Clinical trial NCT02293460
Conditions: Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Keywords: Peripheral neuropathy Disimmune disease Neurology Chronic disease Rare disease
Sponsor: Laboratoire français de Fractionnement et de Biotechnologies
Start date: 2015-05-01; Completion date: 2017-09-29
Enrollment: 44 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Primary objective:

To assess the efficacy of I10E in improving the disability of patients with CIDP.

Secondary objective:

To assess the safety of I10E in patients with CIDP.

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: I10E
Intervention descriptions: intervention 1: Patients who meet all eligibility criteria will receive one dose of IMP at 2g/kg over 2-5 days followed by 7 doses of IMP at 1g/kg over 1-2 day(s), every 3 weeks.

Duration of treatment period: 21 weeks +/- 7 days.

Protocol documents:
SAP_002.pdf: 
 
COVER PAGE 
 
 
TITLE: An international, multicentre, efficacy and safety study of I10E in initial and 
maintenance treatment of patients with Chronic Inflammatory Demyelinating 
Polyradiculoneuropathy 
 
NCT Number: NCT02293460 
 
 
DOCUMENT: Statistical analysis plan (v3.0)  
 
 
VERSION & DATE OF DOCUMENT: Version 3.0; December 7, 2018 




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MODIFICATION HISTORY
Unique Identifier 
for this version
Author
Changes from previous version
V3.0
Refer to Statistical Analysis Plan 
Amendment request form




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TABLE OF CONTENTS
MODIFICATION HISTORY....................................................................................................2
TABLE OF CONTENTS ........................................................................................................4
LIST OF TABLES..................................................................................................................5
1.
LIST OF ABBREVIATIONS............................................................................................6
2.
INTRODUCTION ............................................................................................................8
2.1.
Study Objectives .................................................................................................................... 8
2.1.1.
Primary objective ........................................................................................................... 8
2.1.2.
Secondary objectives...................................................................................................... 8
2.2.
Study Design.......................................................................................................................... 8
2.3.
Sample Size............................................................................................................................ 8
2.4.
Investigational Schedule and Randomisation ........................................................................ 8
2.5.
Evaluation Criteria ................................................................................................................. 9
2.5.1.
Primary efficacy criterion .............................................................................................. 9
2.5.2.
Secondary efficacy criterion .......................................................................................... 9
2.5.3.
Safety criteria ................................................................................................................. 9
2.5.4.
Exploratory criteria ........................................................................................................ 9
2.6.
Study Plan Table .................................................................................................................. 10
3.
GENERAL STATISTICAL CONSIDERATIONS...........................................................13
3.1.
Description of Variables ...................................................................................................... 13
3.2.
Handling of Missing Data and Outliers ............................................................................... 13
3.3.
Handling of Local Laboratory Data..................................................................................... 14
3.4.
Multiplicity Issues, Subgroup Analysis, Interim Analysis, Blinding and Randomisation... 14
3.5.
Definition of the Protocol Deviations and Population......................................................... 15
3.5.1.
Populations................................................................................................................... 15
3.5.2.
Protocol deviations....................................................................................................... 15
4.
STATISTICAL ANALYSIS............................................................................................16
4.1.
Disposition of Patients ......................................................................................................... 16
4.2.
Protocol Deviations.............................................................................................................. 16
4.3.
Demographic and Baseline Characteristics.......................................................................... 17
4.4.
Prior and Concomitant Treatment........................................................................................ 17
4.5.
Compliance .......................................................................................................................... 18
4.5.1.
Course/infusion level ................................................................................................... 18
4.5.2.
Patient level.................................................................................................................. 19
4.6.
Efficacy Analyses................................................................................................................. 19
4.6.1.
Primary efficacy endpoint............................................................................................ 19
4.6.2.
Secondary efficacy endpoints ...................................................................................... 20
4.7.
Safety Analyses.................................................................................................................... 22
4.7.1.
Extent of exposure........................................................................................................ 22


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4.7.2.
Adverse events ............................................................................................................. 24
4.7.3.
Other safety endpoints.................................................................................................. 27
4.8.
Pharmacokinetics ................................................................................................................. 30
4.9.
Exploratory analyses............................................................................................................ 30
4.10.
Changes in the Conduct of the Study or Planned Analysis.................................................. 31
4.10.1.
Efficacy........................................................................................................................ 31
4.10.2.
Safety............................................................................................................................ 31
4.10.3.
Ancillary study............................................................................................................. 31
5.
APPENDICES...............................................................................................................31
5.1.
Listings................................................................................................................................. 31
5.2.
Statistical Software............................................................................................................... 31
5.3.
Standard Operating Procedures............................................................................................ 31
5.4.
Audit and Quality Control.................................................................................................... 32
5.4.1.
Audit............................................................................................................................. 32
5.4.2.
Quality control ............................................................................................................. 32
5.5.
Statistical Review................................................................................................................. 32
5.6.
Bibliography......................................................................................................................... 32
5.7.
Basic Derived Variables....................................................................................................... 33
5.7.1.
Baseline characteristics................................................................................................ 33
5.7.2.
Safety............................................................................................................................ 34
5.7.3.
Exposure....................................................................................................................... 34
5.7.4.
Other characteristics..................................................................................................... 34
5.7.5.
Efficacy........................................................................................................................ 35
5.7.6.
Reference tables for derivations................................................................................... 36
LIST OF TABLES
Table 5–1: Reference ranges for normalization of local laboratory data............................................36
Table 5–2: Normative values for grip strength ...................................................................................37


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1. LIST OF ABBREVIATIONS
Ab
Antibody
ACR
Albumin to Creatinine Ratio
AE
Adverse Event
AER
Albumin Excretion Rate
ALP
Alkaline Phosphatase
ALT
Alanine Amino Transferase
AST
Aspartate Amino Transferase
ATC
Anatomical Therapeutic Chemical
BAFF
B Cell Activating Factor
BMI
Body Mass Index
bpm
Beats per Minute
CGI
Clinical Global Impression
CI
Confidence Interval
CIDP
Chronic Inflammatory Demyelinating Polyradiculoneuropathy
CRA
Clinical Research Associate
CRF
Case Report Form
CRO
Contract Research Organization
CNTN1
Contactin 1
DILI
Drug-induced Liver Injury
dps
Decimal Places
EOS
End of Study
FAS
Full Analysis Set
FCR
FC-gamma Receptors
GFR
Glomerular Filtration Rate
GT
Glutamyl Transferase
Hb
Hemoglobin
HBc
Hepatitis B core Antigen
HBs Ag
Hepatitis B surface Antigen
HCV
Hepatitis C Virus
HIV
Human Immunodeficiency Virus
ICH
International Conference on Harmonization
Ig
Immunoglobulin 
IgA
Immunoglobulin A
IgG
Immunoglobulin G
IMP
Investigational Medicinal Product
INCAT
Inflammatory Neuropathy Course and Treatment


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IVIG(g)
Intravenous Immunoglobulin
KM
Kaplan-Meier
kPa
Kilopascal (Pressure Unit)
LDH
Lactate Dehydrogenase
LFT
Liver Function Test
LLN
Lower Limit of Normal
LOCF
Last Observation Carry Forward
LOESS
Local Polynomial Regression 
MCV
Mean Corpuscular Volume
MDRD
Modified Diet in Renal Disease
MedDRA
Medical Dictionary for Regulatory Activities
MRC
Medical Research Council
NF155
Neurofascin 155
PCR
Protein to Creatinine Ratio
PER
Protein Excretion Rate
PPS
Per Protocol Set
PT
Preferred Term
R-ODS
Rasch-built Overall Disability Scale
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SAS
Statistical Analysis System
SCIG(g)
Subcutaneous Immunoglobulin
SI
Standard International
SMQ
Standardized MedDRA Query
SOC
System Organ Class
SOP
Standard Operating Procedure
SWI
Standard Working Instruction
TAAE
Temporarily Associated Adverse Event
TEAE
Treatment Emergent Adverse Event
TTS
Total Treated Set
ULN
Upper Limit of Normal
USG
Ultrasonography
WHO
World Health Organisation


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2. INTRODUCTION
2.1. Study Objectives
2.1.1. Primary objective
The primary objective of this study is to assess the efficacy of I10E in improving the disability of 
patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).
2.1.2. Secondary objectives
The secondary objective of this study is to assess the safety of I10E in patients with CIDP.
The secondary objectives also include the following exploratory objectives:

To assess a potential relationship between serum total IgG trough levels, biomarkers levels and 
clinical response - as assessed by neurological scales - in patients with CIDP.

To assess a potential relationship between ultrasonography (USG) coupled to neurophysiology 
analysis of nerves and clinical response - as assessed by neurological scales - in patients with 
CIDP (ancillary study in Italy).
2.2. Study Design
This study is a phase III, international, multicentre, single-arm, open-label, prospective study.
2.3. Sample Size
The study is designed to demonstrate superiority of I10E to an historical control in terms of 
responder rate. The historical responder rate with placebo is estimated from the ICE study (Hughes 
RA 2008). As a conservative estimate the upper boundary of the 95% confidence interval (CI) of the 
observed rate is used (observed rate 12/58 = 20.7%, 95% CI [11.2%, 33.3%]). Based on this 
historical placebo responder rate of 33.3% and a 60% responder rate with I10E, 38 evaluable 
patients are needed in order to obtain 90% power using an exact binomial test with a one-sided 
nominal level of significance =2.5%. Presuming 10% non-evaluable patients, 42 patients will be 
included in the study (around one third of all patients will be either Immunoglobulin [Ig]-naïve or 
relapsing Ig-pre-treated).
2.4. Investigational Schedule and Randomisation
Depending on the version of protocol, the total duration of the study for a patient is approximately 
24-27 weeks or 24-29 weeks. Each patient is screened during a maximum of 15 days or 4 weeks. 
The duration of treatment is approximately 21 weeks. A follow-up period of 3 weeks +/- 7 days will 
take place after the administration of the last study drug. At the end of the follow-up period, patients 
will undergo an EOS visit.
Randomisation is not applicable in this single-arm study.


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2.5. Evaluation Criteria
2.5.1. Primary efficacy criterion
The primary efficacy criterion is response rate at the End-of-Study visit (EOS). Response is defined 
as a decrease 1 point in the adjusted inflammatory neuropathy course and treatment (INCAT) 
disability score between baseline and the EOS visit.
2.5.2. Secondary efficacy criterion
The secondary efficacy endpoints are the following:

Response rate at 12 weeks

Time to response

Rate of patient with no change in CIDP treatment at 12 weeks and EOS visit

Changes from baseline to 12 weeks and EOS visit in the following scores:
Adjusted INCAT disability score
Grip strength with the Martin vigorimeter in both hands 
Rasch-built Overall Disability Scale (R-ODS)
Patient and Investigator Clinical Global Impression (CGI)
Medical Research Council (MRC) 12 muscles sum score (0 to 5)
Rasch-modified MRC sum score (0 to 3).
2.5.3. Safety criteria
The safety criteria include:

Treatment emergent adverse events (TEAEs)

Serious adverse events (SAEs)

Temporarily associated adverse events (TAAEs), i.e., AEs that begin during an infusion or 
within 72 hours after an infusion

Clinically significant changes from baseline in vital signs 

Clinically significant changes from baseline in laboratory parameters
2.5.4. Exploratory criteria
Biomarker study

Anti-Contactin 1 (CNTN1) and anti-Neurofascin 155 (NF155) antibodies titers at screening and 
EOS visit

Fcreceptor IIB (FcRIIB) B cells marker levels at visits V2, V3 and V4

B-cell activating factor (BAFF) at visits V2, V3, V4 and EOS visit

Complement components (C3 and C4 antigens, CH50) at visits V2, V3, V4 and EOS visit

Serum total IgG trough levels at each visit, within 24 hours prior to study drug administration






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a
To be done in all patients. See below for actions dependent on urine protein reagent strip result at screening:
Urine protein reagent strip test result
Action
Negative or Trace
No further urine test required
1 cross (1 +)
Verify eligibility after either assessing AER or PER from a 24h-urine collection 
sampled before the first study drug course,
or assessing ACR or PCR from a spot urine sample immediately following the urine 
protein reagent strip test (i.e. urine obtained before study drug administration).
2 crosses (2 +) or more
Patient should be excluded
b
To be performed before study drug administration in patients who at screening tested for urine protein reagent strip result "1 cross 
1 (+) and/or had GFRc in the range of 60-80 mL/min/1.73m2:
Urine protein reagent strip test result
Action
Negative or Trace
No further urine test required
1 cross (1 +) or more
Assess either AER or PER from a 24h-urine collection sampled at least 7 days after 
the end of the previous study drug course
or assess ACR or PCR from a spot urine sample immediately following the urine 
protein reagent strip test (i.e. urine obtained before study drug administration).
At all visits except End of Study visit: The Investigator must review these results in 
time prior to the next study drug administration and consider if any of the Early 
Discontinuation Criteria / Stopping Rules (see Section 5.4 of the protocol) apply.
c
According to modification of diet in renal disease (MDRD) calculation
d
Total bilirubin in all patients; if total bilirubin ULN, free bilirubin will be assessed from the same blood sample, as total bilirubin


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3. GENERAL STATISTICAL CONSIDERATIONS
3.1. Description of Variables
Continuous data will be described using number of valid observations, number of missing 
observations, mean, standard deviation, median, quartiles, minimum and maximum.
Categorical data will be described using number of missing observations, number of valid
observations per category and percentage. Number of missing observations will not be taken into 
account for the calculation of percentages.
For descriptive statistics, the following number of decimal places (dps) will generally be applied:

3 dps for values in [0, 0.9995)

2 dps for values in [0.9995, 9.995)

1 dp for values in [9.995, 99.95)

0 dp for values 99.95
For negative values the same rule will be followed using the absolute value.
For original case report form (CRF) variables the minimum and maximum will use the same number 
of dps as the raw data. Statistics on count variables (e.g. number of infusions) will generally be 
presented with 1 dp while the minimum and maximum will be presented without dp. Percentages 
will be presented with 1 dp. Exceptions from these rules might be applied when necessary.
3.2. Handling of Missing Data and Outliers
Regarding the primary criterion, a patient will be also considered as a non-responder if the patient is 
withdrawn due to lack of efficacy of the treatment (insufficient response to the investigational 
medicinal product [IMP]). In all other cases, if the INCAT score at EOS visit is missing, then the 
Last Observation Carried Forward (LOCF) approach will be applied and the last available adjusted 
INCAT disability score will replace the missing value at EOS visit.
The LOCF approach will also be used to handle the missing data of the secondary endpoint for 
adjusted INCAT and response at week 12 only.
When AEs are documented in the diary, dates of AE onset may be missing and as a result, TAAE 
cannot be defined. For AEs with a missing or incomplete start date, the response to the question 
“Did the AE start within 72 hours of an infusion” will be used for determining if the AE is 
temporally related to the infusion.
Partial dates of first symptoms and partial dates of diagnosis will be imputed by 15 if only the day is 
unknown and by 1st July if day and month are unknown. No imputation will be done if the year is 
unknown.
For the calculation of duration of AEs, partial start and end dates will be imputed with the first and 
last possible date within the period defined by the partial date, respectively. In general, no 


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calculation of duration will be made if either the start date or stop date is missing, i.e., cannot be 
imputed using pre-determined rules. No other general rules for the replacement of missing data are 
planned.
Data listings will always show the original CRF reported values and not the imputed values.
3.3. Handling of Local Laboratory Data
Local laboratory data will first be standardized. Standardization is the process of converting original 
local laboratory results to agreed standard international (SI) units. This process allows laboratory 
parameters to be presented in the same measurement units across the study.
Given that local laboratories are utilized for the study, normalization of the laboratory results will be 
performed (Karvanen 2003). Normalization is the process of transforming results from different 
local laboratories in such a way that the results are directly comparable. For normalization the 
parameter lower and upper limits from a local laboratory (SLo,SUp - see Section 5.7.6. 1) provided by 
Clinical Research Physician are chosen to represent a standard laboratory. The standardized reported 
result (RS) and the local lower and upper limits for given parameter (ILo,IUp) are then placed into an 
expression, of which the now normalized result (RN) may be treated as if it was obtained from a 
central laboratory.
Either  = 	 + 

 ×  −	 known as location-scale formula
Or  =  × 

 known as the scale formula
Note that standardization (i.e., unit conversion to SI unit) will be done prior to normalization; this 
allows the laboratory results to be converted to the same measurements prior to being transformed 
so that results can be directly comparable.
The normalized result will be used for descriptive summaries; displays of laboratory categories such 
as abnormalities and shifts from baseline based on Low (below lower limit of normal [LLN]), 
Normal (between LLN and upper limit of normal [ULN]) and High (above ULN) classifications and 
displays for observed and change values. When normalization of a parameter is not possible (e.g. 
estimated Glomerular Filtration Rate), then the untransformed standardized result will be presented.
Normalizations will be performed using the ranges provided in Section 5.7.6. 1.
3.4. Multiplicity Issues, Subgroup Analysis, Interim Analysis, Blinding and Randomisation
All analyses will be presented according to the following subgroups and overall:

Ig-naïve patients

Relapsing Ig-pretreated patients
However, statistical tests will be performed only for the overall population (not by subgroup).
No interim analyses will be performed and no p-value will be calculated for each subgroup 
separately. Therefore, no adjustment for multiplicity will be needed.


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Secondary and exploratory analyses are purely descriptive even if p-values will be presented, 
therefore no multiplicity issues are present. No p-value will be provided by subgroup.
Summary of TEAEs will also be presented by relevant subgroups (e.g., by age group [65 years and 
65 years], sex, race [white, non-white and unknown], and BMI [30 kg/m2 and 30 kg/m2]).
Likewise, blinding and randomisation is not applicable in this single-arm, open-label trial.
3.5. Definition of the Protocol Deviations and Population
3.5.1. Populations
The definition of analysis sets is as follows:

Total Treated Set (TTS): all patients who received at least one administration of the study drug.

Full Analysis Set (FAS): all TTS patients having an available assessment of the primary efficacy 
criterion.

