Conditions: Healthy Volunteers
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 150
Healthy volunteers: yes

Brief summary:
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:
MB05 is being developed as a potential biosimilar to Synagis® for all indications for which Synagis® is approved. This study is designed to demonstrate PK similarity of the proposed biosimilar test product MB05 and the reference products EU- and US-Synagis®.This is a first-in-human study of the Synagis® biosimilar MB05. The reference product ynagis® was first approved by the US Food and Drug Administration (FDA) in 1998 and by the European Medicines agency (EMA) in 1999.

As a proposed biosimilar, the clinical experience with Synagis® (as described in the Synagis® summary of product characteristics) (most recent versions) is deemed applicable to MB05.

Arms:
arm 1: Sterile vial 100mg/1ml, single-dose 3mg/kg administered as intramuscular injection on day 1. arm 2: Sterile vial 100mg/1ml, single-dose 3mg/kg administered as intramuscular injection on day 1 arm 3: Sterile vial 100mg/1ml, single-dose 3mg/kg administered as intramuscular injection on day 1

Interventions: intervention 1: MB05 (Proposed palivizumab biosimilar) intervention 2: EU-Synagis® intervention 3: US-Synagis®
Intervention descriptions: intervention 1: Single IM dose of 3 mg/kg intervention 2: Single IM dose of 3 mg/kg intervention 3: Single IM dose of 3 mg/kg

Protocol document:
Prot_000.pdf: 
Protocol Title: 
Pharmacokinetic Study Comparing MB05 
(Proposed Palivizumab Biosimilar), EU-sourced 
Synagis® and US-sourced Synagis® in Healthy 
Volunteers.
NCT Number: 
NCT05121246
Protocol version 
date: 
Version 2.0, 07 June 2022 









































































































































































SAP_001.pdf: 
Protocol Title: 
Pharmacokinetic Study Comparing MB05 
(Proposed Palivizumab Biosimilar), EU-sourced 
Synagis® and US-sourced Synagis® in Healthy 
Volunteers.
NCT Number: 
NCT05121246
Statistical 
Analysis Plan 
version date: 
Version 2.0, 15 June 2023






 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 3 of 39 
 
Table of Contents 
1 
Introduction ....................................................................................................................... 7 
2 
Project Overview ............................................................................................................... 8 
2.1 
Description of Study Design .................................................................................. 8 
2.2 
Objectives ............................................................................................................... 8 
2.2.1 
Primary Objectives and Endpoints ..................................................................... 8 
2.2.2 
Secondary Objectives and Endpoints ................................................................ 8 
3 
Sample Size ..................................................................................................................... 10 
4 
Statistical Considerations ................................................................................................ 11 
4.1 
Standard Operating Procedures and Software ...................................................... 11 
4.2 
General Considerations ........................................................................................ 11 
4.3 
Key Definitions .................................................................................................... 12 
4.4 
Multiple Comparisons and Multiplicity ............................................................... 13 
4.5 
Handling of Missing Data .................................................................................... 13 
4.6 
Treatment Group and Visit Display Conventions ................................................ 13 
5 
Analysis Populations ....................................................................................................... 15 
5.1 
Safety Analysis Set (SS) ....................................................................................... 15 
5.2 
Pharmacokinetic Analysis Set (PKS) ................................................................... 15 
5.3 
Per Protocol Pharmacokinetic Analysis Set ......................................................... 15 
5.4 
Immunogenicity Analysis Set (IAS) .................................................................... 15 
6 
Participant Disposition .................................................................................................... 16 
7 
Analysis Set ..................................................................................................................... 17 
8 
Protocol Deviations ......................................................................................................... 18 
9 
Demographics and Baseline information ........................................................................ 19 
10 
Medical History ............................................................................................................... 20 
11 
Prior and Concomitant Medication ................................................................................. 21 
12 
Treatment and Exposure .................................................................................................. 22 
13 
Efficacy............................................................................................................................ 23 
14 
Safety ............................................................................................................................... 24 
14.1 
Adverse Events ..................................................................................................... 24 
14.2 
Safety Laboratory Assessments ............................................................................ 25 
14.3 
Vital Sign Assessments ........................................................................................ 26 
14.4 
12-Lead Electrocardiogram (ECG) ...................................................................... 26 
14.5 
Physical Examinations ......................................................................................... 27 
14.6 
Pregnancy Test and Follicle Stimulating Hormone Test ...................................... 27 
14.7 
Injection Site Reaction ......................................................................................... 27 
14.8 
Body Weight and Body Mass Index ..................................................................... 28 
15 
Pharmacokinetics ............................................................................................................. 29 
15.1 
Data Handing for PK Data ................................................................................... 29 
15.2 
Summary Statistics for Plasma PK Concentration Data ...................................... 29 
15.3 
Summary Statistics for Plasma PK Parameter ..................................................... 29 
15.4 
Concentration-Time Profiles ................................................................................ 30 
15.5 
Plasma PK Parameters .......................................................................................... 30 
15.6 
Other Important PK Considerations ..................................................................... 31 
15.7 
Bioequivalence Analysis ...................................................................................... 32 
16 
Pharmacodynamics .......................................................................................................... 33 
17 
Immunogenicity ............................................................................................................... 34 
18 
Changes to the Planned Analysis .................................................................................... 36 
19 
Interim and Final Analysis .............................................................................................. 37 
19.1 
Interim Analysis ................................................................................................... 37 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 4 of 39 
 
19.2 
Final Analysis (End of Study) .............................................................................. 37 
20 
Appendix 1 Time and Events Schedule........................................................................... 38 
21 
References ....................................................................................................................... 39 
 
