Trial Outcomes & Findings for A Pharmacokinetic Study Comparing MB02 And EU Avastin® In Healthy Male Volunteers (NCT NCT04238650)

NCT ID: NCT04238650

Last Updated: 2021-03-23

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 49 participants
• Primary outcome timeframe: 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.
• Results posted on: 2021-03-23

Participant Flow

A total of 49 subjects were randomized and assigned to one of the study groups (24 to the MB02 arm and 25 to the EU Avastin arm). One subject that was randomized to EU Avastin® withdrew before receiving any study drug dose. Therefore, 48 subjects started the study treatment.

Participant milestones

Measure	MB02 (Bevacizumab Biosimilar) Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. MB02 (Bevacizumab Biosimilar): Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion	EU Approved Avastin® Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion
Overall Study STARTED	24	25
Overall Study COMPLETED	24	24
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	MB02 (Bevacizumab Biosimilar) Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. MB02 (Bevacizumab Biosimilar): Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion	EU Approved Avastin® Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	MB02 (Bevacizumab Biosimilar) n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. MB02 (Bevacizumab Biosimilar): Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion	EU Approved Avastin® n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion	Total n=48 Participants Total of all reporting groups
Age, Continuous	28.3 years STANDARD_DEVIATION 5.9 • n=5 Participants	28.5 years STANDARD_DEVIATION 6.6 • n=7 Participants	28.4 years STANDARD_DEVIATION 6.2 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Weight	67.0 kg STANDARD_DEVIATION 9.48 • n=5 Participants	68.5 kg STANDARD_DEVIATION 9.13 • n=7 Participants	67.75 kg STANDARD_DEVIATION 9.24 • n=5 Participants
BMI	22.54 kg/m^2 STANDARD_DEVIATION 2.26 • n=5 Participants	23.33 kg/m^2 STANDARD_DEVIATION 2.84 • n=7 Participants	22.94 kg/m^2 STANDARD_DEVIATION 2.57 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Population: Overall number of participants analyzed equals to number of subjects who contributed to summary statistics.

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.

Outcome measures

Measure	MB02 (Bevacizumab Biosimilar) n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. MB02 (Bevacizumab Biosimilar): Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion	EU Approved Avastin® n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion
Area Under the Serum Concentration-time Curve From Time Zero to Infinity [AUC(0-∞)]	30200000 ng*h/mL Geometric Coefficient of Variation 14.7	29000000 ng*h/mL Geometric Coefficient of Variation 10.8

SECONDARY outcome

Timeframe: 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.

Population: Overall number of participants analyzed equals to number of subjects who contributed to summary statistics.

To evaluate and compare the Cmax of MB02 and EU Avastin® in Japanese population.

Outcome measures

Measure	MB02 (Bevacizumab Biosimilar) n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. MB02 (Bevacizumab Biosimilar): Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion	EU Approved Avastin® n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion
Maximum Observed Serum Concentration (Cmax)	92900 ng/mL Geometric Coefficient of Variation 22.1	82300 ng/mL Geometric Coefficient of Variation 16.9

SECONDARY outcome

Timeframe: 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.

Population: Overall number of participants analyzed equals to number of subjects who contributed to summary statistics.

To evaluate and compare the AUClast of MB02 and EU Avastin® in Japanese population.

Outcome measures

Measure	MB02 (Bevacizumab Biosimilar) n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. MB02 (Bevacizumab Biosimilar): Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion	EU Approved Avastin® n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion
Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Observable Concentration (AUClast)	28200000 ng*h/mL Geometric Coefficient of Variation 12.3	26800000 ng*h/mL Geometric Coefficient of Variation 9.18

SECONDARY outcome

Timeframe: 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.

To evaluate and compare the tmax of MB02 and EU Avastin® in Japanese population.

Outcome measures

Measure	MB02 (Bevacizumab Biosimilar) n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. MB02 (Bevacizumab Biosimilar): Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion	EU Approved Avastin® n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion
Time of Maximum Observed Serum Concentration (Tmax)	4.50 h Interval 1.52 to 24.0	4.00 h Interval 1.52 to 12.0

SECONDARY outcome

Timeframe: 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.