Per Protocol Set (PPS): all FAS patients without any major deviations from protocol (see Section
3.5.2).
If a patient is treated with a non-allowed treatment during the study period, then all efficacy 
variables measured after the intake of these non-allowed treatments will be censored for the efficacy 
analyses.
The TTS will be used for the analysis of safety data.
The FAS will be used for the primary analysis of efficacy data and the PPS to test its robustness.
3.5.2. Protocol deviations
The protocol deviations and corresponding categories are defined in the protocol deviation plan as 
well as their consequence for the inclusion in the different analysis sets. The following protocol 
deviations categories will be studied:

Deviations regarding inclusion criteria

Deviations regarding exclusion criteria

Deviations regarding the study drug 

Deviations regarding safety assessments

Deviations regarding assessment of laboratory parameters (including biomarkers)

Deviations regarding visit windows

Deviations regarding informed consent

Deviations regarding forbidden treatments during the study

Deviations regarding overdose/misuse of study drug

Other protocol deviations

Deviations regarding the primary efficacy endpoint

Deviations regarding other efficacy endpoints

Deviations regarding exploratory endpoints


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
Deviations regarding the ancillary study
All the protocol deviations which occurred during the study will be examined during the final data 
review meeting. All adjudicated protocol deviations will be presented in data listings.
4. STATISTICAL ANALYSIS
4.1. Disposition of Patients
In order to describe population, descriptive statistics (number, or number and percentages) as well as 
a listing will be provided for the following patients:

Patients screened (patients who signed informed consent)

Patients enrolled

Patients with a screening failure

Patients who were re-screened

Patients who received study treatment (TTS)
Patients participating in the ancillary study
Patients who completed the study
Patients withdrawn early from the study and reasons for study discontinuation [Adverse event 
(AE), Protocol deviation, Withdrawal of consent, Lost to follow-up, Insufficient response to 
IMP, Other]
Patients withdrawn early due to insufficient response of IMP with reason for insufficient 
response (INCAT, MRC sum score, R-ODS, Grip strength, CGI-Patient, CGI-Investigator, 
Clinical examination, Premature termination of IMP) and follow-up treatment (IVIg, 
Corticosteroids, Immunomodulatory or immunosuppressive agent or Other)

Patients included in the FAS

Patients included in the PPS 
Percentages for patients enrolled, failed screening or re-screened will be calculated using the number 
of unique patients screened as the denominator. For the TTS, percentages will be calculated using 
the number of patients enrolled as the denominator, any other populations will use number of 
patients within the TTS as the denominator. For screen failure patients, a listing will be produced 
with the reason for screening failure and the specifications provided by the investigator. For patients 
who discontinued the study, a listing will be produced with the reasons of study discontinuation and 
the specifications provided by the investigator. Listings will also be produced for study entry, end of
study (EOS) and patient study visits.
4.2. Protocol Deviations
The absolute number of deviations as well as the number and percentage of patients with at least one 
protocol deviations will be tabulated by deviation category and Minor/Major. Deviation details will 
be provided in a listing.


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4.3. Demographic and Baseline Characteristics
Unless otherwise specified, the baseline value is defined as the last available value before the first 
IMP course.
The following characteristics will be summarized in patients of the TTS. If the FAS significantly 
differs (at least 10%) from the TTS, the characteristics will also be summarized in the FAS.

Demographic characteristics:
Age at screening (years)
Age in class: [65 years and 65 years]
Gender
Race

Clinical examination:
Weight (kg)
Height (cm) 
Body mass index (BMI) [kg/m²] (section 5.7.1)
BMI in class: [30 kg/m2 and 30 kg/m2]

History of CIDP disease:
Time since the date of first symptoms (years) (section 5.7.1)
Time since the date of diagnosis (years) (section 5.7.1)
Time between first symptoms and diagnosis (years) (section 5.7.1)
Diagnostic categories of CIDP
Clinical criteria of CIDP (typical / atypical)
Electrophysiological criteria of definite CIDP
Supportive criteria of CIDP
Current INCAT disability score (arms, legs and global non-adjusted INCAT scores and global 
adjusted INCAT score)

Prior medications
Prior medications will be presented by therapeutic subgroup (level 2) and chemical subgroup 
(level 4) according to version WHO_DDE_B2_DECEMBER_1_2014 of the World Health 
Organization's (WHO) Anatomical Therapeutic Chemical (ATC) classification system. The 
term ‘prior medication’ refers to any medication given up to 2 months before screening or 
judged relevant by the Investigator.

Medical and surgical history
Medical and surgical history will be classified by preferred term (PT) and system organ class 
(SOC) using the version 17.1 of the Medical Dictionary for Regulatory Activities (MedDRA).
4.4. Prior and Concomitant Treatment
Prior medications are any medications the patient received up to 2 months before screening or 
judged relevant by the Investigator. Thus, a prior medication is defined as a medication with a date 
of screening start date + 2 months. If a medication has a partial start date, the earliest possible date 
within the partial date is used.


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Concomitant medications are any medications the patient received at any time during the study, i.e. 
from screening to EOS visit. Thus a concomitant medication is defined as a medication with a 
treatment period which has at least one day in common with the period of screening to EOS visit, 
i.e.

Date of screening Start date of medication Date of EOS visit or

Date of screening End date of medication Date of EOS visit or

Start date of medication Date of screening and Date of EOS visit End date of medication 
If a medication has a partial start date or end date, the earliest possible date within the partial start 
date is used and the last possible date within the partial end date.
Prior and concomitant medications will be summarized using TTS and will be classified according 
to version WHO_DDE_B2_DECEMBER_1_2014 of the WHO ATC classification system. Separate 
tables and listings will be produced for prior and concomitant medications presenting the number 
and percentage of patients with at least one medication by therapeutic subgroup (level 2) and 
chemical subgroup (level 4). The tables will be sorted by decreasing incidence of therapeutic 
subgroup and by decreasing incidence of chemical subgroup within therapeutic subgroup.
4.5. Compliance
Study treatment compliance will be summarized using the TTS. Treatment compliance will be 
presented by course, by infusion and by patients as described below. The term Planned refers to the 
treatment dose and frequency planned at enrollment. The term Prescribed refers to the treatment 
dose and frequency reported at each IMP course and infusion.
4.5.1. Course/infusion level
Compliance will be described on the course level using the following criteria:

Prescribed course dose (g/kg) = Theoretical course dose (g/kg) 20%
Theoretical course dose is defined according to the protocol as
a. 2 g/kg at the first course and 1 g/kg at subsequent courses for patients with a BMI 30 kg/m2
b. 1.6 g/kg at the first course and 0.8 g/kg at subsequent courses for patients with a BMI 
30 kg/m2

Time since previous course = 3 weeks 7 days

Courses administered within
a. 2 to 5 days (first course)
b. 1 to 3 days (subsequent courses)

Duration of the flow rate of the first course infusion remains unchanged for at least 25 minutes

Flow rate of the first infusion of a course 0.5 mL/kg/h

Overall course compliance: A course is compliant if all above course compliance criteria are 
fulfilled and all infusions of the course are compliant


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4.5.2. Patient level
Compliance will be described by patients using the following criterion:

Total patient compliance: A patient is compliant if all courses of the patient are compliant.
Non-compliant courses and infusions will be listed by patient showing all of the above criteria. The 
criterion leading to non-compliance will be flagged.
4.6. Efficacy Analyses
The efficacy analyses will be performed on the FAS. The analyses of the primary endpoint will be 
repeated on the PPS as sensitivity analysis (only if the PPS is different from the FAS). All efficacy 
endpoints will be analyzed overall and by subgroups of relapsing Ig-pretreated patients and Ig-naïve 
patients. Endpoints will also be listed by patient status (Ig-naïve/Ig-pretreated).
If a patient is treated with a non-allowed treatment during the study period, then all efficacy 
variables measured after the intake of these non-allowed treatments will be censored for the efficacy 
analyses. Assessments of primary and secondary criteria after a forbidden treatment will be flagged 
in all listings.
The following treatments are not allowed during the study:

Any other investigational product administered within the last month prior to screening

Plasma exchange, blood products or derivatives other than the study drug.

Immunomodulatory or immunosuppressant agents (e.g. including but not limited to 
cyclophosphamide, cyclosporine, interferon-, interferon-1a, anti-CD20, alemtuzumab, 
aziathioprine, etanercept, mycophenolate mofetil, methotrexate) and hemotopoeitic stem cell 
transplantation.

Oral or systemic corticosteroids therapy if administered with an increasing dosage or introduced 
at a dose higher than 10 mg daily prednisolone or equivalent. Topical corticosteroids are 
allowed.
4.6.1. Primary efficacy endpoint
The primary efficacy criterion is the response rate of the patients at EOS visit. Response is defined 
as a patient with a decrease of at least 1 point between baseline and the EOS visit in the adjusted 
INCAT disability score.
The primary analysis of the primary efficacy criterion will be done using the baseline and last 
available assessment of the adjusted INCAT disability score after the first study drug administration. 
That is, if the score at EOS visit is missing, then the Last Observation Carried Forward (LOCF) 
approach will be applied and the last available adjusted INCAT disability score will replace the 
missing value at EOS visit.
Similarly, if the assessment of the adjusted INCAT disability score is censored due to an intake of a 
forbidden treatment, the adjusted INCAT disability score from the last assessment before the intake 
of the forbidden treatment is used as replacement for the assessment of the EOS visit.


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The response rate at the EOS visit will be tested against the historical response rate of 33.3% with a 
one-sided Clopper-Pearson test (exact binomial test (Clopper 1934) at the nominal level of 
significance of =2.5% for the overall set of patients, one-sided Clopper-Pearson test will not be 
performed by subgroup.
The null and alternative hypotheses are as follows:
H0: I10E 33.3%
H1: I10E 33.3%
The number and percentage of responders at EOS will be presented with descriptive statistics. The 
associated exact 95% Clopper-Pearson confidence interval will be calculated for the proportion of 
responders. A table will be produced for the subgroup of patients with response at EOS visit 
presenting the earliest visit at which response was achieved.
The primary analysis will be performed using the FAS and a sensitivity analysis will be performed 
using the PPS.
4.6.2. Secondary efficacy endpoints
The following secondary efficacy endpoints will be studied.
1) Responder rate at 12 weeks
Responder rate at 12 weeks will be presented in the same way as for the primary endpoint with 
exception of the sensitivity analysis using the PPS. Missing assessments at 12 weeks will be 
imputed using the LOCF approach.
2) Time to first response
Time to first response will be analyzed using a Kaplan-Meier (KM) method (Kaplan 1958). 
Patients without response will be considered censored at their last assessment of the (adjusted) 
INCAT disability score. Patients with a non-allowed treatment intake before a first response will 
be considered censored at the date of the first intake of a forbidden treatment.
KM estimates of the mean, median as well as the first and third quartile will be provided together 
with their associated 95% confidence interval. Reason for censoring will be also indicated. A 
KM-plot will be provided showing the incidence of a first response over time. Time of censoring 
will be displayed in the graph. A table will be included below the graph showing the number of 
patients "at risk" (i.e. without a first response), the number of patients with a first response and 
the number of censored patients at the time points 0, 6, 12, 18 and 24 weeks.
Descriptive statistics will be provided for the time to first response on the subset of patients with 
response until EOS.
3) Percentage of patients at 12 weeks and EOS visit with no change in CIDP treatment
The number and % of patients without change in CIDP treatment will be presented at 12 weeks 
and at the EOS visit. The associated exact 95% Clopper-Pearson CI will be calculated. A change 
in CIDP treatment is defined as at least one of the following conditions:
Average dose (g/kg) (see section 5.7.3) of the course is not within 5% of the theoretical study 
treatment dose (g/kg)


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Theoretical dose is 2 g/kg at the first course and 1 g/kg at subsequent courses for patients with 
a BMI 30 kg/m2
Theoretical dose is 1.6 g/kg at the first course and 0.8 g/kg at subsequent courses for patients 
with a BMI 30 kg/m2

Decrease of the time between courses
Time between day 1 of a course and day 1 of the following course is less than 14 days

Addition of corticosteroids (equivalent of more than 10 mg/day of prednisone for more than 
10 days) or immunosuppressive drugs. As this condition is not possible to derive by 
programming, the study physician will review all treatments with corticosteroids and 
immunosuppressive drugs prior to database lock and flag those who fulfil the condition.

Premature discontinuation of study drug due to insufficient response to IMP and start of another 
CIDP treatment, corticosteroids, immunosuppressive drugs or plasma exchange
A listing will provide details about the nature of the CIDP treatment changes.
4) Adjusted INCAT disability score
The adjusted INCAT disability score will be presented with descriptive statistics at each visit. 
The change from baseline in the adjusted INCAT disability score will be analyzed at 12 weeks 
and EOS visit.
Several graphics will be produced:

Boxplots over time of a) the at-visit values and b) change from baseline

Waterfall plots faceted by visit of a) the at-visit values and b) change from baseline
5) Grip strength (kPa) with the Martin vigorimeter in both hands
Actual and normalized (according to the healthy population Merkies 2000) grip strength will be 
presented with descriptive statistics at baseline, week 12 and EOS for the dominant hand and the 
non-dominant hand side by side. The change from baseline in grip strength for the dominant 
hand and the non-dominant hand will be analyzed at 12 weeks and at the EOS visit. The 
assessment at screening will be used for the determination of the dominant hand. Normalization 
according to a healthy population is calculated using the formula (see Section 5.7.5).
6) Rasch-built Overall Disability Scale (R-ODS)
R-ODS will be presented with descriptive statistics at baseline, week 12 and EOS visit. The 
change from baseline in R-ODS will be analyzed at 12 weeks and at the EOS visit.
7) Medical Research Council (MRC) 12 muscles sum score (0 to 5)
The MRC sum score will be presented with descriptive statistics at baseline, week 12 and EOS 
visit. The change from baseline in MRC score will be analyzed at 12 weeks and at the EOS visit.
8) Rasch-modified MRC (0 to 3)
The Rasch-modified MRC sum score will be presented with descriptive statistics at baseline, 
week 12 and EOS visit. The change from baseline in Rasch-modified MRC score will be 
analyzed at 12 weeks and at the EOS visit.
9) Patient and Investigator Clinical Global Impression (CGI)
The CGI-S (Severity of illness) assessment by patients and investigators will be presented side by 
side with descriptive statistics at the visits baseline, week 12 and EOS for the categories Normal, 


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not at all ill / Borderline ill / Mildly ill / Moderately ill / Markedly ill / Severely ill / Among the 
most extremely ill patients (only for the investigator judgment). A shift table will be provided for 
the change from baseline at week 12 and EOS.
The CGI-I (Improvement) assessment by patients and investigators will be presented side by side 
with descriptive statistics at the visits week 12 and EOS for the categories Very much improved / 
Much improved / Minimally improved / No change / Minimally worse / Much worse / Very much 
worse.
The CGI-E (Efficacy index) assessment by patients and investigators will be presented with 
descriptive statistics at the visits week 12 and EOS in a 4×4 cross-table crossing Therapeutic 
effect categories (Marked / Moderate / Minimal / Unchanged or Worse) with Side effect 
categories (None / Do not significantly interfere with patient's functioning / Significantly 
interferes with patient's functioning / Outweighs therapeutic effect). The sum over the number 
and % of patients shown the 4×4 cross-table (16 cells) will correspond to the number of patients 
with valid assessments and 100% respectively. The cross-table will also show a row and column 
with the Total for each dimension corresponding to the separate description of the Therapeutic 
effect and the Side effects.
For the endpoints 4) to 8) the one sample Hodges-Lehmann estimator (Hodges 1963 and Han 2008)
and the associated 95% confidence interval will be calculated for all at-visit values, as well as for the 
change from baseline to 12 weeks and EOS visit for both the overall and patient subgroups. The 
change from baseline for the endpoints 4) to 8) will be tested using a one sample Wilcoxon signed-
rank test, for the overall set of patient only. All statistical tests will be descriptive and will use a two-
sided significance level of =5%.
Statistical tests will not be performed by subgroup.
For all secondary efficacy endpoints, assessments performed after the use of a non-allowed 
treatment will be censored (not used in the statistical summaries).
4.7. Safety Analyses
Safety analyses will be conducted on the TTS. All safety analyses will be performed on the 
subgroups of relapsing Ig-pretreated patients and Ig-naïve patients as well as overall.
4.7.1. Extent of exposure
4.7.1. 1. Patient level analyses
The extent of exposure to IMPs will be summarized on the patient level using the following 
variables:

Duration of study participation (month) from signing of informed consent to EOS (see section
5.7.3)

Duration of treatment exposure (month) from the first day of IMP administration to EOS (see 
section 5.7.3)

Total number of courses

Total number of infusions (see section 5.7.3)


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
Cumulative dose over all infusions (g and g/kg) (see section 5.7.3)

Average dose per course (g and g/kg) (see section 5.7.3)

Maximum dose over all infusions (g and g/kg)

Maximum flow rate over all infusions (mL/kg/h)
4.7.1. 2. Course level analyses
The extent of exposure to IMPs will be summarized on the course level using the following 
variables:

Total number of infusions (At course 1, all subsequent courses and all courses taken together)

Course dose in g and g/kg (At course 1, all subsequent courses and all courses taken together)

Initial flow rate of the first course infusion (mL/kg/h)

Duration of initial flow rate of the first course infusion (min)

Maximum flow rate over all infusions (mL/kg/h)

Duration of the course in days (At course 1, all subsequent courses and all courses taken 
together)
4.7.1. 3. Infusion level analyses
The extent of exposure to IMPs will be summarized on the infusion level using the following 
variables:

Dose (g and g/kg)

Initial flow rate (mL/kg/h)

Maximum flow rate (mL/kg/h)

Duration of the infusion (min)
For patients who experienced at least one infusion with an interruption/discontinuation or a 
decreased flow-rate, a listing will be provided presenting information on all infusions received 
during the given course.
In all three analysis levels, dose (g and g/kg) will be derived based on the prescribed administered 
volume reported in the CRF:

Dose (g)
= Daily volume administered (mL) x batch concentration (i.e. 0.1 g/L)

Dose (g/kg) = Dose (g) / body weight (kg) at the start of the course 
A listing will be provided with the presented variables of each analysis level (patient, course, 
infusion).