 
 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 5 of 39 
 
List of Abbreviations 
 
Abbreviation 
Description 
ADA 
Anti-drug Antibody  
ADR  
Adverse Drug Reaction  
AEs  
Adverse Events  
ALP  
Alkaline Phosphatase  
ALT  
Alanine Aminotransferase  
aPTT  
Activated Partial Thromboplastin Time  
AST  
Aspartate Aminotransferase  
ATC  
Anatomical Therapeutic Class  
AUC0-inf  
Area Under the Concentration-Time Curve From 0 to Infinity  
AUC0-last 
Area Under the Concentration-Time Curve From 0 to Time of Last  
Quantifiable Concentration  
BLQ 
Below The Limit of Quantifiable  
BMI 
Body Mass Index 
CL/F  
Total Apparent Body Clearance  
Cmax  
Maximum Observed Concentration  
CS 
Clinically Significant 
CSR  
Clinical Study Report  
CV 
Coefficient of Variation  
DBP  
Diastolic Blood Pressure  
ECG  
Electrocardiogram  
eCRFs  
Electronic Case Report Forms  
GCP  
Good Clinical Practice  
GGT  
Gamma Glutamyl Transferase  
HDL  
High-Density Lipoprotein  
IAS 
Immunogenicity Analysis Set 
ID  
Identification  
IM 
Intramuscular Injection  
INR  
International Normalized Ratio  
LDH  
Lactate Dehydrogenase  
LDL  
Low-Density Lipoprotein  
MedDRA  
Medical Dictionary for Regulatory Activities  
NCS 
Not Clinically Significant 
PK  
Pharmacokinetics  
PKS 
Pharmacokinetic Analysis Set  
PT  
Preferred Terms  
PT  
Prothrombin Time  
SAEs  
Serious Adverse Events  
SAP  
Statistical Analysis Plan  
SBP  
Systolic Blood Pressure  
SD  
Standard Deviation  
SOC  
System Organ Class  
SOPs  
Standard Operating Procedures  


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 6 of 39 
 
SS  
Safety Analysis Set  
t1/2 
Apparent Terminal Elimination Half-Life  
TEAEs  
Treatment Emergent Adverse Events  
TFLs 
Tables, Listings, And Figures  
Tmax  
Time To Cmax  
TT 
Thrombin time  
UN 
Unknown 
Vz/F  
Apparent Volume of Distribution  
WBC  
White Blood Cells  
WHO-DD  
World Health Organization Drug Dictionary  
Ȝ]  
Terminal Elimination Rate Constant  
 
 
 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 7 of 39 
 
1 INTRODUCTION 
This Statistical Analysis Plan (SAP) provides the outline for the statistical analysis of the data 
collected for MB05-A-01-21 titled: “FANTASY–A Randomised, Double-Blind, 3-arm Parallel 
Study to Compare the Pharmacokinetics, Safety, Immunogenicity and Tolerability of MB05 
(Proposed Palivizumab Biosimilar), EU-sourced Synagis® and US-sourced Synagis®, 
Administered as a Single Dose Intramuscular Injection in Healthy Volunteers.” (Version 2.0 
dated 07 June 2022). 
This SAP is written with consideration of the recommendations outlined in the International 
Council for Harmonisation (ICH) E9 guideline entitled, “Guidance for Industry: Statistical 
Principles for Clinical Trials” and the ICH E3 guideline entitled, “Guidance for Industry: 
Structure and Content of Clinical Study Reports. 
The SAP will be finalized prior to database lock.  Any deviations from the SAP after database 
lock, reasons for such deviations, and all alternatives or additional statistical analyses that may 
be performed will be described the Clinical Study Report (CSR).   
If the SAP differs the statistical considerations in the protocol, details will be given in section 
18. 
Summary of Changes 
Statistical analysis plan version 1.0 was approved and executed on 29-Nov-2022. This SAP 
Version 2.0, 15-Jun-2023 was prepared to include a pharmacokinetic (PK) sensitivity analysis 
and to remove the analysis of neutralising antibody assessments from the analysis plan 
following sponsor confirmation that this test will no longer be performed. Section 5.2 
pharmacokinetic analysis set definition was updated to add the criteria to include subjects “who 
received any amount of study treatment". Section 14.8 was updated to include listings and 
summaries of body mass index (BMI). Additionally, the lead statistician for this study has 
changed to Paul Stevenson, and the PK signatory is Oriol Peris Serrano, and the sponsor medical 
monitor has changed to Andrea Espiragares. Avance Clinical’s address was also updated. 
 
 
 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 8 of 39 
 
2 PROJECT OVERVIEW 
2.1 
Description of Study Design 
This is a multicentre, randomised, double-blind, 3-arm parallel group study.  
Up to a total of 141 participants are planned to be enrolled and randomised to receive a single 
dose of MB05, EU-Synagis® or US-Synagis with participants randomised to Arm A, B or C in 
equal proportions (1:1:1). Participants will be enrolled across multiple sites in Australia and 
New Zealand. 
In Group 1, a total of 9 participants will be enrolled and dosed with 3 mg/kg MB05, 3 mg/kg 
EU-Synagis® or 3 mg/kg US-Synagis® (1:1:1). Once all participants in Group 1 have 
completed the Day 8 visit, a safety review committee (SRC) will meet to review all available 
safety data from Group 1, up to and including Day 8. No additional enrolment or dosing of the 
remaining participants should occur until the safety review is complete. 
Following approval by the SRC, Group 2 may be enrolled (n=132, randomised 1:1:1 MB05: 
EU-Synagis®: US-Synagis®). 
2.2 
Objectives 
2.2.1 
Primary Objectives and Endpoints 
The primary objective of this study is: 
x 
To establish the bioequivalence between MB05 and EU-Synagis®, between MB05 and US-
Synagis® and between EU-Synagis® and US-Synagis® up to Day 99, in terms of: 
o Area under the serum concentration versus time curve from time zero to infinity 
(AUC0-inf)  
o Maximum observed serum concentration (Cmax) 
 The primary endpoint of this study is: 
x 
Bioequivalence between MB05 and EU-Synagis®, between MB05 and US-Synagis® and 
between EU-Synagis® and US-Synagis® will be determined for AUC0-inf and Cmax 
2.2.2 
Secondary Objectives and Endpoints 
The secondary objectives of this study are: 
x 
To compare the pharmacokinetics (PK) of MB05 with EU- Synagis® and US-Synagis® 
following a single 3 mg/kg intramuscular injection (IM) injection in healthy adult 
volunteers. 
x 
To assess the safety and tolerability of MB05, EU- Synagis® and US-Synagis® 
x 
To assess the immunogenicity of MB05, EU- Synagis® and US-Synagis®  
The secondary endpoints of this study are: 
x 
Additional PK parameters to be determined include (but are no limited to): 
o Time to Cmax (Tmax) 
o Apparent terminal elimination half-life (t1/2) 
o Apparent total serum clearance (CL/F)  
o Apparent volume of distribution (Vz/F) 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 9 of 39 
 
o Area under the concentration-time curve from 0 to time of time t (AUCt) 
x 
Safety and tolerability endpoints include: 
o Incidence, type, and severity of Adverse events (AEs)  
o Changes from baseline in clinical laboratory results (haematology, serum chemistry, 
coagulation, and urinalysis)  
o Changes from baseline in vital signs parameters  
o Changes from baseline in physical examination findings  
o Change from baseline in body weight  
o Change from baseline in ECG parameters  
o Incidence, type and severity of injection site reactions  
x 
Immunogenicity endpoints include: 
o Incidence of anti-drug antibody (ADA) against MB05, US- and EU-Synagis®, 
including titres for ADA 
 
