Clinical trial NCT04408989
Conditions: Healthy Volunteers
Sponsor: mAbxience Research S.L.
Start date: 2021-01-11; Completion date: 2021-09-02
Enrollment: 114 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Randomized, double blind, parallel group, single dose, 3 arm study to investigate and compare the PK, safety and immunogenicity profile of MB02-DM with MB02-SP and US-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.

Detailed description:
The primary PK parameter endpoints are Cmax and AUC0-∞ for bevacizumab. The secondary PK endpoints will include all other PK parameters for bevacizumab, including tmax, t1/2, CL and AUC(0-t).

The serum PK parameters of bevacizumab will be calculated using standard noncompartmental methods. An analysis of covariance model will be used to analyse the log-transformed primary PK parameters (AUC\[0 ∞\] and Cmax) and AUC(0-t). The model will include a fixed effect for treatment and body weight as a covariate.

All other PK parameters will not be subject to inferential statistical analysis.

Estimates of geometric mean ratios together with the corresponding 90% confidence intervals (CI) will be derived for the comparisons of the PK parameters as follows:

* MB02-SP versus MB02-DM
* MB02-SP versus US Avastin®
* MB02-DM versus US Avastin®

PK similarity will be achieved if the 90% CIs for the biosimilar-to-reference ratios of PK endpoints (AUC\[0-∞\] and Cmax) fall within the predefined 0.80-1.25 acceptance similarity criteria for all 3 pairwise comparisons; MB02-SP versus MB02-DM; MB02-SP versus US Avastin®; and MB02-DM versus US Avastin®.

All AEs will be listed and summarised using descriptive methodology. All observed or patient-reported AEs will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The incidence of AEs for each treatment will be presented by severity and by association with the study drugs as determined by the Investigator (or designee). Each AE will be coded using the Medical Dictionary for Regulatory Activities. All safety data will be listed and summarised as appropriate.

Immunogenicity data (overall ADA incidence and titters, and neutralising ADA results) will be listed. A summary of the number and percent of subjects testing positive for ADA or neutralising antibodies before the dose of MB02-SP, MB02-DM, or US Avastin® (Day -1) and at scheduled post dose assessments will be presented by treatment arm. All safety data and immunogenicity data summaries will be based on the safety analysis population. Select analyses may be repeated for subsets with or without ADA and de novo ADA formation as appropriate.

Arms: arm 1: Sterile vial 100mg/4ml, single-dose 1mg/kg administered as 90-minute infusion on day 1. arm 2: Sterile vial 100mg/4ml, single-dose 1mg/kg administered as 90-minute infusion on day 1. arm 3: Sterile vial 100mg/4ml, single-dose 1mg/kg administered as 90-minute infusion on day 1.
Interventions: intervention 1: MB02-SP intervention 2: MB02-DM intervention 3: US licenced Avastin®
Intervention descriptions: intervention 1: Solution for intravenous infusion, single dose of 1mg/kg, administered as 90-minute infusion intervention 2: Solution for intravenous infusion, single dose of 1mg/kg, administered as 90-minute infusion intervention 3: Solution for intravenous infusion, single dose of 1mg/kg, administered as 90-minute infusion

Protocol documents:
Prot_000.pdf: 
Protocol Title: 
A Randomised, Double-Blind, Three-Arm, Single 
Dose, Parallel Study To Compare the 
Pharmacokinetics, Safety and Immunogenicity of 
MB02-SP, MB02-DM (Bevacizumab Biosimilar 
Drugs) and US licenced Avastin® in Healthy Male 
Volunteers 
NCT Number: 
NCT04408989 
Protocol version 
date: 
Version 1.0, 26 May 2020 
 
 


Protocol 
CONFIDENTIAL 
Syneos Health Study: 7012755 
Sponsor Reference: MB02-A-06-20 
Version 1.0, 26 May 2020 
Page 1 of 54 
PROTOCOL 
A Randomised, Double-Blind, Three-Arm, Single Dose, Parallel 
Study To Compare the Pharmacokinetics, Safety and 
Immunogenicity of MB02-SP, MB02-DM (Bevacizumab Biosimilar 
Drugs) and US licenced Avastin® in Healthy Male Volunteers 
Protocol Status: Version 1.0 
Protocol Date: 26 May 2020 
Study Drug: MB02-DM, MB02-SP  
Sponsor Reference Number: MB02-A-06-20 
Syneos Health Study Number: 7012755 
EudraCT Number: Not applicable 
Study Sites: 
Auckland Clinical Studies Ltd (ACS)  
Ground Floor 
3 Ferncroft Street 
Grafton, Auckland 1010 
New Zealand 
Christchurch Clinical Studies Trust Ltd (CCST)  
Level 4/264 Antigua Street, Christchurch Central 
City, Christchurch 8011 
New Zealand 
Sponsor: 
mAbxience Research S.L. 
C/ Manuel Pombo Angulo, 28,  
3rd floor, 28050, Madrid,  
Spain 
Contract Research Organization (CRO): 
Syneos Health, LLC/ Health UK Limited 
1030 Sync Street, Morrisville,  
North Carolina 27560,  
United States 
 
 
 
 
 
 
Information described herein is confidential and may be disclosed only with the express written permission of the 
Sponsor. 








Protocol 
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Syneos Health Study: 7012755 
Sponsor Reference: MB02-A-06-20 
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STUDY IDENTIFICATION 
Syneos Health’s Project Manager  
 
Project Manager, Early Phase, APAC 
Syneos Health 
159 Port Rd, Hindmarsh SA 5007 Australia 
 
 
Syneos Health’s Medical Monitor 
 
Medical Director 
159 Port Rd, Hindmarsh SA 5007 Australia  
Email: jon.rankin@syneoshealth.com 
 
 
Sponsor’s Project Manager 
  
Clinical Project Manager 
mAbxience Research S.L. 
C/ Manuel Pombo Angulo 28, 3rd Floor 
28050, Madrid 
 
 
Sponsor’s Medical Contact  
 
Medical Advisor 
mAbxience Research S.L. 
C/ Manuel Pombo Angulo 28, 3rd Floor 
28050, Madrid 
 
 
Study Site 
Auckland Clinical Studies (ACS)  
Ground Floor 
3 Ferncroft Street 
Grafton, Auckland 1010 
New Zealand 
Principal Investigator 
  
 
 
Clinical Laboratory 
Labtests 
37-41 Carbine Road 
Mt Wellington, Auckland 1060 
New Zealand 
LabPlus 
Gate 4, Building 31, Auckland City Hospital, Grafton, 
Auckland 1148 
New Zealand 


Protocol 
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Sponsor Reference: MB02-A-06-20 
Version 1.0, 26 May 2020 
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Study Site 
Christchurch Clinical Studies Trust (CCST)  
Level 4/264 Antigua Street,  
Christchurch Central City, Christchurch 8011 
New Zealand 
Principal Investigators 
 
 
 
Clinical Laboratory 
Canterbury Health Laboratories  
Cnr Tuam and Hagley Ave 
Opposite Churchill Hospital 
Christchurch 8011 
New Zealand 
Bioanalytical Laboratory 
Immunochemistry Department 
Covance Laboratories Ltd. 
Otley Road 
Harrogate, HG3 1PY 
UK 
Statistician 
 
Biostatistician 
159 Port Rd, Hindmarsh SA 5007 Australia  
 
 
 
 


Protocol 
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Syneos Health Study: 7012755 
Sponsor Reference: MB02-A-06-20 
Version 1.0, 26 May 2020 
Page 7 of 54 
SYNOPSIS 
Title of study: A Randomized, Double-Blind, Three-Arm, Single Dose, Parallel Study To Compare 
the Pharmacokinetics, Safety and Immunogenicity of MB02-SP, MB02-DM (Bevacizumab 
Biosimilar Drug) and US-licensed Avastin® in Healthy Male Volunteers. 
Objectives: 
The primary objective of the study is: 
 
To investigate and compare the pharmacokinetic (PK) profiles of MB02-SP (MB02 standard 
procedure), MB02-DM (MB02 defined media) and US-licenced Avastin® (US Avastin®) to 
establish bioequivalence between the 3 study arms. 
The secondary objectives of the study are: 
 
Evaluation and comparison of derived PK parameters not covered by the primary endpoints 
for MB02-SP, MB02-DM and US Avastin®.  
 
To compare the safety profile of MB02-SP, MB02-DM and US Avastin®. 
 
To compare the immunogenicity of MB02-SP, MB02-DM and US Avastin®. 
Study design: 
This will be a Phase 1, double-blind, randomised, parallel-group, single-dose, 3-arm study to 
investigate and compare the PK, safety and immunogenicity profile of MB02-DM with MB02-SP 
and US Avastin® in healthy male subjects. 
Potential subjects will be screened to assess their eligibility to enter the trial within 30 days prior to 
study drug administration. Subjects will be admitted to the Clinical Research Unit (CRU) on Day -1 
and will be confined to the CRU until discharge on Day 3. On Day 1, subjects will receive a single 
1 mg/kg intravenous (IV) dose of the study drug. Subjects will return on Days 4, 5, 6, 7, 8, 10, 14, 
21, 28, 42, 56, 78 and 100 for non-residential visits for the collection of pharmacokinetics (PK) and 
safety assessments. Immunogenicity samples will be collected on Days -1, 14, 28, 56, and 78. 
Number of subjects: 
One hundred and fourteen (114) subjects will participate in the study.  
Diagnosis and main criteria for inclusion: 
Healthy male subjects of any race, in good health, between 18 and 55 years of age, inclusive, with a 
body mass index between 18.5 and 29.9 kg/m2, inclusive, and a body weight between 50 and 95 kg, 
inclusive. Subjects will have relevant clinical laboratory evaluations within normal ranges and be 
able and willing to sign an informed consent form, and to abide by the study restrictions. See protocol 
for detailed inclusion and exclusion criteria.  
Test products, dose, and mode of administration: 
1 mg/kg MB02-SP, administered as a 90-minute IV infusion 
1 mg/kg MB02-DM, administered as a 90-minute IV infusion 
1 mg/kg US Avastin®, administered as a 90-minute IV infusion 
Duration of treatment: 
Planned Screening duration: up to 30 days. 
Planned study duration (Screening to end of study visit): maximum of 19 weeks.  


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Syneos Health Study: 7012755 
Sponsor Reference: MB02-A-06-20 
Version 1.0, 26 May 2020 
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Criteria for evaluation: 
Pharmacokinetics: 
Blood samples will be collected for the analysis of serum concentrations of bevacizumab. The 
primary PK endpoints for bevacizumab will be maximum observed serum concentration (Cmax) and 
area under the serum concentration-time curve (AUC) from time zero to infinity (AUC[0-∞]). The 
secondary PK endpoints for bevacizumab will include time of maximum observed serum 
concentration (tmax), clearance (CL), AUC calculated to the last observable concentration at time t 
(AUC[0-t]) and apparent serum terminal elimination half-life (t1/2). 
Safety: 
Safety endpoints for this study include adverse events (AEs), vital signs measurements, 12-lead 
electrocardiograms, clinical laboratory evaluations and physical examinations. 
Immunogenicity: 
Blood samples will be collected for the assessment of serum concentrations of anti-MB02-DM, anti-
MB02-SP and anti-Avastin® antibodies at he following time points (five samples in total): at baseline, 
prior to study drug administration, which is between Day -1 and Day 1 prior to dosing (time 0 hours) 
and on days: 14, 28, 56 and 78. 
Statistical methods: 
The primary PK parameters are Cmax and AUC(0-∞). The PK parameters for bevacizumab will be 
calculated using standard non-compartmental methods. An analysis of covariance model will be 
used to analyse the log-transformed primary PK parameters (AUC[0-∞].and Cmax) and AUC(0-t). The 
model will include a fixed effect for treatment and body weight as a covariate. 
All other PK parameters will not be subject to inferential statistical analysis. Estimates of geometric 
mean ratios together with the corresponding 90% confidence intervals will be derived for the 
comparisons of the PK parameters as follows: 
 
MB02-SP versus MB02-DM 
 
MB02-SP versus US Avastin® 
 
MB02-DM versus US Avastin® 
PK similarity will be achieved if the 90% confidence intervals (CIs) for the biosimilar-to-reference 
ratios of PK endpoints (AUC[0–∞] and Cmax) fall within the predefined 0.80–1.25 acceptance similarity 
criteria for all 3 pairwise comparisons; MB02-SP versus MB02-DM; MB02-SP versus US Avastin®; 
and MB02-DM versus US Avastin®. 
All AEs will be listed and summarised using descriptive methodology. All observed or patient-
reported AEs will be graded by the National Cancer Institute Common Terminology Criteria for 
Adverse Events (CTCAE) version 5.0. The incidence of AEs for each treatment will be presented by 
severity and by association with the study drugs as determined by the Investigator (or designee). All 
safety data will be listed and summarised as appropriate 
Immunogenicity data (overall anti-drug antibody [ADA] incidence and titters, and neutralising ADA 
results) will be listed. A summary of the number and percent of subjects testing positive for ADA or 
neutralising antibodies before the dose of MB02-SP, MB02-DM, or US Avastin® (Day -1) and at 
scheduled post dose assessments will be presented by treatment arm. 


Protocol 
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Syneos Health Study: 7012755 
Sponsor Reference: MB02-A-06-20 
Version 1.0, 26 May 2020 
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TABLE OF CONTENTS 
1 
INTRODUCTION ...........................................................................................................13 
1.1 
Overview ................................................................................................................13 
1.2 
Summary of Nonclinical Experience .....................................................................13 
1.3 
Summary of Clinical Experience ...........................................................................14 
1.3.1 
Pharmacokinetics .........................................................................................15 
1.3.2 
Efficacy ........................................................................................................15 
1.3.3 
Safety ...........................................................................................................16 
1.3.4 
Immunogenicity ...........................................................................................18 
1.4 
Study Rationale ......................................................................................................19 
1.5 
Benefit-risk Assessment.........................................................................................19 
2 
OBJECTIVES ..................................................................................................................20 
2.1 
Primary Objective ..................................................................................................20 
2.2 
Secondary Objectives.............................................................................................20 
3 
ENDPOINTS ...................................................................................................................21 
3.1 
Primary Endpoints .................................................................................................21 
3.2 
Secondary Endpoints .............................................................................................21 
4 
INVESTIGATIONAL PLAN ..........................................................................................22 
4.1 
Study Design ..........................................................................................................22 
4.2 
Discussion of Study Design ...................................................................................22 
4.3 
Selection of Doses in the Study .............................................................................23 
5 
SELECTION OF STUDY POPULATION .....................................................................24 
5.1 
Inclusion Criteria ...................................................................................................24 
5.2 
Exclusion Criteria ..................................................................................................25 
5.3 
Subject Number and Identification ........................................................................27 
5.4 
Subject Withdrawal and Replacement ...................................................................27 
5.5 
Study Termination .................................................................................................27 
6 
STUDY TREATMENTS .................................................................................................28 
6.1 
Description, Storage, Packaging, and Labelling ....................................................28 
6.2 
Study Treatment Administration............................................................................28 
6.3 
Randomisation .......................................................................................................28 
6.4 
Blinding..................................................................................................................28 
6.5 
Study Treatment Compliance ................................................................................29 
6.6 
Drug Accountability...............................................................................................29 
7 
CONCOMITANT THERAPIES AND OTHER RESTRICTIONS ................................29 
7.1 
Concomitant Medications ......................................................................................29 
7.2 
Diet .........................................................................................................................30 
7.3 
Smoking .................................................................................................................30 
7.4 
Exercise ..................................................................................................................30 


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7.5 
Blood Donation ......................................................................................................30 
7.6 
Contraception .........................................................................................................30 
8 
STUDY ASSESSMENTS AND PROCEDURES ...........................................................32 
8.1 
Pharmacokinetic Assessments ...............................................................................32 
8.1.1 
Pharmacokinetic Blood Sample Collection and Processing ........................32 
8.1.2 
Analytical Methodology ..............................................................................32 
8.2 
Immunogenicity Assessments ................................................................................32 
8.2.1 
Immunogenicity Blood Sample Collection and Processing .........................32 
8.2.2 
Analytical Methodology ..............................................................................32 
8.3 
Safety and Tolerability Assessments .....................................................................32 
8.3.1 
Adverse Events ............................................................................................32 
8.3.2 
Clinical Laboratory Evaluations ..................................................................33 
8.3.3 
Vital Signs ....................................................................................................33 
8.3.4 
12-Lead Electrocardiogram .........................................................................33 
8.3.5 
Physical Examination...................................................................................34 
9 
SAMPLE SIZE AND DATA ANALYSES .....................................................................35 
9.1 
Determination of Sample Size ...............................................................................35 
9.2 
Analysis Populations ..............................................................................................35 
9.2.1 
Pharmacokinetic Population ........................................................................35 
9.2.2 
Safety Population .........................................................................................35 
9.3 
Pharmacokinetic Analyses .....................................................................................35 
9.4 
Safety Analysis ......................................................................................................36 
9.4.1 
Medical Safety Monitoring ..........................................................................36 
9.5 
Interim Analysis .....................................................................................................37 
10 QUALITY CONTROL AND QUALITY ASSURANCE ...............................................38 
10.1 
Auditing .................................................................................................................38 
10.2 
Monitoring .............................................................................................................38 
11 DATA HANDLING AND RECORD KEEPING ...........................................................39 
11.1 
Data Handling ........................................................................................................39 
11.2 
Case Report Form ..................................................................................................39 
11.3 
Records ..................................................................................................................39 
12 ETHICAL AND REGULATORY CONSIDERATIONS ...............................................40 
12.1 
Ethics Committee ...................................................................................................40 
12.2 
Regulatory Considerations .....................................................................................40 
12.3 
Informed Consent...................................................................................................40 
12.4 
Subject Confidentiality ..........................................................................................41 
12.5 
Protocol Amendments ............................................................................................41 
13 ADMINISTRATIVE ASPECTS .....................................................................................42 
13.1 
Disclosure ..............................................................................................................42 
13.2 
Reports and Publications........................................................................................42 


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Sponsor Reference: MB02-A-06-20 
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13.3 
Finances and Insurance ..........................................................................................42 
14 REFERENCES ................................................................................................................43 
15 APPENDICES .................................................................................................................44 
Appendix 1: Schedule of Assessments ..............................................................................45 
Appendix 2: Adverse Event Reporting ..............................................................................49 
Appendix 3: Clinical Laboratory Evaluations ...................................................................53 
Appendix 4: Total Blood Volume......................................................................................54 


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Sponsor Reference: MB02-A-06-20 
Version 1.0, 26 May 2020 
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LIST OF ABBREVIATIONS 
ADA 
anti-drug antibody 
AE 
adverse event 
AUC 
area under the serum concentration-time curve 
AUC(0-) 
AUC from time zero to infinity 
AUC(0-t) 
AUC from time zero to the time of the last observable concentration 
CI 
confidence interval 
CL 
clearance 
Cmax 
maximum observed serum concentration 
CRU 
Clinical Research Unit 
CTCAE 
Common Terminology Criteria for Adverse Events 
EC 
Ethics Committee 
ECG 
electrocardiogram 
eCRF 
electronic Case Report Form 
EMA 
European Medicines Agency 
FIH 
first in human 
FOLFIRI 
leucovorin, fluorouracil and irinotecan 
FOLFOX 
leucovorin, fluorouracil and oxaliplatin 
GI 
gastrointestinal 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for/Conference on Harmonisation 
IMP 
investigational medicinal product 
INR 
international normalised ratio 
IUD 
intrauterine device 
IV 
intravenous 
PK 
pharmacokinetic(s) 
QTcF 
QT interval corrected for heart rate using Fridericia’s method 
RMP 
reference medicinal product 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SOP 
Standard Operating Procedure 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment emergent adverse event 
t1/2 
apparent serum terminal elimination half-life 
tmax 
time of maximum observed serum concentration 
ULN 
upper limit of normal 
VEGF 
vascular endothelial growth factor 
 


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1 
INTRODUCTION 
Please refer to the Investigator’s Brochure (IB)1 for detailed information concerning the 
available pharmacology, toxicology, drug metabolism, clinical studies, and adverse event (AE) 
profile of the investigational medicinal product (IMP). 
1.1 
Overview 
MB02 is a bevacizumab biosimilar product to the originator Reference Medicinal Product 
(RMP) Avastin®. MB02 is currently marketed in different countries outside the European 
Union, and, as part of the clinical development plan, one first-in-human (FIH) study in 
colorectal cancer patients and two pivotal clinical trials have already been completed: a phase 
I comparative pharmacokinetic (PK), safety and immunogenicity study in healthy male 
volunteers and, a phase III comparative efficacy, safety and immunogenicity study in patients 
with stage IIIB/IV non-squamous, non-small cell lung cancer (NSCLC). Avastin® is indicated 
for the treatment of multiple cancer types, administered alone or in combination with 
chemotherapy. Bevacizumab, the active substance of Avastin®, is a recombinant humanised 
monoclonal antibody that specifically binds to all isoforms of the human vascular endothelial 
growth factor (VEGF), neutralising its biological activity. By sequestering VEGF, 
bevacizumab inhibits angiogenesis, inhibiting tumour growth and progression, and sensitising 
tumour vasculature to chemotherapy-induced damage.  
1.2 
Summary of Nonclinical Experience 
A number of nonclinical in vitro and in vivo characterisation and efficacy studies have been 
conducted to demonstrate the similarity of MB02 with the RMP Avastin®. A full in vitro 
characterisation was undertaken, in accordance with European Medicines Agency (EMA) 
guidance on similar biological medicinal products containing monoclonal antibodies.2 MB02 
was shown to be identical to Avastin® in primary structure, and similar in protein conformation, 
posttranslational modification, and purity. MB02 and Avastin® also displayed similar 
mechanism of action, and similar affinity to FcRn receptors in vitro, which was indicative of a 
similar pharmacokinetic (PK) profile in vivo. Based upon these results, MB02 and Avastin® 
were considered similar in terms of physicochemical, structural and biological properties. 
An in vivo toxicokinetic study has been conducted in cynomolgus monkeys. Twice-weekly 
intravenous (IV) doses of 50 mg/kg MB02 or Avastin®, infused over 30 minutes for 28 days, 
were well tolerated, and no clear differences were observed between MB02 and the RMP. 
Pharmacokinetic parameters derived during the toxicokinetic study demonstrated the similarity 
of MB02 to the RMP. Similar levels of accumulation were observed on Day 25 between MB02 
and Avastin ® (with mean accumulation ratios ranging from 3.7 to 4.2 and 3.0 to 3.1, 
respectively). There was no appreciable difference in sex—related differences in exposure to 
MB02 and the RMP, and systemic exposure of MB02 and the RMP were similar on Days 1 
and 25. 