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4.7.2. Adverse events
All AEs occurring during the study will be classified by PT and SOC using the version 17.1 of the 
MedDRA.
Seriousness
Serious if one of the follow-ups is serious / Non-serious otherwise
Seriousness criterion
For each of the criteria listed below: Yes if at least one of the 
follow-ups had Yes for the corresponding criterion / No otherwise
▪
Results in death 
▪
Life-threatening 
▪
In hospitalisation or prolongation of existing hospitalisation 
▪
Persistent or significant disability / incapacity 
▪
Congenital anomaly / birth defect
▪
Important medical event
Start date time
Start date time of the first follow-up
End date time
End date time of the last follow-up
Ongoing
Yes if last sequence follow-up is ongoing / No otherwise
Did the AE start within 72h 
after an infusion?
Yes if the first follow-up started within the first 72h after an 
infusion / No otherwise
Intensity
Maximum (Intensity of follow-ups)
Increasing order of importance: Mild / Moderate / Severe
Action taken
Maximum (Action taken of follow-ups)
Increasing order of importance: None / Dose changed / 
Interruption of IMP / Discontinuation of IMP
Corrective medication
Yes if at least one of the follow-ups had a corrective medication / 
No otherwise
Relationship to study drug
Yes if at least one of the follow-ups had a relationship to study 
drug assessed as Yes / No otherwise
Outcome
Maximum (Outcome of corresponding follow-ups)
Increasing order of importance: Unknown / Recovered without 
sequela / Recovered with sequelae / Recovering / Not recovered / 
Fatal
AEs will be classified as Pre-treatment or Treatment-Emergent according to the date of onset:

Pre-treatment AE defined as an event with a date-time of onset before the first infusion date-
time.

TEAE defined as any event with a date-time of onset on/after the start date-time of the first 
infusion.
Treatment emergent adverse event flag
The following rules for the derivation of the TEAE status will be used in the order of display:

If the date-time of the AE onset is known: TEAE = “Yes” if AE onset date-time start date-time 
of first IMP infusion / “No” otherwise

If the date-time of the AE onset is not known but the complete date of the AE onset is known:


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TEAE = “Yes” if AE onset date start date of first IMP infusion
TEAE = “Yes” if AE onset date = start date of first IMP infusion and investigator’s 
assessment of the time of onset “Before infusion”
TEAE = “No” otherwise

If the date of AE onset is a partial date and the investigator’s assessment of the time of onset is 
not missing: TEAE = “Yes” if investigator’s assessment of the time of onset “During infusion”, 
“72h” or “72h”

If the date of AE onset is a partial date and the investigator’s assessment of the time of onset is 
missing:
TEAE = “Yes” if last possible date in the period defined by the partial date start date of first 
IMP infusion / “No” if the last possible date in the period defined by the partial date start 
date of first IMP infusion

TEAE = “Yes” otherwise
Temporally associated adverse events (TAAEs)
TAAE will be defined according to the item “Schedule” collected in the eCRF. They will include all 
adverse events with Schedule “During infusion”, “Within 72 hours after the end of the infusion”. If 
Schedule is missing then the event will be classified as TEAE by default.
Other significant AEs
Other Significant AEs are based on the definition of relevant AESIs (Adverse Events of Special 
Interest) for I10E. They are defined as standardized MedDRA queries (SMQs) of interest on the 
narrow scope, these are:

Anaphylactic reaction (SMQ) [20000021] narrow scope

Anaphylactic/anaphylactoid shock conditions (SMQ) [20000071] narrow scope

Noninfectious meningitis (SMQ) [20000134]) narrow scope

Embolic and thrombotic events, vessel type unspecified and mixed arterial and venous (SMQ) 
[20000083] narrow scope

Acute renal failure (SMQ) [20000003] narrow scope

Hemolytic disorders (SMQ) [20000019] narrow scope

Eosinophilic pneumonia (SMQ) [20000157] narrow scope
Interstitial lung disease (SMQ) [20000042] narrow scope
Pre-treatment Adverse Events
Pre-treatment AEs will be listed for all enrolled patients.
Summary of treatment Emergent Adverse Events (TEAE)
A summary of the total number of TEAEs, and number and percentage of patients with at least one 
TEAE will be presented. This summary will include the number and percentage of patients having at 
least one TEAE as well as the absolute number of TEAEs in each AE category:

TEAEs

Serious TEAEs by seriousness criterion


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
Drug-related TEAEs

TAAEs

TEAEs by severity (Mild / Moderate / Severe)

TEAEs by Action taken with IMP (None / Dose reduced / Dose increased / Discontinuation of 
IMP / Temporary interruption of IMP, (the action could also be a decrease of infusion flow rate))

TEAEs by outcome (Resolved without sequelae / Resolved with sequelae / Not recovered / 
Recovering / Fatal / Unknown)

Other significant AEs
A similar summary table will be produced for TAAEs as well as drug-related TEAEs and Serious 
TEAEs.
All TEAEs, SAEs, TAAEs and drug-related AEs will be summarized by SOC and PT, showing 
number of TEAEs, and number and percentage of patients with at least one TEAE, sorted by 
decreasing incidence of SOC and PT within SOC in the column “overall”.
Summary of TEAEs will also be presented by relevant subgroups (e.g., by age group [65 years and 
65 years], sex, race [white, non-white and unknown], and BMI [30 kg/m2 and 30 kg/m2]).
The rate of TEAEs by patient, course, infusion and drug-related AEs by course will be presented and 
sorted by decreasing incidence of PT in the column “overall”. Rate is defined as the number of 
events for unique PTs divided by the total number of patients, courses and infusions respectively.
Duration of most-common (those which occurred in at least 10% of the patients in the overall safety 
population) drug-related AEs will be calculated as is outlined in Section 5.7.2 and will be presented 
with descriptive statistics on recovered AEs (i.e., AEs with an outcome of “Recovered without 
sequelae" or "Recovered with sequelae"). Statistical unit of analysis will be the individual who 
recovered from drug-related AE. No imputation will be performed for the purposes of computing 
duration.
The time between the stop time of the last administration of IMP (before the onset of event) to the 
onset of the drug-related AEs will be calculated (in days) as is outlined in Section 5.7.2 and will be 
presented with descriptive statistics using the individual drug-related AE as statistical unit.
All Serious TEAEs, drug-related AEs, AEs leading to dose changes (action taken is not missing, 
“None” or “Not-applicable”) or discontinuation of IMP, and other significant TEAEs will be listed. 
These listings will include the event duration as well as the time elapsed (in days as is outlined in 
Section 5.7.2) between the stop time of the last administration to the onset of the event.
The rate of of drug-related TEAE will be presented by course number and overall. This rate will be 
calculated as the ratio between the number of TEAEs starting during a course and the overall 
number of patients treated at the corresponding course.


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4.7.3. Other safety endpoints
4.7.3. 1. Laboratory data
Quantitative descriptions of laboratory data will be performed on normalized values as outlined in 
Section 3.3 with the exception of hematology differential counts for which standardized values will 
be used because values collected as a ratio of WBC count cannot be normalized into a range in 
absolute unit. For these parameters results expressed in percentages of WBC will be converted to 
absolute count by multiplying WBC count by the value collected in percentage (ranges will not be 
transformed).
4.7.3. 1.1. Patient level analyses
All laboratory values will be reported in SI units. Summary displays for laboratory safety data 
(hematology and chemistry) will be produced by visit for both observed and change from baseline 
values of the different laboratory analyses. Laboratory tests taken only at screening, those in case of 
a qualifying event (e.g., thrombosis or hemolysis), and urine protein reagent strip test results will be 
presented in the laboratory listings. The following clinical parameters will be summarized:

Hematology:
Complete blood count + differentials, hemoglobin (Hb), mean corpuscular volume (MCV), 
platelet counts
Haptoglobin

Biochemistry:
Creatininemia, glomerular filtration rate according to MDRD
LDH
Total and free bilirubin (total bilirubin in all patients; if total bilirubin ULN, free bilirubin 
will be assessed from the same blood sample, as total bilirubin)
AST, ALT, alkaline phosphatase (ALP), GT
Total serum protein level
Serum IgA levels
Laboratory values will be classified as normal, low, or high based on standardized normal ranges. 
Laboratory categories will be expressed in terms of the L (below lower limit of normal [LLN]), N 
(between LLN and ULN) and H (above ULN) classifications for numerical measurements and 
normal, abnormal for categorical measurements. The number and percentage of patients with 
abnormal values will be summarized for each laboratory parameter by visit. These summaries will 
include the number and percentage of patients with “any pre-treatment visit” and “any on-treatment 
visit post baseline” abnormality for each parameter. These displays will ensure that all abnormal 
values will be captured.
LNH shifts in clinical laboratory values (hematology and chemistry) from baseline to each visit post 
first dosing will be summarized by visit. Patients with values outside the normal range will be 
flagged.
A scatter plot of the values at the EOS assessment as well as the minimum and maximum values of 
each patient during the treatment follow-up against the values at baseline will be prepared for each 
parameter. The first diagonal will be displayed by a dotted line.


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4.7.3. 1.2. Course and infusion level analyses
Descriptive statistics of laboratory parameters at screening, before and 96h after the 1st IMP course, 
before the start of each subsequent course and at the EOS assessment will be provided for laboratory 
parameters as well as for the clinical assessment. The change from before first IMP course to 96h 
after the 1st IMP course as well as to before subsequent courses will be presented as well as the 
minimum and maximum values of each patient during the complete treatment follow-up. The 
complete treatment follow-up of maximum and minimum presentations includes all post-baseline 
assessments, along with any unscheduled assessment results which do not contribute to by visit 
descriptive summaries. Similarly, shift tables for the clinical assessment will be produced showing 
the change from before the first IMP course to 96h after the 1st IMP course as well as to before 
subsequent courses.
A graphical display of the evolution of each laboratory parameter by course will be presented with 
connected box-and-whisker plots. The number of observations at each visit will be displayed in the 
graph.
Detection of hemolysis will be evaluated at course level. The number and percentage of course with 
hemolysis will be displayed by subgroup and overall in accordance with the IVIg-associated 
hemolysis criteria published by Health Canada (Health Canada 2009), adapted to the study as 
follows:

Drop in hemoglobin by at least 1 g/dL compared to baseline and

At least one of the two criteria below are met
Positive direct Coombs test 
At least 2 of the following criteria are met (in absence of negative direct Coombs test):
Reticulocyte count increased by at least 50 x 109/L compared to baseline
LDH increased by at least 20% compared to baseline
Haptoglobin value is lower than the lower limit of normal (LLN)
Free bilirubin (or total bilirubin if the free bilirubin is not documented) increased compared 
to baseline and value is greater than the upper limit of normal (ULN)
In the following situations the courses will be excluded from the analysis:
Criterion for hemoglobin value cannot be evaluated/calculated
Criterion for hemoglobin is evaluable, direct Coombs test neither positive or negative (missing or 
not-done) and
3 or 4 out of 4 criteria (Reticulocytes, LDH, Haptoglobin, free/total bilirubin) cannot be 
evaluated/calculated or
1 or 2 out of 4 criteria (Reticulocytes, LDH, Haptoglobin, free/total bilirubin) cannot be 
evaluated/calculated and less than two of the remaining criteria are met
A listing of all hemoglobin, reticulocytes, LDH, haptoglobin and bilirubin values will be provided 
for patients with at least one blood sample for which the aforementioned criteria for hemolysis is 
met. A listing of the excluded courses will be also given.
All abnormalities, clinically significant or not, will be listed. Pregnancy status and test results will 
also be listed, including the method of contraception used (if any).


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4.7.3. 2. Vital signs
Vital signs parameters including systolic and diastolic blood pressure (mmHg), heart rate (bpm), 
weight, and body temperature (°C) (calculated value according to the way the temperature was 
measured) will be summarized.
4.7.3. 2.1. Patient level analyses
Descriptive statistics of vital sign values will be presented for the following time points:
a) Screening
b) Before the 1st IMP infusion
c) 30-45 min and 60-75 min after the start of the first infusion 
d) 30-45 min after the end of the first infusion 
e) 96h after the end of the 1st course
f)
EOS
Change from time point b) will be presented for time points c) to e). The minimum and maximum of 
each parameter during the patient's complete treatment follow-up will be presented. The complete 
treatment follow-up of maximum and minimum presentations includes all post-baseline 
assessments, along with unscheduled assessment results which do not contribute to by visit and by 
timepoint descriptive summaries.
A scatter plot of the values at the end of study assessment as well as the minimum and maximum 
values of each patient during the treatment follow-up against the values at baseline will be prepared 
for each parameter. The first diagonal will be displayed by a dotted line.
4.7.3. 2.2. Course and infusion level analyses
Descriptive statistics of vital sign values will be presented at the following time points:
a) Before the start of the course (only first infusion of a course)
b) 30-45 min and 60-75 min after the start of the infusion 
c) 30-45 min after the end of the infusion
Change from before start of the course to time points b) and c) will be presented as well.
A graphical display of the evolution pre-dose values (before IMP infusion) of each vital sign 
parameter over time (by course). The evolution of (before start of the course, time points b) and c) at 
each day) will be also presented with connected box-and-whisker plots by course. The number of 
observations at each visit will be displayed in all graphs.
All abnormalities, clinically significant or not, will be listed in both patient level and course/infusion 
level formats. If a patient assessment has no timepoint attributed then these assessments are 
classified as unscheduled.


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4.7.3. 3. Thrombo-embolic physical examination
Number and percentage of patients with at least one abnormal thrombo-embolic sign will be 
presented by visit together with the absolute number of signs for the following:

Arterial thrombo-embolic signs

Venous thrombo-embolic signs
4.7.3. 4. Complete physical examination
Physical examination results will be listed.
4.8. Pharmacokinetics
Not Applicable.
4.9. Exploratory analyses
The following exploratory endpoints will be analyzed and summarised by visit using FAS for 
absolute value and change from baseline.

Anti-CNTN1 and anti-NF155 antibodies titers at EOS visit

FcRIIB B cells marker levels at visits V2, V3 and V4

BAFF and complement components (C3 and C4 antigens, CH50) at visits V2, V3, V4 and 
EOS visit

Serum total IgG trough levels before each course
In order to explore the relationship between the biomarkers and clinical response at EOS a 
univariate logistic regression model will be applied. Each biomarker will be studied separately at 
each visit. The by visit univariate model will use the biomarker change from baseline (quantitative) 
as a single exploratory variable, with the clinical response at EOS being the dependent variable.
To explore the relationship of the total IgG trough level and the adjusted INCAT disability score a 
linear mixed model will be used using the patient as random factor. A scatterplot will show all 
values and the estimated regression line and its 95% confidence band.
A non-parametric regression method will also be applied (e.g. LOESS, splines or generalised 
additive models) in order to explore departures from linearity. The result of the estimated regression 
line will also be shown in a scatterplot together with the 95% confidence band. Similar exploration 
of the relationship between the biomarkers and other clinical response variables will be conducted as 
needed using generalized linear mixed models.
A listing of the biomarker data will be produced. In addition, a listing of patients included in the 
ultrasonography ancillary study will be provided. However, no statistical analysis will be done (see 
section 4.10.3). The listing will include information on the consent date for the ancillary study and 
whether data were collected (Yes/No).


Study I10E-1302 - Statistical Analysis Plan V3.0
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Confidential
4.10.
Changes in the Conduct of the Study or Planned Analysis
This section describes the changes from protocol.
4.10.1.Efficacy
Planned analysis associated with the ultrasonography ancillary study will not be performed due to 
non-collection of required data.
The protocol (section 12.9.2.2) states for secondary efficacy data that “A LOCF approach will be 
used to handle the missing data of secondary endpoints. All details to handling of missing data will 
be provided in the SAP”. However LOCF approach will only be used for criteria using adjusted-
INCAT.
4.10.2.Safety
The protocol (section 12.10.2) incorrectly states that “Vitals signs […] will be measured before each 
infusion”. However, vital signs are assessed only before the start of each course and not before each 
infusion. Therefore, the data before start of each infusion cannot be presented.
The protocol did not prospectively define an appropriate analysis of “Detection of hemolysis” 
therefore an additional analysis has been defined in accordance with the IVIg-associated hemolysis 
criteria published by Health Canada in section 4.7.3. 1.2 of the SAP.
4.10.3.Ancillary study
For logistical reasons, no data (other than the data related to the Informed Consent) is collected. 
Therefore no statistical analysis will be performed for this part of the study, only the disposition will 
be presented.
5. APPENDICES
5.1. Listings
All data will be presented in patient listings (includes those data recorded after the use of a non-
allowed treatment). All listings produced will be ordered by patient status (Ig-naïve, relapsing Ig-
pretreated, other, screen failure), patient identifier, visit and date unless otherwise specified.
5.2. Statistical Software
Statistical analyses will be conducted on IQVIATM servers using SAS version 9.4.
5.3. Standard Operating Procedures
All programming activities will be performed according to CRO’s Standard Operating Procedures.
At the time of v2.0 of the SAP, it was planned that the following Standard Operating Procedures 
will be followed:


Study I10E-1302 - Statistical Analysis Plan V3.0
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Confidential

LFB SOP 203/05919 Statistical Analysis Plan

LFB SOP 204/06045 Statistical Analysis Plan Template

LFB SOP 203/05921 Statistical Programming

LFB SOP 203/05924 Statistical Analysis

LFB SOP 203/05897 Controlled Version of Study Documents

LFB SOP 203/05926 Quality Control of Statistical Documents
However -because the entire set of biometry SOPs were updated in 2017 and came into force early 
2018- the following SOPs will also be used regarding the oversight/Quality Control activities 
performed internally at LFB:

LFB SOP 202/16747 Document versioning

LFB SOP 202/16694 History form

LFB SOP 203/17019 Statistical Analysis Plan

LFB SOP 204/17029 Statistical Analysis Plan Amendment request form

LFB SOP 202/16911 Statistical Validation Plan

LFB SOP 202/17028 Statistical Tables, Listings and Figures production
More details are available in the Statistical Validation Plan.
5.4. Audit and Quality Control
5.4.1. Audit
An audit/inspection may be carried out by qualified Sponsor staff, by subcontracted auditors or by 
representatives of national or foreign Competent Authorities to ensure that the study is conducted as 
per protocol and in accordance with regulatory requirements, and to ensure the validity of the data.
5.4.2. Quality control
A statistical validation plan will be created describing quality control steps for analysis datasets, 
tables, listings and graphs.
5.5. Statistical Review
Statistical review of analysis datasets, tables, listings and graphs will be performed to ensure the 
accuracy and completeness of the statistical package (datasets and outputs). The outcome of review 
will be documented using quality control sheets.
5.6. Bibliography
Guideline (SWI) for Biostatistics and Statistical Programming
ICH E3 “Structure and Content of Clinical Study Reports”
ICH E9 “Statistical Principles of Clinical Trials”


