A Pharmacokinetic Study Comparing MB02 And EU Avastin® In Healthy Male Volunteers
Condition: Healthy Volunteers; Male; Japanese
Intervention: MB02 (Bevacizumab Biosimilar); EU approved Avastin®
Intervention description: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion; Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion
Intervention MeSH terms: Bevacizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 49.0
Sex: Male
Minimum age: 20 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      A Randomised, Double Blind, Two-Arm, Single Dose, Parallel Phase I Study To Compare the
      Pharmacokinetics, Safety and Immunogenicity of MB02 (a Proposed Bevacizumab Biosimilar Drug)
      and EU Approved Avastin® in Japanese Healthy Male Volunteers.

      During the course of the study, the similarity in pharmacokinetics will be assessed by
      sampling the levels of drug in the blood, and by comparing these levels among the different
      administration arms. Safety, tolerability, and immunologic response to the administered drugs
      will also be evaluated throughout.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Able to comprehend and willing to sign an informed consent form (ICF) and to abide by
             the study restrictions. Subjects must have signed an informed consent before any
             study-related procedure or evaluation is performed.

          2. Healthy Japanese males aged ≥20 to ≤55 years, inclusive, at Screening.

          3. Subjects with Body mass index (BMI) between ≥18.5 to ≤28 kg/m2 and total body weight
             between ≥50 and ≤100 kg, at Screening

          4. Subject must have no clinically relevant abnormalities identified by a detailed
             medical history.

          5. Systolic blood pressure ≤140 mm Hg and diastolic blood pressure ≤90 mm Hg.

          6. Computerized (12-lead) electrocardiogram (ECG) recording without signs of clinically
             relevant pathology.

          7. All other values for hematology, coagulation and for biochemistry and urinalysis tests
             of blood and urine within the normal range or showing no clinically relevant
             deviations as judged by the Investigator, according to the following laboratory
             values:

             Adequate bone marrow function

               -  Absolute neutrophil count ≥1.5 × 109 L

               -  Platelet count ≥100 × 109 L

               -  Hemoglobin >10 g/dl

             Adequate liver function:

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ ULN

               -  Alkaline phosphatase (ALP) ≤1.5 × ULN

               -  Total bilirubin <1.5 × ULN

               -  Serum albumin: >3.5 g/dL

               -  Low density lipoprotein cholesterol ≤139 mg/dL

               -  High density lipoprotein cholesterol ≥ 40 mg/dL

               -  Creatine kinase (CK) <2 ULN at D-1

             Adequate coagulation:

             • International normalised ratio (INR) 0.8 to 1.3

             Adequate renal function:

               -  Blood urea nitrogen: ≤1.5 × ULN

               -  Creatinine: <1.5 mg/dL

               -  Urine dipstick for proteinuria <2+.

          8. All intermittent medications should have been stopped at least 30 days prior to
             admission to the clinical research center.

          9. Subjects agree to use contraception.

         10. Ability and willingness to abstain from alcoholic beverages (alcohol) 48 hours prior
             to admission to the clinical research center.

        Exclusion Criteria:

          1. History of relevant allergy/hypersensitivity (including allergy to drug or its
             excipients).

          2. Previous treatment with an anti VEGF antibody like bevacizumab or any other protein or
             antibody targeting the VEGF receptor.

          3. History of bleeding disorders or protein C, protein S, and/or factor V Leiden
             deficiency.

          4. Known history of clinically significant essential hypertension (subjects under any
             antihypertensive treatment included), orthostatic hypotension, fainting spells or
             blackouts for any reason, cardiac failure or history of thromboembolic conditions.

          5. History of GI perforation, ulcers, gastro oesophageal reflux, inflammatory bowel
             disease, diverticular disease, diverticular disease, any fistulae, pulmonary
             hemorrhage (hemoptysis) or reversible posterior leukoencephalopathy syndrome.

          6. Any out-of-range laboratory values considered clinically significant by the
             investigator.

          7. Significant history or clinical manifestation of any metabolic, allergic,
             dermatological, hepatic, renal, haematological, pulmonary, cardiovascular,
             gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as
             determined by the Investigator (or designee).

          8. Any current or recent history of active infections, including localized infections.
             (Within 2 months prior Screening Visit for any serious infection which requires
             hospitalization or intravenous anti-infective, and within 14 days prior Screening
             Visit for any active infection which requires oral treatment). A negative result for
             human immunodeficiency virus (HIV), Hepatitis B (Hep B), and hepatitis C (Hep C) is
             required for participation. If subject shows positive Hepatitis B test, but results
             are compatible with prior immunisation and not infection may be included at the
             discretion of the Investigator.

          9. Clinically relevant history of alcoholism, addiction or drug/chemical abuse prior to
             Check-in, and/or positive urinary drug test screen and/or positive breath alcohol test
             at Screening or Check in. Average intake of more than 24 units of alcohol / wk. (1
             unit of alcohol equals ~250mL of beer, 100mL of wine or 35mL of spirits). Positive
             urine drug screen (opiates, methadone, cocaine, amphetamines (including ecstasy or
             methamphetamines), cannabinoids, barbiturates, benzodiazepines, tricyclic
             antidepressants and phencyclidine).

         10. Treatment with non-topical medications within 7 days prior to study drug
             administration, with the exception of hormonal contraceptives, multivitamins, vitamin
             C, food supplements and a limited amount of acetaminophen, which may be used
             throughout the study.

         11. Participation in a clinical study involving administration of an investigational drug
             (new chemical entity) in the past 60 days prior to Check-in, or within 5 half lives of
             the investigational drug used in the study.

         12. Subjects considered unsuitable for inclusion by the investigator (e.g., inability to
             understand and comply with the study requirements or presence of any condition which,
             in the opinion of the investigator, would not allow safe participation in the study).

         13. Strenuous exercise within seven days prior to admission to the clinical research
             center.

         14. Significant or acute illness within 15 days prior to drug administration that may
             impact safety assessments per the judgement of the investigator.

         15. Unsuitable veins for infusion and/or venepuncture.

         16. History of, or planned surgery, including suturing, dental surgery or wound dehiscence
             within 30 days of dosing, or within 30 days of the last study visit. Presence of a
             nonhealing wound or fracture.

         17. Medically significant dental disease or dental neglect with signs and or symptoms of
             local or systemic infection that would likely require a dental procedure during the
             course of the study.

         18. Use or intend to use slow-release medications/products considered to still be active
             within 30 days prior to Check-in, unless deemed acceptable by the Investigator (or
             designee).

         19. Have received a live or attenuated vaccine from 3 months prior to Screening or have
             the intention to receive a vaccine during the study.

         20. Intend to travel to a region where a vaccination will be required due to endemic
             disease within 3 months of dosing.

         21. Use of tobacco- or nicotine-containing products within 1 year prior to Check-in, or
             positive cotinine test upon Screening or Check-in.

         22. Receipt of blood products within 60 days prior to Check-in.

         23. Person who performed blood sampling more than 400 mL within 90 days before
             administration of investigational drug, more than 200 mL blood within 30 days, or
             blood donation of blood plasma / platelet component within 14 days.

         24. History of abnormal peripheral sensation including paraesthesia and/or numbness in
             arms and/or legs.

         25. Have previously received Bevacizumab either under present study or under any other
             circumstances.