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1.3 
Summary of Clinical Experience 
In the earlier phases of its development, the biosimilar bevacizumab candidate MB02 was 
manufactured according to good manufacturing practice (GMP) at CMC Biologics/Aptuit and 
was referred to as BEVZ92. The manufacturing process was then transferred to other facilities 
in Spain (GH Genhelix S.A.), and due to the change of manufacturing sites and the associated 
CMC procedures, the product used in the development program for MB02 intended to support 
mAbxience’s regulatory submissions in highly regulated countries (EU, US and JP) was 
MB02-SP. More recently, an optimized upstream manufacturing process was implemented for 
MB02, using fully chemically defined media for cell culture, meeting most up-to-date industry 
and regulatory expectations (this product is referred to as MB02-DM).  An in vitro analytical 
comparability was performed and confirmed the high comparability of MB02 manufactured by 
either manufacturing processes.  
A first-in-human study in patients with metastatic colorectal cancer (BEVZ92-A-01-13) was 
conducted, comparing the PK, safety, efficacy and immunogenicity of 5 mg/kg MB02 to 
5 mg/kg Avastin® when administered in combination with leucovorin, fluorouracil and 
oxaliplatin (FOLFOX) or leucovorin, fluorouracil and irinotecan (FOLFIRI) chemotherapy 
regimens as first-line treatments. In this study, a MB02 drug product made at a different 
manufacturing site to the to-be marketed product was used and therefore, only safety data is 
included here to contribute to the overall benefit/risk assessment. 
As part of the clinical development programme for MB02, and, in order to obtain evidence on 
similar PK, efficacy and safety, including immunogenicity, two pivotal clinical studies were 
conducted with MB02-SP and completed.  
One study (MB02-A-02-17) was a double-blind, randomised, parallel-group, single-dose 3 arm 
study in 114 healthy male volunteers to compare pharmacokinetic (PK), safety and 
immunogenicity between MB02 and RMP (Avastin). The primary objective of the study was 
to investigate and compare the PK profiles of MB02, US Avastin®, and EU Avastin® to 
establish bioequivalence between the 3 study arms. The evaluation and the comparison of the 
derived PK parameters not covered by the primary endpoints for MB02, US Avastin®, and EU 
Avastin® were included within the secondary objectives of the study. The primary endpoints 
were AUC(0-inf) and Cmax. PK similarity between MB02 and the RMP was achieved if the 
90% CIs for MB02 to RMP ratios for the aforementioned endpoints fell within the predefined 
equivalence margin, [0.80–1.25]. Statistical analysis for equivalence was also undertaken for a 
secondary PK endpoint, area under the curve from time zero to the time of last measurable 
concentration (AUC0-t).” 
The second pivotal study (MB02-C-02-17) is a multicenter, randomized, double-blind study 
conducted in 627 patients with non-squamous non-small cell lung cancer, stage IIIB/IV to 
assess and compare efficacy, safety and immunogenicity of MB02 with EU-approved Avastin® 
in combination with carboplatin and paclitaxel in patients with Stage IIIB/IV non-squamous 
NSCLC. The primary study objective was to confirm therapeutic equivalence in terms of 
response, i.e. to compare the ORRs of MB02 and EU-approved Avastin® when they are 
administered in combination with carboplatin and paclitaxel in subjects with Stage IIIB/IV 
non-squamous NSCLC as assessed according to RECIST (version 1.1), as well as assess the 
PFS and overall survival at week 18 and at week 52 compared to Avastin®.  
MB02/Avastin® plus chemotherapy was repeated every 21 days for 6 cycles unless there is 
evidence of disease progression or intolerance of the study treatment. After 6 cycles (i.e., at the 


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start of Cycle 7), subjects can continue to receive MB02/Avastin® monotherapy treatment 
every 3 weeks until evidence of disease progression or until unacceptable toxic effects develop. 
The study ends at Week 52, after which point no further assessments of efficacy would be 
made. Subjects eligible were randomized centrally in a 1:1 manner and stratified by sex 
(male/female), 
smoking 
status 
(smoker/non-smoker), 
disease 
diagnosis 
(newly 
diagnosed/recurrent disease) and disease stage (IIIB/IV).  
1.3.1 
Pharmacokinetics 
Pharmacokinetics in Study MB02-A-02-17 
A total of 114 subjects (38 subjects in each arm) were included in the PK population.  
On Day 1, subjects received a single 3 mg/kg IV dose of the study drug. Subjects were followed 
for up to 100 days for the collection of PK samples, safety and immunogenicity assessments. 
The mean demographic parameters of age, gender, race, weight and height were well 
distributed across treatment arms and all subjects in the MB02, US-Avastin® and EU-
Avastin® treatment arms completed the study.  
Following the 90-minute IV infusion of 3 mg/kg doses of MB02, US or EU Avastin® on Day 
1, the maximum observed serum concentrations of bevacizumab were delayed, with median 
tmax occurring between 2.51 and 4 hours after the start of infusion. Several subjects 
experienced a longer delay in tmax, up to 72 hours after the start of infusion. After reaching 
Cmax, observed serum concentrations declined in a biphasic manner with a slow terminal 
elimination phase.  
The 3 mg/kg IV dose of MB02 and EU Avastin®, and the 3 mg/kg IV dose of EU and US 
Avastin® were both considered bioequivalent in terms of the AUCs and Cmax as the 90% CI 
for the geometric least square (LS) means ratios for all 3 protein-unadjusted parameters (the 
primary PK parameters [AUC0-inf and Cmax] and a secondary PK parameter [AUC0-t]) were 
fully contained within the predefined bioequivalence limits of 0.80 to 1.25, while the statistical 
comparison of 3 mg/kg IV dose of MB02 and US Avastin® was not considered to demonstrate 
bioequivalence as the 90% CI of geometric LS means ratios were not fully contained within 
the bioequivalence limits, with the upper CI exceeding the 1.25 limit for all 3 parameters.  
The certificate of testing documents showed that although the protein content of each batch of 
MB02, US- and EU-Avastin® were within the specified range, variability existed in the actual 
protein content between batches. When adjusting for protein content MB02, EU-Avastin® and 
US-Avastin® were all considered bioequivalent (i.e. the geometric LS means ratios for all 3 
protein-unadjusted parameters were fully contained within the predefined bioequivalence 
limits of 0.80 to 1.25). 
1.3.2 
Efficacy 
As part of the overall biosimilarity exercise, the clinical development programme of MB02 
was designed to demonstrate comparable clinical efficacy with the RMP and not to demonstrate 
efficacy per se.  
The data to support equivalent clinical efficacy of MB02 and the RMP is derived from the pivotal 
study MB02-C-02-17, in patients with non-squamous NSCLC. 


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Efficacy in Study MB02-C-02-17 
A total of 627 subjects were randomized to receive MB02 (315 subjects) or Avastin® (312 
subjects) and were included in the ITT set.  
Objective response (OR) was assigned to subjects if they experienced either complete response 
(CR) or partial response (PR). At Week 18, subjects were assessed by an independent radiology 
review committee (IRC) using computed tomography and/or magnetic resonance imaging 
scanning to determine the occurrence of objective response (OR, including CR or PR), 
according to RECIST v1.1 criteria. The primary endpoint, Objective Response Rate (ORR), 
was calculated as the proportion of subjects reporting an OR at study Week 18. 
At the Week 18 cut-off, the IRC assessment of OR was comparable for subjects receiving 
MB02 (OR of 40.3%; 95% CI: 34.9 to 46.0] or Avastin® (OR of 44.6%; 95% CI: 39.0 to 50.3) 
in combination with carboplatin and paclitaxel. An RR of 1.013 (90% CI: 0.957 to 1.072) was 
well within the boundaries of the similarity margin predefined by the FDA (0.73, 1.36). 
Similarly, the 95% CI of 0.947 to 1.084 was also completely contained. An RD of 0.011 (90% 
CI: -0.037% to 0.059) was also well within the similarity margin predefined by the EMA (-
12%, +12%). Again, the 95% CI was also completely contained 0.046 to 0.068). The ORR 
results were consistent with the investigator response assessments. The measures suggest that 
for the primary efficacy endpoint of ORR, the clinical efficacy of MB02 and Avastin® is highly 
similar. 
The ORR results for MB02 and Avastin® were also similar to the published data of 
bevacizumab. 
The results of the secondary efficacy endpoints were also similar between treatment groups. 
There was no significant difference in median PFS between subjects treated with MB02 (33.6 
weeks; 90% CI: 28.7 to 35.6) and those treated with Avastin® (36.3 weeks; 90% CI: 34.9 to 
39.0). Likewise, there was no significant difference in RMST estimates of OS in subjects 
treated with MB02 (17.1 weeks) and those treated with Avastin® (17.4 weeks). Importantly, 
data from 82.6% of subjects was censored (259 subjects in each group) at the Week 18 cut-off 
because the subjects were alive. 
1.3.3 
Safety 
In the studies for which safety data are currently available, studies MB02-A-02-17 (Healthy 
Volunteers), MB02-C-02-17 (non-squamous NSCLC) and BEVZ92-A-01-13 (mCRC), the 
safety profiles were within expectations for the respective study populations, concomitant 
therapies and were consistent with the labelling information for the RMP (Avastin SmPC, 
2019). 
Comparative analysis of the number of patients with particular AEs in the BEVZ92/MB02 and 
RMP treatment arms reported a similar profile of AEs in the two treatment groups in all studies. 
No new safety signals were reported for MB02 and no significant differences in the incidence 
of AEs of special interest (gastrointestinal perforations and fistulae, posterior reversible 
encephalopathy syndrome, proteinuria, wound-healing complications, hypertension, arterial 
and venous thromboembolism, congestive heart failure, haemorrhage, pulmonary 
haemorrhage, haemoptysis, neutropenia and infections, hypersensitivity reactions and 
osteonecrosis of the jaw) between BEVZ92/MB02 and RMP were observed in patients with 
mCRC and non-squamous NSCLC receiving concomitant chemotherapy. 


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Safety in Study MB02-A-02-17 
A total of 114 healthy male subjects aged between 18 and 55 years, inclusive, were randomized 
to one of 3 treatment arms in a 1:1:1 ratio (38 subjects per treatment arm). All subjects were 
included in the safety population. Single 3 mg/kg IV doses of MB02, US and EU Avastin® 
were generally well tolerated by healthy subjects in this study. There were no treatment arm-
related trends in the number of subjects who reported a TEAE, and the majority of TEAEs were 
considered unrelated or unlikely related to study drug. The most common drug-related TEAE 
reported was nausea, reported by 4 subjects (3.5%) in total. There were no apparent treatment-
related trends in mean vital signs or ECG data following dosing. A single subject, administered 
US Avastin®, reported an SAE which resolved without treatment by study completion. The 
general profile of TEAEs reported in this study was similar to that observed in previous studies. 
Safety in Study MB02-C-02-17 
A total number of 627 patients were randomized in this study, but 621 were considered within 
the Safety population (6 randomized patients did not receive any dose of study medication). 
Safety data has been obtained up to the Week 18 cut-off point, which corresponds to the 
complete treatment period of bevacizumab (MB02 or EU-Avastin®) in combination with 
carboplatin and paclitaxel chemotherapy. The majority of subjects receiving at least one dose 
of either MB02 or EU-Avastin®, in combination with carboplatin and paclitaxel, experienced 
TEAEs (571/621 subjects [91.7%]). 
There was no statistically significant difference in the number of subjects experiencing TEAEs 
in the MB02 group (287 subjects [92.3%]) compared to the EU-Avastin® group (284 subjects 
[91.6%]). Likewise, when only TEAEs considered related to study drug were considered, no 
statistically significant differences were observed in the TEAEs experienced by subjects in the 
MB02 group (116 subjects [37.3%] and the EU-Avastin® group (112 subjects [36.1%]). 
The number of subjects experiencing a TEAE leading to study drug discontinuation before 
Week 18 was also comparable between treatment groups (42 [13.5%)] subjects administered 
MB02 and 27 [8.7%] subjects administered EU-Avastin®). A total of 109 (17.6%) subjects 
experienced serious TEAEs during the study, with no statistically significant difference in 
serious TEAEs observed between the treatment groups, and for 66 (10.6%) subjects the serious 
TEAEs were considered related to study drug (33 subjects in each treatment group). 
Further, no differences in the severity of reported TEAEs between the MB02 and EU-Avastin® 
treatment groups were observed with the majority of TEAEs classified as Grade 1 or 2. 
Comparison of the frequency of subjects with Grade 3–4 TEAEs did not reveal any statistically 
significant differences. Grade 5 TEAEs were also comparable between treatment groups. The 
frequency of subjects with study drug-related Grade 3 or 4 TEAEs (10.3% vs. 10.3%) was also 
comparable between treatment groups. No clear treatment group-related trends were observed 
for study drug-related TEAEs. 
The most common TEAEs by preferred term (PT) were alopecia (51.2%) and anaemia (31.2%), 
with no clinically significant differences between treatment groups and no observable trends 
within System Organ Classes (SOCs) were reported. When only study drug-related TEAEs 
were considered anaemia (5.0%) and hypertension (4.8%) were the most frequently observed. 
Six subjects had fatal TEAEs considered related to MB02 and three subjects had fatal TEAEs 
related to EU-Avastin®. Fatal TEAEs considered related to study drug only or study drug in 
combination with carboplatin/paclitaxel included: pulmonary haemorrhage (two subjects), 


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acute kidney injury, nephrotic syndrome, haemoptysis, gastric ulcer, acute myocardial 
infarction, cardio-respiratory arrest, and pulmonary embolism (one subject each). 
No observable risk difference between treatment groups with regard to subjects reporting TEAEs 
of special interest was seen. 
Overall, the number, type, and severity of TEAEs, including those of special interest were in 
alignment with the safety profile reported in the bevacizumab Summary of Product Characteristics 
(SmPC) in this population of patients (Avastin SmPC, 2019). There were no new signals or 
observable trends reported for MB02-treated subjects. 
Safety in Study BEVZ92-A-01-13 
The safety population analysed in the bioequivalence study included 140 patients: 69 in the 
MB02 arm and 71 in the Avastin® arm. Almost all patients (96%) experienced at least one 
treatment emergent adverse event (TEAE). A total of 1258 TEAEs were reported, 605 in the 
MB02 arm of the trial. The most frequent TEAEs (with an incidence >10%) were 
gastrointestinal (GI) disorders, general disorders and administration site conditions, nervous 
system disorders, blood and lymphatic system disorders, metabolism and nutrition disorders, 
infections and infestations, and investigations. Fourteen patients had at least one TEAE leading 
to discontinuation from the study drug (8 in the MB02 arm). There was no obvious differential 
pattern relating to the type of AEs in either arm of the trial, regardless of relationship to 
treatment. 
Grade 3 or 4 TEAEs were reported at similar proportions in both arms of the study. Grade 3 
and 4 TEAEs were reported in 79 patients (40 in the MB02 arm). The distribution of Grade 3 
and 4 AEs remained relatively similar between the study arms, and the frequency of AEs 
observed appeared consistent with the known AE profile of bevacizumab and 
FOLFOX/FOLFIRI chemotherapy. 
The safety comparability exercise shows no signals of concern with regard to prior experience 
with regards to Avastin®, and no obvious differences in the safety profile in terms of nature, 
frequency and severity of the AEs reported. The safety profile for the bevacizumab biosimilar, 
MB02, was similar to the reference product, Avastin®, and was within the expectations given 
the underlying disease and concurrent use of chemotherapy. 
1.3.4 
Immunogenicity 
Comparisons of MB02 and EU-approved Avastin® immunogenicity are among the secondary 
objectives of the completed pivotal study MB02-A-02-17 and study MB02-C-02-17 (pivotal 
study in patients with non-squamous NSCLC).   
As described below, immunogenicity data is currently available from the completed pivotal 
study MB02-A-02-17 and the Primary Endpoint Analysis (through Week 18) of MB02-C-02-
17. 
Immunogenicity in Study MB02-A-02-17 
The overall incidence of immunogenicity in both the MB02 and EU-Avastin® treatment arms 
was low. The majority of positive tests for ADAs were transient and occurred at a single timepoint 
with a low titter value. A subject in the MB02 treatment arm, at study Day 28, gave a positive result 
for a treatment-induced nAb with a low titre (< 1).  


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No discernible trend or correlation between ADA status and the measured values for PK parameters 
(AUC0-inf, Cmax and CL) could be observed for either the MB02 or EU-Avastin® treatment arms. 
Likewise, those subjects who developed an ADA or nAb response did not report any treatment-
emergent adverse events (TEAEs) related to infusion reactions or any TEAEs considered 
temporally associated with the development of ADAs or nAbs. 
Immunogenicity in Study MB02-C-02-17 
Initial immunogenicity data from study MB02-C-02-17 is available from the Primary Endpoint 
Analysis and comparable immunogenicity of MB02 and EU-Avastin® was reported. 
The majority of subjects tested negative for ADAs at all timepoints (620 subjects analyzed). The 
global incidence of post-treatment ADAs through Week 18 was 16.9%, with comparable rates 
observed between treatment groups (17.4% vs. 16.5% in the MB02 and EU-Avastin® groups, 
respectively). No discernible trend or correlation between ADA status and safety or efficacy were 
seen. The presence of ADAs was apparently not associated with serious infusion-related reactions 
or anaphylactic reactions 
1.4 
Study Rationale 
This study will conduct a comparison of the PK profile of MB02-SP, MB02-DM and US 
Avastin® in healthy volunteers, fulfilling the criteria for a PK bridging study to generate clinical 
evidence to support minor changes in upstream process. 
1.5 
Benefit-risk Assessment 
Healthy male subjects in the current study will not receive any health benefit (beyond that of 
an assessment of their medical status) from participating in the study. The risks of participation 
are primarily those associated with adverse reactions to the study treatments, although there 
may also be some discomfort from collection of blood samples and other study procedures. 
More information about the known and expected benefits, risks and reasonably anticipated AEs 
associated with MB02 may be found in the IB.1 


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2 
OBJECTIVES 
2.1 
Primary Objective 
The primary objective of the study is: 
 To investigate and compare the PK profiles of MB02-SP (MB02 standard procedure), 
MB02-DM (MB02 define media) and US Avastin® (US-licenced Avastin®) to establish 
bioequivalence between the 3 study arms. 
2.2 
Secondary Objectives 
The secondary objectives of the study are: 
 Evaluation and comparison of derived PK parameters not covered by the primary 
endpoints for MB02-SP, MB02-DM and US Avastin®.  
 To compare the safety profile of MB02-SP, MB02-DM and US Avastin®. 
 To compare the immunogenicity of MB02-SP, MB02-DM and US Avastin®. 


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3 
ENDPOINTS 
3.1 
Primary Endpoints 
The PK outcome endpoints of MB02-DM, MB02-SP and US Avastin® derived from the serum 
concentration-time profile from Days 1 to 100 following IV administration are as follows: 
 area under the serum concentration‑time curve from time zero to infinity (AUC[0-∞]) 
 maximum observed serum concentration (Cmax) 
3.2 
Secondary Endpoints 
 Evaluation of all other PK parameters for MB02-SP, MB02-DM and US Avastin®, 
including 
o Time of maximum observed serum concentration (tmax) 
o AUC from time zero to the time of the last observable concentration (AUC[0-t]) 
o Clearance (CL) 
o Apparent serum terminal elimination half-life (t1/2) 
 The safety outcome measures for this study are as follows: 
o incidence and severity of AEs 
o incidence of laboratory abnormalities, based on haematology, clinical 
chemistry, and urinalysis test results 
o 12-lead electrocardiogram (ECG) parameters 
o vital sign measurements 
o physical examinations. 
  The immunogenicity of MB02-SP, MB02-DM and US Avastin®. 
o Determination of serum concentrations of anti-MB02-DM, anti-MB02-SP and 
anti-Avastin® antibodies. 


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4 
INVESTIGATIONAL PLAN 
4.1 
Study Design 
This will be a Phase 1, double-blind, randomised, parallel-group, single-dose 3-arm study to 
investigate and compare the PK, safety and immunogenicity profile of MB02-DM with MB02-
SP and US Avastin® in healthy male subjects. A total of 114 subjects will be randomised to 
one of following 3 arms in a 1:1:1 ratio: 
 Arm 1: MB02-SP as a 90-minute IV infusion 
 Arm 2: MB02-DM as a 90-minute IV infusion 
 Arm 3: US Avastin® sourced from the US, as a 90-minute IV infusion. 
Thirty-eight subjects will be dosed in each arm. Potential subjects will be screened to assess 
their eligibility to enter the trial within 30 days prior to study drug administration. 
Subjects will be admitted to the Clinical Research Unit (CRU) on Day -1 and will be confined 
to the CRU until discharge on Day 3. On Day 1, subjects will receive a single 1 mg/kg IV dose 
of the study drug. Subjects will return on Days 4, 5, 6, 7, 8, 10, 14, 21, 28, 42, 56, 78 and 100 
for non-residential visits for the collection of PK samples and safety assessments. 
Immunogenicity samples will be collected on Days -1, 14, 28, 56, and 78. 
The total duration of trial participation for each subject (from Screening through to the end of 
study visit) is anticipated to be a maximum of 19 weeks. The end of the study is defined as the 
date of the last subject’s last assessment (planned or unplanned). 
A Schedule of Assessments is presented in Appendix 1. 
4.2 
Discussion of Study Design 
The clinical PK properties of MB02 have been investigated in a previous open-label study 
conducted in metastatic colorectal cancer patients, which demonstrated that MB02 was 
bioequivalent to the RMP, Avastin®. This study aims to compare PK, immunogenicity and 
safety of MB02-DM versus MB02-SP and US Avastin® in healthy volunteers. 
A single-dose, parallel-group design was chosen for this study due to the long half-life of 
bevacizumab of approximately 20 days, and the potential of ADA response, as recommended 
in EMA guidance 2,5 The study will be double-blinded as the secondary objective of comparing 
the safety profile of MB02-DM and, MB2-SP to US Avastin® is considered subjective. The 
collection of serum samples through Day 1 to Day 100 will allow the PK parameters for MB02-
DM, MB02-SP and US Avastin® to be adequately described. 
Assessment of PK in a single-dose study in healthy volunteers is expected to be the most 
sensitive setting possible to detect differences in PK between MB02-DM, MB02-SP and US 
Avastin®. The use of healthy volunteers avoids factors that can confound the interpretation of 
PK, safety and tolerability results in patient studies, including varying tumour burden and 
complications arising from the disease state, comorbidities and concomitant therapies and 
medications. The selection of only male subjects avoids the documented influence of sex upon 
bevacizumab clearance.5 


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4.3 
Selection of Doses in the Study 
Intravenous doses were chosen for this study as this is the intended clinical route of 
administration for MB02-DM, MB02-SP and US Avastin®. Therapeutic doses in the 
prescribing instructions for Avastin® range from 5 mg/kg every 2 weeks up to 15 mg/kg every 
3 weeks. A lower dose level of 1 mg/kg for MB02-DM, MB02-SP and US Avastin® was chosen 
based upon the dosages used in previously published studies of bevacizumab PK6,7, and to 
balance considerations of safety in healthy volunteers and the need to capture the full PK 
profile. The results of the in vivo repeating dose toxicokinetic study demonstrated the similarity 
of MB02 to the RMP, with regards to the pharmacokinetic parameters, and further supported 
the safe administration of MB02 at doses <5 mg/kg in clinic. 


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5 
SELECTION OF STUDY POPULATION 
5.1 
Inclusion Criteria 
Subjects must satisfy all of the following criteria at the Screening visit unless otherwise stated: 
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. 
3. Total body weight between 50 and 95 kg, inclusive, at Screening. 
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 non-haemolytic 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 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) 
≤1.5 x 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 ≤ 4.9 mmol/L 
 High density lipoprotein cholesterol ≥ 0.85 mmol/L 
 Creatine kinase (CK) <2 × 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 as detailed in Section 7.6. 
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. 


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5.2 
Exclusion Criteria 
Subjects will be excluded from the study if they satisfy any of the following criteria at the 
Screening visit unless otherwise stated: 
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 alcohol breath test and/or urinary drug test screen 
(Appendix 3, confirmed by repeat) 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 (Appendix 3). 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). 


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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. 
Subjects may previously have been screened on a generic basis to determine their eligibility 
for inclusion in Phase 1 clinical studies conducted at the CRU. If generic Screening was 
performed within the specified study Screening window, selected study-specific procedures 
will be repeated either at an additional Screening visit or on admission to the CRU on Day -1. 
If generic Screening was performed outside the specified Screening window, all study-specific 
Screening assessments will be repeated either at an additional Screening visit or on admission 
to the CRU on Day -1. 