Study I10E-1302 - Statistical Analysis Plan V3.0
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Confidential
Clopper C, Pearson ES. Ther use of confidance or fiducial limits illustrated in the case of the 
binomial. Bimetrika. 1934;26(4):404-13.
Han L. Calculating the point estimate and confidence interval of Hodges-Lehmann's median using 
SASsoftware. SESUG 2008 the Proceedings of the SouthEast SAS Users Group, Paper ST-154.
Health Canada. Intravenous immune globulin (IVIg): hemolytic reactions. Canadian Adverse 
Reaction Newsletter, volume 19, issue 4, October 2009.
Hodges JL, Lehmann EL. Estimates of location based on ranks tests. Ann Math Statist. 
1963;34(2):598-611.
Hughes RA, Donofrio P, Bril V, Dalakas MC, Deng C, Hanna K, Hartung HP, Latov N, Merkies IS, 
van Doorn PA; ICE Study Group. Intravenous immune globulin (10% caprylate-chromatography 
purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE 
study): a randomised placebo-controlled trial. Lancet Neurol. 2008;7(2):136-44. Erratum in: Lancet 
Neurol. 2008; 7(9):771.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 
1958;53(282):457-81.
Karvanen J. The Statistical Basis of Laboratory Data Normalization. Drug Inf J. 2003;37:101-7 -
0092-8615/2003.
Merkies IS, Schmitz PI, Samijn JP, Meché FG, Toyka KV, van Doorn PA. Assessing grip strength 
in healthy individuals and patients with immune-mediated polyneuropathies. Muscle Nerve. 
2000;23(9):1393-1401.
Additionally, the following reference from Lexjansen (PharmaSUG-2000) was used to implement 
the Hodge-Lehmann estimations:
Chris Deker. Calculating a Nonparametric Estimate and Confidence Interval Using SAS Software.
5.7. Basic Derived Variables
5.7.1. Baseline characteristics
BMI (kg/m²)
=
 !ℎ#(%!)
' !ℎ#(()
)
Time since the date of first symptoms 
(years)
=
(Date of screening −Date of first symptoms + 1)
365.25
Time since the date of diagnosis (years)
=
(Date of screening −date of diagnosis + 1)
365.25
Time between first symptoms and 
diagnosis (years)
=
(Date of diagnosis −date of first symptoms + 1)
365.25


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5.7.2. Safety
Adverse Event Duration
The duration of AEs will be calculated as:
AE Duration (days) = AE stop date – AE start date + 1
Similar formula will be used for any duration-related calculations.
Time to AE onset
The time to onset of an AE since the previous infusion will be calculated as:
Time to AE onset (days) = AE start date – Date of previous IMP infusion+1
Similar formula will be used for any time to event-related calculations.
5.7.3. Exposure
Duration of study participation 
(months)
=
(EOS visit date −date of informed consent + 1)
30.4375
Duration of treatment exposure 
(months)
=
(EOS visit date −date of first IMP infusion + 1)
30.4375
Total number of infusions
=
K(number of infusions at course M)
NO
PQR
Cumulative dose over all infusions
(g and g/kg)
=
S K(dose at infusion % of course M)
NTU
VQR
NO
PQR
with WU the number of infusions at course j of the patient
Average dose per course
(g and g/kg)
=
1
WX
S K(dose at infusion % of course M)
NTU
VQR
NO
PQR
Actual administered dose (g)
=
Batch titer  !
200 ([ Volume infused(([)
200
Average dose (g/kg)
=
Actual dose administered (g)
Subject Weight (kg)
Where batch is set to the theoretical level based on nominal I10E concentration of 10%.
5.7.4. Other characteristics
Body Mass Index (BMI)


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BMI (kg/m2) = Weight (kg) / (Height (m) x Height (m))
Disability Scores
INCAT/Adjusted INCAT disability score = arm disability score + leg disability score
5.7.5. Efficacy
Normalized grip strength (%)
=
^_`abc_d e`fb_ (gh`)
^_di`j e`fb_ (gh`) kl `m_ nf`aa `jd m_jd_c ×100


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5.7.6. Reference tables for derivations
5.7.6. 1. Reference ranges for local laboratory normalization
The following ranges have been reviewed and agreed by LFB Clinical Research Physician of the 
study:
Table 5–1: Reference ranges for normalization of local laboratory data
Laboratory test
Reference Ranges
Formula
Test name
Short
name
Standard
Units
Lower Limit of
Normal (LLN): 
SLo
Upper Limit of
Normal (ULN)
SUp
Alanine Aminotransferase
ALT
IU/L
5
35
location-scale
Alkaline Phosphatase
ALP
IU/L
42
141
location-scale
Aspartate Aminotransferase
AST
IU/L
8
30
location-scale
Bilirubin
BILI
µmol/L
3
17
location-scale
Bilirubin, Free
BILIF
mg/dL
0,2
0,8
location-scale
Creatinine
CREAT
µmol/L
44
106
location-scale
D-Dimer
DDIMER
ug/L
0
500
location-scale
Ery. Mean Corpuscular 
Volume
MCV
fL
79
96
location-scale
Erythrocytes
RBC
1012/L
4
5
location-scale
Gamma Glutamyl 
Transferase
GGT
IU/L
8
35
location-scale
Glomerular Filtration Rate
GFR
mL/min/1.73m2
60
.
scale
Haptoglobin
HAPTOG
mg/dL
40
200
location-scale
Hematocrit
HCT
%
36
48
location-scale
Hemoglobin
HGB
g/dL
12
16
location-scale
Hemoglobin A1C
HBA1C
mmol/mol
20
42
location-scale
Lactate Dehydrogenase
LDH
IU/L
250
450
location-scale
Leukocytes
WBC
109/L
4
10
location-scale
Platelets
PLAT
109/L
150
450
location-scale
Protein
PROT
g/dL
6
8
location-scale
Protein Excretion Rate
PROTEXR
mg/day
0
100
location-scale


Study I10E-1302 - Statistical Analysis Plan V3.0
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5.7.6. 2. Normative values for grip strength
Normative values (Merkies 2000) for quantitative grip strength assessment with the Martin 
vigorimeter for both hands in healthy subjects (kPa) are presented in Table 5–2:
Table 5–2: Normative values for grip strength
Age (year)
Median values (KPa)
per age span and gender
Males
Females
15-19
122
90
20-24
146
106
25-29
154
112
30-34
153
109
35-39
148
104
40-44
141
104
45-49
134
98
50-54
126
92
55-59
116
84
60-64
105
76
65-69
97
71
70-74
91
67
75-79
82
63
80-84
75
59
85
64
54

Prot_003.pdf: 
&29(53$*(

7,7/(An international, multicentre, efficacy and safety study of I10E in initial and 
maintenance treatment of patients with Chronic Inflammatory Demyelinating 
Polyradiculoneuropathy 
1&71XPEHUNCT02293460 
'2&80(17Protocole (v6.0)  
9(56,21	'$7(2)'2&80(17: Version 6.0; May 3, 2017 




LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03 May 2017, incorporated the amendment N°3
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7$%/(2)&217(176
SYNOPSIS ............................................................................................................................................ 9 
1. 
INTRODUCTION AND BACKGROUND INFORMATION ............................................... 21 
1.1. 
Disease and context .............................................................................................................. 21 
1.2. 
Target ................................................................................................................................... 25 
1.3. 
Non-Clinical and Clinical Information ................................................................................ 25 
1.4. 
Rationale of the study........................................................................................................... 27 
2. 
STUDY OBJECTIVES .............................................................................................................. 31 
2.1. 
Primary objective ................................................................................................................. 31 
2.2. 
Secondary objective ............................................................................................................. 31 
2.3. 
Exploratory objectives ......................................................................................................... 31 
3. 
STUDY DESIGN ........................................................................................................................ 31 
3.1. 
Design and study periods ..................................................................................................... 31 
3.2. 
Endpoints ............................................................................................................................. 32 
3.3. 
Study Investigational Site(s) ................................................................................................ 34 
3.4. 
Data and Safety Monitoring Board ...................................................................................... 34 
3.5. 
Scientific Committee ............................................................................................................ 34 
4. 
DURATION AND DATES OF THE STUDY ......................................................................... 35 
5. 
STUDY POPULATION............................................................................................................. 35 
5.1. 
Number of patients ............................................................................................................... 35 
5.2. 
Eligibility Criteria ................................................................................................................ 35 
5.3. 
Duration of Patient participation .......................................................................................... 37 
5.4. 
Discontinuation criteria / Stopping rule(s) ........................................................................... 37 
6. 
STUDY DRUG AND CLINICAL SUPPLIES ......................................................................... 38 
6.1. 
Study Drug ........................................................................................................................... 38 
6.2. 
Medical device ..................................................................................................................... 43 
7. 
PRIOR AND CONCOMITANT MEDICATION ................................................................... 43 
7.1. 
Prior Medication................................................................................................................... 43 
7.2. 
Concomitant Medication ...................................................................................................... 43 
8. 
STUDY PLAN ............................................................................................................................ 44 
8.1. 
Patient recruitment ............................................................................................................... 44 
8.2. 
Sequence of study procedures .............................................................................................. 47 
8.3. 
At any course........................................................................................................................ 55 
8.4. 
Central biological handling sampling .................................................................................. 56 
8.5. 
Ultrasonography (for Italian site only) ................................................................................. 56 
8.6. 
Compliance with the study plan ........................................................................................... 56 
9. 
SAFETY ...................................................................................................................................... 56 
9.1. 
Reference Safety Information Document............................................................................. 56 


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03 May 2017, incorporated the amendment N°3
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9.2. 
Benefit / Risk Information ................................................................................................... 56 
9.3. 
Risk minimisation actions throughout the protocol ............................................................. 58 
9.4. 
Alternative therapeutic management - handling emergencies ............................................. 59 
9.5. 
Definition and reporting of (serious) adverse events ........................................................... 59 
10. 
ASSESSMENT OF EFFICACY AND SAFETY ................................................................. 64 
10.1. Assessment of Efficacy ........................................................................................................ 64 
10.2. Assessment of Safety ........................................................................................................... 65 
11. 
DATA MANAGEMENT ....................................................................................................... 66 
11.1. eCRF completion guidelines ................................................................................................ 66 
11.2. eCRF and Data Handling ..................................................................................................... 67 
12. 
STATISTICS .......................................................................................................................... 68 
12.1. Trial Objectives and Design ................................................................................................. 68 
12.2. Statistical Analysis Plan ....................................................................................................... 68 
12.3. Sample Size Determination .................................................................................................. 68 
12.4. Randomization ..................................................................................................................... 68 
12.5. Protocol Deviations and Analysis Sets ................................................................................ 69 
12.6. General rules for handling of missing or inconsistent data .................................................. 69 
12.7. Demographic and baseline characteristics ........................................................................... 69 
12.8. Study drug and concomitant treatments ............................................................................... 69 
12.9. Efficacy Analysis ................................................................................................................. 70 
12.10. 
Safety Analysis ................................................................................................................ 71 
12.11. 
Exploratory Analysis ........................................................................................................ 72 
13. 
STUDY REPORT .................................................................................................................. 73 
14. 
CONFIDENTIALITY AND PUBLICATION ..................................................................... 73 
14.1. Patient confidentiality .......................................................................................................... 73 
14.2. Use of information ............................................................................................................... 73 
15. 
ARCHIVING .......................................................................................................................... 74 
16. 
RESPONSIBILITIES OF PARTICIPANTS ....................................................................... 75 
16.1. Responsibilities of the Investigator(s) .................................................................................. 75 
16.2. Responsibilities of the monitor ............................................................................................ 77 
16.3. Responsibilities of the data manager.................................................................................... 77 
17. 
ETHICS AND REGULATORY CONSIDERATIONS ...................................................... 78 
18. 
AUDIT AND INSPECTION ................................................................................................. 79 
19. 
REFERENCES ....................................................................................................................... 80 
20. 
APPENDICES ........................................................................................................................ 83 
20.1. Scales / score used ................................................................................................................ 83 


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/,672)7$%/(6
Table 1–1: Differential diagnosis of CIDP ......................................................................................... 22 
Table 1–2: Diagnostic criteria and diagnostic categories of CIDP ..................................................... 23 
Table 1–3: Diagnostic Categories ....................................................................................................... 24 
Table 20–1: INCAT disability scale ................................................................................................... 83 
Table 20–2: MRC scale ....................................................................................................................... 85 
Table 20–3: Final 24-item of CIDP R-ODS ....................................................................................... 87 
/,672)),*85(6
Figure 8–1: Sequence of study procedure ........................................................................................... 46 
Figure 20–1: Martin vigorimeter ......................................................................................................... 90 


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Page 5/90
/,672)$%%5(9,$7,216$1''(),1,7,212)7(506
JGT
J Glutamyl Transferase
Ab
Antibody 
ACR
Albumine to Creatinine Ratio
AE
Adverse Event
AER
Albumin Excretion Rate
ALP
Alkaline Phosphatase 
ALT
Alanine Aminotransferase 
AMS
Aseptic Meningitis Syndrome
ANSM
Agence Nationale de Sécurité du Médicament et des produits de santé 
AST
Aspartate Aminotransferase
ATC
Anatomical Therapeutic Chemical 
BAFF
B Cell Activating Factor
BMI
Body Mass Index
BPWP
Blood Products Working Party 
CGI
Clinical Global Impression
CHMP
Committee for Human Medicinal Product 
CI
Confidence Interval 
CIDP
Chronic Inflammatory Demyelinating Polyradiculoneuropathy 
CKD
Chronic Kidney Disease 
CMAP
Compound Muscle Action Potential 
CNTN1
Contactin 1 
CRO
Contract Research Organization
CSA
Cross Section Area
CSP
Code de la Santé Publique 
CV
Curriculum Vitae
DAT
Direct Antiglobulin Test
DCFs
Data Clarification Forms
EC
Ethics Committee
eCRF
Electronic Case Report Form


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03 May 2017, incorporated the amendment N°3
Page 6/90
EFNS 
European Federation of Neurological Societies 
EMA
European Medicines Agency 
EOS
End of Study 
EU
European Union 
FAS
Full Analysis Set
Fc฀5
Fc฀฀5HFHSWRU
FPI
First Patient In
FU
Follow-up 
GBS
Guillain Barré Syndrome
GCP
Good Clinical Practice 
GFR
Glomerular Filtration Rate
GM1
Ganglioside M1
HAV
Hepatitis A Virus
Hb
Haemoglobin  
HBc
Hepatitis B core Antigen
HBs Ag
Hepatitis B surface Antigen
HBV
Hepatitis B Virus
HCV
Hepatitis C Virus
HIV
Human Immunodeficiency Virus
HLGT
High Level Group Term 
ICH
International Conference on Harmonisation 
IEC/IRB
Independent Ethics Committee (IEC) / International Review Board (IRB)
Ig
Immunoglobulin 
IgA
Immunoglobulin A 
IgG
Immunoglobulin G 
IMP
Investigational Medicinal Product 
INCAT
Inflammatory Neuropathy Course And Treatment  
ITP
Immune ThrombocytoPenia 
IVIg
Intravenous Immunoglobulin 


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03 May 2017, incorporated the amendment N°3
Page 7/90
kPa 
kiloPascals
LDH
Lactate Dehydrogenase
LFB
Laboratoire Français du Fractionnement et des Biotechnologies  
LLN
Lower Limit of Normal 
LLT
Lowest Level Term
LOCF
Last Observation Carried Forward
LPO
Last Patient Out
MAG 
Myelin-Associated Glycoprotein  
MCV
Mean Corpuscular Volume 
MDRD
Modified Diet in Renal Disease 
MedDRA
Medical Dictionary for Regulatory Activities
MGUS
Monoclonal Gammopathy of Undetermined Significance  
MMN
Multifocal Motor Neuropathy 
MRC
Medical Research Council 
MRI
Magnetic Resonance Imaging
NCR
No Carbon Required 
NCS
Nerve conduction study 
NF155 
Neurofascin 155 
NYHA
New York Heart Association
PCR
Protein to Creatinine Ratio
PER
Protein Excretion Rate
PID
Primary Immune Deficiency
PNS
Peripheral Nerve Society
PPS
Per Protocol Set
PT
Preferred Term
RBC
Red Blood Cells 
R-ODS
Rasch-built Overall Disability Scale
RR
Relative Risk
SAE
Serious Adverse Event 


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03 May 2017, incorporated the amendment N°3
Page 8/90
SAP
Statistical Analysis Plan
SCIg
Sub-Cutaneous immunoglobulin 
SPC
Summary of Product Characteristics
SOC
System Organ Class
SUSAR
Suspected and Unexpected Serious Adverse Reaction
TAAE
Temporally-Associated Adverse Event
TEAE
Treatment-Emergent Adverse Event
TTS
Total Treated Set 
ULN
Upper Limit of Normal
USG
Ultrasonography 
WHO
World Health Organisation 
























LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03 May 2017, ncorporated the amendment N°3
Page 20/90
Urine protein reagent strip test result
Action
Negative or Trace
No further urine test required
1 cross (1 +)
Verify eligibility after either assessing AER or PER from a 24h-urine collection 
sampled before the first study drug course, 
or assessing ACR or PCR from a spot urine sample immediately following the urine 
protein reagent strip test (i.e. urine obtained before study drug administration).
2 crosses (2 +) or more
Patient should be excluded
E7REHSHUIRUPHGEHIRUHVWXG\GUXJDGPLQLVWUDWLRQLQSDWLHQWVZKRDWVFUHHQLQJWHVWHGIRUXULQHSURWHLQUHDJHQWVWULSUHVXOWFURVV
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
Urine protein reagent strip test result
Action
Negative or Trace
No further urine test required
1 cross (1 +) or more
Assess either AER or PER from a 24h-urine collection sampled at least 7 days after the 
end of the previous study drug course
or assess ACR or PCR from a spot urine sample immediately following the urine 
protein reagent strip test (i.e. urine obtained before study drug administration).
At all visits except End of Study visit: The Investigator must review these results in 
time prior to the next study drug administration and consider if any of the Early 
Discontinuation Criteria / Stopping Rules (see Section 5.4) apply.
F$FFRUGLQJWR0'5'FDOFXODWLRQ
G7RWDOELOLUXELQLQDOOSDWLHQWVLIWRWDOELOLUXELQ!8/1IUHHELOLUXELQZLOOEHDVVHVVHGIURPWKHVDPHEORRGVDPSOHDVWRWDOELOLUXELQ


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03May 2017, incorporated the amendment N°3
Page 21/90
,1752'8&7,21$1'%$&.*5281',1)250$7,21
'LVHDVHDQGFRQWH[W
CIDP is an acquired paralytic illness affecting peripheral nerves and caused by a demyelinating 
process. The underlying pathologic mechanisms are still unclear. Yet, an autoimmune aetiology is 
largely thought to be probable. 
CIDP is a rare disease. The various epidemiological studies show that prevalence may vary from 
1.24 to 8.9/100 000 [1] [2]. Due to the ambiguities of diagnosing CIDP, the true prevalence of the 
disease may be underestimated or overestimated [3]. 
 'LDJQRVWLFFULWHULDIRU&,'3
Diagnostic criteria for CIDP have been defined by expert groups. These diagnostic criteria sets 
combine clinical, electrophysiological and biological features.
The typical clinical presentation of CIDP includes symmetric sensory and motor symptoms in the 
proximal and distal segments of all four limbs, associated with areflexia and evolving over more 
than 2 months. The disease may show either continuous or stepwise progression over months to 
years or may take a more fluctuating course.
However, clinical features are heterogeneous and there are many borderline clinical forms, such as 
purely motor forms, purely sensory forms or Lewis-Sumner syndrome. Furthermore, frequent 
association with other diseases such as diabetes mellitus, monoclonal gammopathy with or without 
antibodies 
to 
myelin-associated 
glycoprotein, 
connective 
tissue 
diseases 
or 
human 
immunodeficiency virus infection may complicate the diagnosis.
Electrodiagnostic tests are mandatory to confirm the diagnosis of CIDP [4]. Electrodiagnostic 
criteria for CIDP are closely linked to diagnostic criteria of peripheral nerve demyelination. They 
include reduced motor nerve conduction velocity, motor nerve conduction block, abnormal temporal 
dispersion, prolonged motor distal latency and prolonged F wave latency or absent F waves [5]. 
Cerebrospinal fluid examination may assist the diagnosis. Usually there is an albumino-cytological 
dissociation with an elevated protein level and a leukocyte count 10/mm3.
Nerve biopsy is not often used for the diagnosis as it might cause an unacceptable increase in 
neurological symptoms [6]. However, when an affected portion of nerve is examined, segmental 
demyelinating lesions are found associated with inflammatory signs such as endoneurial oedema and 
infiltration by macrophages and T lymphocytes. The demyelination and re-myelination process often 
produces the so-called "onion bulb" formations. There is usually a superimposed axonal 
degeneration.  








LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03May 2017, incorporated the amendment N°3
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Three therapeutic options have proved to be efficacious in CIDP: IVIg, oral corticosteroids and 
plasma exchange. The EFNS/PNS guideline recommends the use of IVIg or corticosteroids as first 
line treatment. Plasma exchange, which is less widely available and less tolerated, is only 
recommended as an alternative in case IVIg and corticosteroids are inadequate. The American 
Academy of Neurology considers that IVIg should be offered for the long-term treatment of CIDP 
(Level A recommendation) [9].  
Regarding IVIg, a meta-analysis in a Cochrane review of 5 double blind placebo-controlled 
randomised trials showed that a significantly higher proportion of patients improved in disability 
within one month after IVIg treatment compared with placebo [10]. Only one study (ICE study) had 
a long-term follow-up; in this study, 57 responder patients were re-randomised for an extension 24 -
week phase between either IVIg at 1 g/kg or placebo every 3 weeks. The percentage of relapse was 
13% with the IVIg and 45% with the placebo (p=0.011) [11]. 
7DUJHW
The specific mechanism of action of IVIg in CIDP is not understood. However, studies in other 
diseases treated with IVIg have demonstrated that IVIg may inhibit autoantibody production, 
neutralize pathogenic antibodies, and decrease antibody-dependent cellular cytotoxicity by blocking 
Fc-receptors (FcJR) on macrophages [12] and upregulate inhibitory FcJ receptor FcJRIIB on B cells
[13]. Furthermore, peripheral blood from participants treated with IVIg shows increased CD8-
positive suppressor T-cell function. 
The B-cell activating factor BAFF contributes to B-cell homeostasis and (auto-) antibody 
production. BAFF was recently identified as one key molecule in the development of autoimmune 
diseases and acts by down-regulation in CIDP. In 2013 Bick et al identified BAFF as a new target 
for IVIg in CIDP treatment and provide a new FcJR independent, mechanism of action for IVIg.  
1RQ&OLQLFDODQG&OLQLFDO,QIRUPDWLRQ
The study drug is I10E, a ready-to-use liquid human normal immunoglobulin preparation for IV
administration (ATC Code: J06BA02). I10E is manufactured by LFB BIOMEDICAMENTS (see 
Section 6.1.1 Description of study drug).  
Marketing Authorization Application (MAA) was submitted in Intravenous Immunoglobulin (IVIg) 
Core Summary of Product Characteristics (SPC) indications through the Decentralized Procedure 
(DCP) in the following European Union Member States: Austria, Belgium, Czech Republic, 
Denmark, Finland, Germany, Greece, Hungary, Italy, Luxembourg, the Netherlands, Spain, 
Slovakia, Sweden, and the United Kingdom.The first national marketing authorization was granted
in the United Kingdom in August 2015, then in Denmark, Germany, Hungary, Belgium and Finland. 
I10E MAA dossier was also submitted in Mexico and approved in April 2015 in the core SPC 
indications, multifocal motor neuropathy and Birdshot retinochoroidopathy. 
This section summarises the available clinical and non-clinical data of I10E. 
 1RQFOLQLFDOGDWD
I10E meets specifications of the European Pharmacopoeia Monograph 0918 on IVIg. Non-clinical 
safety studies of I10E were performed in accordance with Good Laboratory Practice. For more 
information, refer to the Investigator’s Brochure. 


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03May 2017, incorporated the amendment N°3
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 &OLQLFDOGDWD
As of 08 October 2015, 107 patients have been treated with I10E in open-label clinical studies: 
62 patients with primary immune deficiency (PID) in study I10E-0718 (completed), 38 patients with 
immune thrombocytopenia (ITP) in study I10E-0719 (completed) and 7 patients with chronic 
inflammatory demyelinating polyneuropathy (CIDP) in an ongoing single-arm study I10E-1302 
(PRISM study). In addition, 22 patients with multifocal motor neuropathy (MMN) have been 
enrolled in an ongoing double-blind cross-over randomized study I10E-0901 (LIME study) and at 
least 17 of them were administered with I10E.
In PID patients, a total of 766 infusions at a dose ranging from 0.22 to 0.97 g/kg were administered. 
I10E has proved to be effective in preventing serious bacterial infections (SBIs) with an annual SBI 
rate below the EMA/FDA requirement of 1/patient. I10E exhibited a PK profile comparable to 
those of other IVIgs with a mean terminal half-life of 33.6 days. 
In chronic primary ITP patients, a total of 73 infusions were administered at a median dose of 
1.0 g/kg on one day, 70 of them being administered on 2 consecutive days. I10E was effective in 
increasing rapidly the platelet count and reducing and preventing bleedings with a response rate of 
63.2% of patients using the stringent definition of response of the revised EMA guideline on the 
clinical investigation of IVIg and 83.8% using the primary efficacy endpoint of the previous EMA 
guideline.  
Monitoring of adverse events (AEs), vital signs, ECG and laboratory parameters showed a safety 
profile comparable to that of other IVIg in patients with PID or chronic ITP.  
In MMN patients, the ongoing study I10E-0901 (LIME study) compares I10E to Kiovig®
maintenance therapy at a dose of 1.0 g/kg every 4 weeks up to 2.0 g/kg every 4 to 8 weeks for 
approximately one year. The enrolment in the study is completed. 
In CIDP patients, the study I10E-1302 (PRISM study) aims at evaluating the safety and efficacy of 
one dose of 2.0 g/kg of I10E followed by 7 doses of 1.0 g/kg every 3 weeks. A total of 42 patients 
are planned to be enrolled in the study. 
As of 08 October 2015, no serious adverse reactions were reported in both study I10E-0901 and 
study I10E-1302.  
An extension of study I10E-1302, namely study I10E-1306 (PRISM-2 study) has been initiated to 
assess the efficacy and safety of a reduced maintenance dose of I10E in responder patients at the end 
of study I10E-1302. For more information, refer to the Investigator’s Brochure. 
I10E dose regimen required in this protocol is already commonly used in treatment of CIDP with 
IVIg and has shown a favourable benefit to risk ratio. The dose of I10E recommended in this 
protocol will not exceed the doses used in current practice in patients with CIDP as well as in other 
indications of immunomodulation.  
This section is not intended to be all inclusive regarding risks and benefits. The investigator must 
become familiar with all sections of the I10E Clinical Investigator's Brochure.


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5DWLRQDOHRIWKHVWXG\
LFB BIOTECHNOLOGIES wishes to develop I10E for the CIDP indication. As required by the 
European Guideline EMA/CHMP/BPWP/94038/2007 rev.4 [14], confirmatory data of I10E in CIDP 
should be provided to Health Authorities in order to get registered in this indication. Published 
literature already indicates a beneficial effect of IVIg in CIDP.
The objective of this study is to provide confirmatory data on the efficacy and safety of I10E in the 
initial and maintenance treatment phases of CIDP. In Ig-naive patients and in patients with a relapse 
after withdrawal of Ig treatment, an improvement of the neurological status is expected with I10E. 
The study will include both types of CIDP patients.  
Two main studies named “ICE” and “PRIMA” have already proven the efficacy and safety of 
Gamunex£ (IVIg 10% from Talecris Biotherapeutics, NC, USA) and Privigen£ (IVIg 10% from 
CSL Behring GmbH) respectively.
Study design, primary endpoint and patient selection criteria in this study have been chosen as close 
as possible to the previous studies (ICE and PRIMA), in particular to “PRIMA” study as it was 
validated by EMA via a scientific advice (Privigen® EPAR EMA/CHMP/749630/2012).  
CIDP patients either Ig-naive or relapsing after Ig treatment withdrawal for at least 3 months will be 
screened and enrolled. They will receive I10E at a dose of 2g/kg during the first course, then a dose 
of 1g/kg every 3 weeks during 7 following courses. The treatment and follow-up period will be 
24 weeks, as recommended by the EFNS/PNS guideline [4]. 
The primary endpoint will be the responder rate at the EOS visit. Responders are defined as patients 
with a decrease t1 point in the adjusted INCAT disability score between baseline and the EOS visit.
 'LVDELOLW\DQGLPSDLUPHQWVFDOHV
In 2013, Els K. Vanhoutte, Catherina G. Faber and Ingemar S.J. Merkies [40] published outcome 
measures in inflammatory peripheral neuropathies on behalf of the PeriNomS study group the 196th
ENMC international workshop. Their recommendations on the best scales for CIDP have been 
included in the current protocol. The following scales will therefore be assessed at 12 weeks and 
EOS visit as part of secondary endpoints: 
x Adjusted INCAT disability score; 
x Grip strength with the Martin vigorimeter in both hands, Rasch-built Overall Disability Scale (R-
ODS); 
x Patient and Investigator Clinical Global Impression (CGI): Severity (CGI-S), Efficacy (CGI-E) 
and Improvement (CGI-I);
x Medical Research Council (MRC) 12 muscles sum score (0 to 5) and Rasch-modified MRC (0 
to 3); 
x Original INCAT disability score.
 ,PPXQRORJLFDOEDFNJURXQGDQGUHVHDUFKRIELRPDUNHUV
The pathogenesis of CIDP is not fully understood. T cells, B cells, macrophages, cytokines and 
chemokines, autoantibodies and complement are the main effectors involved in the pathogenesis of 
CIDP and are therefore the main target of therapies. Immune cells and soluble mediators are 


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regulated by IVIg and this regulation is correlated in many instances with IVIg response. Numerous 
biomarkers have been proposed in CIDP but none seems to predict the response to IVIg accurately. 
This trial gives the opportunity to assess specific biomarkers, their modulation by IVIg treatment 
and their correlation with clinical response. 
IVIg seems to work by a direct competition and quantitative blockade of autoantibody action by 
different mechanisms. 
In 2013 Professor Isabel Illa highlighted IgG4 anti-contactin1 (CNTN1) and anti-neurofascin 
(NF155) autoantibodies as poor prognostic factors after IVIg therapy: in her series, the presence of 
at least one of these autoantibodies identified a lack of response to IVIg [15]. Anti-CNTN1 and anti-
NF155 antibodies were associated to small subgroups of CIDP patients with specific phenotypic 
features. 
The concept of an aberrant B cell response as a pathogenic part of CIDP is widely accepted. IgG 
mediated effector functions require the interaction with their FcJR on effector cells. The type II 
FcJRIIB (CD32B) is the only inhibitory FcJR and is expressed on circulating monocytes and B 
cells. On B cells, signalling trough this receptor inhibits transformation of B cells into antibody 
secreting plasma cells [16]. Recent works has shown that this receptor is modulated by IVIg in 
CIDP patients [17] [18] [19]. 
The immune status of patients as well as their modulation by a high dose of IVIg (2g/kg) will be 
documented by monitoring the expression of the FcJRIIB B cell marker in blood. 
Other soluble biomarkers such as (BAFF) contribute to B-cell homeostasis and autoantibody 
production [20]. 
Complement components have been shown to be modulated by IVIg [21] [22]. Scavenging of 
complement fragments is a mechanism believed to be important in the efficacy of IVIg. Binding of 
IgG molecules to potentially harmful complement fragments (C3b, C4b) blocks deposition of these 
fragments onto their target and the formation of amplification convertases, decreasing activation of 
C5 and deposition of the C5b-C9 membrane attack complex.
The modulation of the complement pathway following IVIg treatment can be monitored by the 
combined dosage of CH50 (ELISA-based assay) for the quantitative determination of functional 
classical, mannose binding lectin and alternative complement pathways, and the quantitative dosage 
of C3 and C4 proteins (routinely performed by nephelometry) in serum samples.  
Serum concentrations of these markers in samples will be measured in order to document their 
modulation at both high (2g/kg) and low (1g/kg) doses of IVIg and to assess whether the modulation 
is dose dependent. 
Analyses of these biomarkers should advance understanding of immune modulation and mechanism 
of action of IVIg in CIDP. 
 1HXURSK\VLRORJLFDOH[DPLQDWLRQ$QFLOODU\VWXG\,WDOLDQVLWHVRQO\
Monolateral nerve conduction studies (NCS) will be performed through the following minimum 
neurophysiological protocol. Local laboratory standards will be employed. 
Motor nerve conduction studies will be performed in the following nerves: 


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
median nerve: the motor response will be recorded with surface electrodes over the 
abductor pollicis brevis muscle and the sites of stimulation will be at the wrist (1 cm 
proximal volar wrist fold) and at the elbow; 

ulnar nerve: the motor response will be recorded with surface electrodes over the 
abductor digiti minimi muscle and the stimulation site will be at the wrist, above and 
below elbow (3 cm above and below elbow) and axilla; 

deep fibular nerve: the motor response will be recorded with surface electrodes over the 
extensor digitorum communis and the sites of stimulation will be proximal to the 
anterior tarsal tunnel, 2 cm distal the proximal margin of fibular head and in the popliteal 
fossa.
Motor nerve conduction velocities, distal latencies, and amplitude of the negative phase of 
compound muscle action potentials will be measured. 
F wave studies will be performed in the ulnar nerve with measurement of mean F latency and 
frequency of F response. 
Sensory nerve conduction studies: 

orthodromic sensory NCS of the median nerve will be recorded at the wrist and the 
stimulation with ring electrodes will be at digit III;

orthodromic sensory NCS of the ulnar nerve will be recorded at the wrist and the 
stimulation with ring electrodes will be at digit V;

antidromic sensory NCS of the sural nerve will be recorded at posterior-lateral malleolus 
and the site of stimulation will be at the posterior-distal leg with the cathode at 12 cm 
from the active electrode.
As methods differ from site to site, all participating centers must provide complete information on 
their laboratory's standard NCS protocols. 
If clinically indicated, additional studies may be performed at the discretion of the examiner.
 3HULSKHUDOQHUYHXOWUDVRQRJUDSK\$QFLOODU\VWXG\,WDOLDQVLWHVRQO\
High-resolution ultrasound (USG) of peripheral nerves is a valuable complement to 
neurophysiology especially in the work-out of mononeuropathies. Less is known on 
polyneuropathies, where the great heterogeneity made difficult the identification of a specific
alteration pattern. In previous studies in CIDP patients, nerve USG showed diffuse enlargement of 
cross sectional area (CSA) of peripheral nerves trunks and cervical roots [23] [24] [25] [26] [27]. 
Recently, USG findings in CIDP have been shown not only to contribute to the diagnosis, but also to 
mirror the underlying pathophysiological mechanisms. Nerve enlargement was statistically related 
to disability and muscle strength, and the relationship between duration of symptoms and USG 
classes was highly significant [28]. 
For the nerve USG evaluation, USG systems equipped with medium (the lowest being around 6 Hz) 
and high-frequency (15-18 MHz) broadband probes will be used. USG will be performed in the 
neurophysiologically evaluated side. Additional nerves may be evaluated at the discretion of the 
examiner.
Nerve assessment required and pre-determined site of measurements are:
ƒ Median: wrist, mid-forearm, elbow, mid-humerus and axilla 


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03May 2017, incorporated the amendment N°3
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ƒ Ulnar: wrist, mid-forearm, elbow, mid-humerus and axilla 
ƒ Fibular: fibular head and popliteal fossa 
ƒ Sural: median third of the leg
Optional assessments (for skilled USG operators) are: 
ƒ Supraclavicular brachial plexus (strongly suggested) 
ƒ Radial at humeral sulcus
ƒ Posterior interosseus nerve under the supinator muscle 
ƒ C5-C6-C7 cervical roots.
USG outcome measures will be: 
1) Maximal/minimal CSA for each nerve along the visible course;
2) Intra-nerve and inter-nerve variability; 
3) USG immune-related classification.
1. Maximal and minimal CSA.
The method to calculate CSA (just inside the hyperechoic rim of the nerve in transversal section) is 
usually the “ellipse method” when applicable (when the nerve in the transverse scan has an elliptical 
or roundish shape) or the “tracing method” when the nerve has an “irregular” shape. Echogenicity 
alteration not associated with CSA alteration will be not considered.
In addition to the pre-determined sites of imaging, maximal (MAX-CSA) and minimal (MIN-CSA) 
CSA enlargement along the visible course will be recorded for each nerve.
The CSA of whole plexus will be bilaterally measured. Moreover, after identification of the cervical 
spinal root level, CSA of each root (from C5 to C7) are measured just before entering the spine [29]. 
Each centre will use its own previously established CSA normative values. Every participating 
centre has to submit their normative values in advance. If not available, normative values adopted in 
the coordinating site will be used.
2. Intra- and inter-nerve variability
"Intra-nerve CSA variability" (for each nerve: maximal CSA/minimal CSA) and "inter-nerve CSA 
variability" (for each patient: maximal intra-nerve CSA variability/minimal intra-nerve CSA 
variability) will be evaluated [30] [31]. Intra-nerve variability will be evaluated only in ulnar, 
median and fibular nerves, having sural nerve a very short assessable segment (with only a single 
measure taken).
Normal values of upper cut-off of intra-nerve ratio are for median nerve 2.3 and for the ulnar nerve 
2.1. Concerning inter-nerve variability the upper cut-off value is 1.9. 


