Clinical trial NCT04238650
Conditions: Healthy Volunteers Male Japanese
Sponsor: mAbxience Research S.L.
Start date: 2019-08-02; Completion date: 2019-12-27
Enrollment: 49 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A Randomised, Double Blind, Two-Arm, Single Dose, Parallel Phase I Study To Compare the Pharmacokinetics, Safety and Immunogenicity of MB02 (a Proposed Bevacizumab Biosimilar Drug) and EU Approved Avastin® in Japanese Healthy Male Volunteers.

During the course of the study, the similarity in pharmacokinetics will be assessed by sampling the levels of drug in the blood, and by comparing these levels among the different administration arms. Safety, tolerability, and immunologic response to the administered drugs will also be evaluated throughout.

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

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 AUClast. 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 versus EU Avastin®

A mixed effects model with treatment arm as fixed effect will be used to compare natural-logarithmic transformed PK parameters (AUC\[0-∞+, AUClast and Cmax) between the two treatment arms (MB02 vs EU-approved Avastin®)

PK similarity between arms will be concluded if the 90% confidence intervals (CIs) for the geometric mean test/reference ratio of AUC(0-∞) fell within the predefined 0.80-1.25 bioequivalence interval.

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 titers, 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, EU 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: Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1. arm 2: Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
Interventions: intervention 1: MB02 (Bevacizumab Biosimilar) intervention 2: EU approved Avastin®
Intervention descriptions: intervention 1: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion intervention 2: Solution for intravenous infusion, single dose of 3mg/kg, administered as 90- minute infusion

Protocol documents:
Prot_002.pdf: 
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TABLE OF CONTENTS 
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Summary of Clinical Experience 
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Primary Objective 
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SELECTION OF STUDY POPULATION 
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Inclusion Criteria 
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Randomisation 
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Study Treatment Compliance 
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Drug Accountability 
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CONCOMITANT THERAPIES AND OTHER RESTRICTIONS 
7.1
Concomitant Medications 
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Diet 
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Exercise 
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Blood Donation 
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Contraception 
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STUDY ASSESSMENTS AND PROCEDURES 
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Pharmacokinetic Assessments 
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Pharmacokinetic Blood Sample Collection and Processing 
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Immunogenicity Assessments 
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Immunogenicity Blood Sample Collection and Processing 
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Analytical Methodology 
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Safety and Tolerability Assessments 
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Adverse Events 
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8.3.2
Clinical Laboratory Evaluations 
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8.3.3
Vital Signs 
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8.3.4
12-Lead Electrocardiogram 
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8.3.5
Physical Examination 
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APPENDIX 1


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9
SAMPLE SIZE AND DATA ANALYSES 
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9.1
Determination of Sample Size 
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9.2
Analysis Populations 
9.2.1
Pharmacokinetic Population 
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9.2.2
Safety Population 
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9.3
Pharmacokinetic Analyses 
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9.4
Safety Analysis 
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9.4.1
Medical Safety Monitoring 
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Interim Analysis 
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QUALITY CONTROL AND QUALITY ASSURANCE 
10.1
Auditing and Inspection 
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10.2
Monitoring 
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11
DATA HANDLING AND RECORD KEEPING 
11.1
Data Handling 
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11.2
Case Report Form 
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11.3
Records 
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ETHICAL AND REGULATORY CONSIDERATIONS 
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REFERENCES 
 0%–,QYHVWLJator’s Brochure. (Version -XO\
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APPENDICES 


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Appendix 1: Schedule of Assessments 


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SAP_003.pdf: 
Protocol Title: 
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NCT Number: 
EdϬϰϮϯϴϲϱϬ
Statistical 
Analysis Plan 
version date: 
Version ϭ.0, ϭϯ :ĂŶƵĂƌǇϮϬϮϬ


Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0)
Page 1 of 25
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
A RANDOMISED, DOUBLE BLIND, TWO-ARM, SINGLE DOSE, PARALLEL PHASE I 
STUDY TO COMPARE THE PHARMACOKINETICS, SAFETY AND IMMUNOGENICITY 
OF MB02 (A PROPOSED BEVACIZUMAB BIOSIMILAR DRUG) AND EU APPROVED 
AVASTIN® IN JAPANESE HEALTHY MALE VOLUNTEERS
Sponsor Protocol No.: MB02-A-04-18 
Syneos Health Clinique Inc. Project No.: 7004567 
Final Version: 1.0 
Date: 13-JAN-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 