 
 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 10 of 39 
 
3 SAMPLE SIZE 
Up to a total number of 141 healthy subjects (male and female) are planned to be enrolled in the 
study. Subjects who meet the entry criteria will be randomised to receive a single dose of MB05, 
EU-sourced Synagis® or US-sourced Synagis® in a 1:1:1 fashion.  
The reported coefficients of variation (CVs) for AUC and Cmax for Synagis® vary between 
0.25 and 0.35. Based on a worst-case CV of 0.35 (Robbie et al., 2012), alpha of 0.05 (i.e., 
utilising a two-sided 90% CI around the mean difference) and a true hypothesised ratio for the 
mean difference of 1, a total of 135 subjects (45 subjects per arm respectively), 1:1:1 ratio) will 
provide approximately 85% power to demonstrate bioequivalence of MB05 with EU-sourced 
Synagis® and US-sourced Synagis®. Assuming a 5% dropout, a total of 141 subjects (47 
subjects per arm) are sufficient for this measure. 
 
 
 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 11 of 39 
 
4 STATISTICAL CONSIDERATIONS 
4.1 
Standard Operating Procedures and Software 
Data will be handled and processed per the sponsor representative’s (Avance) Standard 
Operating Procedures (SOPs), which are written based on the principles of Good Clinical 
Practice (GCP).  
All data conversions and statistical analyses will be performed using SAS® Version 9.4 or higher 
(SAS Institute, Cary, North Carolina, USA) with program code prepared specifically for the 
study by qualified Avance statisticians and SAS® programmers. 
4.2 
General Considerations 
All data collected during the study (data originating from the electronic Case Report Forms 
(eCRFs) or electronic transfers will be presented in the data listings.  Event-based listings will 
be sorted by treatment arm, participant identification and event start date/time (i.e., AE start 
date/time).  Assessment-based listings will be sorted by treatment arm, parameter name 
(alphabetically unless specifically stated otherwise), participant identification, visit and time 
point (if applicable). 
Unless otherwise stated, the following methods will be applied: 
x Continuous variables: Descriptive statistics will include the number of non-missing 
values (n), arithmetic mean, standard deviation (SD), median, minimum, and maximum 
values.   
The minimum and maximum values will be displayed to the same decimal precision as 
the source data, the arithmetic mean and median values will be displayed to one more 
decimal than the source data, and the SD values will be displayed to two more decimals 
than the source data for the specific variable. 
The appropriate precision for derived variables will be determined based on the 
precision of the data on which the derivations are based, and statistics will be presented 
in accordance with the abovementioned rules. 
x Categorical variables:  Descriptive statistics will include frequencies and percentages 
per category.  The denominator in all percentage calculations will be the number of 
Participants in the relevant analysis population with non-missing data, unless 
specifically stated otherwise.  Percentages will be rounded to one decimal place and will 
not be displayed for zero frequencies. 
x Presentation of p-values and confidence intervals: 90% confidence intervals will be 
computed, and reported to four significant figures, p-values will be displayed up to three 
decimal places and as “<0.001” if the value is below 0.001.  
x Repeat/unscheduled assessments:  Only values collected at scheduled study visits/time 
points will be presented in summary tables. If a repeat assessment was performed, the 
result from the original assessment will be presented as the result at the specific 
visit/time point. All collected data will be included in the data listings. If an unscheduled 
visit was intended to replace the missing assessment for a scheduled visit this should be 
documented clearly before values are carried forward as a scheduled visit assessment. 
x Assessment windows: All assessments will be included in the data listings and the 
protocol specified visit windows will not be applied to exclude assessments that were 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 12 of 39 
 
not performed on the protocol specified visit days. Protocol visit windows will be as per 
CRF data collection. 
x Result display convention:  Results will be centre aligned in all summary tables and 
listings. Participant identification, visit, and parameter labels and comments may be left 
aligned if required. 
x Conversion of categorical values: In some instance, continuous variables may be 
expressed as a range (i.e., < 9). The original source data captured will be displayed in 
data listing (i.e., <9), while values may be converted to another number for summary 
table purposes and the calculation of change from baseline values. As an example, a 
value of < 9 may be converted to one significant figure less as 8.  
x Date and time display conventions:  The following display conventions will be applied 
in all outputs where dates and/or times are displayed: 
R Date only:  YYYY-MM-DD 
R Date and time:  YYYY-MM-DD/HH:MM 
If only partial information is available, unknown components of the date or time will be 
presented as UN (Unknown), for example “2022-UN-UN” or “UN:UN” for time. 
4.3 
Key Definitions 
The following definitions will be used: 
x Date of the First Study Treatment Administration:  The date of the first study treatment 
administration is defined as the earliest date on which a study treatment was 
administered. 
x Baseline: The Baseline value is defined as the last available valid, non-missing 
observation for each Participant prior to first study treatment administration on Day 1.  
Repeat and unscheduled assessments will be included in the derivation of the Baseline 
values only if Baseline value is missing. 
x Change from Baseline:  The change from Baseline value is defined as the difference 
between the result collected/derived at a particular visit and the Baseline value. 
The change from Baseline value at each visit will be calculated for all continuous 
parameters using the following formula: 
Change from Baseline Value = Result at specified visit – Baseline Value 
The change from Baseline value will only be calculated if the specific visit result and 
the Baseline value for the parameter are both available and will be treated as missing 
otherwise. 
 
x Study Day:  The study day of an event is defined as the relative day of the event starting 
with the date of the first study treatment administration (reference date) as Day 1 (there 
will be no Day 0). 
The study day of events occurring before the first study treatment administration will be 
calculated as: 
Study Day = (Date of Event - Date of First Study Treatment Administration) 
For events occurring on or after Day 1, study day will be calculated as: 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 13 of 39 
 