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5.3 
Subject Number and Identification 
After signing the ICF, subjects will be assigned a unique Subject number at Screening which 
will be used to identify subjects on all study documentation.  
Replacement subjects (Section 5.4) will be assigned a subject number corresponding to the 
number of the subject they are replacing plus 1000 (eg, Subject 1101 replaces Subject 101). 
This will be followed for all subjects, regardless of whether they are dosed or not.  
5.4 
Subject Withdrawal and Replacement 
A subject is free to withdraw from the study at any time. In addition, a subject will be 
withdrawn from dosing if any of the following criteria are met: 
 Change in compliance with any inclusion/exclusion criterion that is clinically relevant 
and affects subject safety as determined by the Investigator (or designee) 
 Noncompliance with the study restrictions that might affect subject safety or study 
assessments/objectives, as considered applicable by the Investigator (or designee) 
 Any clinically relevant sign or symptom that in the opinion of the Investigator (or 
designee) warrants subject withdrawal. 
If a subject is withdrawn from dosing, the Sponsor will be notified and the date and reason(s) 
for the withdrawal will be documented in the subject’s electronic Case Report Form (eCRF). 
If a subject is withdrawn, efforts will be made to perform all Follow-up assessments, if possible 
(Appendix 1). Other procedures may be performed at Investigator’s (or designee’s) and/or 
Sponsor’s discretion. If the subject is in-house, these procedures should be performed before 
the subject is discharged from the clinic. The Investigator (or designee) may also request that 
the subject return for an additional Follow-up Visit. All withdrawn subjects will be followed 
until resolution of all their AEs or until the unresolved AEs are judged by the Investigator (or 
designee) to have stabilised. 
Subjects who are withdrawn for nondrug related reasons may be replaced following discussion 
between the Investigator and the Sponsor. Subjects withdrawn as a result of AEs thought to be 
related to the study drug will generally not be replaced.  
5.5 
Study Termination 
The study may be discontinued at the discretion of the Investigator (or designee), Sponsor, or 
Sponsor’s Medical Monitor if any of the following criteria are met: 
 Adverse events unknown to date (ie, not previously reported in any similar 
investigational study drug trial with respect to their nature, severity, and/or duration) 
 Increased frequency and/or severity and/or duration of known, anticipated, or 
previously reported AEs (this may also apply to AEs defined at Check-in as baseline 
signs and symptoms) 
 Medical or ethical reasons affecting the continued performance of the study 
 Difficulties in the recruitment of subjects 
 Cancellation of drug development. 


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6 
STUDY TREATMENTS 
6.1 
Description, Storage, Packaging, and Labelling 
MB02 (MB02-SP and MB02-DM IV solution, 25 mg/mL), and US Avastin® (bevacizumab IV 
solution, 25 mg/mL) will be supplied by the Sponsor, along with batch/lot numbers and 
certificates of analysis. 
MB02-DM, MB02-SP and US Avastin® will be diluted to the required dose for administration 
with 100 mL of sodium chloride (9 mg/mL, 0.9%) solution for injection using aseptic 
technique.5 
6.2 
Study Treatment Administration 
Doses of MB02-DM, MB02-SP and US Avastin® will be administered as a slow IV infusion, 
(duration approximately 90 minutes). Subjects will be dosed in numerical order while supine. 
In the event of a significant infusion reaction, the infusion will be slowed or stopped, depending 
on the symptoms/signs present. 
In the event of acute hypertension (increase by >20mmHg diastolic or >160/100 mmHg if 
previously within normal limits) during the infusion, the infusion will be stopped and may be 
resumed at a slower rate if blood pressure returns to the pre-treatment range within one hour. 
If the infusion is slowed, the infusion should be completed at the slower rate, as tolerated. If 
the infusion is stopped, a single attempt to restart the infusions at a lower rate may be made 
after resolution of symptoms. Supportive care should be employed in accordance with the 
symptoms and signs. 
Any changes or stopping of infusions should be recorded in the subject’s eCRF alongside the 
AE which caused the slowing or stopping of the infusion. 
6.3 
Randomisation 
A computer generated randomization schedule will be prepared by the assigned 
biostatistician (a Syneos Health biostatistician) prior to the start of the study. The schedule 
will be generated through the statistical analysis system (SAS) software, version 9.4. 
Subjects will be randomly assigned to 1 of 3 treatment arms and stratified into 2 groups based 
on weight (≥50.0 to <72.5kg, and ≥72.5 to ≤95.0 kg respectively).  
For subjects who are replaced the replacements should take the same treatment assignment as 
the original subject to ensure that the planned treatment allocation ratio is retained. 
6.4 
Blinding 
The following controls will be employed to maintain the double blind status of the study: 
 The Investigator and other members of staff involved with the study will remain blinded 
to the treatment randomisation code during the assembly procedure. 
To maintain the blind, the Investigator will be provided with a sealed randomisation code for 
each subject, containing coded details of the treatment. These individual sealed envelopes will 


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be kept in a limited access area that is accessible 24 hours a day. If, in order to manage subject 
safety (in the event of possibly treatment related SAEs or severe AEs), the decision to unblind 
resides with the Investigator. Whenever possible, and providing it does not interfere with or 
delay any decision in the best interest of the subject, the Investigator will discuss the intended 
code-break with the Sponsor. If it becomes necessary to break the code during the study, the 
date, time and reason will be recorded in the subject's source data and on the individual 
envelope and will be witnessed by a second person. 
Where the subject experiences a suspected unexpected serious adverse reaction (SUSAR) the 
Sponsor pharmacovigilance team may be unblinded prior to notification of the relevant 
competent authorities and ethics committee in order to provide appropriate information. 
6.5 
Study Treatment Compliance 
The following measures will be employed to ensure treatment compliance: 
 All doses will be administered under the supervision of suitably qualified study site 
staff 
 At each dosing occasion, a predose and postdose inventory of MB02-DM, MB02-SP 
and US Avastin® will be performed. 
6.6 
Drug Accountability 
The Investigator (or designee) will maintain an accurate record of the receipt of the IMP and 
study drugs received. In addition, an accurate drug disposition record will be kept, specifying 
the amount dispensed to each subject and the date of dispensing. This drug accountability 
record will be available for inspection at any time. At the completion of the study, the original 
drug accountability record will be available for review by the Sponsor upon request. 
For each batch of unit doses, the empty used unit dose containers will be discarded upon 
satisfactory completion of the compliance and accountability procedures. Any unused 
assembled unit doses will be retained until completion of the study. 
At the completion of the study, retention samples allowing for 5 separate full characterisation 
assays to be performed will be retained at the Study Site, as per regulatory requirements. Any 
additional unused MB02-DM, MB02-SP and US Avastin® will be returned to the Sponsor or 
disposed of by the Study Site, per the Sponsor’s written instructions. 
7 
CONCOMITANT THERAPIES AND OTHER RESTRICTIONS 
7.1 
Concomitant Medications 
Subjects will refrain from use of any prescription and/or non-prescription medications/products 
during the study until the end of study visit, unless the Investigator (or designee) and/or 
Sponsor have given their prior consent. 
Paracetamol (up to 2 g/day for up to 3 consecutive days) is an acceptable concomitant 
medication if prescribed by the Investigator due to an AE. The administration of any other 
concomitant medications during the study is prohibited without prior approval of the 
Investigator (or designee), unless its use is deemed necessary in a medical emergency. Any 


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medication taken by a subject during the course of the study and the reason for its use will be 
documented in the source data. 
Premedication for infusions is not planned. However, if an infusion reaction occurs, appropriate 
medication may be used as determined by the Investigator. 
7.2 
Diet 
While confined at the study site, subjects will receive a standardised diet at scheduled times 
that do not conflict with other study-related activities. Subjects will be fasted overnight (at least 
8 hours) before collection of fasting blood samples for safety laboratory tests. 
On Day 1 the subjects will be fasted overnight (at least 8 hours) prior to dosing. Food will be 
allowed from 4 hours post end of infusion. In addition to this, same fasting rule applies for all 
non-residential visits. 
Caffeine-containing foods and beverages will not be allowed from 24 hours before Check-in 
until discharge and from 24 hours before non-residential visits. 
Decaffeinated tea and coffee will be available with morning and evening meals whilst resident 
at the clinic. 
Consumption of alcohol will not be permitted from 48 hours prior to Check-in and 
non-residential visits. Alcohol intake will be limited to a maximum of 2 units/day on all other 
days, whilst not in the CRU, from Screening through the final visit. 
7.3 
Smoking 
Subjects will not be permitted to use tobacco- or nicotine-containing products within 1 year 
prior to Check-in until the final visit. 
7.4 
Exercise 
Subjects are required to refrain from collision sports throughout the whole participation in the 
study and to refrain from strenuous exercise from 7 days before Check-in and 7 days before 
non-residential visits and will otherwise maintain their normal level of physical activity during 
this time (ie, will not begin a new exercise program nor participate in any unusually strenuous 
physical exertion). 
7.5 
Blood Donation 
Subjects are required to refrain from donation of blood from 90 days prior to Screening, plasma 
from 14 days prior to Screening, or platelets from 42 days prior to Screening until 90 days after 
the final visit. 
7.6 
Contraception 
Subjects with partners of childbearing potential must use a male barrier method of 
contraception (ie, male condom) in addition to a second method of acceptable contraception. 
The acceptable methods of contraception include: 


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 Intrauterine device (IUD; eg, Mirena) 
 Established use of oral, implanted, transdermal, or hormonal method of contraception 
associated with inhibition of ovulation 
 Male sterilisation, with verbal confirmation of surgical success 
 Bilateral tubal ligation 
 Established use of progesterone only oral contraception, where inhibition of ovulation 
is not the primary mode of action 
 Diaphragm, cap, or sponge in conjunction with spermicide. 
Subjects who practice true abstinence, because of the subject’s lifestyle choice (ie, the subject 
should not become abstinent just for the purpose of study participation) are exempt from 
contraceptive requirements. Periodic abstinence (eg, calendar, ovulation, symptothermal, 
postovulation methods) and withdrawal are not acceptable methods of contraception. If a 
subject who is abstinent at the time of signing the ICF becomes sexually active they must agree 
to use contraception as described above. 
Sexual intercourse with female partners who are pregnant or breastfeeding should be avoided 
unless condoms are used from the time of dosing until 120 days after dosing. Male subjects are 
required to refrain from donation of sperm from Check-in until 120 days after the dose of study 
drug. 
For subjects who are exclusively in same sex relationships, a barrier method of contraception 
(ie male condom) should be used from the time of dosing until 120 days after dosing. 


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8 
STUDY ASSESSMENTS AND PROCEDURES 
Every effort will be made to schedule and perform the procedures as closely as possible to the 
nominal time, giving considerations to appropriate posture conditions, practical restrictions, 
and the other procedures to be performed at the same timepoint. 
The order of priority for scheduling procedures around a timepoint is (in descending order of 
priority): 
 
Dosing 
 
Blood samples 
 
Any other procedures (ECGs will be scheduled before vital sign measurements). 
8.1 
Pharmacokinetic Assessments 
8.1.1 
Pharmacokinetic Blood Sample Collection and Processing 
Blood samples (approximately 1 x 3.5 mL for bevacizumab) will be collected by venepuncture 
or cannulation at the times indicated in the Schedule of Assessments in Appendix 1. Procedures 
for collection, processing, and shipping of PK samples will be detailed in a separate document. 
8.1.2 
Analytical Methodology 
Serum concentrations of bevacizumab will be determined using a validated analytical 
procedure. Specifics of the analytical method will be provided in a separate document. 
8.2 
Immunogenicity Assessments 
8.2.1 
Immunogenicity Blood Sample Collection and Processing 
Blood samples (approximately 1 x 3.5 mL for ADA and 1 x 3.5 mL for NAB) will be collected 
by venepuncture or cannulation at the times indicated in the Schedule of Assessment in 
Appendix 1. Procedures for cannulation, processing and shipping of immunogenicity samples 
will be detailed in a separate document. 
8.2.2 
Analytical Methodology 
Serum concentrations of anti-MB02-DM, anti-MB02-SP and anti-Avastin® antibodies will be 
determined using a validated analytical procedure. Specifics of the analytical method will be 
provided in a separate document. 
8.3 
Safety and Tolerability Assessments 
8.3.1 
Adverse Events 
Adverse event definitions, assignment of severity and causality, and procedures for reporting 
SAEs are detailed in Appendix 2. 


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The condition of each subject will be monitored from time of signing the ICF to final discharge 
from the study. In addition, subjects will be observed for any signs or symptoms and asked 
about their condition by open questioning, such as “How have you been feeling since you were 
last asked?”, at least once each day while resident at the study site and at each study visit. 
Subjects will also be encouraged to spontaneously report AEs occurring at any other time 
during the study. 
Any AEs and remedial action required will be recorded in the subject’s source data. The nature, 
time of onset, duration, and severity will be documented, together with an Investigator’s (or 
designee’s) opinion of the relationship to drug administration. 
Adverse events recorded during the course of the study will be followed up, where possible, 
until resolution. This will be completed at the Investigator’s (or designee’s) discretion. 
8.3.2 
Clinical Laboratory Evaluations 
Blood and urine samples will be collected for clinical laboratory evaluations (including clinical 
chemistry, haematology, urinalysis, coagulation, and serology) at the times indicated in the 
Schedule of Assessments in Appendix 1. Clinical laboratory evaluations are listed in 
Appendix 3. 
Subjects will be asked to provide urine samples for a drugs of abuse screen, cotinine test, and 
undergo an alcohol breath test at the times indicated in the Schedule of Assessments in 
Appendix 1. An Investigator (or designee) will perform a clinical assessment of all clinical 
laboratory data. 
8.3.3 
Vital Signs 
Supine blood pressure, supine pulse rate, respiratory rate, aural body temperature and pulse 
oximetry will be assessed at the times indicated in the Schedule of Assessments in Appendix 1. 
Vital signs may also be performed at other times if judged to be clinically appropriate or if the 
ongoing review of the data suggests a more detailed assessment of vital signs is required. 
All measurements will be performed singly and repeated once if outside the relevant clinical 
reference range. 
Subjects must be supine for at least 5 minutes before blood pressure and pulse rate 
measurements. 
8.3.4 
12-Lead Electrocardiogram 
Resting 12-lead ECGs will be recorded after the subject has been supine and at rest for at least 
5 minutes at the times indicated in the Schedule of Assessments in Appendix 1. Single 12-lead 
ECGs will be repeated once if either of the following criteria apply: 
 QT interval corrected for heart rate using Fridericia’s method (QTcF) > 500 msec 
 QTcF change from the baseline (predose) is > 60 msec. 
Additional 12-lead ECGs may be performed at other times if judged to be clinically appropriate 
or if the ongoing review of the data suggests a more detailed assessment of ECGs is required. 
The Investigator (or designee) will perform a clinical assessment of each 12-lead ECG. 


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8.3.5 
Physical Examination 
A full physical examination or symptom-directed physical examination will be performed at 
the timepoints specified in the Schedule of Assessments in Appendix 1. 


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9 
SAMPLE SIZE AND DATA ANALYSES 
A detailed statistical analysis plan (SAP) describing full details of the planned analyses will be 
issued to the Sponsor for review and will be finalised prior to database lock. The following 
analyses represent an outline of the planned methodology. 
9.1 
Determination of Sample Size 
Up to 114 subjects will be enrolled in order that 108 complete the study. 
A sample size of 36 subjects per arm (108 subjects in total) will provide at least 90% power 
for all the pairwise comparisons for primary endpoints (AUC and Cmax) using a percent 
coefficient of variation (CV%) of 25% in both PK parameters for the similarity objective if the 
true ratio is equal to 1.05 or less. 
A conservative estimate of CV% was based on a prior MB02 study 8 and information from the 
public domain 9. Model-based simulations from a developed population PK literature model, 
accounting for similarity between bevacizumab sources (EU/US), intrinsic PK altering factors 
(body weight, sex, serum albumin and alkaline phosphatase), between subject variability and 
residual variability, showed that a sample size of 90 subjects provided at least 90% probability 
of concluding PK similarity for the all pairwise comparisons in terms of Cmax and AUC(0–∞). 
Simulations also showed that the probability of concluding PK similarity in terms of AUC(0-t) 
is almost the same as AUC(0–∞) 
A maximum of 5% loss of data due to premature discontinuation is expected therefore, the 
sample size is increased to 114 subjects in total, with 38 subjects per arm. 
9.2 
Analysis Populations 
9.2.1 
Pharmacokinetic Population 
The PK population will include all subjects who received the full dose of MB02-DM, MB02-
SP or US Avastin®, did not have any major protocol deviations, and have evaluable PK data 
for at least one timepoint. 
Further details of subjects considered for exclusion from the PK population will be provided 
in the SAP, detailing major deviations (for statistical analyses) prior to database lock. 
9.2.2 
Safety Population 
The safety population will include all subjects exposed to MB02-DM, MB-SP or US Avastin®, 
and have at least 1 post dose safety assessment. 
9.3 
Pharmacokinetic Analyses 
The primary PK parameter endpoints are Cmax and AUC0-∞ for bevacizumab. The secondary 
PK endpoints will include all other PK parameters for bevacizumab, including tmax, t1/2, CL and 
AUC(0-t). 


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The serum PK parameters of bevacizumab will be calculated using standard noncompartmental 
methods. An analysis of covariance model will be used to analyse the log-transformed primary 
PK parameters (AUC[0-∞] and Cmax) and AUC(0-t). The model will include a fixed effect for 
treatment and body weight as a covariate. 
All other PK parameters will not be subject to inferential statistical analysis. 
Estimates of geometric mean ratios together with the corresponding 90% confidence intervals 
(CI) will be derived for the comparisons of the PK parameters as follows: 
 MB02-SP versus MB02-DM 
 MB02-SP versus US Avastin® 
 MB02-DM versus US Avastin® 
PK similarity will be achieved if the 90% CIs for the biosimilar-to-reference ratios of PK 
endpoints (AUC[0–∞] and Cmax) fall within the predefined 0.80–1.25 acceptance similarity 
criteria for all 3 pairwise comparisons; MB02-SP versus MB02-DM; MB02-SP versus US 
Avastin®; and MB02-DM versus US Avastin®. 
9.4 
Safety Analysis 
All AEs will be listed and summarised using descriptive methodology. All observed or patient-
reported AEs will be graded by the National Cancer Institute Common Terminology Criteria 
for Adverse Events version 5.0. The incidence of AEs for each treatment will be presented by 
severity and by association with the study drugs as determined by the Investigator (or 
designee). Each AE will be coded using the Medical Dictionary for Regulatory Activities. All 
safety data will be listed and summarised as appropriate. 
Immunogenicity data (overall ADA incidence and titters, and neutralising ADA results) will 
be listed. A summary of the number and percent of subjects testing positive for ADA or 
neutralising antibodies before the dose of MB02-SP, MB02-DM, or US Avastin® (Day -1) and 
at scheduled post dose assessments will be presented by treatment arm. All safety data and 
immunogenicity data summaries will be based on the safety analysis population. Select 
analyses may be repeated for subsets with or without ADA and de novo ADA formation as 
appropriate. 
9.4.1 
Medical Safety Monitoring 
It is the responsibility of the Investigator to oversee the safety of the subject at the clinical site. 
This safety monitoring will include careful assessment and appropriate reporting of AEs as 
noted above. 
A safety review committee comprising at minimum the Principal Investigator and Sponsor 
Medical Contact will review all available safety data monthly, or more frequently if indicated. 
In advance of each meeting, Syneos Health will prepare blinded tables/listings based on a 
snapshot of data available in the eCRFs, including those for subject status, AEs, and laboratory 
results. 


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9.5 
Interim Analysis 
No interim analyses are planned for this study. 


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10 
QUALITY CONTROL AND QUALITY ASSURANCE 
10.1 
Auditing 
Quality control and quality assurance will be performed according to Syneos Health standard 
operating procedures (SOPs) or per Sponsor request and as applicable according to the contract 
between Syneos Health and the Sponsor. 
The study may be audited or reviewed by an independent quality assurance department, Ethics 
Committee (EC), and/or regulatory authority at any time. The Investigator will be given notice 
before an audit occurs. The study site will permit study-related monitoring, audits, EC review, 
and regulatory inspections by providing direct access to source data/documents. 
Measures will be undertaken to protect the confidentiality of records that could identify 
subjects, respecting the privacy and confidentiality rules in accordance with applicable 
regulatory requirements. 
10.2 
Monitoring 
Syneos Health will designate a Blinded Study Monitor and an Unblinded Study Monitorwho 
will be responsible for monitoring this clinical study. The Study Monitor will monitor the study 
conduct, eCRF and source documentation completion and retention, and accurate study drug 
accountability. To this end, the Study Monitor will visit the study site at suitable intervals and 
be in frequent contact through verbal and written communication. It is essential that the Study 
Monitor has access to all documents, related to the study and the individual participants, at any 
time these are requested. In turn, the Study Monitor will adhere to all requirements for subject 
confidentiality as outlined in the ICF. The Investigator and Investigator’s staff will be expected 
to cooperate with the Study Monitor, to be available during a portion of the monitoring visit to 
answer questions, and to provide any missing information. 


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11 
DATA HANDLING AND RECORD KEEPING 
11.1 
Data Handling 
Syneos Health will be responsible for data management of this study, including quality 
checking of the data. The study site will be responsible for data entry into the electronic data 
capture (EDC) system. A comprehensive validation check program will verify the data. 
Discrepancies will be generated automatically in the system at the point of entry or added 
manually for resolution by the study site staff. 
Syneos Health will produce a Data Management Plan that describes the quality checking to be 
performed on the data. Laboratory data and other electronic data will be sent directly to Syneos 
Health, using Syneos Health standard procedures to handle and process the electronic transfer 
of these data. 
11.2 
Case Report Form 
Data from all parts of the trial will be captured on source paper or electronic data documents 
and then entered into the EDC system by staff at the trial site. Following data entry, the eCRF 
pages and the data entry will undergo quality control checks in accordance with Syneos Health 
procedures. Any discrepancies will be resolved in the database. 
Following all data validation steps, the Principal Investigator (or designee) will electronically 
sign the completed electronic data prior to database lock. 
11.3 
Records 
Records and documents, including signed ICF, pertaining to the conduct of this study must be 
retained in the study site archive for at least 15 years after the end of the study. No records may 
be destroyed during the retention period without the written approval of the Sponsor. No 
records may be transferred to another location or party without written notification to the 
Sponsor. 


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12 
ETHICAL AND REGULATORY CONSIDERATIONS 
12.1 
Ethics Committee 
Prior to the start of the study, the following documents will be reviewed and approved by the 
appropriate EC: 
 Protocol 
 ICF 
The EC will be informed by the Investigator (or designee) of any changes to the approved 
protocol. 
The EC must provide written approval of any substantial protocol amendments likely to affect 
the safety of the subjects or the conduct of the study. The EC must be notified of non substantial 
protocol amendments. 
The EC will be informed by the Investigator (or designee) of serious and unexpected AEs. The 
Investigator will provide the EC with progress reports at least annually and a report following 
completion, termination, or discontinuation of the Investigator’s participation in the study. 
12.2 
Regulatory Considerations 
The study will be conducted in accordance with the protocol and with: 
 Consensus ethical principles derived from international ethics guidelines, including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences Ethical Guidelines 
 International Conference on Harmonisation (ICH) E6 Guideline for Good Clinical 
Practice 
 Applicable local laws and regulations. 
The Investigator will be responsible for the overall conduct at the study site and adherence to 
the requirements of the ICH guidelines and all other applicable local regulations. 
12.3 
Informed Consent 
Prior to starting participation in the study, each subject will be provided with a most updated 
version of study-specific ICF giving details of the study drugs, procedures, and potential risks 
of the study. Subjects will be instructed that they are free to obtain further information from 
the Investigator (or designee) and that their participation is voluntary and they are free to 
withdraw from the study at any time. 
Following discussion of the study with CRU personnel, subjects will sign one original of the 
ICF in the presence of a suitably trained member of staff to indicate that they are freely giving 
their informed consent. A copy will be given to the subject, and the original will be maintained 
in the subject’s records. 