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Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 3 of 25 
TABLE OF CONTENTS 
SIGNATURES ................................................................................................................... 2 
LIST OF ABBREVIATIONS ............................................................................................ 4 
1. 
Introduction ................................................................................................................. 6 
2. 
Study Objectives .......................................................................................................... 7 
2.1 
Primary objective ..................................................................................................... 7 
2.2 
Secondary objectives ............................................................................................... 7 
3. 
Study Design ............................................................................................................... 8 
3.1 
General Design ........................................................................................................ 8 
3.2 
Study Procedures ..................................................................................................... 8 
3.3 
Drug Administration ................................................................................................ 8 
3.4 
Subject Withdrawal and Replacement ..................................................................... 8 
4. 
Changes from the Protocol ........................................................................................ 10 
5. 
Study Endpoints ........................................................................................................ 11 
5.1 
Safety Endpoints .................................................................................................... 11 
6. 
Analysis Populations ................................................................................................. 12 
6.1 
Safety Population ................................................................................................... 12 
7. 
Interim Analyses ........................................................................................................ 13 
8. 
Study Population and Exposure ................................................................................ 14 
8.1 
Subject Disposition ................................................................................................ 14 
8.2 
Protocol Deviations ............................................................................................... 14 
8.3 
Demographics and Baseline Characteristics .......................................................... 14 
8.4 
Medical History ..................................................................................................... 15 
8.5 
Prior and Concomitant Medications ...................................................................... 15 
8.6 
Study Drug Administration ................................................................................... 15 
9. 
Safety Analyses ......................................................................................................... 16 
9.1 
Physical Examination Findings ............................................................................. 16 
9.2 
Adverse Events ...................................................................................................... 16 
9.3 
Laboratory Parameters ........................................................................................... 18 
9.4 
Vital Signs ............................................................................................................. 19 
9.5 
Electrocardiogram.................................................................................................. 20 
10. 
Percentages and Decimal Places ............................................................................... 21 
11. 
Data Handling ............................................................................................................ 22 
12. 
Handling of Missing Data ......................................................................................... 23 
13. 
Software to be Used .................................................................................................. 24 
14. 
Reference List ............................................................................................................ 25 
 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 4 of 25 
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 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 5 of 25 
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 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 6 of 25 
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-04-18, Version 1.2, dated 10 July 2019 (Syneos Project No. 7004567). 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 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 7 of 25 
2. 
Study Objectives 
2.1 
Primary objective 
x To demonstrate PK similarity, as primary assessed by the Area Under the Concentration-
time curve extrapolated to infinity (AUC(0-∞)) between the two study arms, MB02 and EU 
Avastin®. 
2.2 
Secondary objectives 
x Evaluation and comparison of derived PK parameters not covered by the primary 
endpoints for MB02 and EU Avastin®. 
x To compare the safety profile of MB02 and EU Avastin®. 
x To compare the immunogenicity of MB02 and EU Avastin®. 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 8 of 25 
3. 
Study Design 
3.1 
General Design 
This will be a Phase 1, double-blind, randomised, parallel-group, single-dose two-arm study to 
investigate and compare the PK, safety and immunogenicity profiles of MB02 with EU-approved 
Avastin® in Japanese healthy male subjects. A total of forty-eight subjects were randomised to 
one of following 2 arms in a 1:1 ratio: 
x Arm 1: MB02 as a 90 minute IV infusion 
x Arm 2: Avastin® sourced from the EU, as a 90 minute IV infusion. 
Twenty-four 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 3 mg/kg of one of the following treatments by IV infusion 
over 90 minutes. A total of 48 healthy adult male volunteers will be dosed; 24 subjects per 
treatment group, randomly assigned to one of the 2 treatment arms.  
Treatment A (MB02):  
3 mg/kg dose of MB02 (a proposed bevacizumab 
biosimilar drug), administered as a 90 minute IV 
infusion. 
Treatment B (EU Avastin®):  
3 mg/kg dose of EU-approved 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. 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 9 of 25 
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. 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 10 of 25 
4. 
Changes from the Protocol 
No changes in planned analyses were done compared to the protocol. 
 
 
 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 11 of 25 
5. 
Study Endpoints 
5.1 
Safety Endpoints 
The safety outcome measures for this study are as follows (refer to Section 9):  
x Incidence and severity of AEs  
x Incidence of laboratory abnormalities, based on haematology, clinical chemistry, 
coagulation and urinalysis test results  
x 12-lead electrocardiogram (ECG) parameters  
x Vital sign measurements  
x Physical examinations  
The immunogenicity of MB02 and EU Avastin® (refer to Section 9) 
x Determination of serum concentrations of anti-MB02 and anti-Avastin® antibodies.  