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3. USG immune-related classification
On the basis of previous USG observations [28] USG pattern is classified as follows:
Class 1: large nerves, with hypoechoic segments and increased nerve CSA. Enlarged fascicles 
may be seen or the nerve may appear enlarged and hypoechoic without fascicular structure.
Class 2: large nerve, with segments with increased nerve CSA and coexistence of hyper and 
hypoechogenic enlarged (or normal) fascicles (in other words, in the same point we observe 
fascicles with hyperechoic and other fascicles with hypoechoic structure). 
Class 3: normal nerve size, but changes in echogenicity (nerve appears hyperechoic with 
reduced CSA). The edge of the nerve and surrounding is not clear. The hyperechoic rim of 
epineurium is not clearly identified. Fascicles are not well visualized.
Only CIDP patients enrolled in Italian centres will undergo USG examination coupled with 
neurophysiology, as Italian sites already have nerve examination-trained ultra-sonographers.  
678'<2%-(&7,9(6
3ULPDU\REMHFWLYH
To assess the efficacy of I10E in improving the disability of patients with CIDP.
6HFRQGDU\REMHFWLYH
To assess the safety of I10E in patients with CIDP.
([SORUDWRU\REMHFWLYHV
 To assess a potential relationship between serum total IgG trough levels, biomarkers levels 
and clinical response – as assessed by neurological scales – in patients with CIDP.
 To assess a potential relationship between USG coupled to neurophysiology analysis of nerves 
and clinical response – as assessed by neurological scales – in patients with CIDP (ancillary 
study in Italy).
678'<'(6,*1
Study design is outlined in Figure 8–1. 
'HVLJQDQGVWXG\SHULRGV
This is a phase III, international, multicentre, single-arm, open-label, prospective study. 
Study periods are as follows: 


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03May 2017, incorporated the amendment N°3
Page 32/90
 6FUHHQLQJ
The screening period goes from signature of informed consent to first study drug administration. 
The screening biological tests should be performed and their results checked by the Investigator 
within a period of 4 weeks before first study drug administration.
The exclusion and inclusion criteria (except those related to screening biological assesments) will be 
verified prior to screening. The screening biological test results will be verified before the first study 
drug administration.
The screening period shall not exceed 4 weeks.  
 %DVHOLQH
Baseline data are those obtained during the screening period before first study drug administration. 
If multiple results are available for a given assessment, the most recent will be considered. 
 ,QFOXVLRQ
A patient is considered included once he/she receives the first study drug administration.
 7UHDWPHQW
Patients who meet all the eligibility criteria will receive one dose of study drug at 2 g/kg over 2 to 
5 days. Three (3) weeks later, they will start to receive 7 doses of study drug at 1 g/kg over 1 to 
2 day(s) each, every 3 weeks (+/- 7 days). 
Investigators or Study Nurses will call patients 4 days (+/-1 day) after the end of each study 
treatment course to document potential AEs and TAAEs (see Section 8.2.4).
Duration of the treatment period will be approximately 21 weeks.
 )ROORZXSDQG(QGRIVWXG\
A follow-up visit will occur 3 weeks +/- 7 days after the last study drug administration. At the end of 
the follow-up period, patients will undergo an EOS visit. This visit occurs 3 weeks after the 8th
course of study drug. In the event of premature discontinuation from the study drug or patient 
withdrawal from the study, an EOS visit is performed within 7 days and prior to administration of 
any other treatment for CIDP (See Section 8.2.7). The reason for premature study drug
discontinuation / study withdrawal should be accurately assessed and entered into the eCRF.  
The total duration of the study for a patient is approximately 24 to 29 weeks.
(QGSRLQWV
 3ULPDU\HIILFDF\HQGSRLQW
The primary efficacy endpoint will be the responder rate at EOS visit.


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5HVSRQGHUVDUHGHILQHGDVSDWLHQWVZLWKDGHFUHDVHSRLQWLQWKHDGMXVWHG,1&$7disability score 
between baseline and the EOS visit. 
 6HFRQGDU\HIILFDF\HQGSRLQWV
The secondary efficacy endpoints will be: 
 Responder rate at 12 weeks. 
 Time to response.  
 Percentage of patients at 12 weeks and EOS visit with no change in CIDP treatment. 
 Changes from baseline to 12 weeks and EOS visit in the following scores: 
x Adjusted INCAT disability score; 
x Grip strength with the Martin vigorimeter in both hands; 
x Rasch-built Overall Disability Scale (R-ODS);
x Patient and Investigator Clinical Global Impression (CGI);
x Medical Research Council (MRC) 12 muscles sum score (0 to 5) and Rasch-modified MRC 
(0 to 3). 
 6DIHW\HQGSRLQWV
Safety will be evaluated by the assessement of treatment-emergent adverse events (TEAEs) and 
temporally-associated AEs (TAAEs) – including SAEs – from first study drug administration to the 
EOS visit, as well as by assessment of clinically significant changes from baseline in vital signs and 
laboratory tests.  
 ([SORUDWRU\HQGSRLQWV
The following exploratory endpoints will be considered:  
Biomarker study:
 Anti-CNTN1 and anti-NF155 antibodies titers at screening and EOS visit.  
 FcJRIIB B cells marker levels at visits V2, V3 and V4.  
 B cell activating factor (BAFF) and Complement components (C3 and C4 antigens, CH50) at 
visits V2, V3, V4 and EOS visit. 
 Serum total IgG trough levels at each visit, within 24 hours prior to study drug administration.
Ancillary study in Italian sites only:
x Change from baseline to EOS visit in nerve conduction velocities, distal latencies, amplitude of 
the negative phase of compound muscle action potentials and F wave for the following peripheral 
nerves: median nerve, ulnar nerve and deep fibular nerve (F wave assessed on ulnar nerve only). 
x Change from baseline to EOS visit in nerve maximal/minimal cross section area (CSA), intra-
nerve and inter-nerve variability and USG immune-related classification (see Section 1.4.4.
Peripheral nerve ultrasonography), in the following peripheral nerves: median nerve, ulnar nerve, 
fibular nerve and sural nerve. 


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6WXG\,QYHVWLJDWLRQDO6LWHV
This study will be conducted in approximately 37 recognised referral centres and/or centres of 
expertise for neuromuscular diseases or peripheral neuropathies in France, Italy, Spain, Tunisia, 
Turkey, the United Kingdom, Germany and Poland. 
Enrolment will be competitive and will take place in parallel in all sites.
Investigators are encouraged to inform their colleagues about this study, so that any eligible patient 
could be referred to them. Material such as doctor-to-doctor letters, posts on specialised websites or 
conferences could be provided by the Sponsor. 
'DWDDQG6DIHW\0RQLWRULQJ%RDUG
No DSMB will be set-up for this study for the following reasons: 
 IVIgs are used in current medical practice in this indication with a favourable benefice-to-risk
ratio.
 Dosages administered in this study are those recommended by scientific societies (EFNS/PNS 
and American Academy of Neurology) and are used in current medical practice. 
 Investigators selected in this study have established competence in the treatment of CIDP, in 
particular in the use of IVIg for this indication and work within renowned reference centres. 
 Previous human experience with I10E showed a comparable safety profile with other IVIgs. 
 Neither interim analysis, nor arbitration on study continuation or early termination or redesign
is planned.  
6FLHQWLILF&RPPLWWHH
A scientific committee will be set up for the following activities:
x Protocol review 
x Participation in the Investigator’s meeting, including training of investigators on specific scales 
and evaluations used in this protocol. 
x Medical support for medical data review if needed.
Its membership is the following:
 Prof. Eduardo Nobile-Orazio, MD, PhD, Prof. of Neurology (Italy)
 Prof. Richard Hughes, MD, FRCP, Emeritus Prof. of Neurology (United Kingdom) 
 Prof. Isabel Illa, MD, PhD, Prof. of Neurology (Spain) 
 Prof. Jean-Marc Léger, MD, Co-Chair National Referral Center for rare neuromuscular 
diseases (France)
 Prof. Jean-Marie Grouin, PhD, Associate Professor in Statistics (France)
 Prof. Luca Padua, MD, PhD, Prof of Neurology and Ultrasonography (Italy)
 Dr. Ingemar Merkies, MD, PhD, Neurologist- Clinimetrician (The Netherlands) 


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03May 2017, incorporated the amendment N°3
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'85$7,21$1''$7(62)7+(678'<
The FPI is planned in Q1 2015 and the LPO is planned in Q4 2017. 
678'<3238/$7,21
1XPEHURISDWLHQWV
42 patients will be included in the trial to ensure 38 evaluable patients (around one third of all 
patients will be either Ig-naïve or relapsing Ig-pretreated). 
A patient will be considered evaluable if he/she has an assessment of the primary endpoint after the 
first study drug administration.
(OLJLELOLW\&ULWHULD
Before any study-related procedure is undertaken, written informed consent must be obtained (see 
Section 8.1.1). 
A patient is eligible if all the inclusion criteria and none of the exclusion criteria are met.
 ,QFOXVLRQFULWHULD
1. Male or female patient aged 18 years or more.
2.

Definite or probable CIDP according to the European Federation of Neurological 
Societies (EFNS)/Peripheral Nerve Society (PNS) guidelines 2010 clinical and 
neurophysiological criteria.  

Pure motor CIDP, provided that a diagnosis of multifocal motor neuropathy has been 
ruled out. 

CIDP associated with monoclonal gammopathy of undetermined significance (MGUS), 
provided that anti-MAG antibodies titer is lower than the used technique's negativity 
threshold (1000 BTU for Bühlmann ELISA technique). 

Lewis-Sumner syndrome. 
3. Score of at least 2 on the adjusted INCAT disability scale.
4. Patient who either : 
a)
has never been previously treated with Ig (Ig-naïve patient)
OR
b)
was previously treated with Ig but is in clinical relapse following treatment 
withdrawal. In the latter case, the last Ig course shall have been administered no less 
than 3 months prior to screening. 
5. Covered by national healthcare insurance system as required by local regulations. 
6. Written informed consent obtained prior to any study-related procedures.


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03May 2017, incorporated the amendment N°3
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 ([FOXVLRQFULWHULD
1. History of severe allergic reaction or serious adverse reaction to any immunoglobulin (Ig). 
2. Clinically documented lack of response to previous Ig treatment. 
3. History of IgA deficiency (IgA d70 mg/L), unless the absence of anti-IgA antibodies has been 
documented.  
4. Known hypersensitivity to human Ig or to any of the excipients of I10E (glycine and 
polysorbate 80). 
5. History of cardiac insufficiency (NYHA III/IV), uncontrolled cardiac arrhythmia, unstable 
ischemic heart disease, or uncontrolled hypertension.  
6. History of venous thromboembolic disease, myocardial infarction or cerebrovascular accident. 
7. Risk factor for blood hyperviscosity such as cryoglobulinemia or haematologic malignancy with 
monoclonal gammopathy.  
8. History of personal or familial congenital thrombophilia or acquired thrombophilia.  
9. Factors contributing to venous stasis such as long-term bed confinement.
10. Body Mass Index (BMI) t40 kg/m². 
11. Protein-losing enteropathy characterised by total serum protein level 60 g/L and serum 
albumin levels 30 g/L. 
12. History of kidney transplantation, nephrotic syndrome (defined as proteinuria !3.5 g per 
24 hours accompanied by hypoalbuminemia and edema), or any acute or chronic kidney disease 
that in the opinion of the investigator and/or nephrologist would preclude the use of I10E and/or 
interfere with the assessment of the safety and efficacy of I10E.
AND/OR
Chronic kidney disease (CKD) for more than 3 months as documented by at least one of the 
 
following: 
x glomerular filtration rate (GFR) <60 mL/min/1.73m2 measured according to the 
Modified Diet in Renal Disease (MDRD) formula
 
 
AND/OR
x urine protein reagent strip: t2 crosses
 
 
AND/OR
x urine protein reagent strip: one cross with one of the following: 
R albumin excretion rate (AER) !300 mg/24 hours or protein excretion rate 
(PER) !500 mg/24 hours (24h-urine collection) 
OR
R albumin to creatinine ratio (ACR) >30 mg/mmol or protein to creatinine ratio 
(PCR) !50 mg/mmol (spot urine sample).
13. Serum levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) !2 times 
upper limit of normal (ULN) range.


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14. Any other ongoing disease that may cause chronic peripheral neuropathy, such as toxin 
exposure, dietary deficiency, uncontrolled diabetes, hyperthyroidism, cancer, systemic lupus 
erythematosus or other connective tissue diseases, infection with HIV, HBV or HCV, Lyme 
disease, multiple myeloma, Waldenström's macroglobulinaemia, amyloidosis, and hereditary 
neuropathy. 
15. Woman with positive results on a urine pregnancy test or breastfeeding woman or woman of 
childbearing potential without an effective contraception. 
Effective contraceptives are injectable, patch or oral combined oestro progestative or 
progestative contraceptives, Copper T or levonorgest releasing intra-uterine devices, depot 
intramuscular medroxyprogesterone, subcutaneous progestative contraceptive implants, 
condoms or occlusive caps (diaphragm or cervical/vault caps) with spermicide, true abstinence 
(when this is in line with the preferred and usual lifestyle of the patient).  
16. Any other serious medical condition that would interfere with the clinical assessment of CIDP 
or use of I10E or prevent the patient from complying with the protocol requirements. 
17. Increasing dosage or introduction of a systemic corticosteroids therapy, or corticosteroids 
therapy at a dose higher than 10 mg prednisolone per day, or equivalent within the last 3 months 
prior to screening. Topical corticosteroids are permitted.
18. Treatment within 12 months prior to screening with immunomodulatory or immunosuppressant 
agents (including but not limited to cyclophosphamide, cyclosporine, interferon-D, interferon-
E1a, anti-CD20, alemtuzumab, aziathioprine, etanercept, mycophenolate mofetil, methotrexate)
or haemopoetic stem cell transplantation.  
19. Plasma exchange, blood products or derivatives administered within the last 3 months prior to 
screening. 
20. Administration of another investigational product within the last month prior to screening.  
21. Drug or alcohol abuse. 
22. Anticipated poor compliance of patient with study procedures. 
'XUDWLRQRI3DWLHQWSDUWLFLSDWLRQ
The duration of the treatment for a patient is approximately 21 weeks. The total duration of the study 
for a patient (including the screening period) is approximately 24-29 weeks.
'LVFRQWLQXDWLRQFULWHULD6WRSSLQJUXOHV
All patients are free to withdraw from participation in this study at any time, for any reason, and 
without prejudice. The Investigator must withdraw from the study any patient who requests to stop 
participating in the study. Patients who withdraw their consent will be asked to undergo the study 
assessments scheduled at the EOS visit. They will be advised that participation to the EOS visit is 
voluntary but is their best interest. 
The Investigator must discontinue study drug administration to a patient and perform an EOS visit at 
the request of the Sponsor or if the patient: 
 Experiences an AE - including an AE due to a clinically significant laboratory abnormality -
that justifies study drug premature discontinuation. 


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03May 2017, incorporated the amendment N°3
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Undergoes protocol deviation that could endanger the patient safety. 
 Becomes pregnant.
Moreover, the Investigator may discontinue a patient from study drug administration if:
ƒ Either the patient's adjusted INCAT disability score increases by 1 point, compared to 
baseline,
AND
Judging on the clinical examination and/or the neurological scales assessments, the 
Investigator considers change in patient's treatment (such as, administration of another 
IVIg, increase or initiation of a corticotherapy, immunosuppressive therapy, plasma 
exchange) is mandatory. Clinical examination findings as well as neurological scales 
assessments will have to be reported on the EOS visit as appropriate; 
ƒ Or the patient's adjusted INCAT disability score increases by at least 2 points compared 
to baseline.
If a patient is prematurely discontinued, the date and reason of discontinuation will be documented 
in the eCRF.  
If a patient is withdrawn because of an AE, he/she will be followed up until complete resolution or 
stabilisation of the AE. 
Patients lost to follow-up will be considered as discontinued from the study. A patient will be 
considered as lost to follow-up only after having exhausted all means of contact. Investigators must 
make every effort to contact the patient and/or his/her family or relatives to obtain the maximum of 
the per protocol requested information. All contact attempts will be documented in the patient’s 
medical records.
678'<'58*$1'&/,1,&$/6833/,(6
6WXG\'UXJ
 'HVFULSWLRQRIVWXG\GUXJ
The study drug is I10E. 
I10E will be supplied, free of charge, by LFB BIOTECHNOLOGIES. 
 ,(VWXG\GUXJ
Pharmaceutical form
I10E is a ready-to-use liquid human normal immunoglobulin preparation for intravenous 
administration (ATC Code: J06BA02). I10E is manufactured by LFB BIOMEDICAMENTS.
I10E contains 10% (100 mg/mL) of proteins, 98% at least of which are IgG. The other ingredients 
are glycine (18.8 mg/mL) and polysorbate 80 (0.05 mg/mL): these excipients have been chosen for 
their stabilising properties and good tolerance.  


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I10E is produced by fractioning plasma proteins and then extracting and purifying 
immunoglobulins.  
More information is available in the current Investigator’s Brochure of I10E.
 3DFNDJLQJ
The primary packaging of I10E is a sterile type-1 glass vial, sealed with a bromobutyl-rubber 
stopper.  
Each I10E box will contain one vial of human normal immunoglobulin 20g/200mL or 10g/100mL. 
 /DEHOOLQJ
The Investigational Medicinal Product will be labelled individually. A system of tear-off labels will 
insure traceability. 
Labels will carry the following required regulatory texts. Each vial is labelled with at least the 
following information: 
 Study LFB N° I10E-1302 
 I10E - Human Normal Immunoglobulin - 100 mg/mL (vial: 20g/200mL or 10g/100mL) 
 Batch Number CLIXXXX
 Use by date: MM/YYYY
 Treatment Number: XXXX
 Patient N°XX-XX (to be filled) 
 Investigator name (to be filled) 
 Infusion date (to be filled) 
 For intravenous use only 
 Solution for infusion 
 Storage requirements: according to the labelling
 Protect from light, do not freeze 
 The standard caution statement:
 Medicinal Product derived from human plasma 
 For clinical use only 
 For use under medical supervision 
 LFB BIOTECHNOLOGIES's name, address and phone number 
Labels will be adapted to local requirements and translated into the local language when legally 
required. 
 0DQDJHPHQWRIVWXG\GUXJDW+RVSLWDO3KDUPDF\
 6KLSPHQWDQGVWXG\GUXJUHFHSWLRQ
Shipments of study drug to Hospital Pharmacy will be organised by the Sponsor's drug distributor at
controlled temperature according to the labelling. 