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12.4 
Subject Confidentiality 
The results from Screening and data collected during the study will be recorded in the subject’s 
eCRF. To maintain confidentiality, the subjects will be identified only by a unique subject 
identification number. 
Subject medical information obtained by this study is confidential and may only be disclosed 
to third parties as permitted by the ICF signed by the subject, unless permitted or required by 
law. 
12.5 
Protocol Amendments 
Substantial protocol amendments will be submitted to the EC and to regulatory authorities in 
accordance with local regulatory requirements. Approval must be obtained from the EC and 
regulatory authorities (as locally required) before implementation of any changes, except for 
changes necessary to eliminate an immediate hazard to subjects or any non substantial changes, 
as defined by regulatory requirements. 


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13 
ADMINISTRATIVE ASPECTS 
13.1 
Disclosure 
All information provided regarding the study, as well as all information collected and/or 
documented during the course of the study, will be regarded as confidential. The Investigator 
(or designee) agrees not to disclose such information in any way without prior written 
permission from the Sponsor. 
13.2 
Reports and Publications 
Any publication of the results, either in part or in total (eg, articles in journals or newspapers, 
oral presentations, abstracts) by the Investigator or their representative, shall require prior 
notification and review, within a reasonable time frame, by the Sponsor, and cannot be made 
in violation of the Sponsor’s confidentiality restrictions or to the detriment of the Sponsor’s 
intellectual property. 
13.3 
Finances and Insurance 
Financing and insurance will be addressed in a separate agreement. 


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14 
REFERENCES 
1. MB02– Investigator’s Brochure. (Version 9.0, 19 May 2020) 
2. EMA Guideline on similar biological medicinal products containing biotechnology-derived 
proteins as active substance: clinical and nonclinical issues, CHMP/BMWP/42832/2005 
Rev1 of 18 December 2014 (effective 1 July 2015) 
3. Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference 
Product. US Dept of Health and Human Services; Food and Drug Administration; Centre 
for Drug Evaluation and Research (CDER); Center for Biologics Evaluation and Research 
(CBER). December 2016. 
4. EMA Guideline on similar biological medicinal products. CHMP/437/04 Rev 1 of 
23 October 2014 (effective 30 April 2015). 
5. Genentech 
Inc 
(2016) 
Avastin® 
(bevacizumab) 
prescribing 
information. 
http://www.gene.com/download/pdf/avastin_prescribing.pdf. Accessed 29 June 2017. 
6. Willem Hettema et. al. A randomised, single-blind, Phase I trial (INVICTAN-1) assessing 
the bioequivalence and safety of BI 695502, a bevacizumab biosimilar candidate, in healthy 
subjects. Expert Opin Investig Drugs. 2017, Aug;26(8):889-896 
7. N Tajima et. al. A phase 1 study comparing the proposed biosimilar BS-503a with 
bevacizumab in healthy male volunteers. Pharmacol Res Perspect. 2017, 20;5(2):e00286. 
8. mAbxience; Bioequivalence Study Bevacizumab Biosimilar (BEVZ92) Versus 
Bevacizumab (AVASTIN®) in First-line Treatment mCRC Patients (MB02-A-01-13). 
mAbxience SA, Madrid, Spain. 
9. Beverly Knight, Danielle Rassam, Shanmei Liao, Reginald Ewesuedo. A phase I 
pharmacokinetics study comparing PF-06439535 (a potential biosimilar) with 
bevacizumab in healthy male volunteers. Cancer Chemother Pharmacol. 2016; 77: 839–
846. 
 
 


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15 
APPENDICES 
 


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Appendix 1: Schedule of Assessments 


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Screening 
(Day -30 
to -1) 
Day 
-1 
1 
2 
3 
4 
(±1) 
5 
(±1) 
6 
(±1) 
7 
(±1) 
8 
(±1) 
10 
(±1) 
14 
(±1) 
21 
(±1) 
28 
(±1) 
42 
(±1) 
56 
(±1) 
78 
(±1) 
100/ 
EOS 
(±1) 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic data 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urinary drug screen 
and cotinine test 
Xa 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alcohol breath test 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height and body 
weightb 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study residency: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomisation 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check-in 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check-out 
 
 
 
 
X 
 
 
 
 
  
 
 
 
 
 
 
 
 
Non-residential visitg 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study drug 
administration: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MB02 or Avastin® 
 
 
Day 1 (0 h) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pharmacokinetics: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood samplinge 
 
 
Predose, 
EOIf, 2, 3, 
4, 5, 6, 8, 
12 h 
24 h 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling 
 
Xg 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 
X 
 
Safety and 
tolerability: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event 
recording 
X 
X 
Ongoing 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serious adverse event 
recording 
X 
X 
Ongoing 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Prior/concomitant 
medication monitoring 
X 
X 
Ongoing 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


Protocol 
CONFIDENTIAL 
Syneos Health Study: 7012755 
Sponsor Reference: MB02-A-06-20 
Version 1.0, 26 May 2020 
Page 47 of 54 
 
Screening 
(Day -30 
to -1) 
Day 
-1 
1 
2 
3 
4 
(±1) 
5 
(±1) 
6 
(±1) 
7 
(±1) 
8 
(±1) 
10 
(±1) 
14 
(±1) 
21 
(±1) 
28 
(±1) 
42 
(±1) 
56 
(±1) 
78 
(±1) 
100/ 
EOS 
(±1) 
Clinical laboratory 
evaluations 
X 
X 
 
 
X 
 
 
 
 
X 
 
X 
X  
X 
X 
X 
X 
X 
Supine blood pressure, 
pulse rate, respiratory 
ratee 
X 
X 
Predose, 
0.5, 1, 
EOIf, 2h 
X 
 
 
X 
 
 
X 
X 
 
X 
 
 
 
 
X 
Pulse oximetry 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aural body temperature 
X 
 
 
X 
 
 
 
 
 
 
X 
 
X 
 
 
 
 
X 
12-lead ECG 
X 
X 
 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
Physical examination 
Xc 
Xd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xd 
Abbreviations: ECG = electrocardiogram  
a. To be performed during screening period, from Day -3 to Day -1. This procedure may be done in-house, if positive result, this should be repeated at local laboratory. 
b. Height measured at Screening only 
c. Can be performed between the Screening visit and predose assessments 
d. Symptom-directed physical examination 
e. All times stated are post-start of infusion. 
f. EOI: End of infusion. 
g The following windows are allowed: 
Procedure 
Time Point 
Tolerance Window 
Notes 
PK (Blood Samples) 
Predose  
- 10 min to 0 h 
 
1,5h post* 
- 0 / + 5 min 
Immediately after the end of Infusion 
2h post 
±5 min 
 
3h – 6h post 
±10 min 
 
8h – 24h post 
±20 min 
 
Day 3, 4, 5, 6, 7, 8 
±30 min 
 
Day 10, 14, 21, 28, 42, 56, 78, 100 
±1440 min 
 
Immunogenicity (Blood Samples) 
Day -1  
Day -1 to 0 h 
 
Day 14, 28, 56, 78 
±1440 min 
 
 Clinical Safety Laboratory Sampling 
Day 14, 21, 28, 42, 56, 78, 100 
±1440 min 
 
Supine blood pressure, pulse rate, 
respiratory rate 
Predose  
-90 min to 0 h 
 
30min – 2h post 
±10 min 
Except 1.5h post 
1.5h post * 
-0 / +10 min 
After the end of Infusion 
Day 2, 5, 8 
±30 min 
 
Day 10, 21, 100 
±1440 min 
 


Protocol 
CONFIDENTIAL 
Syneos Health Study: 7012755 
Sponsor Reference: MB02-A-06-20 
Version 1.0, 26 May 2020 
Page 48 of 54 
Procedure 
Time Point 
Tolerance Window 
Notes 
Aural body temperature 
Screening 
Normally done during the visit - no 
windows needed 
 
Day 2 
±30 min 
 
Day 10, 21, 100 
±1440 min 
 
12-lead ECG 
Screening 
Normally done during the visit - no 
windows needed 
 
Day -1 
Day -1 to 0 h 
 
Day 3, 8 
±30 min 
 
Day 100 
±1440 min 
 
IV infusion time 
Day 1 
No window allowed 
 
 


Protocol 
CONFIDENTIAL 
Syneos Health Study: 7012755 
Sponsor Reference: MB02-A-06-20 
Version 1.0, 26 May 2020 
Page 49 of 54 
Appendix 2: Adverse Event Reporting 
Adverse Events 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product, which does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavourable and/or unintended sign 
(including an abnormal laboratory finding), symptom or disease temporally associated with the 
use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product. 
The causal relationship between an AE and the study drug will be defined as below: 
 Not Related: when the AE is definitely caused by the subject’s clinical state, or the 
study procedure/conditions 
 Unlikely Related: when the temporal association between the AE and the drug is such 
that the drug is not likely to have any reasonable association with the AE 
 Possibly Related: when the AE follows a reasonable temporal sequence from the time 
of drug administration but could have been produced by the subject’s clinical state or 
the study procedures/conditions 
 Probably Related: when the AE has a reasonable time relationship to study drug 
administration and is unlikely to be attributed to concurrent disease or other drugs or 
chemicals 
 Related: when the AE follows a reasonable temporal sequence from administration of 
the drug, abates upon discontinuation of the drug, follows a known or hypothesised 
cause-effect relationship, and (if appropriate) reappears when the drug is reintroduced 
The severity of an AE or SAE will be recorded in the eCRF following the National Cancer 
Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, outlined 
below: 
 Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated 
  Grade 2 Moderate; minimal, local or non-invasive intervention indicated; limiting age-
appropriate instrumental activities of daily living 
  Grade 3 Severe or medically significant but not immediately life-threatening; 
hospitalisation or prolongation of hospitalisation indicated; disabling; limiting self-care 
activities of daily living 
  Grade 4 Life-threatening consequences; urgent intervention indicated 
  Grade 5 Death related to AE 
An AE that is assessed as severe (CTCAE Grade 3 or higher) should not be confused with a 
SAE. Severity is a category utilised for rating the intensity of an event; both AEs and SAEs 
can be assessed as severe. An event is defined as ‘serious’ when it meets one of the predefined 
outcomes, as described in the section “Serious Adverse Events”, outlined below. 
Every reasonable effort will be made to follow-up subjects who have AEs. Any subject who 
has an ongoing AE at the final visit will be followed up, where possible, until resolution or 


Protocol 
CONFIDENTIAL 
Syneos Health Study: 7012755 
Sponsor Reference: MB02-A-06-20 
Version 1.0, 26 May 2020 
Page 50 of 54 
until, in the opinion of the Investigator, the event is stabilised or determined to be chronic. 
Details of AE follow-up or resolution must be documented in the eCRF. This will be completed 
at the Investigator’s (or designee’s) discretion. 
Adverse Drug Reactions 
All noxious and unintended responses to an IMP (ie, where a causal relationship between an 
IMP and an AE is at least a reasonable possibility) related to any dose should be considered 
adverse drug reactions. 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or severity 
of which is not consistent with the applicable product information (eg, Investigator’s Brochure 
for an unapproved IMP). 
Follow-up of adverse events 
All investigators should follow-up subjects with AEs until the event is resolved or until, in the 
opinion of the Investigator, the event is stabilised or determined to be chronic. Details of AE 
follow-up or resolution must be documented in the eCRF. 
Subjects should be followed up until final discharge from the study, and any AEs that occur 
during this time should be reported according to the procedures outlined below. 
All subjects with unresolved AEs at the end of the study, except those who dropped out before 
randomisation or starting active treatment, must be included in a safety follow-up visit to check 
response of AEs. 
Follow-up can be waived in specific cases after consultation with the Sponsor. This permission 
must be documented per case and retained in the Sponsor File. 
Documentation and reporting of adverse events  
Adverse events should be reported and documented in accordance with the procedures outlined 
below; AEs will be recorded in the eCRF from the signing of the informed consent form (ICF) 
until final discharge from the study. The following data should be documented for each AE: 
 Description of the symptom event 
 Classification as ‘serious’ or ‘not serious’ 
 Severity 
 Date of first occurrence and date of resolution (if applicable) 
 Action taken 
 Causal relationship 
 Outcome of event (unknown, recovered, recovering, not yet recovered, recovered with 
sequelae, death [with date and cause reported]). 
 
Serious Adverse Events 
A serious AE (SAE) is defined as any untoward medical occurrence that at any dose either: 
 Results in death 
 Is life-threatening 


Protocol 
CONFIDENTIAL 
Syneos Health Study: 7012755 
Sponsor Reference: MB02-A-06-20 
Version 1.0, 26 May 2020 
Page 51 of 54 
 Requires inpatient hospitalisation or prolongation of existing hospitalisation 
 Results in persistent or significant disability/incapacity (disability is defined as a 
substantial disruption of a person’s ability to conduct normal life functions) 
 Is a congenital anomaly/birth defect. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalisation may be considered SAEs when, based upon appropriate medical judgement, 
they may jeopardise the patient or subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. These events should be collected in the 
eCRF under the seriousness criteria “Important Medical Event”. 
Instances of death or congenital abnormality, if brought to the attention of the Investigator at 
any time after cessation of the study treatment and considered by the Investigator to be possibly 
related to the study treatment, will be reported to the Sponsor. 
Definition of Life-threatening 
An AE is life-threatening if the subject was at immediate risk of death from the event as it 
occurred (ie, does not include a reaction that might have caused death if it had occurred in a 
more serious form). For instance, drug-induced hepatitis that resolved without evidence of 
hepatic failure would not be considered life-threatening even though drug-induced hepatitis 
can be fatal. 
Definition of Hospitalisation 
Adverse events requiring hospitalisation should be considered serious. In general, 
hospitalisation signifies that the subject has been detained (usually involving an overnight stay) 
at the hospital or emergency ward for observation and/or treatment which would not have been 
appropriate at the CRU. When in doubt as to whether hospitalisation occurred or was necessary, 
the AE should be considered as serious. 
Hospitalisation for elective surgery or routine clinical procedures, which are not the result of 
an AE, need not be considered AEs and should be recorded on a Clinical Assessment Form and 
added to the electronic Case Report Form. If anything untoward is reported during the 
procedure, this must be reported as an AE and either ‘serious’ or ‘nonserious’ attributed 
according to the usual criteria. 
Serious Adverse Event Reporting 
The Investigator will complete an SAE report form and forward it by facsimile to the Sponsor 
Safety Department immediately (no more than 24 hours) after becoming aware of an SAE. Full 
details for SAE reporting and contact information can be found in the Site Safety Instruction. 
All serious adverse reactions will be considered as SUSARs and will follow the expedited 
SUSAR reporting process described below. The Investigator should not wait to receive 
additional information to fully document the event before notification of a SAE, though 
additional information may be requested. Where applicable, information from relevant 
laboratory results, hospital case records, and autopsy reports should be obtained. 
Instances of death, congenital abnormality, or an event that is of such clinical concern as to 
influence the overall assessment of safety, if brought to the attention of the Investigator at any 
time after cessation of study drug administration and linked by the Investigator to this study, 
should be reported to the Safety department within 24 hours. 


Protocol 
CONFIDENTIAL 
Syneos Health Study: 7012755 
Sponsor Reference: MB02-A-06-20 
Version 1.0, 26 May 2020 
Page 52 of 54 
Other events subject to immediate notification (within 24 hours), include but are not limited 
to: 
 Pregnancy of female partner of a study subject 
 Infusion site reaction (grade 3 according to the CTCAE and higher or classified as serious 
to be reported) 
 Medication errors, namely overdose, leading to a suspected adverse reaction. 
 
Follow-up of serious adverse events 
All SAEs will be followed clinically until they are resolved or until a stable situation has been 
reached. Depending on the event, follow-up may require additional tests or medical procedures 
as indicated, and/or referral to a medical specialist. Follow-up information on SAEs should be 
reported until recovery or until a stable situation has been reached. 
The final outcome of the SAE should be reported in a final SAE report. 
Reporting of pregnancy 
Pregnancies of the female partner of a male subject should be reported to the Sponsor’s Safety 
Department. Pregnancies must be reported to pharmacovigilance by email/fax within 24 hours 
after the event was known to the Investigator, using the pregnancy report form. 
The Investigator is encouraged to provide outcome information of the pregnancy of the female 
partner of a male subject, if this information is available to the Investigator and the female 
partner gives her permission. If the outcome of the pregnancy meets the criteria for immediate 
classification as an SAE (ie, spontaneous or therapeutic abortion, stillbirth, neonatal death, or 
congenital anomaly - including that in an aborted fetus), the Investigator should follow the 
procedures for reporting SAEs. In the case of a live “normal” birth, the Sponsor should be 
informed as soon as the information is available. All neonatal deaths that occur within 30 days 
of birth should be reported, without regard to causality, as SAEs. 
In addition, any infant death after 30 days from birth that the Investigator suspects to be related 
to in utero exposure to the investigational medicinal product(s) should also be reported. 
 
Unexpected Adverse Reaction Definition 
An unexpected adverse reaction is any untoward and unintended response that is related to the 
administration of the study drug at any dose that is not consistent with the applicable product 
information (eg, Investigators Brochure for an unauthorised investigational medicinal product 
or summary of product characteristics for an authorised product). 
All SUSARs will be the subject of expedited reporting. The Sponsor and/or delegate shall 
ensure that all relevant information about a SUSAR that is fatal or life-threatening is reported 
to the relevant competent authorities and EC within 7 days after knowledge by the Sponsor of 
such a case and that relevant follow-up information is communicated within an additional 8 
days. All other SUSARs will be reported to the relevant competent authorities and EC within 
15 days after knowledge by the Sponsor of such a case. All Investigators should follow-up 
SUSARs until the events are resolved or until, in the opinion of the Investigator, the events are 
stabilised or determined to be chronic. 
 
 


Protocol 
CONFIDENTIAL 
Syneos Health Study: 7012755 
Sponsor Reference: MB02-A-06-20 
Version 1.0, 26 May 2020 
Page 53 of 54 
Appendix 3: Clinical Laboratory Evaluations 
Clinical chemistry: 
Haematology: 
Urinalysis: 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Aspartate aminotransferase 
Calcium 
Chloride 
Total cholesterol 
HDL cholesterol 
LDL cholesterol 
Creatinine 
Creatine kinase 
Gamma-glutamyl transferase 
Lactate dehydrogenase 
Glucose 
Inorganic phosphate 
Potassium 
Sodium 
Total bilirubin 
Direct bilirubin 
Total protein 
Triglycerides 
Urea 
Uric acid 
Haematocrit 
Haemoglobin 
Mean cell haemoglobin 
Mean 
cell 
haemoglobin 
concentration 
Mean cell volume 
Platelet count 
Red blood cell (RBC) count 
White blood cell (WBC) count 
WBC differential: 
Basophils 
Eosinophils 
Lymphocytes 
Monocytes 
Neutrophils 
 
Blood 
Glucose 
Ketones 
pH 
Protein 
Specific gravity 
Urobilinogen 
Microscopic 
examinationc  
Serologya: 
Urinary drug screenb: 
Coagulation 
Hepatitis B surface antigen 
Hepatitis B surface antibody 
(anti-HBs) 
Hepatitis 
B 
core 
antibody 
(anti HBc) 
Hepatitis C antibody 
Human immunodeficiency (HIV-
1 and HIV-2) antibodies 
 
Including but not limited to: 
Cotinine 
Amphetamines/methamphetamines 
Barbiturates 
Benzodiazepines 
Cocaine (metabolite) 
Methadone 
Phencyclidine 
Opiates 
Tetrahydrocannabinol/cannabinoids 
International normalised 
ratio 
Prothrombin time 
Activated 
partial 
thromboplastin time 
Alcohol breath test 
 
 
a Only analysed at Screening. The following tests should be performed: Hepatitis B surface antigen (HbsAg) and 
Hepatitis B core antibody (anti HBc). If both negatives, no further tests are required. If Hepatitis B surface antigen 
(-) and Hepatitis B core antibody (+) then Hepatitis B surface antibody (anti HBs) should be performed. 
b Only analysed at Screening and Check-in. 
c Upon a positive urine test from leucocytes, blood, nitrite or protein, the Investigator may require further urine 
analysis, such as flow cytometry. Results of additional urine analyses will be included in the database. If the flow 
cytometry examination shows a different result than the urine sticks, the urine will be investigated by fully 
automated digital imaging where leukocytes, erythrocytes, casts in urine will be analyzed. 


Protocol 
CONFIDENTIAL 
Syneos Health Study: 7012755 
Sponsor Reference: MB02-A-06-20 
Version 1.0, 26 May 2020 
Page 54 of 54 
Appendix 4: Total Blood Volume 
The following blood volumes will be withdrawn for each subject. 
 
Volume per blood 
sample (mL) 
Maximum number of 
blood samples 
Total 
amount 
of 
blood (mL) 
Clinical laboratory 
evaluations 
9.7 
11 
106.7 
Serology 
3.5 
1 
3.5 
Bevacizumab 
pharmacokinetics 
3.5 
24 
84 
Immunogenicity samples: 
 
 
 
ADA 
3.5 
5 
17.5 
NAB 
3.5 
5 
17.5 
Total: 
229.2 
 
If extra blood samples are required, the maximum blood volume to be withdrawn per subject 
will not exceed the volume of a normal blood donation. 

