A Pharmacokinetic Study Comparing MB02 And US And EU Avastin® In Healthy Male Volunteers

NCT03293654 | Completed Phase 1 Results

• 1 other identifier: MB02 A 02 17
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (2)

• Cmax: Maximum Observed Serum Concentration

  To compare the pharmacokinetic (PK) profiles of MB02, US Avastin® and EU Avastin® (in terms of Cmax) to establish bioequivalence between the 3 study arms. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) for the geometric LS means ratios are fully contained within the predefined bioequivalence limits of 0.80 to 1.25.

  Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.

• AUC(0-∞); Area Under the Serum Concentration-time Curve From Time Zero to Infinity

  To compare the pharmacokinetic (PK) profiles of MB02, US Avastin® and EU Avastin® (in terms of AUC\[0-∞\]) to establish bioequivalence between the 3 study arms. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) for the geometric least square means (GLSM) ratios are fully contained within the predefined bioequivalence limits of 0.80 to 1.25.

  Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.

Secondary Outcomes (6)

• Tmax: Time of Maximum Observed Serum Concentration

  Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.

• AUC(0-t) = Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Observable Concentration;

  Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.

• CL: Total Body Drug Clearance After IV Administration

  Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.

• t1/2: Apparent Serum Terminal Elimination Half-life

  Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.

• Immunogenicity

  Day -1, Day 14, 28, 56, and 78

Other Outcomes (3)

• AUC(0-∞) Adjusted: Protein-adjusted Area Under the Serum Concentration-time Curve From Time Zero to Infinity

  Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.

• AUC(0-t) Adjusted: Protein Adjusted Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Observable Concentration

  Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.

• Cmax Adjusted: Protein Adjusted Maximum Observed Serum Concentration

  Predose, 1.5 h after end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.

Study Arms (3)

MB02 (Bevacizumab Biosimilar)

EXPERIMENTAL

Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.

Drug: MB02

US licenced Avastin®

ACTIVE COMPARATOR

Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.

Drug: US licenced Avastin®

EU approved Avastin®

ACTIVE COMPARATOR

Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.

Drug: EU approved Avastin®

Interventions

MB02 DRUG

Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.

Also known as: MB02 (Bevacizumab Biosimilar)

MB02 (Bevacizumab Biosimilar)

US licenced Avastin® DRUG

Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.

Also known as: Bevacizumab (United States)

US licenced Avastin®

EU approved Avastin® DRUG

Solution for intravenous infusion, single dose of 3mg/kg, administered as 90-minute infusion.

Also known as: Bevacizumab (European Union)

EU approved Avastin®

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: Only male subjects may be enrolled
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males of any race, between 18 and 55 years of age, inclusive, at Screening.
• Body mass index between 18.5 and 29.9 kg/m2, inclusive, at Screening.
• Total body weight between 60 and 95 kg, inclusive, at Screening.
• 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).
• Relevant clinical laboratory evaluations of haematology, coagulation, urinalysis and clinical chemistry within normal range at Screening and Check in as follows. 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 (\<51.30 µmol/L in subjects with Gilbert's syndrome)
• Blood urea nitrogen ≤1.5 × ULN
• Creatinine \< 132.63 µmol/L
• Serum albumin: \>35 g/L
• Low density lipoprotein cholesterol ≤ ULN

You may not qualify if:

• 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).
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
• Any current or recent history of active infections, including localised infections.
• 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.
• Known history of clinically significant essential hypertension, orthostatic hypotension, fainting spells or blackouts for any reason, cardiac failure or history of thromboembolic conditions.
• 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.
• Clinically relevant history of alcoholism, addiction or drug/chemical abuse prior to Check-in, and/or positive alcohol breath test and/or urinary drug test screen at Screening or Check in.
• History of bleeding disorders or protein C, protein S, and/or factor V Leiden deficiency.
• History of clinically signifiant haemorrhage, epistaxis, GI bleeding, haemorrhoids and/or haemoptysis.
• History of GI perforation, ulcers, gastro oesophageal reflux, inflammatory bowel disease, diverticular disease, or any fistulae.
• 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.
• 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.
• 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.
• 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).

Sponsors & Collaborators

• mAbxience Research S.L.: lead

Study Sites (2)

PAREXEL International - Northwick Park Hospital

Harrow, HA1 3UJ, United Kingdom

Location

Covance Clinical Research Unit Limited

Leeds, LS2 9LH, United Kingdom

Location

MeSH Terms

Interventions

Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Susana Millan
• Organization: mAbxience

susana.millan@mabxience.com

+34917711500

Study Officials

• Sunu Valasseri, MBBS, MSc

  Covance

  PRINCIPAL INVESTIGATOR

• Muna Albayaty, MBChB,FFPM,MSc

  Parexel

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2017
• First Posted: September 26, 2017
• Study Start: December 7, 2017
• Primary Completion: May 29, 2019
• Study Completion: May 29, 2019
• Last Updated: March 23, 2021
• Results First Posted: June 16, 2020

Record last verified: 2020-10

Locations

GB (2)