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

NCT04238663 | Completed Phase 1 Results FDA Drug

• 1 other identifier: MB02 A 05 18
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 1

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 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, 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 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, 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 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, 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 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, 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 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, 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 hours (end of infusion), 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 3-8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 78, and Day 100.

• Immunogenicity: Number of Participants With Anti-bevacizumab Antibodies (Including Neutralizing Antibodies)

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

Study Arms (3)

MB02 (Bevacizumab Biosimilar)

EXPERIMENTAL

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

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

Drug: EU approved Avastin®

US licenced Avastin®

ACTIVE COMPARATOR

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

Drug: US licenced 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®

US licenced Avastin® DRUG

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

US licenced 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 and Check-in.
• Total body weight between 60 and 95 kg, inclusive, at Screening and Check-in.
• 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 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

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. (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).
• 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 urinary test for alcohol or drugs of abuse at Screening or Check in.
• History of bleeding disorders or protein C, protein S, and/or factor V Leiden deficiency.
• History of clinically significant 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 (1)

Early Phase Clinical Unit (EPCU) PAREXEL International GmbH

Berlin, 14050, Germany

Location

Related Publications (1)

• Sinn A, Garcia-Alvarado F, Gonzalez V, Huerga C, Bullo F. A randomized, double blind, single dose, comparative study of the pharmacokinetics, safety and immunogenicity of MB02 (bevacizumab biosimilar) and reference bevacizumab in healthy male volunteers. Br J Clin Pharmacol. 2022 Mar;88(3):1063-1073. doi: 10.1111/bcp.15032. Epub 2021 Sep 4.

  PMID: 34374114 DERIVED

Results Point of Contact

• Title: Susana Millan
• Organization: mAbxience Research SL

susana.millan@mabxience.com

+34917711500

Study Officials

• Angela Sinn, MD

  Early Phase Clinical Unit (EPCU) PAREXEL International GmbH

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• 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: September 24, 2019
• Primary Completion: March 17, 2020
• Study Completion: March 17, 2020
• Last Updated: October 25, 2023
• Results First Posted: February 24, 2021

Record last verified: 2021-03

Locations

DE (1)