To evaluate and compare the t1/2 of MB02 and EU Avastin® in Japanese population.

Outcome measures

Measure	MB02 (Bevacizumab Biosimilar) n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. MB02 (Bevacizumab Biosimilar): Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion	EU Approved Avastin® n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion
Apparent Serum Terminal Elimination Half Life (t1/2)	430 h Geometric Coefficient of Variation 16.4	450 h Geometric Coefficient of Variation 12.9

SECONDARY outcome

Timeframe: 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.

To evaluate and compare the CL of MB02 and EU Avastin® in Japanese population.

Outcome measures

Measure	MB02 (Bevacizumab Biosimilar) n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. MB02 (Bevacizumab Biosimilar): Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion	EU Approved Avastin® n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion
Total Body Clearance (CL)	0.00660 L/h Geometric Coefficient of Variation 18.3	0.00702 L/h Geometric Coefficient of Variation 14.4

SECONDARY outcome

Timeframe: 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.

To evaluate and compare the Vz of MB02 and EU Avastin® in Japanese population.

Outcome measures

Measure	MB02 (Bevacizumab Biosimilar) n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. MB02 (Bevacizumab Biosimilar): Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion	EU Approved Avastin® n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion
Volume of Distribution (Vz)	4.10 L Geometric Coefficient of Variation 13.2	4.56 L Geometric Coefficient of Variation 12.5

SECONDARY outcome

Timeframe: Day 1 - Day 70

Population: TEAEs were assessed in the Safety population. Subjects receiving MB02 or EU Avastin® and with at least 1 post-dose safety assessment comprised the Safety population.

Compare the incidence of TEAEs reported in each treatment arm using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.

Outcome measures

Measure	MB02 (Bevacizumab Biosimilar) n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. MB02 (Bevacizumab Biosimilar): Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion	EU Approved Avastin® n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion
Incidence of Treatment-related Adverse Events (Safety) Subjects with TEAEs	8 participants	12 participants
Incidence of Treatment-related Adverse Events (Safety) TEAEs of mild severity	8 participants	9 participants
Incidence of Treatment-related Adverse Events (Safety) TEAEs of moderate severity	2 participants	6 participants
Incidence of Treatment-related Adverse Events (Safety) TEAEs of severe severity	0 participants	0 participants
Incidence of Treatment-related Adverse Events (Safety) Related TEAEs	0 participants	2 participants
Incidence of Treatment-related Adverse Events (Safety) Subjects with SAEs	0 participants	0 participants
Incidence of Treatment-related Adverse Events (Safety) Subjects discontinued due to TEAEs	0 participants	0 participants

SECONDARY outcome

Timeframe: Day -1, Day 14, 28, 50 and 70.

Population: Safety population.

Incidence of anti-bevacizumab antibodies (ADA), including neutralizing antibodies (Nab). Subjects who tested positive at baseline are not included here.

Outcome measures

Measure	MB02 (Bevacizumab Biosimilar) n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. MB02 (Bevacizumab Biosimilar): Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion	EU Approved Avastin® n=24 Participants Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion
Incidence of ADA Including Nab (Immunogenicity) ADA positive	0 participants	1 participants
Incidence of ADA Including Nab (Immunogenicity) nAb positive	0 participants	1 participants
Incidence of ADA Including Nab (Immunogenicity) NO seroconversion	24 participants	23 participants

Adverse Events

MB02 (Bevacizumab Biosimilar)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