SAP_001.pdf: 
Statistical 
Analysis Plan 
Title: 
A Randomised, Double-Blind, Three-Arm, Single 
Dose, Parallel Study To Compare the 
Pharmacokinetics, Safety and Immunogenicity of 
MB02-SP, MB02-DM (Bevacizumab Biosimilar 
Drugs) and US licenced Avastin® in Healthy Male 
Volunteers 
NCT Number: 
NCT04408989 
Statistical 
Analysis Plan 
version date: 
Version 1.0, 20 May 2021 
 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 1 of 81 
 
 
 
 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
 
 
 
A RANDOMISED, DOUBLE BLIND, THREE-ARM, SINGLE DOSE, PARALLEL STUDY 
TO COMPARE THE PHARMACOKINETICS, SAFETY AND IMMUNOGENICITY OF 
MB02-SP, MB02-DM (BEVACIZUMAB BIOSIMILAR 
DRUGS) AND US LICENCED AVASTIN® IN HEALTHY MALE VOLUNTEERS 
 
 
Sponsor Protocol No.: MB02-A-06-20 
Syneos Health Clinique Inc. Project No.: 7012755 
 
 
Final Version: 1.0 
Date: 26-MAY-2020  
 
 
 
Contract Research Organization: 
Syneos Health, LLC/ Health UK Limited 
1030 Sync Street, Morrisville, 
North Carolina 27560, 
United States 
Sponsor:  
mAbxience Research S.L. 
C/ Manuel Pombo Angulo, 28,  
4th floor, 28050 Madrid, 
Spain 
 
 
 
CONFIDENTIAL 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 2 of 81 
Revision History 
Version # 
Date (DD-Mmm-YYYY) 
Document Owner 
Revision Summary 
 Draft 0.1 
04 May 2021 
  
 
Final 1.0 
20 May 2021 
 
 


Statistical Analysis Plan (Without PK and Immunogenicity analysis)
mAbxience Research S.L.
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20)
20 May 2021 (Final 1.0)
Page 3 of 81
Signature Approvals
I confirm that I have reviewed this document and agree with the content.
Syneos Health Approval
, Biostatistician II 
Name, Title
Lead Biostatistician 
Signature
Date (DD-Mmm-YYYY)
, Biostatistician II
Name, Title
Senior Reviewing Biostatistician
Signature
Date (DD-Mmm-YYYY)
, Principal Stat Programmer
Name, Title
Lead Programmer
Signature
Date (DD-Mmm-YYYY)
, Principal Medical Writer
Name, Title
Lead Medical Writer
Signature
Date (DD-Mmm-YYYY)
mAbxience Research S.L.
, Medical Advisor
Name, Title
Sponsor Contact
Signature
Date (DD-Mmm-YYYY)


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 4 of 81 
TABLE OF CONTENTS 
Revision History ..........................................................................................................2 
Signature Approvals.....................................................................................................3 
TABLE OF CONTENTS .............................................................................................4 
LIST OF ABBREVIATIONS .......................................................................................6 
1. 
Introduction ...........................................................................................................8 
2. 
Study Objectives....................................................................................................9 
2.1 
Primary objective ...............................................................................................9 
2.2 
Secondary objectives ..........................................................................................9 
3. 
Study Design ....................................................................................................... 10 
3.1 
General Design ................................................................................................ 10 
3.2 
Study Procedures.............................................................................................. 10 
3.3 
Drug Administration......................................................................................... 10 
3.4 
Subject Withdrawal and Replacement ............................................................... 10 
3.5 
Determination of Sample Size........................................................................... 11 
3.6 
Randomization and Blinding............................................................................. 11 
4. 
Changes from the Protocol ................................................................................... 13 
5. 
Study Endpoints .................................................................................................. 14 
5.1 
Primary Endpoints............................................................................................ 14 
5.2 
Secondary Endpoints ........................................................................................ 14 
6. 
Analysis Populations............................................................................................ 15 
6.1 
Safety Population ............................................................................................. 15 
7. 
General Aspects for Statistical Analysis................................................................ 16 
7.1 
General Methods .............................................................................................. 16 
7.2 
Summary Statistics: .......................................................................................... 16 
7.3 
Key Definitions ................................................................................................ 16 
7.4 
Missing Data .................................................................................................... 17 
7.5 
Visit Windows ................................................................................................. 17 
8. 
Interim Analyses.................................................................................................. 18 
9. 
Study Population and Exposure ............................................................................ 19 
9.1 
Subject Disposition .......................................................................................... 19 
9.2 
Protocol Deviations .......................................................................................... 19 
9.3 
Demographics and Baseline Characteristics....................................................... 19 
9.4 
Medical History ............................................................................................... 20 
9.5 
Prior and Concomitant Medications .................................................................. 20 
9.6 
Study Drug Administration ............................................................................... 20 
10. 
Safety Analyses ................................................................................................... 21 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 5 of 81 
10.1 Physical Examination Findings ......................................................................... 21 
10.2 Adverse Events ................................................................................................ 21 
10.3 Laboratory Parameters...................................................................................... 23 
10.4 Vital Signs ....................................................................................................... 24 
10.5 Electrocardiogram ............................................................................................ 25 
11. 
Percentages and Decimal Places ........................................................................... 26 
12. 
Data Handling ..................................................................................................... 27 
13. 
Handling of Missing Data .................................................................................... 28 
14. 
Software to be Used ............................................................................................. 29 
15. 
Reference List ..................................................................................................... 30 
 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 6 of 81 
LIST OF ABBREVIATIONS 
ADA 
Anti-Drug Antibodies 
AE 
Adverse Event 
anti-HBs 
Hepatitis B surface antibody   
anti HBc 
Hepatitis B core antibody  
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
AUC 
Area Under the Curve 
BMI 
Body Mass Index 
BP 
Blood Pressure 
BUN 
Blood urea nitrogen 
CI 
Confidence Interval 
CL 
Total Body Clearance 
CTCAE 
Common Terminology Criteria For Adverse Events 
CR/STBA  
Confinement Report and Subjects to be Analyzed Form 
CSR 
Clinical Study Report  
CV 
Coefficient of Variation 
ECG 
Electrocardiogram 
eCRF 
electronic Case Report Form 
EMA 
European Medicines Agency 
EOI 
End of Infusion 
EOS 
End of Study 
HBsAg 
Surface Antigen Of The Hepatitis B Virus 
HCV 
Human Hepatitis C Virus 
HDL 
High-Density Lipoprotein 
HIV 
Human Immunodeficiency Virus 
HR 
Heart Rate 
INR 
International Normalised Ratio 
IV 
Intravenous  
kg 
Kilogram 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 7 of 81 
LDL 
Low-density Lipoprotein 
m 
Meter 
Max 
Maximum 
MedDRA 
Medical Dictionary For Regulatory Activities 
mg 
Milligram 
Min 
Minimum 
mL 
Milliliter 
mmHg 
Millimeters Mercury  
NAB 
Neutralizing Anti-drug antibodies 
QT 
QT Interval 
QTc 
Corrected QT Interval 
QTcF 
QT corrected with Fridericia’s formula 
RR 
Respiratory Rate 
PT 
Preferred Term  
RBC 
Red Blood Cell   
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System 
SD 
Standard Deviation 
SOC 
System Organ Class 
SOPs 
Standard Operation Procedures 
TEAEs 
Treatment-Emergent Adverse Events 
WBC 
White Blood Cell  
WHO DD 
World Health Organization Drug Dictionary 
 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 8 of 81 
1. 
Introduction 
This statistical analysis plan (SAP) is intended to give a detailed description of the summaries 
and the analyses that will be generated for the mAbxience Research S.L. study protocol No. 
MB02-A-06-20, Version 1.0, dated 26 May 2020 (Syneos Project No. 7012755). Safety and 
tolerability analyses will be described. 
The plan may change due to unforeseen circumstances and any changes made after the plan has 
been finalized will be documented. If additional analyses are required to supplement the planned 
analyses described in the SAP, the changes and justification for the changes will be outlined in 
the Clinical Study Report (CSR). No change will be made without prior approval of the study 
Sponsor. No revision to the SAP is required for changes that do not affect the statistical analysis 
methods, definitions, or rules defined in this document. 
When applicable, all methodology and related processes will be conducted according to Syneos’s 
Standard Operating Procedures (SOPs) as appropriate. Protocol deviations occurring during the 
study will be listed. 
Shells for all statistical tables, figures and listings referred to in this SAP will be displayed in a 
separate document. Statistical analysis plan and shells for PK analysis and immunogenicity   
analysis will be displayed in a separate document and it could be provided by Covance. 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 9 of 81 
2. 
Study Objectives 
2.1 
Primary objective 
x To investigate and compare the pharmacokinetic (PK) profiles of MB02-SP (MB02 
standard procedure), MB02-DM (MB02 defined media) and US-licenced Avastin® (US 
Avastin®) to establish bioequivalence between the 3 study arms. 
2.2 
Secondary objectives 
x Evaluation and comparison of derived PK parameters not covered by the primary 
endpoints for MB02-SP, MB02-DM and US Avastin®. 
x To compare the safety profile of MB02-SP, MB02-DM and US Avastin®. 
x To compare the immunogenicity of MB02-SP, MB02-DM and US Avastin®. 


 
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3. 
Study Design 
3.1 
General Design 
This will be a Phase 1, double-blind, randomised, parallel-group, single-dose 3-arm study to 
investigate and compare the PK, safety and immunogenicity profiles of MB02-DM with MB02-
SP and US Avastin® in healthy male subjects. A total of One hundred and fourteen (114) 
subjects will be randomised to one of following 3 arms in a 1:1:1 ratio: 
x Arm 1: MB02-SP (MB02 standard procedure) as a 90 minute IV infusion 
x Arm 2: MB02-DM (MB02 defined media) as a 90 minute IV infusion 
x Arm 3: US Avastin® sourced from the US, as a 90 minute IV infusion. 
Thirty-eight subjects will be dosed in each arm. Potential subjects will be screened to assess their 
eligibility to enter the trial within 30 days prior to study drug administration.  
3.2 
Study Procedures 
The overall schedule of procedures and assessments is provided in the protocol. 
3.3 
Drug Administration 
Subjects will receive a single dose of 1 mg/kg of one of the following treatments by IV infusion 
over 90 minutes. A total of 114 healthy adult male volunteers will be dosed; 38 subjects per 
treatment group, randomly assigned to one of the 3 treatment arms.  
x 1 mg/kg dose of MB02-SP (bevacizumab biosimilar drug), administered as a 90 minute 
IV infusion. 
x 1 mg/kg dose of MB02-DM (bevacizumab biosimilar drug), administered as a 90 minute 
IV infusion. 
x 1 mg/kg dose of US Avastin®, administered as a 90 minute IV infusion. 
3.4 
Subject Withdrawal and Replacement 
A subject is free to withdraw from the study at any time. In addition, a subject will be withdrawn 
from dosing if any of the following criteria are met: 
x Change in compliance with any inclusion/exclusion criterion that is clinically relevant 
and affects subject safety as determined by the Investigator (or designee); 
x Noncompliance with the study restrictions that might affect subject safety or study 
assessments/objectives, as considered applicable by the Investigator (or designee); 
x Any clinically relevant sign or symptom that in the opinion of the Investigator (or 
designee) warrants subject withdrawal. 


 
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If a subject is withdrawn from dosing, the Sponsor will be notified and the date and reason(s) for 
the withdrawal will be documented in the subject’s electronic Case Report Form (eCRF). If a 
subject is withdrawn, efforts will be made to perform all Follow-up assessments, if possible. 
Other procedures may be performed at Investigator’s (or designee’s) and/or Sponsor’s discretion. 
If the subject is in-house, these procedures should be performed before the subject is discharged 
from the clinic. The Investigator (or designee) may also request that the subject return for an 
additional Follow-up Visit. All withdrawn subjects will be followed until resolution of all their 
adverse events (AEs) or until the unresolved AEs are judged by the Investigator (or designee) to 
have stabilised.   
Subjects who are withdrawn for nondrug related reasons may be replaced following discussion 
between the Investigator and the Sponsor. Subjects withdrawn as a result of AEs thought to be 
related to the study drug will generally not be replaced. 
3.5 
Determination of Sample Size 
Up to 114 subjects will be enrolled in order that 108 complete the study. 
A sample size of 36 subjects per arm (108 subjects in total) will provide at least 90% power for 
all the pairwise comparisons for primary endpoints (AUC and Cmax) using a percent coefficient 
of variation (CV%) of 25% in both PK parameters for the similarity objective if the true ratio is 
equal to 1.05 or less. 
A maximum of 5% loss of data due to premature discontinuation is expected therefore, the 
sample size is increased to 114 subjects in total, with 38 subjects per arm. 
3.6 
Randomization and Blinding 
A computer generated randomization schedule will be prepared by the assigned biostatistician 
prior to the start of the study. The schedule will be generated through the statistical analysis 
system (SAS) software, version 9.4. Subjects will be randomly assigned to 1 of 3 treatment arms 
and stratified into 2 groups based on weight (≥50.0 to <72.5kg, and ≥72.5 to ≤95.0 kg 
respectively). 
For subjects who are replaced the replacements should take the same treatment assignment as the 
original subject to ensure that the planned treatment allocation ratio is retained. 
 
The following controls will be employed to maintain the double blind status of the study:  
x The Investigator and other members of staff involved with the study will remain blinded 
to the treatment randomisation code during the assembly procedure. 
To maintain the blind, the Investigator will be provided with a sealed randomisation code for 
each subject, containing coded details of the treatment. These individual sealed envelopes will 
be kept in a limited access area that is accessible 24 hours a day. If, in order to manage subject 
safety (in the event of possibly treatment related SAEs or severe AEs), the decision to unblind 
resides with the Investigator. Whenever possible, and providing it does not interfere with or 
delay any decision in the best interest of the subject, the Investigator will discuss the intended 
code-break with the Sponsor. If it becomes necessary to break the code during the study, the 
date, time and reason will be recorded in the subject's source data and on the individual envelope 
and will be witnessed by a second person. 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
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20 May 2021 (Final 1.0) 
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Where the subject experiences a suspected unexpected serious adverse reaction (SUSAR) the 
Sponsor pharmacovigilance team may be unblinded prior to notification of the relevant 
competent authorities and ethics committee in order to provide appropriate information. 


 
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4. 
Changes from the Protocol 
No changes in planned analyses were done compared to the protocol. 
 
 
 


 
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5. 
Study Endpoints 
5.1 
Primary Endpoints 
The PK outcome endpoints of MB02-DM, MB02-SP and US Avastin® derived from the serum 
Concentration-time profile from Days 1 to 100 following IV administration are as follows: 
 
x Area under the serum concentration‑time curve from time zero to infinity (AUC[0-∞]) 
x Maximum observed serum concentration (Cmax) 
5.2 
Secondary Endpoints 
x Evaluation of all other PK parameters for MB02-SP, MB02-DM and US Avastin®, 
including 
o Time of maximum observed serum concentration (tmax) 
o AUC from time zero to the time of the last observable concentration (AUC[0-t]) 
o Clearance (CL) 
o  Apparent serum terminal elimination half-life (t1/2) 
x The safety outcome measures for this study are as follows:  
o Incidence and severity of AEs  
o Incidence of laboratory abnormalities, based on haematology, clinical chemistry, 
coagulation and urinalysis test results  
o 12-lead electrocardiogram (ECG) parameters  
o Vital sign measurements  
o Physical examinations  
The immunogenicity of MB02-SP, MB02-DM and US Avastin® 
x Determination of serum concentrations of anti-MB02-DM, MB02-SP, and anti-Avastin® 
antibodies.  


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
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6. 
Analysis Populations 
The analysis of safety and tolerability parameters will be based on the study population detailed 
in Section 6.1.  
6.1 
Safety Population 
The safety population will include all subjects exposed to MB02-DM, MB02-SP or US Avastin®, 
and have at least one post dose safety assessment. 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
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7. 
General Aspects for Statistical Analysis 
7.1 
General Methods 
SAS® for Windows, Release 9.4 (SAS® Institute Inc., Cary, NC, USA) software will be used to 
perform all data analyses.  
All data in the database will be presented in the data listings. Unless otherwise stated, all listings 
will be sorted by randomized treatment group, subject number and assessment date/time 
The following labels for treatment will be used on all tabulations where the results are displayed 
by treatment, in the following order: 
x 1 mg/kg MB02 - SP IV 
x 1 mg/kg MB02 - DM IV 
x 1 mg/kg US - Avastin® IV 
 
7.2 
Summary Statistics: 
Unless otherwise stated, continuous variables will be summarized using the number of 
observations (n), and the statistics mean, median, standard deviation (SD), minimum and 
maximum. The minimum and maximum values will be presented to the same number of decimal 
places as recorded in the case report form (CRF), mean and median will be presented to one 
more decimal place than the raw data and the SD will be presented to two more decimal places 
than the raw data. Summaries of change-from-baseline variables will include only subjects who 
have both a baseline value and corresponding value at the timepoint of interest. Categorical 
variables will be summarized with frequency counts and percentages. Percentages will be  
rounded to one decimal place, with the denominator being the number of subjects in the relevant 
population, unless otherwise stated. 
 
Only data from nominal protocol scheduled visits will be included in the summary tables. Data 
from unscheduled visits will not be included in the summary tables (unless they were used as 
baseline) but will be included in the listings and figures. 
 
7.3 
Key Definitions 
Definition of Baseline 
In general, baseline will be defined for each subject and will be defined as the last available, non-
missing assessment prior to first study drug administration. Unknown, Not Done, Not Applicable 
and other classifications of missing data will not be considered when calculating baseline 
observations. However, valid categorical observations will be considered for baseline 
calculations. 
 
 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
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Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
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7.4 
Missing Data 
All withdrawals will be included in all summaries up to the time of withdrawal. 
 
There will be no imputation for missing data, unless otherwise specified. 
7.5 
Visit Windows 
All assessments will be included in the listings. No visit windows will be applied to assessments. 
 


 
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8. 
Interim Analyses 
No formal interim analysis was planned in the protocol.  


 
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9. 
Study Population and Exposure 
No inferential analysis will be done. Only observed data will be used. 
9.1 
Subject Disposition 
Subject disposition will be summarized by treatments (frequency and the percentage of subjects) 
and overall. The following categories will be summarized by number and/or percentage. 
x Screened and screen failures subjects (overall only). 
x Enrolled and not enrolled subjects (overall only). 
x Subjects who are dosed in each treatment and overall. 
x Subjects who have completed the study in each treatment and overall. 
x Subjects who discontinued in each treatment and overall. 
x Primary reason for discontinuation in each treatment and overall.  
In addition, the number of randomized subjects, number of subjects evaluable for safety (Safety 
Population) will be presented by treatment and overall.  
For subjects enrolled, not enrolled and screen failures, the percentage denominator will be the 
number of screened subjects. For all other calculations, the percentage denominator will be the 
number of subjects dosed in each treatment. For overall, the percentages will be based on the 
overall number of subjects dosed (safety population).  
Subject study completion and discontinuation information will be listed. This listing will include 
the following information: 
x Subject identifier and randomization number 
x Study day/Date of informed consent 
x Study day/Date of randomization (for randomized subjects) 
x Study Treatment received (for randomized subjects) 
x Study Day/ Date of study completion or discontinuation 
x Primary reason for discontinuation 
9.2 
Protocol Deviations 
The protocol deviations will be categorized and listed by subject. 
9.3 
Demographics and Baseline Characteristics 
Descriptive statistics (sample size (n), mean, median, standard deviation [SD], minimum [Min], 
and maximum [Max]) will be calculated for continuous variables (age, body mass index [BMI], 


 
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height, and weight) considering last results (scheduled or unscheduled) obtained at screening. 
Frequency counts and percentages will be tabulated for categorical variables (gender, ethnicity, 
and race). All summaries will be presented by treatment for safety population. All demographic 
characteristics will be listed by subject. 
9.4 
Medical History 
Medical history will be listed by subject. The Medical Dictionary for Regulatory Activities 
(MedDRA®) Version 22.1 will be used to classify all medical history findings by System Organ 
Class (SOC) and Preferred Term (PT). 
Urine drug screen, cotinine test and alcohol breath test will be listed only. 
9.5 
Prior and Concomitant Medications 
The use of prior and/or concomitant medications will be monitored throughout the study and 
listed by subject. The World Health Organization Drug Dictionary (WHO DD) Version Mar 
2020, format B3 will be used to classify all medication reported during the study. 
All prior and concomitant medications will be listed by subject. 
9.6 
Study Drug Administration 
The study drug administration details (including treatment received, infusion interruption, start 
and stop date and time of administration, total dose) will be listed by subject. 


 
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10. 
Safety Analyses 
Safety and tolerability data will be evaluated through the assessment of AEs, clinical laboratory 
parameters (clinical chemistry, hematology, cogulation, urinalysis and serology), 12-lead 
electrocardiogram (ECG), vital signs and physical examination. AEs, laboratory values, 12-lead 
ECG and vital signs will be summarized overall or according to the treatment, as appropriate. 
The analysis of the safety variables will be based on safety population. 
Safety data will be summarized, but will not be subjected to inferential analysis. 
10.1 
Physical Examination Findings 
A full physical examination or symptom-directed physical examination will be performed at 
screening. Additionaly, symptom-directed physical examination will be performed at Day -1 
(check-in) and Day 100 (End of Study (EOS)). A full physical examination or symptom-directed 
physical examination includes assessments of the following: Eye/Ear/Nose/Throat, General 
Appearance, Oral, Head and Neck, Chest/Lungs, Cardiovascular Abdomen, Musculoskeletal, 
Lymphatic, Dermatologic, Neurologic, Extremities, Psychiatric from the subject. 
Body measurements, including height and body weight, will be measured and BMI will be 
calculated at screening. Body weight will also be measured at Day -1 (check-in). Body 
measurements will be summarized (mean, median, SD, min, max, and sample size) in 
demographic tables (safety population). 
Any abnormal findings judged to be clinically significant will be documented as medical history 
or as an AE, during screening (non a TEAE) or after receiving treatment (TEAE). Any physical 
examination findings documented as AEs will be included in the AE summaries. 
10.2 
Adverse Events 
Treatment-emergent AEs (TEAEs) will be listed and summarised using descriptive 
methodology. TEAEs will be defined as AEs that occur on or after the date and time of study 
drug administration. Any AE that first occurs pre-dose but worsens in severity or is deemed to be 
related to the study drug after the first study drug administration will also be considered a TEAE. 
All AEs will be collected and documented during the course of the study. Subjects will be 
followed-up until final discharge from the study, and any AEs that occur during this time should 
be reported according to the procedures outlined below: 
x All subjects with unresolved AEs at the end of the study, except those who dropped out 
before randomisation or starting active treatment, must be included in a safety follow-up 
visit to check response of AEs. 
x Follow-up can be waived in specific cases after consultation with the Sponsor. This 
permission must be documented per case and retained in the Sponsor File. 
The incidence of TEAEs and treatment-related AEs will be summarized using the safety 
population. The Medical Dictionary for Regulatory Activities (MedDRA®), Version 23.0 will be 
used to classify all AEs reported during the study by SOC and PT. 


