Pharmacokinetic Study Comparing MB02 And US And EU Avastin® In Healthy Male Volunteers
Condition: Healthy Volunteers
Intervention: MB02 (Bevacizumab Biosimilar); EU approved Avastin®; US licenced 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; 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: 115.0
Sex: Male
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Randomized, double blind, parallel group, single dose, 3 arm study to investigate and compare
      the pharmacokinetics (PK), safety and immunogenicity profile of MB02 with US and EU Avastin®
      in healthy male subjects.

      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. Males of any race, between 18 and 55 years of age, inclusive, at Screening.

          2. Body mass index between 18.5 and 29.9 kg/m2, inclusive, at Screening and Check-in.

          3. Total body weight between 60 and 95 kg, inclusive, at Screening and Check-in.

          4. In good health, determined by no clinically significant findings from medical history,
             physical examination, 12-lead ECG, vital sign measurements, and clinical laboratory
             evaluations (congenital nonhaemolytic hyperbilirubinemia [eg, Gilbert's syndrome] is
             acceptable) at Screening or Check-in as assessed by the Investigator (or designee).

          5. Relevant clinical laboratory evaluations of haematology, coagulation, urinalysis and
             clinical chemistry within the following ranges at Screening and Check in. A single
             repeat test will be allowed at each timepoint.

               -  Absolute neutrophil count ≥1.5 × 109 L

               -  Platelet count ≥100 × 109 L

               -  Haemoglobin >10 g/dl

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ ULN

               -  Alkaline phosphatase (ALP) ≤1.5 × ULN

               -  Total bilirubin ≤ 1.5 ULN with direct bilirubin <20% in case of total bilirubin >
                  ULN

               -  Blood urea nitrogen ≤1.5 × ULN

               -  Creatinine <132.63 µmol/L

               -  Serum albumin: ≥35 g/L

               -  Total cholesterol ≤ 7.75 mmol/L

               -  Triglycerides ≤ 3.42 mmol/L

               -  Creatine kinase (CK) ≤3 × ULN

               -  International normalised ratio (INR) 0.8 to 1.3

               -  Urine dipstick for proteinuria <2+

          6. Systolic blood pressure ≥90 mmHg and <140 mmHg and diastolic blood pressure ≥50 mmHg
             and <90 mmHg at Screening and Check in.

          7. Subjects agree to use contraception.

          8. 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.

        Exclusion Criteria:

          1. 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).

          2. History of significant hypersensitivity, intolerance, or allergy to any drug compound,
             food, or other substance, unless approved by the Investigator (or designee).

          3. Any current or recent history of active infections, including localised 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).

          4. 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.

          5. Presence of a nonhealing wound or fracture.

          6. Known history of clinically significant essential hypertension, orthostatic
             hypotension, fainting spells or blackouts for any reason, cardiac failure or history
             of thromboembolic conditions.

          7. 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.

          8. Clinically relevant history of alcoholism, addiction or drug/chemical abuse prior to
             Check-in, and/or positive urinary test for alcohol or drugs of abuse at Screening or
             Check in.

          9. History of bleeding disorders or protein C, protein S, and/or factor V Leiden
             deficiency.

         10. History of clinically significant haemorrhage, epistaxis, GI bleeding, haemorrhoids
             and/or haemoptysis.

         11. History of GI perforation, ulcers, gastro oesophageal reflux, inflammatory bowel
             disease, diverticular disease, or any fistulae.

         12. Alcohol consumption of >24 units per week. One unit of alcohol equals ½ pint (285 mL)
             of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.

         13. Positive hepatitis panel, positive human immunodeficiency test. Subjects whose results
             are compatible with prior immunisation and not infection may be included at the
             discretion of the Investigator.

         14. Participation in a clinical study involving administration of an investigational drug
             (new chemical entity) in the past 90 days prior to Check-in, or within 5 half lives of
             the investigational drug used in the study.

         15. 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).

         16. Use or intend use of any prescription medications/ nonprescription products known to
             alter drug absorption, metabolism, or elimination processes, including St. John's
             wort, within 30 days prior to Check-in, unless deemed acceptable by the Investigator
             or designee.

         17. Use or intend to use any nonprescription medications/products including vitamins,
             minerals, and phytotherapeutic/herbal/plant derived preparations within 7 days prior
             to Check-in, unless deemed acceptable by the Investigator (or designee).

         18. Have received a live or attenuated vaccine from 3 months prior to Screening or have
             the intention to receive a vaccine during the study.

         19. Intend to travel to a region where a vaccination will be required due to endemic
             disease within 3 months of dosing.

         20. Previous treatment with an anti VEGF antibody or any other protein or antibody
             targeting the VEGF receptor.

         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. Donation of blood from 90 days prior to Screening, plasma from 14 days prior to
             Screening, or platelets from 42 days prior to Screening.

         24. Poor peripheral venous access.

         25. History of abnormal peripheral sensation including paraesthesia and/or numbness in
             arms and/or legs.

         26. Have previously completed or withdrawn from this study or any other study
             investigating bevacizumab, and/or have previously received bevacizumab.

         27. Subjects who, in the opinion of the Investigator (or designee), should not participate
             in this study.

         28. Vulnerable subjects (e.g. persons kept in detention).

         29. Subjects who are study site employees or immediate family members of a study site or
             Mabxience employee.