EU Approved Avastin®

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	MB02 (Bevacizumab Biosimilar) n=24 participants at risk Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. MB02 (Bevacizumab Biosimilar): Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion	EU Approved Avastin® n=24 participants at risk Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. EU approved Avastin®: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion
Infections and infestations Nasopharyngitis	8.3% 2/24 • Number of events 2 • Day 1-Day 70 Coded according to Medical Dictionary for Regulatory Activities (version 22.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 5.0). For the purpose of safety reporting in healthy volunteers, all serious adverse events were considered unexpected and reported as suspected unexpected adverse reactions (SUSARs).	25.0% 6/24 • Number of events 6 • Day 1-Day 70 Coded according to Medical Dictionary for Regulatory Activities (version 22.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 5.0). For the purpose of safety reporting in healthy volunteers, all serious adverse events were considered unexpected and reported as suspected unexpected adverse reactions (SUSARs).
Infections and infestations Pharyngitis	4.2% 1/24 • Number of events 1 • Day 1-Day 70 Coded according to Medical Dictionary for Regulatory Activities (version 22.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 5.0). For the purpose of safety reporting in healthy volunteers, all serious adverse events were considered unexpected and reported as suspected unexpected adverse reactions (SUSARs).	16.7% 4/24 • Number of events 5 • Day 1-Day 70 Coded according to Medical Dictionary for Regulatory Activities (version 22.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 5.0). For the purpose of safety reporting in healthy volunteers, all serious adverse events were considered unexpected and reported as suspected unexpected adverse reactions (SUSARs).
Investigations Blood Creatine Phosphokinase Increased	12.5% 3/24 • Number of events 4 • Day 1-Day 70 Coded according to Medical Dictionary for Regulatory Activities (version 22.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 5.0). For the purpose of safety reporting in healthy volunteers, all serious adverse events were considered unexpected and reported as suspected unexpected adverse reactions (SUSARs).	4.2% 1/24 • Number of events 1 • Day 1-Day 70 Coded according to Medical Dictionary for Regulatory Activities (version 22.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 5.0). For the purpose of safety reporting in healthy volunteers, all serious adverse events were considered unexpected and reported as suspected unexpected adverse reactions (SUSARs).
Investigations Alanine Aminotransferase Increased	8.3% 2/24 • Number of events 3 • Day 1-Day 70 Coded according to Medical Dictionary for Regulatory Activities (version 22.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 5.0). For the purpose of safety reporting in healthy volunteers, all serious adverse events were considered unexpected and reported as suspected unexpected adverse reactions (SUSARs).	8.3% 2/24 • Number of events 2 • Day 1-Day 70 Coded according to Medical Dictionary for Regulatory Activities (version 22.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 5.0). For the purpose of safety reporting in healthy volunteers, all serious adverse events were considered unexpected and reported as suspected unexpected adverse reactions (SUSARs).
Investigations Aspartate Aminotransferase Increased	8.3% 2/24 • Number of events 3 • Day 1-Day 70 Coded according to Medical Dictionary for Regulatory Activities (version 22.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 5.0). For the purpose of safety reporting in healthy volunteers, all serious adverse events were considered unexpected and reported as suspected unexpected adverse reactions (SUSARs).	4.2% 1/24 • Number of events 1 • Day 1-Day 70 Coded according to Medical Dictionary for Regulatory Activities (version 22.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 5.0). For the purpose of safety reporting in healthy volunteers, all serious adverse events were considered unexpected and reported as suspected unexpected adverse reactions (SUSARs).
Investigations Blood Lactate Dehydrogenase Increased	8.3% 2/24 • Number of events 3 • Day 1-Day 70 Coded according to Medical Dictionary for Regulatory Activities (version 22.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 5.0). For the purpose of safety reporting in healthy volunteers, all serious adverse events were considered unexpected and reported as suspected unexpected adverse reactions (SUSARs).	0.00% 0/24 • Day 1-Day 70 Coded according to Medical Dictionary for Regulatory Activities (version 22.1), and graded on the basis of the US National Cancer Institute's Common Terminology for Adverse Events (version 5.0). For the purpose of safety reporting in healthy volunteers, all serious adverse events were considered unexpected and reported as suspected unexpected adverse reactions (SUSARs).

Additional Information

Susana Millan

mAbxience

Phone: +34917711500

Email: susana.millan@mabxience.com

Results disclosure agreements

• Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results.
• Publication restrictions are in place

Restriction type: OTHER