Study Day = (Date of Event - Date of First Study Treatment Administration) + 1 
Study days will only be calculated for events with complete dates and will be undefined 
for events that are ‘Ongoing’ at the end of the study. 
x Actual Time from First Dose (hours) in PK related outputs is defined as: 
 (Date/Time of PK Sample collection) – (Date/Start Time of First Dose on Day 1). 
x Actual Time Deviation (hours) in PK related outputs is defined as:  
(Actual PK Sample Collection Time Post Dose) – (Scheduled PK Sample Collection 
Time Post Dose). 
x AE Duration: Adverse event duration (in days, to two decimal places), calculated as  
(Resolution Date + Resolution Time) – (Onset Date + Onset Time) 
AE duration will only be calculated for events with complete dates/times and will be 
undefined for events that are ‘Ongoing’ at the end of the study. 
4.4 
Multiple Comparisons and Multiplicity  
No multiplicity adjustment will be carried out for this study. 
4.5 
Handling of Missing Data 
In general, all data will be analysed as collected and missing values will not be imputed or 
replaced unless stated otherwise. 
4.6 
Treatment Group and Visit Display Conventions 
Summary Table: 
In summary table, the representation as below:  
x Arm A: 3 mg/kg MB05  
x Arm B: 3 mg/kg EU-Synagis®  
x Arm C: 3 mg/kg US-Synagis®  
x Overall 
Data Listing: 
In data listing, the following labels will be used: 
x Arm A: 3 mg/kg MB05  
x Arm B: 3 mg/kg EU-Synagis®  
x Arm C: 3 mg/kg US-Synagis®  
Visit labels: 
The following visit labels will be used:  
x Screening (Listing only) 
x Day -1 (Listing only) 
x Baseline (Table only) 
x Day 1  


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 14 of 39 
 
x Day 2  
x Day 3  
x Day 4 
x Day 5 
x Day 6 
x Day 8 
x Day 15 
x Day 22 
x Day 29 
x Day 36 
x Day 43 
x Day 57 
x Day 71 
x Day 85 
x End of Study  
x Early Termination (Listing only) 
x Unscheduled (Listing only) 
For listings, these labels will be used, with visit representing baseline (either screening/baseline 
or unscheduled visit marked as “[1]” with a footnote indicating it is baseline value). These visit 
displays will be sorted by date of visit within each Participant: 
 
 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 15 of 39 
 
5 ANALYSIS POPULATIONS 
5.1 
Safety Analysis Set (SS) 
The Safety Analysis Set will be defined as all randomized participants who received any amount 
of study treatment and will be based on the actual treatment received, if this differs from that to 
which the participant was randomized to. The Safety Analysis Set will be used for the 
summaries of all safety, baseline, and demographic data. 
5.2 
Pharmacokinetic Analysis Set (PKS) 
The Pharmacokinetic Analysis Set will be defined as all randomized participants who received 
any amount of study treatment and where there is sufficient data for reliable estimates of Cmax 
(as determined by the study Pharmacokineticist). 
5.3 
Per Protocol Pharmacokinetic Analysis Set 
The per protocol pharmacokinetic analysis set will include all subjects in the PK Analysis Set 
who have no major protocol violations that impact on pharmacokinetics. Subjects who do not 
complete the sampling per schedule but have sufficient data points to construct each 
concentration-time profile will be considered PK evaluable. 
5.4 
Immunogenicity Analysis Set (IAS) 
The Immunogenicity Analysis Set will be defined as all randomized participants who receive 
any amount of study treatment and who have at least 1 evaluable immunogenicity parameter 
post-dose and will be summarized according to the treatment actually received, if this differs 
from that to which the participant was randomized. The immunogenicity Analysis Set will be 
used for the summaries of all immunogenicity data.   
 
 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 16 of 39 
 
6 PARTICIPANT DISPOSITION 
The following participant disposition information will be reported: 
Summary of Disposition: 
 
x Number of Participants Completed 
x Number of Participants Not Completed 
x Reason for Non-Completion (percentage denominator based on number of withdrawn 
Participants) 
Counts and percentages will be reported for summary of disposition and will be provided using 
the Safety Analysis Set for treatment groups defined in Section 4.6.  
Listings will be provided for summary of disposition along with the date of study 
completion/discontinuation and the primary reason for non-completion. The listing will be 
provided by treatment groups (Section 4.6) sorted by Participant Identification (ID) for the 
Safety Analysis Set. 
 
 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 17 of 39 
 
7 ANALYSIS SET 
The following analysis set information will be reported: 
x Participants included in Safety Analysis Set 
x Participants included in Pharmacokinetic Analysis Set 
x Participants included in Per Protocol Pharmacokinetic Analysis Set 
x Participants included in Immunogenicity Analysis Set 
Counts and percentages for these participants under different population sets will be provided 
using the Safety Analysis Set for treatment groups defined in Section 4.6. 
Listings will be provided by treatment groups (Section 4.6) sorted by Participant ID for the 
Safety Analysis Set. 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 18 of 39 
 
8 PROTOCOL DEVIATIONS 
The following protocol deviations, but not be limited will be reported: 
x Inclusion/Exclusion Criteria – participant enrolled without meeting eligibility criteria. 
x Laboratory – deviations in lab sample processing, storage or shipment, or lab 
kits/supplies. 
x Visit Schedule visit window deviations, missed study visits. 
x IP Dosing and/or Accountability – participant received wrong treatment dosed outside 
of the protocol timepoints or received treatment not stored per protocol. 
x Concomitant Medication – participant received medication prohibited by the protocol. 
x Study Procedure/Tests – assessment window deviations, missed study assessments, 
incorrect order of assessments, assessments not conducted per protocol. 
x Randomisation 
x Safety Reporting (AEs/SAEs) – SAEs not reported within the expected turn-around-
time per regulatory reporting requirements (i.e., 24 hours from awareness). Pregnancy 
not reported within the expected turn-around time per regulatory reporting requirements 
(i.e., 24 hours from awareness). 
x Protocol Discontinuation Criteria – participant remained on the study after meeting 
protocol withdrawal criteria. 
x Informed Consent – any informed consent issues, including Participant not consented 
prior to study assessments/procedures commencing, new clinical study procedures 
performed before participant was re-consented, initial consent not signed/dated/ 
initialled per local regulatory guidelines. 
x Data Protection and Privacy 
x Participant Compliance – compliance issues with study requirements including diet and 
physical activity restrictions, study visit attendance. 
All protocol deviations will be assessed between Avance and the Sponsor during study before 
database lock and unblinding. 
The number of participants with at least one protocol deviations, and the category of protocol 
deviations will be summarized in accordance with Section 4.2 using the Safety Analysis Set for 
treatment groups defined in Section 4.6. 
Listing of all protocol deviations will be provided by treatment group (Section 4.6) sorted by 
Participant ID for the Safety Set A separate protocol deviation listing will be created for the 
Pharmacokinetic Analysis Set. 
 In addition, all available data collected in General Common Forms originating from the 
electronic Case Report Forms (eCRFs) will be provided in data listing by treatment groups 
(defined in Section 4.6) sorted by Participant ID for the Safety Set. 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 19 of 39 
 