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Upon receipt, the Hospital Pharmacist will inventory the study drugs and complete the 
acknowledgement of receipt form which has to be returned to the drug distributor. Should any 
abnormality of the supply boxes be observed, the Hospital Pharmacist must immediately inform the 
drug distributor.  
Re-supply of the sites with study drug will be organised as necessary by the drug distributor upon 
Pharmacist's request.  
 6WXG\GUXJVWRUDJH
The Hospital Pharmacist will be responsible for the appropriate storage of the study drug at the 
study site.
Study drug must be stored in a safe and locked place according to the storage temperature 
requirements with no access by unauthorized personnel. 
I10E must be stored under controlled and monitored temperature. I10E must be protected from light 
(kept in their boxes) and must not be frozen. 
The Hospital Pharmacist must immediately inform the Monitor of any non-respect of the required 
storage conditions. Any temperature deviation must be reported within 1 working day to the 
Sponsor, using a temperature deviation form. The official written approval for the use of treatment 
must be obtained from the Sponsor prior to any dispensation/administration. In the meantime, study 
drug under temperature deviation should be placed under quarantine at controlled temperature as per 
the labelling. In case of decision to not use the study drug, the vials will be stored under quarantine 
at ambient temperature until shipment back to the drug distributor. 
 3UHSDUDWLRQRIVWXG\GUXJDQGGLVSHQVLQJ
The Investigator will write a prescription sheet (on a quadruplicate No Carbon Required (NCR) 
paper) prior to the first infusion of each treatment course. The original prescription sheet, the 2nd and 
the 3rd NCR copy will be sent to the Hospital Pharmacist. The 4th will be kept in the Investigator site 
file.
The prescription will give the following information:
x Study LFB BIOTECHNOLOGIES I10E-1302 
x Patient identification: Patient number  
x Patient weight (in kg)
x Infusion dosage (in mL) 
x Planned infusion(s) date(s).
The Hospital Pharmacist will prepare the study drug for the infusions, according to the infusion 
dosage indicated in the prescription. The product should be at room or body temperature before it is 
administered to the patient. Prior to transfer, study drug will be checked for cloudiness, colour, 
soapy solution or deposits. If it does not conform to the description, the study drug must not be 
dispensed and the Hospital Pharmacist should immediately alert the Monitor.
For each study drug vial that is to be dispensed for infusion, the Hospital Pharmacist will stick one 
tear-off label on the prescription sheet (original), which will be filled in the Pharmacy study file for 
traceability purposes. 


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 6WXG\GUXJUHWXUQGHVWUXFWLRQDQGUHFDOO
When closing the investigational site, all used and unused study drug vials, including empty vials,
must be returned to the Sponsor's drug distributor except in case of specific local regulatory 
requirements. 
The Pharmacist must not destroy the used/unused study drugs without written authorization from the 
Sponsor. 
6.1.2. 4.1.Return
The return preparation of used/unused study drugs will be performed by the Hospital Pharmacist and 
the Monitor. 
For French sites only, return will be organised by Sponsor's drug distributor. The person in charge of 
study drug at site level should fill in and send (e-mail or fax) to drug distributor the "IMP Return 
Request Form" in which the Hospital Pharmacist will set a date and time for courier pick up. The 
Hospital Pharmacist or a delegate should be available at the predetermined date and time when the 
boxes will be collected from the investigational site.
For other countries, return will be arranged via the Monitors after obtaining the import authorization
from the French Competent Authority (ANSM). The Pharmacist should inform the Sponsor's drug 
distributor of the expected receipt date through "IMP Return Notification Form". 
6.1.2. 4.2.Destruction
After complete reconciliation, consolidated destruction of returned and stored vials will be 
performed by drug distributor upon Sponsor's request. 
In case of any on-site destruction required, site must obtain from LFB BIOTECHNOLOGIES a 
written authorization for destruction which will be filed along with the certificate of destruction in 
the IMP section of the Pharmacy site file.
Destruction of infusion lines will be carried out by the centre under Investigator's responsibilities. 
6.1.2. 4.3.Recall
The Sponsor or its representative and the Investigator/Hospital Pharmacist will inform each other of 
any suspected or identified study drug defect. Study drug must immediately be put in quarantine as 
per the storage temperature requirements and no further administration of the concerned batch(es) 
must be done until Sponsor’s instructions. 
The Monitor or the drug distributor will organize with the Investigator/Hospital Pharmacist the 
return of the concerned batch(es) as per the Sponsor return procedure. Depending on the study 
status, new batch(es) may be sent to the investigational site.


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 $GPLQLVWUDWLRQRIVWXG\GUXJWRSDWLHQWV
 6WXG\GUXJGRVDJHDQGWUHDWPHQWVFKHGXOH
The study drug dosage should be at 2 g/kg for the first adminitration, then at 1g/kg for the rest of the 
study.  
For patients with BMI t30 kg/m², the dose must be reduced by 20% i.e 1.6 g/kg for the first 
administration and 0.8 g/kg for the rest of study.  
It is not recommended to change the study drug dose or frequency of administration during the 
study.  
Under no circumstances will the Investigator/Hospital Pharmacist allow the study drug to be used 
other than as directed by the protocol. 
Before any infusion, the Investigator will rule out any study drug over or under dosage in regards to 
patient’s body weight and protocol requirements. 
 0HWKRGRIDGPLQLVWUDWLRQ
Before administration to a patient, the Investigator will check that the label corresponds to his/her 
prescription for the patient (study number, patient number, study drug dose).  
Study drug will be administered with an infusion pump.  
The infusion flow rate must be compliant with the Investigator’s Brochure of I10E. 
For the first day of any study drug course, the initial flow rate will not exceed 0.5 mL/kg/h during 
the first 30 minutes. If well tolerated, the rate of administration may be increased up to 1 mL/kg/h 
during 30 minutes, then - at the Investigator's discretion - gradually increased up to 2, 4 and 
6 mL/kg/h as a maximum flow rate.  
In patients older than 65 years, the maximum infusion flow rate should be 2 mL/kg/h. 
On the subsequent days of any study drug course, the flow rate is at the Investigator's discretion (up 
to 6 mL/kg/h; up to 2 mL/kg/h for patients older than 65 years).
 7UDFHDELOLW\DFFRXQWDELOLW\DQGGRFXPHQWDWLRQ
Each study drug course should be documented in the patient's medical file, including doses, time and 
flow rate changes.
The prescribed dose, the date and time of administration and the exact dose administered will be 
recorded in the eCRF.
The Sponsor will provide specific forms for study drug accountability, which will be kept up-to-date 
by the Hospital Pharmacist throughout the study. At the end of the study, it must be possible to 
reconcile the number of study drugs sent by the drug distributor with the number of study drugs
delivered to patients and the number of unused study drugs.
 &RPSOLDQFH
Compliance with treatment is defined as dose(s) administered within 20% of the prescribed dose(s). 
Both prescribed and administered doses will be recorded in the eCRF. 


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As the study drug will be administered only under the direct supervision of a physician familiar with 
the requirements of the study protocol, compliance should not be an issue. Nevertheless, the reason 
for any non-compliance must be recorded in the eCRF.
0HGLFDOGHYLFH
Infusion pump and perfusion lines will be provided by the Sponsor.  
35,25$1'&21&20,7$170(',&$7,21
3ULRU0HGLFDWLRQ
The term ‘prior medication’ refers to any medication given up to 2 months before screening. 
All relevant prior medications taken within two months prior to screening must be recorded in the 
patient’s medical file and documented on the appropriate pages of the eCRF. Moreover, any prior 
medication taken more than two months prior to screening which is, in the opinion of the 
investigator, clinically relevant to the patient's condition will also be recorded.
The following medications are not allowed before screening because they could interfere with the 
assessment of study drug efficacy:
x Any other investigational product administered within the last month prior to screening. 
x Plasma exchange, blood products or derivatives administered within the last 3 months prior to 
screening.
x Immunomodulatory 
or 
immunosuppressant 
agents 
(including 
but 
not 
limiting 
to 
cyclophosphamide, cyclosporine, interferon-D, interferon-E1a, anti-CD20, alemtuzumab, 
aziathioprine, etanercept, mycophenolate mofetil, methotrexate) or haemopoetic stem cell 
transplantation administered during the last 12 months prior to screening. 
x Systemic corticosteroids therapy if administered with an increasing dosage or introduced, or 
administered at a dose higher than 10 mg prednisolone per day, or equivalent. Topical 
corticosteroids are permitted.
x Loop diuretics administered during the last 24 hours before IVIg infusion planned date. In this 
case, the study drug infusion date will have to be postponed. 
&RQFRPLWDQW0HGLFDWLRQ
The term ‘concomitant medication’ refers to any medication that the patient receives at any time
during the study, i.e. from screening to EOS visit. This includes the screening/baseline period,  
treatment period and follow-up as defined in the protocol. At each visit, the Investigator will ask the 
patient about any medication taken since the last visit. All concomitant medication must be recorded 
in the patient’s medical file and documented on the appropriate pages of the eCRF. 
Treatments not allowed during the study are the following:
 Plasma exchange, blood products or derivatives other than the study drug.


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 Immunomodulators/immunosuppressors 
agents 
(e.g. 
including 
but 
not 
limited 
to 
cyclophosphamide, cyclosporine, interferon-D, interferon-E1a, anti-CD20, alemtuzumab, 
aziathioprine, etanercept, mycophenolate mofetil, methotrexate) and haemotopoeitic stem cell 
transplantation. 
 Introduction or increasing dose of systemic corticosteroids therapy, and/or systemic 
corticosteroids therapy at a dose higher than 10 mg prednisolone per day, or equivalent. 
Topical corticosteroids are permitted.
 Loop diuretics administered during the last 24 hours hours before IVIg infusion planned date. 
In this case, the study drug infusion date will have to be postponed. 
Routine pre-medication (to prevent known drug related adverse reaction) are not recommended to 
avoid masking potential AEs. However, patients who have routinely been receiving pre-medication
with previous Ig treatments may continue to receive the same pre-medication.  
Other medications which are necessary for the patient’s welfare or well-being may be given at the
discretion of the Investigator. 
All concomitant medications must be recorded in the patient’s medical records and documented on 
the appropriate pages of the eCRF.
678'<3/$1
The method for assessing each study parameter is described in Section 10. 
See also Table 1–1: study flow chart. 
3DWLHQWUHFUXLWPHQW
 ,QIRUPHG&RQVHQW
The Investigator provides each patient with relevant, comprehensive, verbal and written information 
regarding the objectives and procedures of the study, as well as the possible risks involved. A patient 
information sheet will be given to the patient.
The patient should have enough time and opportunity to inquire about study details. All his/her 
questions should be answered in a satisfactory manner. The patient must be informed about his/her 
right to withdraw from the study at any time. 
Signed informed consent must be obtained from the patient prior to undertaking any study-related 
procedure and before a blood sample is taken for the screening tests.  
One original of the informed consent form, signed and dated by both the patient and the Investigator, 
will be given to the patient. A second original is filed at the Investigator’s site. The process of 
obtaining consent will be documented in the patient’s file. 
 6FUHHQLQJ
The screening period starts when the patient signs his/her informed consent and ends right before 
study drug is first administered.


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The exclusion and inclusion criteria (except those related to screening biological assesments) will be 
verified prior to screening. The screening biological test results will be verified before the first study 
drug administration.
The screening biological tests should be performed and their results checked by the Investigator 
within a period of 4 weeks before the first study drug administration.
Baseline data are those obtained during the screening period before the first study drug 
administration. If multiple results are available for one single test, the most recent one will be 
considered.
If the patient is a woman of childbearing potential, investigator must caution her not to become 
pregnant, while participating to the clinical study. The patient must be willing to employ an effective 
contraception mean.
Effective contraceptives are injectable, patch or oral combined oestro-progestative or progestative 
contraceptives, copper T or levonorgest-releasing intra-uterine devices, depot intramuscular 
medroxyprogesterone, subcutaneous progestative contraceptive implants, condoms or occlusive caps 
(diaphragm or cervical/vault caps) with spermicide, true abstinence (when this is in line with the 
preferred and usual lifestyle of the patient).
After the patient has signed his/her informed consent, a blood sample will be drawn for biological 
tests. The screening biologic tests should be performed and the results checked by the Investigator 
within a period of 4 weeks before the first study drug administration. 
The 4-week period should ensure the availability of the screening tests results.
An eCRF will be completed for each patient who has signed an informed consent form. In case of 
screening failure, the reason will be documented in the eCRF.
 3DWLHQW$OORFDWLRQ
Patient numbers will be composed of 4 digit numbers as shown here below:
_BB_BB_ _BB_BB_
Site        - Screening  -
A two-digit numbers will be allocated to each site at the beginning of the study.
Investigators will allocate a screening number to each patient who has signed an informed consent. 
Screening numbers will be two-digit numbers starting with 01 and attributed sequentially according 
to the chronological order of informed consent signatures in the site. 
Assigned by the 
Investigator
Assigned by 
the Sponsor


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)LJXUH±6HTXHQFHRIVWXG\SURFHGXUH
XOWUDVRQRJUDSK\FRXSOHGWRHOHFWURSK\VLRORJ\RQO\IRU,WDOLDQVLWHV



LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03 May 2017, incorporated the amendment N°3
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6HTXHQFHRIVWXG\SURFHGXUHV
 9LVLW6FUHHQLQJ
The following visit procedures will be carried out during the screening: 
 Informed consent signature. 
 Check of inclusion and exclusion criteria. 
 Demographic and biometric information (gender, age, weight, BMI…). 
 Relevant medical history and ongoing concomitant diseases. 
 Listing of prior medications.
 Complete physical examination.
 Vital signs: temperature, heart rate, systolic and diastolic blood pressure.
 Neurological status assessment: 
ƒ INCAT disability score (adjusted INCAT disability score will be deduced from reported 
values). 
 Biological tests in local laboratory:
ƒ Haematology: 
ƒ Complete blood count + differentials, haemoglobin (Hb), mean corpuscular volume 
(MCV), platelets count.  
ƒ Haptoglobin.  
ƒ Reticulocytes, direct Coombs test.
ƒ Biochemistry: 
ƒ Creatininemia, glomerular filtration rate according to MDRD. 
ƒ LDH. 
ƒ Total and free bilirubin (total bilirubin in all patients; if total bilirubin ! ULN, free 
bilirubin will be assessed from the same blood sample, as total bilirubin). 
ƒ AST, ALT, ALP, JGT. 
ƒ HbA1c (only for patients with a known history of diabetes mellitus). 
ƒ Total serum protein level. 
ƒ HBs Ag, anti HBs & anti HBc Ab, HIV, HCV tests.
ƒ Serum IgA levels.
ƒ Urine protein reagent strip test:
If urine protein reagent strip test result
= Negative or Trace
Action: No further urine test required
If urine protein reagent strip test result
= 1 cross (1 +)
Action: Verify eligibility after either assessing AER or PER from a 24h-urine 
collection sampled before the first study drug course
or assessing ACR or PCR from a spot urine sample immediately following the urine 
protein reagent strip test (i.e. urine obtained before study drug administration).
If urine protein reagent strip test result
= 2 crosses (2 +) or more
Patient should be excluded
ƒ Urine Pregnancy test for female patients of child bearing potential. 


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03 May 2017, incorporated the amendment N°3
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 Analysis at centralised laboratory: 
ƒ Anti-CNTN1 and anti-NF155 antibodies. 
 Ultrasonography coupled to neurophysiology (for Italian sites only). 
 AEs assessment.  
 Listing of ongoing concomitant treatments.
 Delivery of Patient diary with instruction for use. The patient should document in the diary 
any AE that occus outside of hospital (including start and end date and time) and any 
medication taken during the study. The patient should come back at each visit with the diary 
and the Investigator should assess and evaluate patient information recorded in the diary and 
report appropriate relevant information in the eCRF. 
Abnormal findings at screening physical and biological tests should be reported as baseline findings 
in patient medical history. All clinical or laboratory abnormalities other than those found on 
mandatory study screening tests should be reported as an adverse event if clinically significant.
 9LVLW)LUVWVWXG\GUXJFRXUVH
(As soon as the biologic results of screening are available, no later than 4 weeks after the start of the 
screening).
The following study procedured will be carried out at the 1st study drug course:
x Before the 1st study drug course (within 24 hours before study drug course) 
 Complete physical examination.
 Biometric information: weight.
 Vital signs: temperature, heart rate, systolic and diastolic blood pressure.
 Baseline neurological status assessment: 
ƒ INCAT disability score (adjusted INCAT disability score will be deduced from reported 
values). 
ƒ Patient and Investigator CGI-S. 
ƒ MRC-sum-score. 
ƒ Rasch-modified MRC sum score. 
ƒ R-ODS.
ƒ Grip strength with Martin vigorimeter in both hands.  
 Biological tests in local laboratory: 
ƒ Serum total IgG trough levels. 
ƒ C3 and C4 antigens.
ƒ Serum reference sample for long term storage. 
 Analysis at centralised laboratory: 
ƒ BAFF.
ƒ CH50.
ƒ FcJRIIB. 


