Phase I, Double Blind, Randomized, Parallel-Arm, Single-Dose, Pharmacokinetic and Safety Study of Bevacizumab-biosimilar (RPH-001) Compared to Bevacizumab-innovator (Avastin®, Roche) in Healthy Male Volunteers

INTERVENTION: Product Code: RPH‐001 Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: bevacizumab biosimilar Current Sponsor code: RPH‐001 Other descriptive name: BEVACIZUMAB BIOSIMILAR Concentration unit: mg/kg milligram(s)/kilogram Concentration type: equal Concentration number: 5‐ Trade Name: Avastin® Product Name: Avastin® Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: BEVACIZUMAB CAS Number: 216974‐75‐3 Concentration unit: mg/kg milligram(s)/kilogram Concentration type: equal Concentration number: 5‐ CONDITION: Non‐Small Cell Lung Cancer ; MedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non‐small cell lung cancer System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: 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. Primary end point(s): Primary Pharmacokinetic Endpoints: Cmax, AUC(o‐t), and AUC(0‐8).; Secondary Objective: To assess safety (including immunogenicity) and tolerability of test and reference products. Timepoint(s) of evaluation of this end point: 100 days after the administration of IMP SECONDARY OUTCOME: Secondary end point(s): Secondary Pharmacokinetic Endpoints: tmax, t1/2, ?z, CL, Vss; Safety Endpoints: Physical examinations, laboratory tests, vital signs, electrocardiogram (ECG) evaluations, adverse events (AEs) and serious adverse events (SAEs). Timepoint(s) of evaluation of this end point: 100 days after the administration of IMP 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 < s