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

NCT04238650 | Completed Phase 1 Results

• 1 other identifier: MB02 A 04-18
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers; Male; Japanese

Outcome Measures

Primary Outcomes (1)

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

  To compare the pharmacokinetic (PK) profiles of MB02 and EU Avastin® (in terms of AUC(0-∞)\]) in Japanese population to establish bioequivalence between the 2 study drugs.

  Predose, 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 38, Day 50, Day 62, and Day 70.

Secondary Outcomes (8)

• Maximum Observed Serum Concentration (Cmax)

  Predose, 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 38, Day 50, Day 62, and Day 70.

• Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Observable Concentration (AUClast)

  Predose, 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 38, Day 50, Day 62, and Day 70.

• Time of Maximum Observed Serum Concentration (Tmax)

  Predose, 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 38, Day 50, Day 62, and Day 70.

• Apparent Serum Terminal Elimination Half Life (t1/2)

  Predose, 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 38, Day 50, Day 62, and Day 70.

• Total Body Clearance (CL)

  Predose, 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 38, Day 50, Day 62, and Day 70.

Study Arms (2)

MB02 (Bevacizumab Biosimilar)

EXPERIMENTAL

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

Drug: MB02 (Bevacizumab Biosimilar)

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 (Bevacizumab Biosimilar) DRUG

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

MB02 (Bevacizumab Biosimilar)

EU approved Avastin® DRUG

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

EU approved Avastin®

Eligibility Criteria

• Age: 20 Years - 55 Years
• Gender Eligibility Details: Only Japanese male subjects may be enrolled
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Healthy Japanese males aged ≥20 to ≤55 years, inclusive, at Screening.
• Subjects with Body mass index (BMI) between ≥18.5 to ≤28 kg/m2 and total body weight between ≥50 and ≤100 kg, at Screening
• Subject must have no clinically relevant abnormalities identified by a detailed medical history.
• Systolic blood pressure ≤140 mm Hg and diastolic blood pressure ≤90 mm Hg.
• Computerized (12-lead) electrocardiogram (ECG) recording without signs of clinically relevant pathology.
• 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

You may not qualify if:

• History of relevant allergy/hypersensitivity (including allergy to drug or its excipients).
• Previous treatment with an anti VEGF antibody like bevacizumab or any other protein or antibody targeting the VEGF receptor.
• History of bleeding disorders or protein C, protein S, and/or factor V Leiden deficiency.
• 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.
• 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.
• Any out-of-range laboratory values considered clinically significant by the investigator.
• 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).
• 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.
• 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).
• 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.
• 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.
• Strenuous exercise within seven days prior to admission to the clinical research center.
• Significant or acute illness within 15 days prior to drug administration that may impact safety assessments per the judgement of the investigator.
• Unsuitable veins for infusion and/or venepuncture.
• 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.

Sponsors & Collaborators

• mAbxience Research S.L.: lead

Study Sites (1)

SOUSEIKAI Hakata Clinic

Fukuoka, 812-0025, Japan

Location

Related Publications (1)

• Eto T, Karasuyama Y, Gonzalez V, Del Campo Garcia A. A randomized, single-dose, pharmacokinetic equivalence study comparing MB02 (proposed biosimilar) and reference bevacizumab in healthy Japanese male volunteers. Cancer Chemother Pharmacol. 2021 Oct;88(4):713-722. doi: 10.1007/s00280-021-04324-z. Epub 2021 Jul 16.

  PMID: 34269848 DERIVED

Results Point of Contact

• Title: Susana Millan
• Organization: mAbxience

susana.millan@mabxience.com

+34917711500

Study Officials

• Takashi ETO, MD

  SOUSEIKAI Hakata Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: January 16, 2020
• First Posted: January 23, 2020
• Study Start: August 2, 2019
• Primary Completion: December 27, 2019
• Study Completion: December 27, 2019
• Last Updated: March 23, 2021
• Results First Posted: February 1, 2021

Record last verified: 2021-02

Locations

JP (1)