9 DEMOGRAPHICS AND BASELINE INFORMATION 
The demographics variables to be reported are listed below: 
x Age (years) at baseline 
x Sex 
x Women of child-bearing potential 
x Race 
x Ethnicity  
x Height (cm) at baseline 
x Weight (kg) at baseline 
x BMI (kg/m2) at baseline 
These variables will be summarized using descriptive statistics in accordance with Section 4.2 
under the Safety Analysis Set for treatment groups defined in Section 4.6. Demographics 
variables will also be listed by treatment groups (Section 4.6) under the Safety analysis Set 
sorted by Participant ID. 
The following baseline information analysis will be listed by treatment groups (Section 4.6) 
under the Safety analysis Set sorted by Participant ID. 
x Urine Drug Screen 
x Alcohol Breath Test 
x Serology 
x COVID-19 Test 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 20 of 39 
 
10  MEDICAL HISTORY 
Medical history conditions will be coded using the version 25.0 of the Medical Dictionary for 
Regulatory Activities (MedDRA) that is available at the time of study commencement.  Terms 
will be coded to the full MedDRA hierarchy, but the system organ class (SOC) and preferred 
terms (PT) will be of primary interest for the analysis. Where SOC and PT are reported, the 
display will be sorted by the descending order by SOC and then by PT in the Overall treatment 
group. 
Medical history listings will be provided by treatment groups (Section 4.6) sorted by Participant 
ID for the Safety Analysis Set, along with start date, end date/ongoing status of medical history.


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 21 of 39 
 
11 PRIOR AND CONCOMITANT MEDICATION 
Prior and concomitant medications will be coded using World Health Organization Drug 
Dictionary (WHO-DD) (the version of WHODRUG GLOBAL B3 March 2022).  
x Prior Medications: Prior medications are defined as any medication where the use was 
stopped prior to the first administration of the study medication. 
x Concomitant Medications: Concomitant medications are defined as medications (other 
than the study drug) taken at least once after the start of first study drug administration.  
Medications stopped prior to the day of first study drug administration will not be 
considered concomitant medications, but they will be coded by WHO-DD and listed. If 
a clear determination cannot be made as to whether the medication is concomitant or not 
due to missing or incomplete data, the medication will be treated as concomitant 
medication taken during the study. 
The number and percentage of Participants using at least one concomitant medication will be 
displayed together with the number and percentage of Participants using at least one medication 
within each anatomical therapeutic class (ATC-Level 2) and preferred name. These will be 
summarized under the Safety Analysis Set for treatment groups defined in Section 4.6. Where 
ATC-Level 2 and preferred name are reported, the display will be sorted by the descending 
order by ATC-Level 2 and then by PT in the Overall treatment group. 
Listing of full details of prior and concomitant medications (medication taken, therapeutic class, 
start and stop dates/ongoing status, indication, routes, frequency, and dosage) will be provided 
by treatment group (Section 4.6) sorted by Participant ID and start date for the Safety Analysis 
Set.  


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 22 of 39 
 
12 TREATMENT AND EXPOSURE 
All study drug administration information (study drug administered [Yes/No], reason not 
administered, date and time (start time/end time) of administration, location, route, total dose 
[mg]/total volume [mL], dose interruption, reason for dose interruption, start time of 
interruption, volume administered prior to interruption, dose restarted, following the protocol, 
reason for not following the protocol, and entire volume not administered ) will be listed by 
treatment group (Section 4.6) sorted by Participant ID and visit for the Safety Analysis Set.


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 23 of 39 
 
13 EFFICACY 
No efficacy analysis is planned for this study. 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 24 of 39 
 
14 SAFETY 
All safety endpoints will be analyzed using the safety analysis set. 
14.1 
 Adverse Events 
AE verbatim terms will be coded using the version 25.0 of the Medical Dictionary for 
Regulatory Activities (MedDRA). AEs and SAEs are defined in the study protocol.  
x Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that 
occurred or worsened from the first administration of study drug. If determination cannot 
be made as to whether the event is treatment emergent due to missing or incomplete 
data, the adverse event will be treated as treatment emergent. 
x Treatment-Related are defined as any TEAEs reported with the causality of “Possibly”, 
“Probably”, “Definitely” to study treatment.  
All AE summaries will be restricted to TEAEs only. 
The TEAE summaries will include: 
x Overall Summary of TEAEs 
o TEAEs 
o Treatment Related TEAEs 
o Serious TEAEs 
o Serious Treatment Related TEAEs 
o TEAEs leading to death 
o TEAEs leading to study withdrawal 
The following table summaries will be presented by SOC and PT by treatment groups defined 
in Section 4.6:  
x TEAE summary by SOC and PT 
x TEAE summary by SOC, PT and Severity 
x TEAE summary by SOC, PT and relationship (study treatment) 
x Serious TEAE summary by SOC and PT 
x Treatment Related TEAE summary by SOC and PT 
x Serious Treatment-Related TEAE summary by SOC and PT 
x Treatment Related TEAE summary by SOC, PT and Severity 
x TEAE summary if events leading to study withdrawal by SOC and PT 
The above items will be presented using summary tables, which will include the number of 
participants (%) experiencing an event and the number of events and the number of events. If a 
Participant experienced the same adverse event multiple times, this will only be counted once 
for the purpose of counting the number of Participants experiencing that adverse event. 
Summary tables will be done for the Safety Analysis Set for treatment groups defined in Section 
4.6. Where SOC and PT are reported, the display will be sorted by the descending order by SOC 
and then by PT in the Overall treatment group. 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 25 of 39 
 