 
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Incidence of subjects who experienced TEAEs (as well as number of events) will be presented 
by treatment and overall, by SOC, and PT, investigator-assessed relationship and also by 
severity. Each subject may only contribute once to each of the incidence rates, for a TEAE 
following a given treatment, regardless of the number of occurrences; the highest severity or 
highest relationship will be presented, as appropriate. In each table, SOC will be presented in 
descending order of overall incidence rate in terms of frequency of subjects and then in 
frequency of events (alphabetical order will be used in case of equal rates). For each SOC, PT 
will be presented the same way. 
The causal relationship of an AE to the study drug will be assessed according to the study 
protocol as: 
Not Related:  
when the AE is definitely caused by the subject’s clinical state, or the 
study procedure/conditions 
Unlikely Related:  
when the temporal association between the AE and the drug is such that 
the drug is not likely to have any reasonable association with the AE 
Possibly Related:  
when the AE follows a reasonable temporal sequence from the time of 
drug administration but could have been produced by the subject’s clinical 
state or the study procedures/conditions 
Probably Related:  
when the AE has a reasonable time relationship to study drug 
administration and is unlikely to be attributed to concurrent disease or 
other drugs or chemicals 
Related:  
when the AE follows a reasonable temporal sequence from administration 
of the drug, abates upon discontinuation of the drug, follows a known or 
hypothesised cause-effect relationship, and (if appropriate) reappears 
when the drug is reintroduced. Treatment-related AEs will be those 
reported as Possibly Related, Probably Related or Related to Study Drug.  
The severity of an AE or serious AE (SAE) will be recorded in the eCRF following the National 
Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, 
outlined below: 
Grade 1: 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
Grade 2: 
Moderate; minimal, local or non-invasive intervention indicated; limiting age-
appropriate instrumental activities of daily living 
Grade 3: 
Severe or medically significant but not immediately life-threatening; 
hospitalisation or prolongation of hospitalisation indicated; disabling; limiting 
self-care activities of daily living 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
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Grade 4: 
Life-threatening consequences; urgent intervention indicated 
Grade 5: 
Death related to AE 
 SAEs will be listed separately by subjects. 
10.3 
Laboratory Parameters 
Clinical laboratory (clinical chemistry, hematology, coagulation and urinalysis) results will be 
obtained at screening, Day -1 (check-in), Day 3, Day 8, Day 14, Day 21, Day 28, Day 42, Day 
56, Day 78 and Day 100 (EOS). 
Clinical chemistry parameters include the following: albumin, aspartate aminotransferase (AST), 
alanine aminotransferase (ALT), alkaline phosphatase (ALP), Urea, low-density lipoprotein 
(LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, total cholesterol, 
Uric acid, Calcium, Chloride, Inorganic phosphate, Potassium, Creatinine, Creatine kinase, 
Gamma-glutamyl transferase, Lactate dehydrogenase, Glucose, Sodium, Total bilirubin, Direct 
bilirubin, and Total protein. 
Hematology parameters include the following: Haematocrit, Haemoglobin, Mean cell 
haemoglobin, Mean cell haemoglobin concentration, Mean cell volume, Platelet count, Red 
blood cell (RBC) count, White blood cell (WBC) count and WBC differentials as Basophils, 
Eosinophils, Lymphocytes, Monocytes, and Neutrophils. 
Coagulation parameters include the following: International normalised ratio (INR), Prothrombin 
time and Activated partial thromboplastin time. 
Urinalysis parameters include the following: Complete microscopic examination, pH, Specific 
gravity, Urobilinogen, Protein, Ketones, Blood, and Glucose. Unless otherwise specified, 
microscopic examination will be performed on abnormal findings and results will be listed. 
Serology parameters including: Hepatitis B surface antigen (HBs Ag), Hepatitis B surface 
antibody (anti-HBs), Hepatitis B core antibody (anti HBc), Hepatitis C antibody and Human 
immunodeficiency HIV antigen antibodies will be performed at screening. 
Urinary drug screen including: Cotinine, Amphetamines/methamphetamines, Barbiturates, 
Benzodiazepines, Cocaine (metabolite), Methadone, Phencyclidine, Opiates, 
Tetrahydrocannabinol/cannabinoids, and Breath alcohol test will be performed at screening and 
at Day -1 (check-in). 
Listings of all clinical laboratory results, including those unscheduled, will be provided with the 
abnormal values flagged with "L" for low and "H" for high for continuous parameters, and “A” 
for abnormal for categorical parameters.  
Descriptive statistics (mean, median, SD, min, max, and sample size) for each clinical laboratory 
test (continuous variables) will be presented by treatment for each timepoints. Change from 
baseline descriptive statistics for post-dose measurements as well as for EOS will be presented. 
Baseline will be defined as the last results (scheduled or unscheduled) obtained prior to the study 


Statistical Analysis Plan (Without PK and Immunogenicity analysis)
mAbxience Research S.L.
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20)
20 May 2021 (Final 1.0)
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drug administration. Unscheduled results will not be included in the summary tables except for 
baseline calculation if applicable. For categorical variables (urinalysis tests), the number of 
subjects (frequency and percentage) will be tabulated for each individual result (e.g., negative, 
positive, trace). Results from repeat tests will not be included in the summary statistics unless the 
repeat was required (and documented as such) due to technical reasons or an invalid initial result.
A summary table of shifts from baseline to EOS measurements will be provided. Baseline will be 
defined in the same manner as described in the preceding paragraph for continuous variables. 
The shift tables representing the categorical change of laboratory results (normal, abnormal not 
clinically significant, or abnormal clinically significant) from baseline to each post baseline visit 
will be presented. Results from repeat tests will not be included in the summary statistics unless 
the repeat was required (and documented as such) due to technical reasons or an invalid initial 
result.
If more than one clinical laboratory is used for the study, a formula that takes into consideration 
the relative normal ranges of each test of laboratories used will be applied to normalize these 
data. The conversion formula used will depend on the typical distribution of the normal range for 
each laboratory test; the two formula used are presented below:
x
Hemoglobin, hematocrit, and platelet count test results are considered to have a normal 
distribution (Chuang-Stein, 1992) and the following formula will be used (Karvanen J., 
2003):
x
The remaining hematology, biochemistry, and urinalysis test results are considered to have a 
non-normal distribution (Chuang-Stein, 1992) and the following formula will be used 
(Karvanen J., 2003):
U= upper limit; L= lower limit; s= primary facility result; and x= secondary facility results.
Prior to applying these formulae, if required, units will be adjusted.
10.4
Vital Signs
Supine blood pressure, supine pulse rate, respiratory rate (RR) will be assessed at screening, 
Day -1 (check-in), predose, 0.5H, 1H, End of infusion (EOI) and 2H of Day 1, Day 2, Day 5, 
Day 8, Day 10, Day 21, and Day 100 (EOS). Aural body temperature will be assessed at 


 
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20 May 2021 (Final 1.0) 
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screening, Day 2, Day 10, Day 21 and Day 100 (EOS) and pulse oximetry (PO) will be assessed 
at screening only. 
Subjects must be supine for at least 5 minutes before blood pressure and pulse rate 
measurements. 
Descriptive statistics (mean, median, SD, min, max, and sample size) will be presented by 
treatment for each timepoint and for each vital sign measurement. Change from baseline 
descriptive statistics for post-dose measurements as well as for EOS will be presented. Baseline 
will be defined as the last results (scheduled or unscheduled) obtained prior to the study drug 
administration. Unscheduled results will not be included in the summary tables except for 
baseline calculation if applicable. Results from repeat tests will not be included in the summary 
statistics unless the repeat was required (and documented as such) due to technical reasons or an 
invalid initial result. 
A listing of all vital signs results will be provided by subject. 
10.5 
Electrocardiogram 
12-lead ECGs will be recorded after the subject has been supine and at rest for at least 5 minutes 
at screening, Day -1, Day 3, Day 8 and Day 100 (EOS). The quantitative ECG measurements are 
heart rate (HR), PR interval, QRS interval, QT interval, QTcF (Fridericia formula correction). 
Single 12 lead ECGs will be repeated once if either of the following criteria apply: 
• 
QT interval corrected for heart rate using Fridericia’s method (QTcF) > 500 msec 
• 
QTcF change from the baseline (predose) is > 60 msec. 
Descriptive statistics (mean, median, SD, min, max, and sample size) will be presented by 
treatment for each time point and for each ECG measurement. Change from baseline descriptive 
statistics for post-dose measurements as well as for EOS will be presented. Baseline will be 
defined as the last results (scheduled or unscheduled) obtained prior to the study drug 
administration. Unscheduled results will not be included in the summary tables except for 
baseline calculation if applicable. Results from repeat tests will not be included in the summary 
statistics unless the repeat was required (and documented as such) due to technical reasons or an 
invalid initial result.  
Furthermore, a shift table representing the categorical change of ECGs results (normal, abnormal 
not clinically significant, or abnormal clinically significant) from baseline to each post baseline 
visit will be presented. 
A listing of all ECG results will be provided with the abnormal values flagged.  
Additionally, the listing of QT interval corrected for HR using Fridericia’s method (QTcF) > 500 
msec and QTcF change from the baseline (predose) is > 60 msec will be provided by subjects. 
 
 


 
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11. 
 Percentages and Decimal Places 
If not otherwise specified, the following rules will be applied, with the exception of PK tables 
and listings described below: 
x Percentages will be presented to one decimal place. 
x Percentages equal to 0 or 100 will be presented as such without a decimal place. 
x Minimum and maximum will be presented with the same precision as the original values; 
Mean, and median will be presented with one more decimal place than the original 
values, and standard deviation, will be presented with two more decimal place than the 
original values. 


 
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12. 
Data Handling 
The safety data will be received as SAS® datasets from the Syneos data management facility. 
Screening failures and ineligible volunteer’s data (subject disposition) will be received from the 
clinical site as source data. The serum concentrations and Immunogenicity data will be provided by 
Covance. 


 
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13. 
Handling of Missing Data  
For safety,  
x If an AE is recorded with an onset date corresponding to a dosing day, but the time is 
missing, then the AE will be assigned to the treatment. 
x If an AE is recorded with an onset date that does not correspond to the dosing day, but 
the time is missing, then the AE will be assigned to the treatment if AE onset date is after 
dosing date. 
x If an AE is recorded with an onset date where day and time are both missing, then the AE 
allocation to the treatment will be done on a case by case basis considering available 
information (e.g., AE onset date, AE end date, AE comments, subject disposition). 
 


 
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14. 
Software to be Used 
The safety data tables and listings will be created using SAS®, release 9.4.  The study report text 
will be created using Microsoft® Office Word 2010, or a higher version. 


 
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15. 
Reference List 
x Chuang-Stein C. Summarizing laboratory data with different reference ranges in multi-
center clinical trials. Drug Information Journal. 1992; 26:77-84. 
x Karvanen J. The statistical basis of laboratory data normalization. Drug Information 
Journal. 2003; 37:101-107. 
 
 


 
 
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Table/Figure/Listing Shells (Without PK and Immunogenicity analysis) 
 
 
 
A RANDOMISED, DOUBLE-BLIND, THREE-ARM, SINGLE DOSE, PARALLEL STUDY 
TO COMPARE THE PHARMACOKINETICS, SAFETY AND IMMUNOGENICITY OF 
MB02-SP, MB02-DM (BEVACIZUMAB BIOSIMILAR DRUGS) AND US LICENCED 
AVASTIN® IN HEALTHY MALE VOLUNTEERS 
 
Sponsor Protocol No.: MB02-A-06-20 
Syneos Health Clinique Inc. Project No.: 7012755 
 
 
Final Version: 1.0 
Date: 26-MAY -2020 
 
 
 
Contract Research Organization: 
Syneos Health, LLC/ Health UK Limited 
1030 Sync Street, Morrisville, 
North Carolina 27560, 
United States 
Sponsor:  
mAbxience Research S.L. 
C/ Manuel Pombo Angulo, 28, 4th floor, 
28050 Madrid, 
Spain 
 
 
 
 
CONFIDENTIAL 
 
 


 
 
Statistical Analysis Plan (Table/Figure/Listing Shells) 
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Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
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TABLE OF CONTENTS 
TABLE OF CONTENTS ............................................................................................... 32 
1. 
Tables, Figures and Data Listings Formatting ....................................................... 33 
Table 1-1 Layout Specifications........................................................................... 33 
2. 
Summary TFLs.................................................................................................... 34 
Table 2-1 List of Table Shells .............................................................................. 34 
Table 2-3 List of Data Listings Shells .................................................................. 36 
3. 
CSR In-text Tables .............................................................................................. 37 
4. 
Summary Tables .................................................................................................. 40 
5. 
Listings ............................................................................................................... 62 
 
 


 
 
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1. 
Tables, Figures and Data Listings Formatting 
The table, figure, and data listing (TFL) shells are presented in order to provide a framework for 
displaying the study data. The shells may change due to unforeseen circumstances. The shells 
may not be truly representative of every aspect of the study (e.g., sampling time points, assessed 
laboratory parameters, calculated parameters, units), but are intended to illustrate the general 
layout of the tables, figures, and data listings that will be included in the final report. 
The default tables, listings, and figures layout will be as presented in Table 1-1: 
Table 1-1 Layout Specifications 
Orientation 
Portrait 
Landscape 
Paper Size 
Letter 
Letter 
Margins 
Top: 3.05 cm 
Bottom: 2.54 cm 
Left: 2.54 cm 
Right: 2.54 cm 
Top: 3.05 cm 
Bottom: 2.2 cm 
Left: 1.9 cm 
Right: 1.9 cm 
Font 
Table text: Times new Roman 9 or 10 pts 
Table title: Times new Roman 12 pts 
Table legend: Times new Roman 9 or 10 pts 
The font size may be reduced as necessary to allow additional columns to be presented, but not at 
the expense of clarity. Also the orientation may be changed to portrait if appropriate. 
1.1 
Headers 
x All output should have the following header at the top left of each page: 
x mAbxience Research S.L. 
x All output should have Page n of N at the top or bottom right corner of each page. TLFs 
are internally paginated in relation to the total length (i.e., the page number should 
appear sequentially as page n of N, where N is the total number of pages in the table). 
x The date output was generated should appear along with the program name as a footer 
on each page. 
 


 
 
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2. 
Summary TFLs 
Table 2-1 List of Table Shells 
Table 
Number 
Title 
 
In-Text Table 
10.1-1 
Subject Disposition 
 
 
 
Demographic Data Summary Tables 
14.1-1 
Summary of Demographic Characteristics of Subjects Included in the Safety Population 
14.1-2 
Summary of Protocol Deviations – Safety Population 
 
 
 
Safety Data Summary Tables 
14.3.1-1 
Overview of Treatment-Emergent Adverse Events – Safety Population 
14.3.1-2 
Frequency of Subjects Experiencing Treatment-Emergent Adverse Events and Number of Events 
Summarized per Treatment – Safety Population 
14.3.1-3 
Frequency of Subjects Experiencing Treatment-Emergent Adverse Events Summarized per 
Treatment and Severity – Safety Population 
14.3.1-4 
Number of Treatment-Emergent Adverse Events Summarized per Treatment and Severity – Safety 
Population 
14.3.1-5 
Frequency of Subjects Experiencing Treatment-Emergent Adverse Events Summarized per 
Treatment and Relationship – Safety Population 
14.3.1-6 
Number of Treatment-Emergent Adverse Events Summarized per Treatment and Relationship – 
Safety Population 
14.3.1-7 
Frequency of Subjects Experiencing Treatment-Emergent Adverse Events Leading to 
Discontinuation Summarized per Treatment– Safety Population 
14.3.1-8 
Frequency of Subjects Experiencing Serious Treatment-Emergent Adverse Events Summarized per 
Treatment– Safety Population 
14.3.4-1 
Clinical Chemistry Summary Descriptive Statistics and Change from Baseline – Safety Population 
14.3.4-2 
Frequency of Subjects – Clinical chemistry Shifts from Baseline – Safety Population 
14.3.4-3 
Hematology Summary Descriptive Statistics and Change from Baseline – Safety Population 
14.3.4-4 
Frequency of Subjects – Hematology Shifts from Baseline – Safety Population 
14.3.4-5 
Urinalysis (pH and Specific Gravity) Summary Descriptive Statistics and Change from Baseline – 
Safety Population 
14.3.4-6 
Frequency of Subjects – Urinalysis (pH and Specific Gravity) Shifts from Baseline – Safety 
Population 
14.3.4-7 
Coagulation Summary Descriptive Statistics and Change from Baseline – Safety Population 
14.3.4-8 
Frequency of Subjects –  Coagulation Shifts from Baseline – Safety Population 
14.3.4-9 
Urinalysis Frequency Summary – Categorical Results – Safety Population 
14.3.4-10 
Frequency of Subjects – Urinalysis Shifts from Baseline – Categorical Results – Safety Population 
14.3.4-11 
Vital Signs Summary Descriptive Statistics and Change from Baseline – Safety Population 
14.3.4-12 
Electrocardiograms Summary Descriptive Statistics and Change from Baseline – Safety Population 


 
 
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14.3.4-13 
Frequency of Subjects –   Electrocardiograms Shifts from Baseline – Safety Population 


 
 
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Table 2-3 List of Data Listings Shells 
 
 
 
Listing 
Number 
Title 
 
Subject Characteristics Listings 
16.2.1-1 
Subjects Completion and Discontinuation Information 
16.2.2-1 
Protocol Deviations 
16.2.4-1 
Demographics 
16.2.4-2 
Medical History Findings at Screening  
16.2.4-3 
Prior and Concomitant Medications  
16.2.4-4 
Study Drug Administration 
16.2.4-5 
Interruption of IV Infusion 
16.2.4-6 
Assignments to Analysis Populations 
16.2.4-7 
Cotinine Test 
16.2.4-8 
Urine Drug Screen 
16.2.4-9 
Alcohol Breath Test 
16.2.4-10 
Randomization  
 
 
 
Safety Data Listings 
16.2.7-1 
Non-Treatment-Emergent Adverse Events 
16.2.7-2 
Treatment-Emergent Adverse Events 
16.2.7-3 
Serious Adverse Events 
16.2.7-4 
Treatment-Emergent Adverse Events with NCI-CTCAE of Grade 3 or Higher 
16.2.7-5 
Treatment-Emergent Adverse Events Leading to Study Drug Withdrawal/Discontinuation 
16.2.8-1 
Clinical Laboratory – Clinical chemistry 
16.2.8-2 
Clinical Laboratory – Hematology 
16.2.8-3 
Clinical Laboratory –  Urinalysis 
16.2.8-4 
Clinical Laboratory – Coagulation 
16.2.8-5 
Clinical Laboratory – Serology 
16.2.8-6 
Clinical Laboratory – Urine Drug Screen and Alcohol Breath Tests 
16.2.8-7 
Vital Signs Result 
16.2.8-8 
Pulse oximetry Results 
16.2.8-9 
Electrocardiogram Result 
16.2.8-10 
QT interval corrected for heart rate using QTcF > 500 msec 
16.2.8-11 
QTcF change from the baseline (predose) is > 60 msec 
16.2.8-12 
Physical Examination Findings by Subject 


 
 
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3. 
CSR In-text Tables 


 
 
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Table 10.1-1 Subject Disposition 
Category 
1 mg/kg MB02 - SP IV 
1 mg/kg MB02 - DM  IV 
1 mg/kg US - Avastin® IV 
Overall 
 
 
 
 
 
Screened  
 
- 
- 
xx 
Screening Failures1,2  
 
- 
- 
x ( xx.x) 
Not Enrolled1,3 
 
- 
- 
x ( xx.x) 
Enrolled1,4 
 
- 
- 
x ( xx.x) 
 
 
 
 
 
Safety Population  
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
 
 
 
 
 
Randomized  
xx 
xx 
xx 
xx 
Dosed 
 
 
xx 
xx 
xx 
xx 
Not Dosed 
xx 
xx 
xx 
xx 
Completed Study5,6 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
 
 
 
 
 
Number of Subjects Discontinued7 
xx 
xx 
xx 
xx 
 Primary Reason for Discontinuation7, 8 
 
 
 
 
 Adverse Event 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
 Death 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
 Lost To Follow-up 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
 Physician Decision 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
 Protocol Deviation 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
 Study Terminated by Sponsor 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
 Informed Consent Withdrawn  
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
 Withdrawal by Subject 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
  
 
 
 
 
 Other 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
Programming Note: 
1 Percentage based on the number of screened subjects. 
2 Screening failures include subjects who did not meet project criteria. 
3 Not enrolled include subjects who were judged eligible but decided not to participate on study or who were not selected to participate in the study since there was already a sufficient 
number of subjects. 


 
 
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Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
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4 Enrolled include subjects who were judged eligible and accepted to participate in the trial after having signed the approved final version of the study informed consent form and also 
those identified as standby who may replace subjects who withdraw from the study before dosing. 
5 Completed study include subjects who complete the study until follow-up visit without major protocol deviation. 
6 Percentage based on the number of dosed subjects for a given treatment. 
7 Overall, each subject could only contribute once to each reason for discontinuation, regardless of the number of occurrences. 
8 Percentage based on the number of discontinued subjects per treatment group or overall, as appropriate. 
Data source: Listings 16.2.1-1 and 16.2.4-4. 
 
 


 
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20 May 2021 (Final 1.0) 
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4. 
Summary Tables 
 


 
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Table 14.1-1 Summary of Demographic Characteristics of Subjects Included in the Safety Population 
Category 
Statistic 
1 mg/kg MB02 - SP IV 
1 mg/kg MB02 - DM  IV 
1 mg/kg US - Avastin® IV 
Age (years) 
N 
xx 
xx 
xx 
 
Mean 
xx x 
xx.x 
xx x 
 
SD 
xx x 
xx.x 
xx x 
 
Median  
xx x 
xx.x 
xx x 
 
Min, Max  
xx-xx 
xx-xx 
xx-xx 
 
 
 
 
 
Gender 
 
 
 
 
Male 
n (%) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
 
 
 
 
 
Ethnicity 
 
 
 
 
Not Hispanic or Latino 
n (%) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
Hispanic or Latino 
n (%) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
Not Reported 
n (%) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
Unknown 
n (%) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
 
 
 
 
 
Race 
 
 
 
   
Am Indian: 
 
 
 
 
Asian 
n (%) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
Black  
n (%) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
Australian Aborigine/Torres Strait Islander 
n (%) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
Pacific Islander 
n (%) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
White 
n (%) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
Other 
n (%) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
 
 
 
 
 
Height (cm) 
N 
xx 
xx 
xx 
 
Mean  
xx.xx 
xx xx 
xx.xx 
 
SD  
xx.xx 
xx xx 
xx.xx 
 
Median  
xx.xx 
xx xx 
xx.xx 
 
Min, Max  
xx xx-xx xx 
xx.xx-xx.xx 
xx xx-xx xx 
 
 
 
 
 
Weight (kg) Screening  
N 
xx 
xx 
xx 
 
Mean  
xx.xx 
xx xx 
xx.xx 
 
SD  
xx.xx 
xx xx 
xx.xx 


 
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Median  
xx.xx 
xx xx 
xx.xx 
 
Min, Max 
xx xx-xx xx 
xx.xx-xx.xx 
xx xx-xx xx 
 
 
 
 
 
Weight (kg)  Day -1 
N 
xx 
xx 
xx 
 
Mean  
xx.xx 
xx xx 
xx.xx 
 
SD  
xx.xx 
xx xx 
xx.xx 
 
Median  
xx.xx 
xx xx 
xx.xx 
 
Min, Max 
xx xx-xx xx 
xx.xx-xx.xx 
xx xx-xx xx 
 
 
 
 
 
Weight (≥50.0 to <72.5 kg) (kg) 
N 
xx 
xx 
xx 
 
Mean  
xx.xx 
xx xx 
xx.xx 
 
SD  
xx.xx 
xx xx 
xx.xx 
 
Median  
xx.xx 
xx xx 
xx.xx 
 
Min, Max 
xx xx-xx xx 
xx.xx-xx.xx 
xx xx-xx xx 
 
 
 
 
 
Weight (≥72.5 to ≤95.0 kg) (kg) 
N 
xx 
xx 
xx 
 
Mean  
xx.xx 
xx xx 
xx.xx 
 
SD  
xx.xx 
xx xx 
xx.xx 
 
Median  
xx.xx 
xx xx 
xx.xx 
 
Min, Max 
xx xx-xx xx 
xx.xx-xx.xx 
xx xx-xx xx 
 
 
 
 
 
BMI (kg/m2) 
N 
xx 
xx 
xx 
 
Mean  
xx xxx 
xx xxx 
xx xxx 
 
SD  
xx xxx 
xx xxx 
xx xxx 
 
Median  
xx xxx 
xx xxx 
xx xxx 
 
Min, Max  
xx xx-xx xx 
xx.xx-xx.xx 
xx xx-xx xx 
 
 
 
 
 
Programming Note: 
1) 
Refer to the note below for additional instructions 
 
N: Number of subjects dosed; n (%): Number and percent of subjects; SD: Standard Deviation. 
Am Indian: American Indian or Alaskan Native; Black: Black or African American;  
BMI: body mass index. 


 
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Last results (scheduled or unscheduled) obtained at screening were used to generate this table. 
Data source: Listing 16.2.4-1 
 
 
 


 
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Table 14.1-2 Summary of Protocol Deviations – Safety Population 
 
 
Protocol Deviation Category 
1 mg/kg MB02 - SP IV 
(N= xxx) 
1 mg/kg MB02 - DM IV 
(N= xxx) 
1 mg/kg US - Avastin® IV 
(N= xxx) 
 
 
 
 
  Category 1 
 xx (xx.x%) 
 xx (xx.x%) 
 xx (xx.x%) 
  Category 2 
 xx (xx.x%) 
 xx (xx.x%) 
 xx (xx.x%) 
  Category 3 
 xx (xx.x%) 
 xx (xx.x%) 
 xx (xx.x%) 
etc 
 xx (xx.x%) 
 xx (xx.x%) 
 xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Notes: Include categories as available in the source protocol deviation log. 
 


