E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Small Cell Lung Cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate and compare pharmacokinetic profile of RPH-001 (TRPHARM) versus EU sourced Avastin® (Roche), after single IV administration at 5 mg/kg fixed dose. |
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E.2.2 | Secondary objectives of the trial |
To assess safety (including immunogenicity) and tolerability of test and reference products. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
I-1. Healthy male subjects aged 18 to 55 years inclusive. I-2. Adult healthy male subjects between 18.0 and 30.0 kg/m2 body mass index (inclusive) and body weight ≥ 60 kg and ≤ 100 kg (inclusive). I-3. Certified as healthy by a comprehensive clinical assessment (detailed medical history [hypo-, hypertension, allergy, other diseases, major surgery, micturition, defecation, sleep, illness within the last 3 weeks prior start of the trial, registration of life style and habits such as consumption of alcohol, nicotine, coffee, tea, coke, special diet, drug abuse]) and complete physical examination (general state and abnormal findings per system: endocrine/metabolic, allergies, drug sensitivities, head, neck, eyes, ears, nose, throat, cardiovascular, respiratory, gastrointestinal, hepatic/biliary, urogenital, musculoskeletal, Lymph nodes, skin, and neurological/psychiatric). I-4. Normal vital signs after 10 minutes resting in supine position: • 90 mmHg < systolic blood pressure (SBP) <140 mmHg • 45 mmHg < diastolic blood pressure (DBP) <90 mmHg • 40 bpm < heart rate (HR) <100 bpm I-5. Normal standard 12-lead electrocardiogram (ECG) after 10 minutes resting in supine position in the following ranges; 120 ms<PR<220 ms, QRS<120 ms, QTc≤430 ms, and normal ECG tracing unless the Investigator considers an ECG tracing abnormality to be not clinically relevant. I-6. Subjects whose clinical laboratory test results are normal, or where outside the reference range is judged as not clinically relevant by the Investigator I-7. Having given written informed consent prior to undertaking any study-related procedure. I-8. Negative Quantiferon TB gold test. |
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E.4 | Principal exclusion criteria |
E-1. Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, or infectious disease, or signs of acute illness. E-2. Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month). E-3. Blood or plasma donation, or transfusion with any volume, within 3 months before inclusion. E-4. Symptomatic hypotension, irrespective of the decrease in blood pressure. E-5. Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician. E-6. Major surgery including appendectomy with in last 12 weeks. E-7. History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per day). E-8. Current smoker of more than 5 cigarettes or equivalent per day during the study and unable to completely stop smoking during the hospitalization. E-9. Excessive consumption of beverages containing xanthine bases such as tea, coffee, coke etc. (more than 500 mg xanthine per day). E-10. Medication with drugs known to alter organs or systems such as barbiturates, phenothiazines, cimetidine, omeprazole etc. within the last 2 months. E-11. Any medication (including St John’s Wort) within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of the medication, any vaccination within the last 28 days and any biologics (antibody or its derivatives) given within 4 months before inclusion. E-12. Any subject who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development. E-13. Any subject in the exclusion period of a previous study according to applicable regulations. E-14. Any subject who cannot be contacted in case of emergency. E-15. Any subject who is the Investigator or any Sub-investigator, research assistant, pharmacist, study coordinator, or other staff thereof, directly involved in conducting the study. E-16. Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen, anti hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab). E-17. Positive result on urine drug screen (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates). E-18. Positive alcohol test at screening or baseline visits E-19. Any contraindications to biological molecules according to the applicable labeling. E-20. Vegetarian diet E-21. Participation in another clinical trial at same time or within the preceding 3 months (calculated from the date of the final examination of the previous study), except for previous BE trials in which case 8 weeks are sufficient.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Pharmacokinetic Endpoints: Cmax, AUC(o-t), and AUC(0-∞).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
100 days after the administration of IMP |
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E.5.2 | Secondary end point(s) |
Secondary Pharmacokinetic Endpoints: tmax, t1/2, λz, CL, Vss Safety Endpoints: Physical examinations, laboratory tests, vital signs, electrocardiogram (ECG) evaluations, adverse events (AEs) and serious adverse events (SAEs). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
100 days after the administration of IMP |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Yes |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | Yes |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 6 |