All AEs will be listed and will include the verbatim term, SOC, PT, SAE, start/end date/time, 
causality/severity, relationship to study treatment, relationship to procedure of injection, 
outcome, action taken, and study withdrawal. A separate listing will be created for SAEs. These 
listings will be presented by treatment groups (Section 4.6) sorted by Participant ID and AE 
start date for the Safety Analysis Set, along with age, sex, race, and baseline weight of the 
Participant. 
14.2 
 Safety Laboratory Assessments 
The following laboratory measurements will be taken at the time points specified in the study 
procedure schedule (Section 20): 
x Haematology: Haemoglobin, Haematocrit, Thrombocyte count (platelets), Reticulocyte 
count, White blood cells (WBC) count with differential: Neutrophil count, Eosinophil 
count, Basophil count, Lymphocyte count, and Monocyte count 
x Coagulation: Prothrombin time (PT), International normalized ratio (INR), Activated 
partial thromboplastin time (aPTT) and Thrombin time (TT)/thrombin clotting time 
(TCT). 
x Chemistry: Sodium, Potassium, Chloride, Bicarbonate, Phosphate, Calcium, Glucose, 
Amylase, Lipase, Uric acid, Albumin, Protein, Lactate dehydrogenase (LDH), Creatine 
kinase, Creatinine or creatinine clearance (Cockroft/Gault), Urea, Alkaline phosphatase 
(ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma 
Glutamyl Transferase (GGT), Total bilirubin (total and direct), Total cholesterol, high-
density lipoprotein (HDL), low-density lipoprotein (LDL), Triglycerides, Magnesium 
x Urinalysis and Urine Microscopy: pH, Specific gravity, Glucose, Protein, Ketones, 
Bilirubin, Blood, Nitrite, Urobilinogen, Leukocyte esterase 
For the haematology, coagulation, chemistry, continuous data summary statistics (as described 
in Section 4.2) will be presented for values and change from baseline value at each scheduled 
post baseline visit.  
In addition, Shift tables from Baseline at each visit for haematology, coagulation, and chemistry 
lab parameters (low, normal, and high) will also be presented using counts and percentages.  
For urinalysis, the urinalysis table will present counts and percentages of normal, abnormal 
clinically significant and non-clinically significant for the reported results at baseline and each 
post baseline visit for all parameters (as described in Section 4.2)  
These summary tables will be based on the Safety Analysis Set for treatment groups defined in 
Section 4.6. 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 26 of 39 
 
The listings of laboratory parameters (haematology, coagulation, chemistry, and urinalysis) will 
include all the information collected. In addition, the observations that are used as the baseline 
record (value) for each parameter will be flagged, and the change from baseline values (where 
applicable) at each scheduled post baseline (scheduled and unscheduled) visit will be presented. 
A separate listing for individual subject profiles to include any laboratory parameters with at 
least one post-dose value outside the laboratory’s reference ranges will be presented. These 
listings will be presented by treatment groups (Section 4.6) sorted by Participant ID and visit 
for the Safety Analysis Set, along with age, sex, race, and baseline weight of the Participant. 
14.3 
 Vital Sign Assessments 
The following vital signs measurements will be taken at the time points specified in the study 
procedure schedule (section 20): 
x 
Systolic blood pressure (SBP) (mmHg) 
x 
Diastolic blood pressure (DBP) (mmHg) 
x 
Pulse Rate (beats/min) 
x 
Respiratory rate (breaths/min) 
x 
Body Temperature (ºC) 
x 
Overall Clinical Interpretation:  
o Normal 
o Abnormal NCS (Not Clinically Significant) 
o Abnormal CS (Clinically Significant) 
The parameter names that will be used in the outputs will comprise of the test name and the unit 
of measure, for example, ‘Systolic Blood Pressure (mmHg)’. Parameters will be sorted in the 
order that the measurements were collected in on the Vital Signs eCRF page within the tables 
and listings. 
Summary statistics for vital sign parameters in accordance to Section 4.2 will be presented for 
baseline and for each scheduled post-baseline visit (which also includes change from baseline). 
In addition, overall clinical interpretation result (Normal, Abnormal not clinically significant, 
Abnormal and clinically significant,) will be summarized by counts and percentages for baseline 
and for each scheduled post baseline visit. These summary tables will be done for the Safety 
Analysis Set for treatment groups defined in Section 4.6. 
The listing of vital sign parameters will include all the information collected. In addition, the 
observations that are used as the baseline record (value) for each parameter will be flagged, 
and the change from baseline values at each post baseline (scheduled and unscheduled) visit 
will be presented. This listing will be presented by treatment groups (Section 4.6) sorted by 
Participant ID and visit for the Safety Analysis Set, along with age, sex, race, and baseline 
weight of the Participant. 
14.4 
 12-Lead Electrocardiogram (ECG) 
The following ECG measurements will be taken at the time points specified in the study 
procedure schedule (Section 20): 
x 
Heart Rate (bpm) 
x 
QT interval (msec) 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 27 of 39 
 
x 
PR interval (msec) 
x 
QRS duration (msec) 
x 
QTcF (msec) 
x 
Overall ECG clinical interpretation 
o Normal 
o Abnormal NCS (Not Clinically Significant) 
o Abnormal CS (Clinically Significant) 
The parameter names that will be used in the outputs will comprise of the test name and the unit 
of measure, for example, ‘Heart Rate (beats/min)’. Parameters will be sorted in the order that 
the measurements were collected in on the ECG eCRF page within the tables and listings. 
For ECG triplicates, the mean of ECG triplicated, and the worst clinical interpretation will be 
taken as the ECG values for each participant at applicable visit.  
Summary statistics for ECG parameters in accordance with Section 4.2 will be presented for 
baseline and for each scheduled post baseline visit (which also includes the change from 
baseline). In addition, overall ECG clinical interpretation result (Normal, Abnormal not 
clinically significant, and Abnormal clinically significant) will be summarized by counts and 
percentages for baseline and for each scheduled post baseline visit. These summary tables will 
be done for the Safety Analysis Set for treatment groups defined in Section 4.6.  
The listing of ECG parameters will include all the information collected. In addition, the 
observations that are used as the baseline record (value) for each parameter will be flagged, and 
the change from baseline values at each post baseline (scheduled and unscheduled) visit will be 
presented. This listing will be presented by treatment group (Section 4.6) sorted by Participant 
ID and visit for the Safety Analysis Set, along with age, sex, race, and baseline weight of the 
Participant. 
14.5 
 Physical Examinations 
The listing of physical examinations (including full and symptom directed examinations) will 
include all the information collected. This listing will be presented by treatment group defined 
in Section 4.6, sorted by Participant ID and visit for the Safety Analysis Set.  
14.6 
Pregnancy Test and Follicle Stimulating Hormone Test 
The listing of pregnancy test (urine and serum based) and FSH test (post-menopausal females 
only) will include all the information collected. This listing will be presented by treatment group 
defined in Section 4.6, sorted by Participant ID and visit for the Safety Analysis Set.  
14.7 
Injection Site Reaction 
The following Injection Site Reaction measurements will be taken at the time points specified 
in the study procedure schedule (Section 20): 
x 
Pain 
x 
Tenderness 
x 
Erythema/Redness 
x 
Induration/Swelling 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 28 of 39 
 