 
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Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
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Table 14.3.1-1 Overview of Treatment-Emergent Adverse Events – Safety Population 
MedDRA® System Organ Class 
 MedDRA® Preferred Term 
Statistic 
1 mg/kg MB02 - SP IV 
1 mg/kg MB02 - DM IV 
1 mg/kg US - Avastin® IV 
Overall 
(N=XX) 
Subjects with TEAEs 
n (%) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
 
 
 
 
 
   
Number of TEAEs 
[E] 
[x] 
[x] 
[x] 
[x] 
 
 
 
 
 
 
Subjects with SAEs 
n(%) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
 
 
 
 
 
 
Total number of SAEs 
[E] 
[x] 
[x] 
[x] 
[x] 
 
 
 
 
 
 
Subjects discontinued due to TEAEs 
n(%) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
 
 
 
 
 
 
Total number of TEAEs leading to 
discontinuation 
[E] 
[x] 
[x] 
[x] 
[x] 
 
 
 
 
 
 
All TEAEs by Severity 
 
 
 
 
 
   Grade 1: Mild 
n (%)[E] 
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
   Grade 2: Moderate 
n (%)[E] 
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
   Grade 3: Severe 
n (%)[E] 
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
   Grade 4: Life Threatening 
n (%)[E] 
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
   Grade 5: Death 
n (%)[E] 
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
   Total 
n (%)[E] 
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
 
 
 
 
 
 
Related TEAEs (possible, probable, related) 
by severity 
 
 
 
 
 
   Grade 1: Mild 
n (%)[E] 
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
   Grade 2: Moderate 
n (%)[E] 
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
   Grade 3: Severe 
n (%)[E] 
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
   Grade 4: Life Threatening 
n (%)[E] 
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
   Grade 5: Death 
n (%)[E] 
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
   Total 
n (%)[E] 
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
 
 
 
 
 
 
E: Number of TEAEs; N: Number of subjects dosed; n (%): Number and percent of subjects with TEAE; MedDRA ®: Medical Dictionary for Regulatory Activities, 
version 23.0; TEAEs: Treatment-Emergent Adverse Events. 
Each subject could only contribute once to each of the incidence rates, regardless of the number of occurrences. 
Overall: Included results from all treatment groups. 
Data source: Listing 16.2.7-2  
 


 
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Table 14.3.1-2 Frequency of Subjects Experiencing Treatment-Emergent Adverse Events and Number of Events Summarized per 
Treatment – Safety Population 
MedDRA® System Organ Class 
 MedDRA® Preferred Term 
Statistic 
1 mg/kg MB02 - SP IV  
(N=XX) 
1 mg/kg MB02 - DM IV 
(N=XX) 
1 mg/kg US - Avastin® IV 
 (N=XX) 
Overall 
(N=XX) 
Number of TEAEs 
E 
xx 
xx 
xx 
xx 
Number of Subjects with TEAEs 
n (%) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
 
 
 
MedDRA® System Organ Class 1 
n(%) [E]  
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
 MedDRA® Preferred Term 1 
n(%) [E]  
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
 MedDRA® Preferred Term 2 
n(%) [E] 
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
 
 
 
 
 
 
MedDRA® System Organ Class 2 
n(%) [E]  
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
 MedDRA® Preferred Term 1 
n(%) [E]  
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
 MedDRA® Preferred Term 2 
n(%) [E] 
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
 
 
 
 
 
 
MedDRA® System Organ Class 3 
n(%) [E]  
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
 MedDRA® Preferred Term 1 
n(%) [E]  
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
 MedDRA® Preferred Term 2 
n(%) [E] 
x ( xx x) [x] 
x ( xx.x) [x] 
x ( xx x) [x] 
x ( xx x) [x] 
 
 
 
 
 
 
Programming Notes: 
1) SOC will be presented in descending order of overall incidence rate in terms of frequency of subjects and then in frequency o f events (alphabetical order will be used in case of equal 
rates). For each SOC, PT will be presented the same way. 
2) Refer to footnotes for additional instructions. 
E: Number of TEAEs; N: Number of subjects dosed; n (%): Number and percent of subjects with TEAE; MedDRA®: Medical Dictionary for Regulatory Activities, 
version 23.0; TEAEs: Treatment-Emergent Adverse Events. 
Each subject could only contribute once to each of the incidence rates, regardless of the number of occurrences. 
Overall: Included results from all treatment groups. 
Data source: Listing 16.2.7-2  
 
 
  
 


 
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Table 14.3.1-3 Frequency of Subjects Experiencing Treatment-Emergent Adverse Events Summarized per Treatment and Severity – 
Safety Population 
 
MedDRA® System Organ Class  
 MedDRA® Preferred Term 
1 mg/kg MB02 - SP IV  
(N=XX) 
1 mg/kg MB02 - DM IV 
 (N=XX) 
n (%) Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Total TEAEs 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Total TEAEs  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MedDRA® System Organ Class 1 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
 
 MedDRA® Preferred Term 1 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
 
 MedDRA® Preferred Term 2 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MedDRA® System Organ Class 2 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
 
 MedDRA® Preferred Term 1 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
 
 MedDRA® Preferred Term 2 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Notes: 
1) 
SOC will be presented in descending order of overall incidence rate in terms of frequency of subjects and then in frequency o f events (alphabetical order will be used in case of 
equal rates). For each SOC, PT will be presented the same way. 
2) 
If the distribution of treatments is presented on more than one page, preserve the order of the SOC and PT as defined in the generation of the global table without severity. 
3) 
Refer to footnotes for additional instructions. 
 
 
 
N: Number of subjects dosed; n (%): Number and percent of subjects with treatment-emergent adverse events; MedDRA®: Medical Dictionary for Regulatory Activities, 
version 23.0. 
Each subject could only contribute once to each of the incidence rates, regardless of the number of occurrence; the highest severity is presented. 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or non-invasive 
intervention indicated; limiting age-appropriate instrumental activities of daily living; Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalisation or prolongation of hospitalisation indicated; disabling; limiting self-care activities of daily living; Grade 4: Life-threatening consequences; urgent 
intervention indicated; Grade 5: Death related to AE. 
Total TEAEs: Includes results from all severities per treatment and overall.  
Overall: Included results from all treatment groups. 
Data source: Listing 16.2.7-2 
 
 


 
Statistical Analysis Plan (Table/Figure/Listing Shells) 
 mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 48 of 81 
Table 14.3.1-3 Frequency of Subjects Experiencing Treatment-Emergent Adverse Events Summarized per Treatment and Severity – 
Safety Population (cont.) 
MedDRA® System Organ Class  
 MedDRA® Preferred Term 
1 mg/kg US - Avastin® IV 
 (N=XX) 
Overall 
(N=XX) 
n (%) Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Total TEAEs 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Total 
TEAEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
MedDRA® System Organ Class 
1 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
 MedDRA® Preferred Term 1 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
 MedDRA® Preferred Term 2 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
MedDRA® System Organ Class 
2 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
 MedDRA® Preferred Term 1 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
 MedDRA® Preferred Term 2 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
x ( xx x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Notes: 
1) 
SOC will be presented in descending order of overall incidence rate in terms of frequency of subjects and then in frequency o f events (alphabetical order will be used in case of 
equal rates). For each SOC, PT will be presented the same way. 
2) 
If the distribution of treatments is presented on more than one page, preserve the order of the SOC and PT as defined in the generation of the global table without severity. 
3) 
Refer to footnotes for additional instructions. 
 
 
 
N: Number of subjects dosed; n (%): Number and percent of subjects with treatment-emergent adverse events; MedDRA®: Medical Dictionary for Regulatory Activities, 
version 23.0 
Each subject could only contribute once to each of the incidence rates, regardless of the number of occurrence; the highest severity is presented. 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or non-invasive 
intervention indicated; limiting age-appropriate instrumental activities of daily living; Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalisation or prolongation of hospitalisation indicated; disabling; limiting self-care activities of daily living; Grade 4: Life-threatening consequences; urgent 
intervention indicated; Grade 5: Death related to AE. 
Total TEAEs: Includes results from all severities per treatment and overall.  
Overall: Included results from all treatment groups. 
Data source: Listing 16.2.7-2 
 


 
Statistical Analysis Plan (Table/Figure/Listing Shells) 
 mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 49 of 81 
Table 14.3.1-4 Number of Treatment-Emergent Adverse Events Summarized per Treatment and Severity – Safety Population 
MedDRA® System Organ Class  
 MedDRA® Preferred Term 
1 mg/kg MB02 - SP IV  
(N=XX) 
1 mg/kg MB02 - DM IV 
 (N=XX) 
E Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Total TEAEs 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Total TEAEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total Number of TEAEs 
 
 
 
 
 
 
 
 
 
 
 
 
MedDRA® System Organ Class 1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 MedDRA® Preferred Term 1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 MedDRA® Preferred Term 2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
MedDRA® System Organ Class 2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 MedDRA® Preferred Term 1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 MedDRA® Preferred Term 2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Notes: 
1) 
SOC will be presented in descending order of overall incidence rate in terms of frequency of subjects and then in frequency o f events (alphabetical order will be used in case of 
equal rates). For each SOC, PT will be presented the same way. 
2) 
If the distribution of treatments is presented on more than one page, preserve the order of the SOC and PT as defined in the generation of the global table without severity. 
 
 
E: Number of treatment-emergent adverse event; N: Number of subjects dosed; MedDRA ®: Medical Dictionary for Regulatory Activities, version 23.0. 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or non-invasive 
intervention indicated; limiting age-appropriate instrumental activities of daily living; Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalisation or prolongation of hospitalisation indicated; disabling; limiting self-care activities of daily living; Grade 4: Life-threatening consequences; urgent 
intervention indicated; Grade 5: Death related to AE. 
Total TEAEs: Includes results from all severities per treatment and overall.  
Overall: Included results from all treatment groups. 
Data source: Listing 16.2.7-2 
 
 


 
Statistical Analysis Plan (Table/Figure/Listing Shells) 
 mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 50 of 81 
Table 14.3.1-4 Number of Treatment-Emergent Adverse Events Summarized per Treatment and Severity – Safety Population (cont.) 
MedDRA® System Organ 
Class  
 MedDRA® Preferred Term 
1 mg/kg US - Avastin® IV 
 (N=XX) 
Overall 
(N=XX) 
E Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Total 
TEAEs 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Total 
TEAEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total Number of TEAEs 
 
 
 
 
 
 
 
 
 
 
 
 
MedDRA® System Organ 
Class 1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 MedDRA® Preferred Term 1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 MedDRA® Preferred Term 2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
MedDRA® System Organ 
Class 2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 MedDRA® Preferred Term 1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 MedDRA® Preferred Term 2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Notes: 
1) 
SOC will be presented in descending order of overall incidence rate in terms of frequency of subjects and then in frequency o f events (alphabetical order will be used in case of equal 
rates). For each SOC, PT will be presented the same way. 
2) 
If the distribution of treatments is presented on more than one page, preserve the order of the SOC and PT as defined in the generation of the global table without severity. 
3) 
Refer to footnotes for additional instructions. 
 
 
E: Number of treatment-emergent adverse event; N: Number of subjects dosed; MedDRA ®: Medical Dictionary for Regulatory Activities, version 22.1. 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or non-invasive 
intervention indicated; limiting age-appropriate instrumental activities of daily living; Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalisation or prolongation of hospitalisation indicated; disabling; limiting self-care activities of daily living; Grade 4: Life-threatening consequences; urgent 
intervention indicated; Grade 5: Death related to AE. 
Total TEAEs: Includes results from all severities per treatment and overall.  
Overall: Included results from all treatment groups. 
Data source: Listing 16.2.7-2 
 
 
 


 
Statistical Analysis Plan (Table/Figure/Listing Shells) 
 mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 51 of 81 
Table 14.3.1-5 Frequency of Subjects Experiencing Treatment-Emergent Adverse Events Summarized per Treatment and 
Relationship – Safety Population 
MedDRA® System Organ 
Class 
   MedDRA® Preferred Term 
1 mg/kg MB02 - SP IV  
(N=XX) 
1 mg/kg MB02 - DM IV 
 (N=XX) 
n (%) 
Not 
related 
Unlikely 
related 
Possibly 
related 
Probably 
related 
Related 
Total related TEAEs 
(possibly + probably +  
related) 
Not 
related 
Unlikely 
related 
Possibly 
related 
Probably 
related 
Related 
Total related TEAEs 
(possibly + probably + 
related) 
 
 
 
 
 
MedDRA® System Organ 
Class 1 
x ( xx.x) x ( xx x) 
x ( xx.x) 
x ( xx x) x ( xx.x) 
x ( xx x) 
x ( xx x) x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
 MedDRA® Preferred Term 1 x ( xx.x) x ( xx x) 
x ( xx.x) 
x ( xx x) x ( xx.x) 
x ( xx x) 
x ( xx x) x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
 MedDRA® Preferred Term 2 x ( xx.x) x ( xx x) 
x ( xx.x) 
x ( xx x) x ( xx.x) 
x ( xx x) 
x ( xx x) x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
 
 
 
 
 
MedDRA® System Organ 
Class 2 
x ( xx.x) x ( xx x) 
x ( xx.x) 
x ( xx x) x ( xx.x) 
x ( xx x) 
x ( xx x) x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
 MedDRA® Preferred Term 1 x ( xx.x) x ( xx x) 
x ( xx.x) 
x ( xx x) x ( xx.x) 
x ( xx x) 
x ( xx x) x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
 MedDRA® Preferred Term 2 x ( xx.x) x ( xx x) 
x ( xx.x) 
x ( xx x) x ( xx.x) 
x ( xx x) 
x ( xx x) x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Notes: 
1) 
SOC will be presented in descending order of overall incidence rate in terms of frequency of subjects and then in frequency of events (alphabetical order will be used in case of 
equal rates). For each SOC, PT will be presented the same way. 
2) 
If the distribution of treatments is presented on more than one page, preserve the order of the SOC and PT as defined in the generation of the global table without relationship. 
3) 
Refer to footnotes for additional instructions. 
N: Number of subjects dosed; n (%): Number and percent of subjects with treatment-emergent adverse event; MedDRA®: Medical Dictionary for Regulatory Activities, 
version 23.0 
Each subject could only contribute once to each of the incidence rates, regardless of the number of occurrences; the highest relationship is presented. 
Total related TEAEs: Includes results from possibly, probably and related relationships per treatment and overall.  
Overall: Included results from all treatment groups. 
Data source: Listing 16.2.7-2 
 
 


 
Statistical Analysis Plan (Table/Figure/Listing Shells) 
 mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 52 of 81 
Table 14.3.1-5 Frequency of Subjects Experiencing Treatment-Emergent Adverse Events Summarized per Treatment and 
Relationship – Safety Population 
MedDRA® System Organ 
Class 
   MedDRA® Preferred Term 
1 mg/kg US - Avastin® IV 
 (N=XX) 
Overall 
(N=XX) 
n (%) 
Not 
related 
Unlikely 
related 
Possibly 
related 
Probably 
related 
Related 
Total related TEAEs 
(possibly + probably +  
related) 
Not 
related 
Unlikely 
related 
Possibly 
related 
Probably 
related 
Related 
Total related TEAEs 
(possibly + probably + 
related) 
 
 
 
 
 
MedDRA® System Organ 
Class 1 
x ( xx.x) x ( xx x) 
x ( xx.x) 
x ( xx x) x ( xx.x) 
x ( xx x) 
x ( xx x) x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
 MedDRA® Preferred Term 1 x ( xx.x) x ( xx x) 
x ( xx.x) 
x ( xx x) x ( xx.x) 
x ( xx x) 
x ( xx x) x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
 MedDRA® Preferred Term 2 x ( xx.x) x ( xx x) 
x ( xx.x) 
x ( xx x) x ( xx.x) 
x ( xx x) 
x ( xx x) x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
 
 
 
 
 
MedDRA® System Organ 
Class 2 
x ( xx.x) x ( xx x) 
x ( xx.x) 
x ( xx x) x ( xx.x) 
x ( xx x) 
x ( xx x) x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
 MedDRA® Preferred Term 1 x ( xx.x) x ( xx x) 
x ( xx.x) 
x ( xx x) x ( xx.x) 
x ( xx x) 
x ( xx x) x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
 MedDRA® Preferred Term 2 x ( xx.x) x ( xx x) 
x ( xx.x) 
x ( xx x) x ( xx.x) 
x ( xx x) 
x ( xx x) x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Notes: 
1) 
SOC will be presented in descending order of overall incidence rate in terms of frequency of subjects and then in frequency of events (alphabetical order will be used in case of 
equal rates). For each SOC, PT will be presented the same way. 
2) 
If the distribution of treatments is presented on more than one page, preserve the order of the SOC and PT as defined in the generation of the global table without relationship. 
3) 
Refer to footnotes for additional instructions. 
 
 


 
Statistical Analysis Plan (Table/Figure/Listing Shells) 
 mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 53 of 81 
Table 14.3.1-6 Number of Treatment-Emergent Adverse Events Summarized per Treatment and Relationship – Safety Population 
MedDRA® System Organ Class 
   MedDRA® Preferred Term 
1 mg/kg MB02 - SP IV  
(N=XX) 
1 mg/kg MB02 - DM IV 
 (N=XX) 
E Not 
related 
Unlikely 
related 
Possibly 
related 
Probably 
related 
Related
Total related TEAEs 
(possibly + probably +  
related) 
Not 
related 
Unlikely 
related 
Possibly 
related 
Probably 
related 
Related
Total related TEAEs 
(possibly + probably +  
related) 
 
 
 
 
 
 
MedDRA® System Organ Class 
1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 MedDRA® Preferred Term 1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 MedDRA® Preferred Term 2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
MedDRA® System Organ Class 
2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 MedDRA® Preferred Term 1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 MedDRA® Preferred Term 2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Notes: 
1) 
SOC will be presented in descending order of overall incidence rate in terms of frequency of subjects and then in frequency of events (alphabetical order will be used in case of 
equal rates). For each SOC, PT will be presented the same way. 
2) 
If the distribution of treatments is presented on more than one page, preserve the order of the SOC and PT as defined in the generation of the global table without relationship. 
 
E: Number of treatment-emergent adverse event; N: Number of subjects dosed; MedDRA ®: Medical Dictionary for Regulatory Activities, version 23.0 
Total related TEAEs: Includes results from possibly, probably and related relationships per treatment and overall.  
Overall: Included results from all treatment groups. 
Data source: Listing 16.2.7-2 
 
 


 
Statistical Analysis Plan (Table/Figure/Listing Shells) 
 mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 54 of 81 
Table 14.3.1-6 Number of Treatment-Emergent Adverse Events Summarized per Treatment and Relationship – Safety Population 
MedDRA® System 
Organ Class 
   MedDRA® 
Preferred Term 
1 mg/kg US - Avastin® IV 
 (N=XX) 
Overall 
(N=XX) 
E Not related 
Unlikely 
related 
Possibly 
related 
Probably 
related 
Related 
Total related 
TEAEs (possibly 
+ probably +  
related) 
Not 
related 
Unlikely 
related 
Possibly 
related 
Probably 
related 
Related 
Total related 
TEAEs (possibly 
+ probably +  
related) 
 
 
 
 
 
 
MedDRA® System 
Organ Class 1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 MedDRA® 
Preferred Term 1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 MedDRA® 
Preferred Term 2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
MedDRA® System 
Organ Class 2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 MedDRA® 
Preferred Term 1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 MedDRA® 
Preferred Term 2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Notes: 
1) 
SOC will be presented in descending order of overall incidence rate in terms of frequency of subjects and then in frequency o f events (alphabetical order will be used in case of 
equal rates). For each SOC, PT will be presented the same way. 
2) 
If the distribution of treatments is presented on more than one page, preserve the order of the SOC and PT as defined in the generation of the global table without relationship 
 
 
E: Number of treatment-emergent adverse event; N: Number of subjects dosed; MedDRA ®: Medical Dictionary for Regulatory Activities, version 22.1. 
Total related TEAEs: Includes results from possibly, probably and related relationships per treatment and overall.  
Overall: Included results from all treatment groups. 
Data source: Listing 16.2.7-2 
 
 
 
 


 
Statistical Analysis Plan (Table/Figure/Listing Shells) 
 mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 55 of 81 
 
Table 14.3.1-7 Frequency of Subjects Experiencing Treatment-Emergent Adverse Events Leading to Discontinuation Summarized 
per Treatment – Safety Population 
MedDRA® System Organ Class 
 MedDRA® Preferred Term 
Statistic 
1 mg/kg MB02 - SP IV  
(N=XX) 
1 mg/kg MB02 - DM IV 
(N=XX) 
1 mg/kg US - Avastin® IV 
 (N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
Number of Subjects with TEAEs 
n (%) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
 
 
 
MedDRA® System Organ Class 1 
n(%)  
x ( xx.x)  
x ( xx x) 
x ( xx.x) 
x ( xx x) 
 MedDRA® Preferred Term 1 
n(%) 
x ( xx.x)  
x ( xx x)  
x ( xx.x)  
x ( xx x)  
 MedDRA® Preferred Term 2 
n(%) 
x ( xx.x)  
x ( xx x)  
x ( xx.x)  
x ( xx x)  
 
 
 
 
 
 
MedDRA® System Organ Class 2 
n(%)  
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
 MedDRA® Preferred Term 1 
n(%)  
x ( xx.x)  
x ( xx x)  
x ( xx.x)  
x ( xx x)  
 MedDRA® Preferred Term 2 
n(%)  
x ( xx.x)  
x ( xx x)  
x ( xx.x)  
x ( xx x)  
 
 
 
 
 
 
MedDRA® System Organ Class 3 
n(%)  
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
 MedDRA® Preferred Term 1 
n(%)  
x ( xx.x)  
x ( xx x)  
x ( xx.x)  
x ( xx x)  
 MedDRA® Preferred Term 2 
n(%)  
x ( xx.x)  
x ( xx x)  
x ( xx.x)  
x ( xx x)  
 
 
 
 
 
 
Programming Notes: 
1) SOC will be presented in descending order of overall incidence rate in terms of frequency of subjects and then in frequency of events (alphabetical order will be used in case of equal 
rates). For each SOC, PT will be presented the same way. 
2) Refer to footnotes for additional instructions. 
N: Number of subjects dosed; n (%): Number and percent of subjects with TEAE; MedDRA®: Medical Dictionary for Regulatory Activities, version 23.0; TEAEs: 
Treatment-Emergent Adverse Events. 
Each subject could only contribute once to each of the incidence rates, regardless of the number of occurrences. 
Overall: Included results from all treatment groups. 
Data source: Listing 16.2.7-2  
 
 
 
 
 


 
Statistical Analysis Plan (Table/Figure/Listing Shells) 
 mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 56 of 81 
 
Table 14.3.1-8 Frequency of Subjects Experiencing Serious Treatment-Emergent Adverse Events Summarized per Treatment – 
Safety Population 
MedDRA® System Organ Class 
 MedDRA® Preferred Term 
Statistic 
1 mg/kg MB02 - SP IV  
(N=XX) 
1 mg/kg MB02 - DM IV 
(N=XX) 
1 mg/kg US - Avastin® IV 
 (N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
Number of Subjects with TEAEs 
n (%) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
 
 
 