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 12 of 25 
6. 
Analysis Populations 
The analysis of safety, tolerability and immunogenicity 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 or Avastin®, and have at least 
one post dose safety assessment. 
 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 13 of 25 
7. 
Interim Analyses 
No formal interim analysis was planned in the protocol.  


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 14 of 25 
8. 
Study Population and Exposure 
No inferential analysis will be done. Only observed data will be used. 
8.1 
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 
8.2 
Protocol Deviations 
The protocol deviations will be categorized and listed by subject. 
8.3 
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], 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 15 of 25 
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 and PK populations. All 
demographic characteristics will be listed by subject. 
8.4 
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). 
8.5 
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 Sep2019, 
format B3 will be used to classify all medication reported during the study. 
All prior and concomitant medications will be listed by subject. 
8.6 
Study Drug Administration 
The study drug administration details (including treatment received, start and stop date and time 
of administration, total dose) will be listed by subject. 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 16 of 25 
9. 
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 signsand 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. 
9.1 
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 70 (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 and PK). 
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. 
9.2 
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 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 22.1 will be 
used to classify all AEs reported during the study by SOC and PT. 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 17 of 25 
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) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 18 of 25 
Grade 4: 
Life-threatening consequences; urgent intervention indicated 
Grade 5: 
Death related to AE 
An SAE is defined as any untoward medical occurrence that at any dose either: 
x Results in death 
x Is life-threatening 
x Requires inpatient hospitalisation or prolongation of existing hospitalisation 
x Results in persistent or significant disability/incapacity (disability is defined as a 
substantial disruption of a person’s ability to conduct normal life functions) 
x 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”. SAEs will be listed separately by subjects. 
9.3 
Laboratory Parameters 
Clinical laboratory (clinical chemistry, hematology, coagulation and urinalysis) results will be 
obtained at screening, Day -1 (check-in), Day 8, Day 14, Day 21, Day 28, Day 38, Day 50, 
Day 62 and Day 70 (EOS). 
Clinical chemistry parameters include the following: albumin, aspartate aminotransferase (AST), 
alanine aminotransferase (ALT), alkaline phosphatase (ALP), Blood urea nitrogen (BUN), 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. 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 19 of 25 
Serology parameters including: Hepatitis B surface antigen (HBs Ag), Hepatitis B surface 
antibody (anti-HBs), Hepatitis B core antibody (anti HBc), Hepatitis C antibody, Human 
immunodeficiency HIV antigen antibodies, and Syphilis (RPR method, TP antibody method) 
will be performed at screening. 
Urinary drug screen including: Cotinine, Amphetamines/methamphetamines, Barbiturates, 
Benzodiazepines, Cocaine (metabolite), Methadone, Phencyclidine, Opiates, 
Tetrahydrocannabinol/cannabinoids, and Tricyclic antidepressants; 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 
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 will include normal, low, and high relative to the laboratory reference ranges (or 
normal-abnormal for categorical variables). 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. 
 
9.4 
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 14, Day 21, Day 28, Day 38, Day 50, Day 62 and Day 70 (EOS). Tympanic 
membrane or axilla body temperature will be assessed at screening, Day 2, Day 10, Day 21 and 
Day 70 (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 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 20 of 25 
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. 
9.5 
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(predose), Day 3, Day 8 and Day 70 (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 screening, Day 1(predose), Day 3, Day 8 and Day 70 (EOS) 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.  
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. 
 
 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 21 of 25 
10. 
 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 
and, mean, standard deviation, and median will be presented with one more decimal place 
than the original values. 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 22 of 25 
11. 
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. 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 23 of 25 
12. 
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). 
 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 24 of 25 
13. 
Software to be Used 
The safety data tables and listings will be created using SAS®, release 9.2 or a higher version. PK 
figures will be created using R version 3.2.2 or higher.  The  study report text will be created 
using Microsoft® Office Word 2010, or a higher version. 


 
Statistical Analysis Plan (Without PK and Immunogenicity analysis) 
mAbxience Research S.L. 
Project Number 7004567 (Sponsor Study Number: MB02-A-04-18) 
13-JAN-2020 (Final 1.0) 
Page 25 of 25 
14. 
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.