Parameters will be sorted in the order that the measurements were collected in on the Injection 
Site Reaction eCRF page within the tables and listings. 
The severity of the injection site reaction parameters will be summarized by counts and 
percentage for baseline and for each scheduled post-baseline visits. These summary tables will 
be done for the Safety Analysis Set for treatment groups defined in Section 4.6. 
The listing of injection site reaction parameters will include all the information collected. In 
addition, the observations that are used as the baseline record for each parameter will be flagged, 
and date/time of assessment, location, and other reaction at injection site (Yes/No) will be 
presented. This listing will be presented by treatment groups (Section 4.6) sorted by Participant 
ID and visit for the Safety Analysis Set. 
14.8 
Body Weight and Body Mass Index 
The listing of body weight assessment and BMI will include all the information collected. This 
listing will be presented by treatment group defined in Section 4.6, sorted by Participant ID and 
visit for the Safety Analysis Set.  
Summary statistics for body weight and BMI in accordance with Section 4.2 will be presented 
for baseline and for each scheduled post baseline visit (which also includes the change from 
baseline). The summary table will be done for the Safety Analysis Set for treatment groups 
defined in Section 4.6.  
The value of BMI that is recorded in the electronic data capture system will be sued for all 
listings and summary tables. BMI to be calculated using the height value recorded at screening. 
 
 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 29 of 39 
 
15 PHARMACOKINETICS 
All PK analyses will be conducted on the plasma concentration data of palivizumab. 
The individual subject listings of PK plasma concentrations will be presented for the Safety 
Analysis Set to include data for placebo subjects, while the summary of plasma concentrations 
will be based on the PK Analysis Set. 
Individual and mean PK parameters and any outputs related to PK parameters (e.g., 
bioequivalence analysis) will be based on the Per Protocol PK Analysis Set. 
Individual plasma concentration over time plots in linear and logarithmic scale will be presented 
for Full PK Analysis population. Mean plasma concentration over time plots will be presented 
for Per-protocol PK population. 
15.1 
 Data Handing for PK Data 
Plasma concentration values not collected or not determined will be treated as missing. The 
plasma concentrations that are below the limit of quantifiable (BLQ) will be designated a value 
of zero for the summary of concentration-time data, except for geometric mean, where they will 
be excluded from the calculation. 
For individual and mean plasma concentration-time plots, BLQ values will be set to zero for 
linear plots and BLQ values will be excluded from presentation semi-logarithmic scale. 
15.2 
Summary Statistics for Plasma PK Concentration Data 
Plasma concentrations of palivizumab will be used as supplied by the laboratory. The units of 
concentration and resulting PK parameters, with amount or concentration in the unit, will be 
presented as they are received from the laboratory. 
The actual sampling date and time and elapsed time relative to dosing time for plasma data will 
be listed by Participant and nominal sampling time, with time deviation (difference in hours 
between nominal and actual sampling times) calculated. These results will also be listed by 
treatment group (Section 4.6), sorted by Participant ID and visit. 
Summary statistics of PK concentration data of palivizumab (number of non-missing 
observation [n], arithmetic mean, standard deviation [SD], coefficient of variation [CV%], 
geometric mean, median, minimum and maximum) will be calculated for each time point and 
summarised by treatment group (Section 4.6). 
When reporting individual values and descriptive statistics for palivizumab concentration data, 
the following rules will apply regarding rounding and precision:  
x Descriptive statistics for PK concentration data will be reported to the same level of 
precision as the individual data for the minimum and maximum, and to 1 additional 
decimal place or 1 additional significant figure – depending on the reporting format of 
the original data with a maximum of 3 significant figures - for the mean (arithmetic and 
geometric), median and standard deviation. 
x Between-Participant CV% will be reported as a percentage to 1 decimal place. 
15.3 
Summary Statistics for Plasma PK Parameter 
Calculated PK parameters will be listed and summarized descriptively, including number of 
non-missing observation (n), arithmetic mean, SD, minimum, median, maximum, coefficient of 
variation [CV(%)], geometric mean, geometric CV%. 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 30 of 39 
 
When reporting individual values and descriptive statistics for PK plasma parameters data for 
palivizumab, the following rules will apply to rounding and precision:  
x Individual values for PK parameters will be reported to 3 significant figures.  
x Descriptive statistics for PK parameters will be reported to 3 significant figures.  
x Between-Participant CV% and geometric CV% will be reported as a percentage to 1 
decimal place.  
x Missing data will not be imputed. 
15.4 
Concentration-Time Profiles 
Individual plasma concentrations of palivizumab over actual time will be plotted with the 
concentration result (y-axis) displayed for the Full PK Analysis population on a linear scale and 
on a logarithmic scale.  
Mean plasma concentrations of palivizumab over scheduled time will be plotted with the 
concentration result (y-axis) displayed for the Per-protocol PK Analysis population on a linear 
scale and on a logarithmic scale.  
15.5 
Plasma PK Parameters 
For PK analysis, the PK samples from pre-dose to Day 99 will be considered. Actual sampling 
times will be used for the PK analysis, with the exception of pre-dose data which will be given 
the nominal time of 0.00 hr. If the actual sampling time is not recorded, the nominal sampling 
time will be used.  
The plasma concentrations below the limit of quantifiable (BLQ) values will be treated as 0 for 
PK analysis. 
The following PK parameters will, where possible be determined from the plasma concentration 
of palivizumab by non-compartmental analysis using Phoenix WinNonlin® software (version 
8.3 or higher).  
Parameter 
Definition 
Cmax 
Individual maximum concentration (Cmax) values are directly determined 
from the plasma concentration time profiles for each Participant. 
C29days 
Individual concentration values on Day 29±1 directly determined from the 
plasma concentration time profiles for each Participant. 
C57days 
Individual concentration values on Day 57±3 directly determined from the 
plasma concentration time profiles for each Participant. 
Tmax 
The time to attain maximum concentration. If the same Cmax concentration 
occurs at different time points, Tmax is assigned to the first occurrence of 
Cmax. 
AUC0-last 
The area under the curve spanning time interval from time zero to the last 
time point with measurable concentration using the linear trapezoidal rule. 
AUC0-168h 
The area under the curve spanning time interval from time zero up to 168h 
post dose using the linear trapezoidal rule 
AUC29days 
The area under the curve spanning time interval from time zero up to 
Day 29±1 post dose using the linear trapezoidal rule 
AUC57days 
The area under the curve spanning time interval from time zero up to 
Day 57±3 post dose using the linear trapezoidal rule 