MedDRA® System Organ Class 1 
n(%)  
x ( xx.x)  
x ( xx x) 
x ( xx.x) 
x ( xx x) 
 MedDRA® Preferred Term 1 
n(%) 
x ( xx.x)  
x ( xx x)  
x ( xx.x)  
x ( xx x)  
 MedDRA® Preferred Term 2 
n(%) 
x ( xx.x)  
x ( xx x)  
x ( xx.x)  
x ( xx x)  
 
 
 
 
 
 
MedDRA® System Organ Class 2 
n(%)  
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
 MedDRA® Preferred Term 1 
n(%)  
x ( xx.x)  
x ( xx x)  
x ( xx.x)  
x ( xx x)  
 MedDRA® Preferred Term 2 
n(%)  
x ( xx.x)  
x ( xx x)  
x ( xx.x)  
x ( xx x)  
 
 
 
 
 
 
MedDRA® System Organ Class 3 
n(%)  
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
 MedDRA® Preferred Term 1 
n(%)  
x ( xx.x)  
x ( xx x)  
x ( xx.x)  
x ( xx x)  
 MedDRA® Preferred Term 2 
n(%)  
x ( xx.x)  
x ( xx x)  
x ( xx.x)  
x ( xx x)  
 
 
 
 
 
 
Programming Notes: 
1) SOC will be presented in descending order of overall incidence rate in terms of frequency of subjects and then in frequency of events (alphabetical order will be used in case of equal 
rates). For each SOC, PT will be presented the same way. 
2) Refer to footnotes for additional instructions. 
 N: Number of subjects dosed; n (%): Number and percent of subjects with TEAE; MedDRA®: Medical Dictionary for Regulatory Activities, version 23.0; TEAEs: 
Treatment-Emergent Adverse Events. 
Each subject could only contribute once to each of the incidence rates, regardless of the number of occurrences. 
Overall: Included results from all treatment groups. 
Data source: Listing 16.2.7-2  
 
 
 


 
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Table 14.3.4-1 Clinical Chemistry Summary Descriptive Statistics and Change from Baseline – Safety Population  
Parameter 
(unit) 
Visit 
Statistic 
1 mg/kg MB02 - SP IV  
(N=XX) 
1 mg/kg MB02 - DM IV 
 (N=XX) 
1 mg/kg US - Avastin® IV 
 (N=XX) 
Parameter 1 
(unit) 
Screening 
n  
xx 
xx 
xx 
xx-xx 
Mean  
xx.x 
xx x 
xx x 
SD  
xx.x 
xx x 
xx x 
Median  
xx.x 
xx x 
xx x 
Min, Max  
xx-xx 
xx-xx 
xx-xx 
 
 
 
 
Day -1 
n  
xx 
xx 
xx 
Mean  
xx.x 
xx x 
xx x 
SD  
xx.x 
xx x 
xx x 
Median  
xx.x 
xx x 
xx x 
Min, Max  
xx-xx 
xx-xx 
xx-xx 
 
 
 
 
Baseline  
n  
xx 
xx 
xx 
Mean  
xx.x 
xx x 
xx x 
SD  
xx.x 
xx x 
xx x 
Median  
xx.x 
xx x 
xx x 
Min, Max  
xx-xx 
xx-xx 
xx-xx 
 
 
 
 
Day 3 
n  
xx 
xx 
xx 
Mean  
xx.x 
xx x 
xx x 
SD  
xx.x 
xx x 
xx x 
Median  
xx.x 
xx x 
xx x 
Min, Max  
xx-xx 
xx-xx 
xx-xx 
 
 
 
 
Day3 - CFB 
n  
xx 
xx 
xx 
Mean  
xx.x 
xx x 
xx x 
SD  
xx.x 
xx x 
xx x 
Median  
xx.x 
xx x 
xx x 
Min, Max  
xx-xx 
xx-xx 
xx-xx 
 
 
 
 
Day 8 
n  
xx 
xx 
xx 
Mean  
xx.x 
xx x 
xx x 
SD  
xx.x 
xx x 
xx x 
Median  
xx.x 
xx x 
xx x 
Min, Max  
xx-xx 
xx-xx 
xx-xx 


 
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Table 14.3.4-1 Clinical Chemistry Summary Descriptive Statistics and Change from Baseline – Safety Population  
Parameter 
(unit) 
Visit 
Statistic 
1 mg/kg MB02 - SP IV  
(N=XX) 
1 mg/kg MB02 - DM IV 
 (N=XX) 
1 mg/kg US - Avastin® IV 
 (N=XX) 
 
 
 
 
Day  - CFB 
n  
xx 
xx 
xx 
Mean  
xx.x 
xx x 
xx x 
SD  
xx.x 
xx x 
xx x 
Median  
xx.x 
xx x 
xx x 
Min, Max  
xx-xx 
xx-xx 
xx-xx 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
End of Study (Day 100)  n  
xx 
xx 
xx 
Mean  
xx.x 
xx x 
xx x 
SD  
xx.x 
xx x 
xx x 
Median  
xx.x 
xx x 
xx x 
Min, Max  
xx-xx 
xx-xx 
xx-xx 
 
 
 
 
End of Study (Day 100) - 
CFB 
n  
xx 
xx 
xx 
Mean  
xx.x 
xx x 
xx x 
SD  
xx.x 
xx x 
xx x 
Median  
xx.x 
xx x 
xx x 
Min, Max  
xx-xx 
xx-xx 
xx-xx 
CFB: Change from baseline; N: Number of subjects dosed; n: Number of subjects; SD: Standard Deviation. 
Baseline is defined as the last results (scheduled or unscheduled) obtained prior to the study drug administration.  
Data source: Listing 16.2.8-1 
 
Note: This table will be repeated for Tables 14.3.4-3, 14.3.4-5, 14.3.4-7, 14.3.4-11 and 14.3.4-12. Please adapt title and footnotes accordingly.  


 
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Table 14.3.4-2 Frequency of Subjects – Clinical Chemistry Shifts from Baseline – Safety Population 
Treatment 
 Parameter  (unit)       
Baseline Flag: 
Normal 
Abnormal NCS 
Abnormal CS 
Post-Baseline Flag: 
Visit 
Normal 
 n (%) 
Abnormal NCS 
n (%) 
Abnormal CS 
n (%) 
Normal 
 n (%) 
Abnormal NCS 
n (%) 
Abnormal CS 
n (%) 
Normal 
 n (%) 
Abnormal NCS 
n (%) 
Abnormal CS 
n (%) 
1 mg/kg MB02 - SP IV (N=XX) 
 
 
 
 
 
 
 
 
 
 
Parameter 1 
Day 3 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 8 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 14 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 21 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 28 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 42 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 56 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 78 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 100 (End of 
Study) 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Parameter 2 
Day 3 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 8 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 14 
x ( xx x) 
x ( xx x) 
x ( xx.x) 
x ( xx.x) 
x ( xx.x) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
Add for all other Treatments 
 and Parameters 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Notes: 
1) 
Preserve parameters, scheduled visits and sorting defined in Summary Descriptive Statistics Table 
2) 
Refer to footnotes for additional instructions. 
3) 
Adapt Data Source to the appropriate laboratory category listing. 
N: Number of subjects dosed; n: Number and percent of subjects. 
Baseline is defined as the last results (scheduled or unscheduled) obtained prior to the study drug administration. 
Percentage based on the number of subjects having available results at baseline and at the specific post-baseline timepoint. 
Data source: Listing 16.2.8-1 
 
Note: This table will be repeated for Tables 14.3.4-4, 14.3.4-6, 14.3.4-8, and 14.3.4-13 please adapts title and footnotes accordingly. 


 
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Table 14.3.4-9 Urinalysis Frequency Summary – Categorical Results – Safety Population 
Parameter (unit) 
Normal Range 
Visit 
Result  
 n (%) 
1 mg/kg MB02 - SP IV 
 (N=XX) 
1 mg/kg MB02 - DM IV 
(N=XX) 
1 mg/kg US - Avastin® IV 
(N=XX) 
Parameter 1(unit) 
Screening 
Negative 
x (xx x) 
x (xx x) 
x (xx x) 
XX-XX 
 
Trace 
x (xx x) 
x (xx x) 
x (xx x) 
 
 
 
 
 
Day -1 
Negative 
x (xx x) 
x (xx x) 
x (xx x) 
 
Trace 
x (xx x) 
x (xx x) 
x (xx x) 
 
 
 
 
 
Baseline 
Negative 
x (xx x) 
x (xx x) 
x (xx x) 
 
Trace 
x (xx x) 
x (xx x) 
x (xx x) 
 
 
 
 
 
Day 8 
Negative 
x (xx x) 
x (xx x) 
x (xx x) 
 
Trace 
x (xx x) 
x (xx x) 
x (xx x) 
 
 
 
 
 
Day 14 
Negative 
x (xx x) 
x (xx x) 
x (xx x) 
 
Trace 
x (xx x) 
x (xx x) 
x (xx x) 
 
 
 
 
 
Day 21 
Negative 
x (xx x) 
x (xx x) 
x (xx x) 
 
Trace 
x (xx x) 
x (xx x) 
x (xx x) 
… 
 
 
 
 
 
 
 
 
 
Day 100 (End of 
Study) 
Negative 
x (xx x) 
x (xx x) 
x (xx x) 
 
Trace 
x (xx x) 
x (xx x) 
x (xx x) 
… 
 
 
 
 
 
Programming Notes: 
1) 
Urine Microscopy parameters will not presented in this table. 
2) 
Evaluate if the units must be added to parameter name if a numeric result was observed. Remove (units) from column header if no numeric results were observed. 
3) 
For each parameter provide normal range of primary facility and, for gender specific parameters, use the same sorting of gender from demographic table. 
4) 
Independently for each parameter, sort results by gradation. 
5) 
Refer to footnotes for additional instructions. 
N: Number of subjects dosed; n (%): Number and percent of subjects.  
Baseline is defined as the last results (scheduled or unscheduled) obtained prior to the study drug administration. 
Percentage based on the number of subjects having available result at each timepoint, independently for each parameter. 
Data source: Listing 16.2.8-3 
 
 


 
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Table 14.3.4-10 Frequency of Subjects – Urinalysis Shifts from Baseline – Categorical Results – Safety Population 
Treatment 
 Parameter (unit)    
Baseline Flag: 
Normal 
Abnormal 
Post-Baseline Flag: 
Visit 
Normal 
n (%) 
Abnormal 
n (%) 
Normal 
n (%) 
Abnormal 
n (%) 
1 mg/kg MB02 - SP IV (N=XX) 
 
 
 
 
 
Parameter 1 
Day 3 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 8 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 14 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 21 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 28 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 42 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 56 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 78 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 100 (End of Study) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
 
 
 
 
 
 
 
 
 
 
 
Parameter 2 
Day 3 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 8 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 14 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 21 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 28 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 42 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 56 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 78 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
Day 100 (End of Study) 
x ( xx x) 
x ( xx.x) 
x ( xx x) 
x ( xx x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Add for all other Treatments and Parameters 
 
 
 
 
 
 
 
 
 
 
 
Programming Notes: 
1) 
Preserve parameters, scheduled visits and sorting defined in Summary Descriptive Statistics Table 
2) 
Refer to footnotes for additional instructions. 
3) 
Adapt Data Source to the appropriate laboratory category listing. 
 
N: Number of subjects dosed; n: Number and percent of subjects. 
Baseline is defined as the last results (scheduled or unscheduled) obtained prior to the study drug administration. 
Percentage based on the number of subjects having available results at baseline and at the specific post -baseline timepoint.  
Data source: Listing 16.2.8-3 


 
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5. 
Listings 
 
 


 
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Listing 16.2.1-1 Subjects Completion and Discontinuation Information 
Subject Treatment  
Date ICF signed 
Completion/ Discontinuation Date 
and Time 
Date of Last Contact With The 
Subject 
Primary Reason for 
Discontinuation 
Comment 
001 
1 mg/kg 
MB02 - 
SP IV 
 
DD-MM-YYYYTHH:MM 
DD-MM-YYYY 
XXX 
XXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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Listing 16.2.2-1 Protocol Deviations 
 
Subject 
Treatment  
Category 
Deviation 
 
1 mg/kg MB02 - SP IV 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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Listing 16.2.4-1 Demographics  
Subject 
Visit 
Treatment  
Age (years) 
Race 
Ethnicity 
BMI (kg/m2) 
Height (cm) 
Weight (kg) 
 
 
 
 
 
 
 
 
 
001 
Screening  
1 mg/kg MB02 - SP IV 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BMI: Body Mass Index. 
Last results (scheduled or unscheduled) obtained at screening were used to generate this listing.  
 
 


 
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Listing 16.2.4-2 Medical History Findings at Screening 
Subject 
Treatment  
Finding 
MedDRA® Preferred Term 
MedDRA® System Organ Class 
Onset Date 
Resolution Date 
(or Ongoing) 
 
 
FINDING 1 
Preferred Term 1 
SOC 1 
YYYY-MM-DDTHH:MM  
YYYY-MM-DDTHH:MM 
 
1 mg/kg MB02 - SP IV  
 
 
 
 
 
 
FINDING 2 
Preferred Term 2 
SOC 2 
YYYY-MM-DDTHH:MM  
ONGOING 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Notes  
1) SOC and Finding will be presented in uppercase. The Preferred Term will be presented in “propcase”. The SAS coding “/~n” between terms will generate the break line. 
2) The SAS coding “/~n” between dates will generate the break line. 
3) If finding is ongoing, replace missing resolution date per ONGOING. 
4) Sort events per Subject, Start Date, Stop Date, SOC and PT. 
5) For incomplete date display, refer to CDISC SDTM Implementation Guide according to ISO 8601 format. 
MedDRA®: Medical Dictionary for Regulatory Activities; MedDRA ® Version 23.0. 
 
 
 
 


 
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Listing 16.2.4-3 Prior and Concomitant Medications  
Subject 
Treatment  
 
Prior/ 
Concomitant 
WHO DDE ATC / 
WHO DDE  Preferred Term / 
Medication 
Dose (unit)/ 
Frequency 
Route 
Onset Date and Time/ 
Resolution Date and Time 
(or Ongoing) 
Indication  
(Condition or AE No.) 
 
 
Prior 
ATC 1/ 
Preferred Term 1/ 
MEDICATION 1/ 
20 (mg) 
QID 
ORAL 
YYYY-MM-DDTHH:MM/ 
YYYY-MM-DDTHH:MM 
 
 
 
 
 
 
 
 
 
 
1 mg/kg MB02 - SP 
IV 
Concomitant 
ATC 2/ 
Preferred Term 2/ 
MEDICATION 2/ 
 
 
YYYY-MM-DDTHH:MM/ 
ONGOING 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Notes: 
1) ATC and Medication will be presented in uppercase. The Preferred Term will be presented in “propcase”. The SAS coding “/~n” between terms will generate the break line. 
2) The SAS coding “/~n” will generate the break line between treatment sequence and treatment, dose with units and frequency. In the same way apply a break line between 
dates. 
3) If medication is ongoing, replace missing resolution date per ONGOING. 
4) Sort events per Subject, Onset Date, Resolution Date, ATC and PT. 
5) For incomplete date display, refer to CDISC SDTM Implementation Guide according to ISO 8601 format. 
ATC: Anatomic Therapeutic Chemical; WHO DDE: World Health Organization Drug Dictionary Enhanced Version Mar 2020, format B3. 
 
 


 
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Listing 16.2.4-4 Study Drug Administration 
Subject 
Treatment  
Drug 
Taken/ 
If No, 
Reason” 
Infusion Start 
Date and Time 
Infusion End 
Date and Time 
Duration 
of 
infusion  
(hh: min) 
Total 
Dose per 
subject 
Weight 
(mg) 
Was the total 
volume 
administered? 
Infusion 
Rate 
(unit) 
Volume 
infused 
(mL) 
Location of 
study drug 
administration 
Fasting 
Status  
Was the 
infusion 
interrupted? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 mg/kg 
MB02 - 
SP IV 
 
YYYY-MM-
DDTHH:MM:SS 
YYYY-MM-
DDTHH:MM:SS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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Listing 16.2.4-5 Interruption of IV Infusion  
Subject 
Treatment  
Drug Interruption 
 Date and Time 
Restart 
 Date and Time 
Reason for interruption 
If Adverse event, please 
select corresponding AE 
No. 
Was the infusion 
restarted? 
 
 
 
 
 
 
 
 
1 mg/kg MB02 - 
SP IV 
YYYY-MM-
DDTHH:MM:SS 
YYYY-MM-
DDTHH:MM:SS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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Listing 16.2.4-6 Assignment to Analysis Populations 
Subject 
Treatment 
Included in Safety Population 
 
 
 
 
101 
1 mg/kg MB02 - SP IV 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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Listing 16.2.4-7 Cotinine Test 
 
Subject 
Treatment 
 
Visit 
 
Test Performed/ If No, 
Reason 
 
Date/Time of Sample 
Collection 
Result 
 
 
 
 
 
 
xxxxx 
1 mg/kg MB02 - SP IV 
Screening 
Yes 
 
ddmmmyyyy / hh mm 
 
Negative 
 
 
Day -1 
Yes 
 
ddmmmyyyy / hh mm 
 
Positive 
 
 
 
 
 
 
xxxxx 
 
Screening 
No 
 
 
 
 
 
Day -1 
Yes 
 
ddmmmyyyy / hh mm 
 
Negative 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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Listing 16.2.4-8 Urine Drug Screen 
 
Subject 
Treatment 
 
Visit 
 
Test Performed/ If No, 
Reason 
 
Date/Time of Sample 
Collection 
Result 
Test Name If 
Positive Results 
 
 
 
 
 
 
 
xxxxx 
1 mg/kg MB02 - SP 
IV 
Screening 
Yes 
 
ddmmmyyyy / hh mm 
 
Negative 
 
 
 
Day -1 
Yes 
 
ddmmmyyyy / hh mm 
 
Positive 
 
 
 
 
 
 
 
 
xxxxx 
 
Screening 
No 
 
 
 
 
 
 
Day -1 
Yes 
 
ddmmmyyyy / hh mm 
 
Negative 
 
 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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Listing 16.2.4-9 Alcohol Breath Test 
 
Subject 
Treatment 
 
Visit 
 
Test Performed/ If No, 
Reason 
 
Date/Time of Sample 
Collection 
Result 
 
 
 
 
 
 
xxxxx 
1 mg/kg MB02 - SP IV 
Screening 
Yes 
 
ddmmmyyyy / hh mm 
 
Negative 
 
 
Day -1 
Yes 
 
ddmmmyyyy / hh mm 
 
Positive 
 
 
 
 
 
 
xxxxx 
 
Screening 
No 
 
 
 
 
 
Day -1 
Yes 
 
ddmmmyyyy / hh mm 
 
Negative 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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Listing 16.2.4-10 Randomization 
Subject 
Treatment 
Subject Was Randomized / If No, Reason 
Randomization Date 
Randomization Number. 
 
 
 
 
 
101 
1 mg/kg MB02 - SP IV 
 
ddmmmyyyy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 






 
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Listing 16.2.8-1 Clinical Laboratory – Clinical chemistry 
Subject 
Treatment  Laboratory Visit 
Collection Date 
and Time  
Parameter(unit) 
Result 
Normalized  
Result  
Normal Range 
Flag 
Interpretation 
 
 
 
 
 
 
 
 
 
 
 
001 
1 mg/kg 
MB02 - 
SP IV 
 
 
YYYY-MM-
DDTHH:MM 
 
 
 
XX.X-XX.X  
H 
Abnormal NCS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Notes: 
1) 
Sort assessments per Subject, Timepoint/Date and parameters. Sorting for parameter should be as defined in Summary Descriptive Statistics Table. 
2) 
For each parameter provide normal range of primary facility and, for gender specific parameters, use the same sorting of gend er from demographic table. 
3) 
If multiple laboratories involved, display standard and normalised results.  Display the ranges in the same way.  The SAS coding “/~n” between results or ranges will generate 
the break line.Take care to use the same precision of both, standard and normalised results/ranges. 
Laboratory facilities could be abbreviated with appropriation description on footnote; BML: Biron Medical Laboratory). 
H: Above normal range; L: Below normal range; N: Normal Range. 
 
Note: Similar layout will be used for Listings 16.2.8-2, 16.2.8-3, 16.2.8-4, 16.2.8-5, and 16.2.8-6. Please adapt title and footnotes accordingly.  
 
 
 
 
 
 
 


 
Statistical Analysis Plan (Table/Figure/Listing Shells)                                                                                                                                              mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 78 of 81 
Listing 16.2.8-7 Vital Signs Result  
Subject 
Treatment  
Visit/ 
Timepoint 
Measurement Date and 
Time 
Parameter(unit) 
Result 
 
 
 
 
 
 
001 
1 mg/kg 
MB02 - SP 
IV 
Screening 
YYYY-MM-
DDTHH:MM 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Notes: 
1) Sort assessments per Subject, Timepoint/Date and parameter. Parameters for each subject to be sorted as defined in Summary Descriptive Statistics Table. 
*The medical judgement for abnormal ECG interpretation is also presented in this column as CS: Clinically significant or NCS: Not clinically significant. 
 
 
 


 
Statistical Analysis Plan (Table/Figure/Listing Shells)                                                                                                                                              mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 79 of 81 
Listing 16.2.8-8 Pulse Oximetry Results  
Subject 
Treatment  
Visit 
Start Date and Time 
Test (unit) 
Result 
Reason, if Test is Not Performed 
 
 
 
 
 
 
 
001 
1 mg/kg 
MB02 - SP 
IV 
Screening 
YYYY-MM-DDTHH:MM 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
Statistical Analysis Plan (Table/Figure/Listing Shells)                                                                                                                                              mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 80 of 81 
Listing 16.2.8-9 Electrocardiogram Result 
Subject 
Treatment  
Visit/Timepoint 
Assessment  Date and Time 
Parameter(unit) 
Result  
Interpretation* 
 
 
 
 
 
 
 
 
1 mg/kg 
MB02 - SP 
IV 
 
YYYY-MM-DDTHH:MM 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Notes: 
1) 
Sort assessments per Subject, timepoint/Date and parameter. Parameters for each subject to be sorted as defined in Summary Descriptive Statistics Table. 
*The medical judgement for abnormal ECG interpretation is also presented in this column as CS: Clinically significant or NCS: Not clinically significant. 
 
Note: Similar layout will be used for Listings 16.2.8-10, and 16.2.8-11. Please adapt title and footnotes accordingly  
 
 


 
Statistical Analysis Plan (Table/Figure/Listing Shells)                                                                                                                                              mAbxience Research S.L. 
Project Number 7012755 (Sponsor Study Number: MB02-A-06-20) 
20 May 2021 (Final 1.0) 
Page 81 of 81 
Listing 16.2.8-12 Physical Examination Findings by Subject  
Subject/Age 
Treatment 
Timepoint 
Examination Date and Time  
Site/System 
Results 
101/29 
1 mg/kg MB02 - SP IV 
Screening 
YYYY-MM-DDTHH:MM 
General Appearance 
Normal 
 
 
 
 
Eye/Ear/Nose/Throat 
Normal 
 
 
 
 
Oral 
Normal 
 
 
 
 
Head and Neck 
Normal 
 
 
 
 
Chest/Lungs 
Normal 
 
 
 
 
Abdomen 
Normal 
 
 
 
 
Lymphatic 
Normal 
 
 
 
 
Neurologic 
Normal 
 
 
 
 
Extremities 
NE 
 
 
 
 
Psychiatric 
NE 
 
 
 
 
Other 
NE 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
NE: not evaluated.