| Pain Score at the Injection Site, Assessed by the Participant Using the 100-millimetre (mm) Visual Analog Scale |  | Day 1: pre-dose, during drug injection, after drug injection while removing the device or syringe, and 2 hours after drug injection | 
| Number of Participants with Skin Irritation and Sensitization Reactions at the Injection Site |  | Day 1 | 
| Number of Participants by Their Ratings of the Comfort of Wearing the On-Body Delivery System Device, as Reported in the Device Monitoring Questionnaire | The ratings will be made on a three-point scale as Good, Acceptable, or Poor. | Day 1 | 
| Number of Healthcare Professionals by Their Ratings of Performance and Ease of Use of the On-Body Delivery System Device, as Reported in the Device Monitoring Questionnaire | The ratings will be made on a three-point scale as Good, Acceptable, or Poor. | Day 1 |