Protocol Number: MB05-A-01-21 
Document Status: Final 2.0 
Version date: 15-Jun-2023
CONFIDENTIAL
Page 31 of 39
AUC0-inf
The area under the plasma concentration-time curve over the time interval 
IURP WLPH  H[WUDSRODWHG WR LQILQLW\  XVLQJ WKH IROORZLQJ IRUPXOD
Where, C't is the predicted concentration at the time t (last time point with a 
measurable plasma concentration above the quantification limit) at which 
TXDQWLILFDWLRQ ZDV VWLOO SRVVLEOH WKH FDOFXODWLRQ RI Ȝ] RU NHO LV JLYHQ EHORZ
AUC%extrap
The percentage of the AUC that has been extrapolated beyond the last 
observed data point, using the following formula 
Ȝ] RU Kel
The apparent terminal elimination rate constant will be estimated from a 
regression of ln(C) versus time over the terminal log-linear drug disposition 
portion of the concentration-time profiles.
t½
The terminal half-life will be calculated from the terminal rate constant using 
the equation: 
CL/F
Apparent total plasma clearance will be calculated as following equation:
Where D = Administered dose; AUC0- = AUC0-inf
Vz/F
Apparent terminal volume of distribution will be calculated according to the 
following equation:
The following will be considered for reporting the PK parameters:
x
The PK parameters which are not determined from PK analyses due to inadequate 
concentration data or missing data will be considered as ‘not estimable (NE)’. 
x
No value of Oz or Kel, CL/F and Vz/F, AUC0-inf, and t1/2 will be reported for cases that 
do not exhibit a terminal log-linear phase in the concentration versus time profile. 
Criteria which may indicate a failure to exhibit a terminal log-linear phase in the 
concentration-versus-time profile include:
o
Positive slope for log regression fit
o
r²adj < 0.75 
o
Time points in the interval used in estimating the half-life span less than one 
half-life
o
Fewer than 3 points with measurable concentration after Tmax
x
Profiles which meet any of the above criteria will be reviewed on a case-by-case basis. 
Any variations from the above criteria will be noted as a comment in the data file of 
parameters.
15.6
Other Important PK Considerations
x
If data permits, the other PK parameters may be reported.  
q


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 32 of 39 
 
x If Tlast = Tmax; Cmax will not be reported for that Participant in the listings. It will be 
footnoted to indicate that sampling timepoints were not appropriate for that Participant. 
15.7 
Bioequivalence Analysis  
The bioequivalence analysis will be conducted for Cmax, AUC0-inf and AUC0-last. Additionally, 
the bioequivalence analysis will also be conducted for concentrations collected on Days 29±1 
day and 57±3 days as well as for partial AUC up to 168 hours, Days 29±1 day and 57±3. Natural 
log-transformed PK parameter Cmax, C29days, C57days, AUC0-last and AUC0-inf, AUC0-168h, and AUC 
up to Days 29 and 57 will be analysed using the general linear model with the treatment as fixed 
via PROC GLM in SAS. For the purpose of the analysis, a preliminary ANCOVA model 
including variables group, age, sex, BMI and weight will be performed. If variables age, sex, 
BMI or weight were to be significant in this analysis, these variables will be kept in the final 
analysis. Upon review of the immunogenicity analysis, secondary ANCOVA analysis including 
ADA as a categorical or numerical variable could be performed. The 90% confidence intervals 
of the geometric least square mean ratio of test and reference i.e., MB05 group means relative 
to the EU-Synagis group means will be obtained by back transformation.  
The following comparisons will be done: 
(1) MB05 as Test VS EU-Synagis® as Reference 
(2) MB05 as Test VS US-Synagis® as Reference  
(3) EU-Synagis® as Test VS US-Synagis® as Reference 
Bioequivalence will be concluded for Cmax, AUC0-last, AUC0-inf and additional parameters C29days, 
C57days and partial areas AUC0-168h, AUC29days and AUC57days between test and refence, if the 90% 
CIs for the ratio of geometric least squares means are contained within the range 80.00% to 
125.00%. However, for Cmax, a wider range 70.00% to 143.00% could also be considered.  


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 33 of 39 
 
16 PHARMACODYNAMICS 
No pharmacodynamics analysis is planned for this study. 
 
 




 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 35 of 39 
 
Subject ADA status is defined based on the sample ADA status as follows: 
x Baseline ADA positive subject: A subject with baseline ADA positive sample 
x Baseline ADA negative subject: A subject with baseline ADA negative sample or no 
evaluable ADA assessment at baseline 
x ADA positive subject: A subject with at least one ADA positive sample relative to 
baseline at any time after initiation of treatment 
x ADA negative subject: A subject with no ADA positive sample (no treatment induced, 
or treatment boosted) after initiation of treatment. 
Immunogenicity data (ADA status [positive or negative] and titers (only applicable when ADA 
result is positive) will be listed by treatment group (Section 4.6) under the IAS, sorted by 
Participant ID and visit. 
ADA status result will be summarized by counts and percentages of subjects testing positive for 
ADA for baseline (Day 1, pre dose) and for each scheduled post baseline visit. ADA titre data 
at each timepoint will be summarised using summary statistics.  
Select analyses may be repeated for subsets with or without ADA and de novo ADA formation 
as appropriate including the association between PK parameters CL/F and AUC0-inf and TI-
ADA status may be explored, as needed. 
These summary tables will be done for the IAS for treatment groups defined in Section 4.6.  
 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 36 of 39 
 
18 CHANGES TO THE PLANNED ANALYSIS 
Not applicable. 


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 37 of 39 
 
19 INTERIM AND FINAL ANALYSIS  
19.1 
Interim Analysis 
No formal interim analyses are planned for this study. 
19.2 
Final Analysis (End of Study) 
The final analysis will be conducted after all Participants have completed the study, the clinical 
database has been locked, and the analysis populations have been approved prior to unblinding. 
The final analysis will be based on the final version of the SAP. Any deviations from the planned 
analysis will be documented in the CSR. 
 
 
 


Protocol Number: MB05-A-01-21 
Document Status: Final 2.0
Version date: 15-Jun-2023
CONFIDENTIAL
Page 38 of 39
20 APPENDIX 1 TIME AND EVENTS SCHEDULE


 
 
Protocol Number: MB05-A-01-21  
Document Status: Final 2.0 
Version date: 15-Jun-2023 
 
CONFIDENTIAL 
 
 
 
Page 39 of 39 
 
21 REFERENCES 
1) Clinical Study Protocol Version 2.0 dated 07 June 2021. 
2) Robbie GJ, Zhao L, Mondick J, Losonsky G, Roskos LK. Population pharmacokinetics 
of palivizumab, a humanized anti-respiratory syncytial virus monoclonal antibody, in 
adults and children. Antimicrob Agents Chemother. 2012 Sep;56(9):4927-36. Erratum in: 
Antimicrob Agents Chemother. 2012 Oct;56(10):5431.