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 AEs assessment. 
 Listing of concomitant medication.
 Patient diary verification. If information on the patient’s diary is not clear, the Investigator will 
ask the patient questions. The investigator may annotate the patient’s diary but must date and 
sign the annotations. 
x During the course of study drug infusion:  
ƒ Collection of infusion parameters. 
ƒ Vital signs measured 30-45 min and 60-75 min after the beginning of the infusion:
temperature, heart rate, systolic and diastolic blood pressure. 
ƒ Listing of concomitant medication if applicable.
ƒ AEs assessment. 
x 30-45 min after the end of study drug infusion:  
ƒ Vital signs: temperature, heart rate, systolic and diastolic blood pressure.
ƒ AEs assessment.  
ƒ Listing of concomitant medication if applicable.
 9LVLWKRXUVDIWHUWKHHQGRIWKHILUVWFRXUVHKRXUV
The following study procedures will be carried out: 
 Complete physical examination.
 Vital signs: temperature, heart rate, systolic and diastolic blood pressure.
 Biological tests in local laboratory:
ƒ Haematology: 
ƒ Complete blood count + differentials, Hb, MCV, platelets count.  
ƒ Haptoglobin. 
ƒ Biochemical: 
ƒ Creatininemia, glomerular filtration rate according to MDRD.
ƒ LDH.
ƒ Total and free bilirubin (total and free bilirubin (total bilirubin in all patients; if total 
bilirubin ! ULN, free bilirubin will be assessed from the same blood sample, as total 
bilirubin). 
ƒ C3 and C4 antigens.
ƒ Urine protein reagent strip test [to be performed in patients who at screening tested for 
urine protein reagent strip result "1 cross 1 (+) and/or had GFR in the range of
60-80 mL/min/1.73m2]:


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If urine protein reagent strip test result
= Negative or Trace
Action: No further urine test required
If urine protein reagent strip test result
= 1 cross (1 +) or more
Action: Assess either AER or PER from a 24h-urine collection sampled at least 7 days 
after the end of the previous study drug course
or assess ACR or PCR from a spot urine sample immediately following the urine 
protein reagent strip test (i.e. urine obtained before study drug administration).
The Investigator must review these results in time prior to the study drug 
administration and consider if any of the Early Discontinuation Criteria / Stopping 
Rules (see Section 5.4) apply.
 Analysis at centralised laboratory: 
ƒ BAFF.
ƒ CH50.
ƒ FcJRIIB (on B cells). 
 AEs assessment. 
 Listing of concomitant medication if applicable.
 Patient diary verification. If information on the patient’s diary is not clear, the Investigator will 
ask the patient questions. The investigator may annotate the patient’s diary but must date and 
sign the annotations. 
 9LVLWVDQG:HHN:HHNDQG:HHNGD\V
The following study procedures will be carried out: 
x Before study drug course (within 24 hours before study drug course) 
 Clinical examination focused on arterial or venous thromboembolic signs. 
 Biometric information: weight.
 Vital signs: temperature, heart rate, systolic and diastolic blood pressure. 
 Neurological assessments:
ƒ INCAT disability score (adjusted INCAT disability score will be deduced from reported 
values). 
-
Biological tests in local laboratory: 
ƒ Haematology: 
ƒ Complete blood count + differentials, Hb, MCV, platelets count. 
ƒ Haptoglobin. 
ƒ Biochemistry:
ƒ Creatininemia, glomerular filtration rate according to MDRD.
ƒ LDH.
ƒ Total and free bilirubin (total bilirubin in all patients; if total bilirubin ! ULN, free 
bilirubin will be assessed from the same blood sample, as total bilirubin). 
ƒ C3 and C4 antigens (only at visit V4, Week 3).
ƒ Serum total IgG trough levels.
ƒ Urine protein reagent strip test [to be performed before study drug administration in 
patients who at screening tested for urine protein reagent strip result "1 cross 1 (+) 
and/or had GFR in the range of 60-80 mL/min/1.73m2]:


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If urine protein reagent strip test result
= Negative or Trace
Action: No further urine test required
If urine protein reagent strip test result
= 1 cross (1 +) or more
Action: Assess either AER or PER from a 24h-urine collection sampled at least 7 days 
after the end of the previous study drug course
or assess ACR or PCR from a spot urine sample immediately following the urine 
protein reagent strip test (i.e. urine obtained before study drug administration).
The Investigator must review these results in time prior to the next study drug 
administration and consider if any of the Early Discontinuation Criteria / Stopping 
Rules (see Section 5.4) apply.
 Blood collection for central analysis: (Week 3 only): 
ƒ BAFF.
ƒ CH50. 
ƒ FcJRIIB (on B cells).
 AEs assessment.
 Listing of ongoing concomitant treatments.
 Patient diary verification. If information on the patient’s diary is not clear, the Investigator will 
ask the patient questions. The investigator may annotate the patient’s diary but must date and 
sign the annotations. 
x During the course of study drug infusion:
ƒ Collection of infusion parameters. 
ƒ Vital signs measured 30-45 min and 60-75 min after the beginning of the infusion:
temperature, heart rate, systolic and diastolic blood pressure. 
ƒ Listing of concomitant medication if applicable.
ƒ AEs assessment. 
x 30-45 min after the end of study drug infusion:
ƒ Vital signs: temperature, heart rate, systolic and diastolic blood pressure.
ƒ AEs assessment.  
ƒ Listing of concomitant medication if applicable.
Four days after the end of study drug administration (+/- 1 day): the Investigator or the Study Nurse 
will call the patient in order to collect information about the possible occurrence of AEs after the 
patient has left the hospital. 
 9LVLW:HHNGD\V
The following study procedures will be carried out: 
x Before study drug course (within 24 hours before study drug course) 
 Clinical examination focused on arterial or venous thromboembolic signs. 
 Biometric information: weight.
 Vital signs: temperature, heart rate, systolic and diastolic blood pressure.
 Neurological status assessment: 
ƒ INCAT disability score (adjusted INCAT disability score will be deduced from reported 
values). 
ƒ Patient and Investigator CGI-S, CGI-E and CGI-I.
ƒ MRC sum score.


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ƒ Rasch-modified MRC sum score.  
ƒ R-ODS.
ƒ Grip strength with Martin vigorimeter in both hands. 
 Biological tests in local laboratory: 
ƒ Haematology: 
ƒ Complete blood count + differentials, Hb, MCV, platelets count.  
ƒ Haptoglobin. 
ƒ Biochemistry:
ƒ Creatininemia, glomerular filtration rate according to MDRD
ƒ LDH.
ƒ Total and free bilirubin (total bilirubin in all patients; if total bilirubin ! ULN, free 
bilirubin will be assessed from the same blood sample, as total bilirubin). 
ƒ Serum total IgG trough levels. 
ƒ Urine protein reagent strip test [to be performed before study drug administration in 
patients who at screening tested for urine protein reagent strip result "1 cross 1 (+) 
and/or had GFR in the range of 60-80 mL/min/1.73m2]:
If urine protein reagent strip test result
= Negative or Trace
Action: No further urine test required
If urine protein reagent strip test result
= 1 cross (1 +) or more
Action: Assess either AER or PER from a 24h-urine collection sampled at least 7 days 
after the end of the previous study drug course
or assess ACR or PCR from a spot urine sample immediately following the urine 
protein reagent strip test (i.e. urine obtained before study drug administration).
The Investigator must review these results in time prior to the next study drug 
administration and consider if any of the Early Discontinuation Criteria / Stopping 
Rules (see Section 5.4) apply.
 AEs assessment. 
 Listing of ongoing concomitant treatments.
 Patient diary verification. If information on the patient’s diary is not clear, the Investigator will 
ask the patient questions. The investigator may annotate the patient’s diary but must date and 
sign the annotations. 
x During the course of study drug infusion:
ƒ Collection of infusion parameters.
ƒ Vital signs measured 30-45 min and 60-75 min after the beginning of the infusion:
temperature, heart rate, systolic and diastolic blood pressure. 
ƒ Listing of concomitant medication if applicable.
ƒ AEs assessment. 
x 30-45 min after the end of study drug infusion:
ƒ Vital signs: temperature, heart rate, systolic and diastolic blood pressure.
ƒ AEs assessment.  
ƒ Listing of concomitant medication if applicable.
Four days after the end of study drug administration (+/- 1 day): the Investigator or the Study Nurse 
will call the patient in order to collect information about the possible occurrence of AEs after the 
patient has left the hospital. 


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 9LVLWVDQG:HHNDQGGD\V
The following study procedures will be carried out: 
x Before study drug course (within 24 hours before study drug course) 
 Clinical examination focused on arterial or venous thromboembolic signs. 
 Biometric information: weight.
 Vital signs: temperature, heart rate, systolic and diastolic blood pressure. 

Neurological assessments: 
ƒ INCAT disability score (adjusted INCAT disability score will be deduced from reported 
values). 

Biological tests in local laboratory:
ƒ Haematology: 
ƒ Complete blood count + differentials, Hb, MCV, platelets count. 
ƒ Haptoglobin. 
ƒ Biochemistry:
ƒ Creatininemia, glomerular filtration rate according to MDRD.
ƒ LDH.
ƒ Total and free bilirubin (total bilirubin in all patients; if total bilirubin ! ULN, free 
bilirubin will be assessed from the same blood sample, as total bilirubin).
ƒ Serum total IgG trough levels. 
ƒ Urine protein reagent strip test [to be performed before study drug administration in 
patients who at screening tested for urine protein reagent strip result "1 cross 1 (+) 
and/or had GFR in the range of 60-80 mL/min/1.73m2]:
If urine protein reagent strip test result
= Negative or Trace
Action: No further urine test required
If urine protein reagent strip test result
= 1 cross (1 +) or more
Action: Assess either AER or PER from a 24h-urine collection sampled at least 7 days 
after the end of the previous study drug course
or assess ACR or PCR from a spot urine sample immediately following the urine 
protein reagent strip test (i.e. urine obtained before study drug administration).
The Investigator must review these results in time prior to the next study drug 
administration and consider if any of the Early Discontinuation Criteria / Stopping 
Rules (see Section 5.4) apply.


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 AEs assessment. 
 Listing of ongoing concomitant treatments.
 Patient diary verification. If information on the patient’s diary is not clear, the Investigator will 
ask the patient questions. The investigator may annotate the patient’s diary but must date and 
sign the annotations. 
x During the course of study drug infusion:
ƒ Collection of infusion parameters. 
ƒ Vital signs measured 30-45 min and 60-75 min after the beginning of the infusion:
temperature, heart rate, systolic and diastolic blood pressure. 
ƒ Listing of concomitant medication if applicable.
ƒ AEs assessment. 
x 30-45 min after the end of study drug infusion:
ƒ Vital signs: temperature, heart rate, systolic and diastolic blood pressure.
ƒ AEs assessment.  
Four days after the end of study drug administration (+/- 1 day): the Investigator or the Study Nurse 
will call the patient in order to collect information about the possible occurrence of AEs after the 
patient has left the hospital. 
 9LVLW:HHNGD\V(QGRIVWXG\YLVLW
At the end of the 24-week treatment and follow-up period, patients undergo an end of study visit 
evaluation. This visit occurs 3 weeks after the 7th course of study drug at a dose of 1 g/kg.  
In the event of premature discontinuation from the study drug or patient withdrawal from the study, 
an end of study visit is performed within 7 days.  
The end of study assessment should be performed before any other treatment including Igs is 
administered.
The reason for premature study drug discontinuation / study withdrawal should be accurately 
assessed and entered into the eCRF.  
The following study procedures will be carried out: 
 Complete physical examination.
 Biometric information: weight.
 Vital signs: temperature, heart rate, systolic and diastolic blood pressure. 
 Neurological status assessment: 
ƒ INCAT disability score (adjusted INCAT disability score will be deduced from reported 
values). 
ƒ Patient and Investigator CGI-S, CGI-E and CGI-I. 
ƒ MRC sum score.
ƒ Rasch-modified MRC sum score. 
ƒ R-ODS.
ƒ Grip strength with Martin vigorimeter in both hands.  
 Biological tests in local laboratory:
ƒ Haematology: 


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ƒ Complete blood count + differentials, Hb, MCV, platelets count. 
ƒ Haptoglobin. 
ƒ Reticulocytes, direct Coombs test
ƒ Biochemistry:
ƒ Creatininemia, glomerular filtration rate according to MDRD.
ƒ LDH.
ƒ Total and free bilirubin (total bilirubin in all patients; if total bilirubin ! ULN, free 
bilirubin will be assessed from the same blood sample, as total bilirubin). 
ƒ AST, ALT, ALP, JGT.
ƒ Total serum protein level. 
ƒ C3 and C4 antigens. 
ƒ Serum total IgG trough levels. 
ƒ HBs Ag, anti HBs & anti HBc Ab, HIV, HCV tests.
ƒ Serum reference sample for long term storage. 
ƒ Urine protein reagent strip test [to be performed before study drug administration in 
patients who at screening tested for urine protein reagent strip result "1 cross 1 (+) 
and/or had GFR in the range of 60-80 mL/min/1.73m2]:
If urine protein reagent strip test result
= Negative or Trace
Action: No further urine test required
If urine protein reagent strip test result
= 1 cross (1 +) or more
Action: Assess either AER or PER from a 24h-urine collection sampled at least 7 days 
after the end of the previous study drug course
or assess ACR or PCR from a spot urine sample immediately following the urine 
protein reagent strip test (i.e. urine obtained before study drug administration).
ƒ Urine Pregnancy test for female patients of child bearing potential. 
 Analysis at centralised laboratory: 
ƒ BAFF.
ƒ CH50.
ƒ Anti-CNTN1 and anti-NF155 antibodies. 
 Ultrasonography coupled to neurophysiology (for Italian sites only). 
 AEs assessment. 
 Listing of concomitant treatments.
 Patient diary verification. If information on the patient’s diary is not clear, the Investigator will 
ask the patient questions. The investigator may annotate the patient’s diary but must date and 
sign the annotations. 
$WDQ\FRXUVH
,QFDVHRIVXVSHFWHGFOLQLFDOYHQRXVWKURPERVLV D-Dimers testing will be performed.
,QFDVHRIVXVSHFWHGKDHPRO\VLVEDVHGRQELRORJLFDOWHVWV (Hb, haptoglobin, LDH, total and free 
bilirubin levels (total bilirubin in all patients; if total bilirubin ! ULN, free bilirubin will be assessed 
from the same blood sample, as total bilirubin)): Reticulocytes and direct Coombs test will be 
performed.


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&HQWUDOELRORJLFDOKDQGOLQJVDPSOLQJ
Details for blood sampling performed for the biomarkers (anti-CNTN1 and anti-NF155 antibodies, 
BAFF, CH50, FcJRIIB), storage and shipment to the central laboratory are described in the 
laboratory manual.
8OWUDVRQRJUDSK\IRU,WDOLDQVLWHRQO\
Details for ultrasonography coupled to neurophysiology examination are described in the 
ultrasonography manual. 
&RPSOLDQFHZLWKWKHVWXG\SODQ
The Investigator should make every effort to comply with the study plan. If the Investigator 
encounters difficulties in complying with the study plan, e.g. with regard to the schedule of visits or 
the required procedures, he/she must alert the Sponsor. The Sponsor may consider it relevant to 
generate an amendment. 
The Investigator should make every effort to avoid the occurrence of deviations from the study plan. 
If deviations occur or if the Investigator knows that a deviation will occur, he/she must promptly 
inform the Sponsor to determine how to manage the deviation. 
6$)(7<
5HIHUHQFH6DIHW\,QIRUPDWLRQ'RFXPHQW
The current version of the Investigator Brochure of I10E, will be the Reference Safety Information 
document to assess the expectedness of AEs.  
%HQHILW5LVN,QIRUPDWLRQ
 3RWHQWLDOULVNVUHODWHGWRWKHVWXG\GUXJ
Common and important adverse reactions associated with IVIg administration are described in the 
European Guideline EMA/CHMP/BPWP/94038/2007 rev.4 of IVIg [14]. 
Adverse reactions such as chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, 
arthralgia, low blood pressure and moderate low back pain may occur occasionally with IVIg. 
Rarely human normal Ig may cause a sudden fall in blood pressure and, in isolated cases, 
anaphylactic reaction, even when the patient has shown no hypersensitivity to previous 
administration.
Cases of reversible aseptic meningitis and rare cases of transient cutaneous reactions have been 
observed with human normal immunoglobulin. Reversible haemolytic reactions have been observed 
in patients, especially those with blood groups A, B, and AB. Rarely, haemolytic anaemia requiring 
transfusion may develop after high dose IVIg treatment.
Increase in serum creatinine level and/or acute renal failure have been observed.


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Very rarely, thromboembolic reactions such as myocardial infarction, stroke, pulmonary embolism, 
deep vein thromboses have been described. 
Important potential risks that could be anticipated with I10E administration are those known with 
IVIg preparations: 
Hypersensitivity
True hypersensitivity reactions are rare. They can occur in patients with anti-IgA antibodies. 
Rarely, human normal immunoglobulins can induce a fall in blood pressure with anaphylactic 
reaction, even in patients who had tolerated previous treatment with human normal 
immunoglobulins. 
To minimize risk of anaphylactic reactions, patients with IgA deficiency will be excluded, except if 
the absence of anti-IgA antibodies is documented [37] [38]. The patients with a known 
hypersensitivity to the active substance or to any of the excipients of I10E will be excluded.  
Thromboembolism 
There is clinical evidence of an association between IVIg administration and thromboembolic events 
such as myocardial infarction, cerebral vascular accident (including stroke), pulmonary embolism 
and deep vein thromboses. Such an association is assumed to be related to a relative increase in 
blood viscosity through the high influx of immunoglobulins in at-risk patients.  
To minimize the risk of thromboembolic events, patients with a history of venous thromboembolic 
disease, myocardial infarction or cerebrovascular accident will be excluded. As well, patients with 
uncontrolled cardiac arrhythmia and patients with unstable ischemic heart disease will not be 
allowed to participate to the study.
Acute renal failure
Cases of acute renal failure have been reported in patients receiving IVIg therapy. In most cases, risk
factors have been identified. These included pre-existing renal insufficiency, diabetes mellitus, 
hypovolaemia, overweight, concomitant nephrotoxic medicinal products and age over 65. 
To minimize the risk of acute renal failure, patients with a chronic kidney disease (CKD) defined as 
abnormalities of kidney structure or function, present for !3 months, with implications for health, 
i.e. patients with persistent albuminuria category A3 and/or GFR 60 mL/min/1.73m2 (measured 
according to the MDRD calculation) will be excluded [39].  
The use of loop diuretics is also not allowed if used within 24 hours prior to study drug
administration. 
Aseptic meningitis syndrome (AMS)
Aseptic meningitis syndrome has been reported to occur in association with IVIg treatment. 
Discontinuation of IVIg treatment has resulted in remission of AMS within several days without 
sequelae. AMS may occur more frequently in association with high-dose of IVIgs.
Haemolytic anaemia
IVIg products can contain blood group antibodies which may act as haemolysins and induce in vivo 
coating of red blood cells with immunoglobulin, causing a positive direct antiglobulin reaction 
(Coombs’ test) and, rarely, haemolysis. Haemolytic anaemia can develop subsequent to IVIg 
therapy due to enhanced red blood cells (RBC) sequestration.  
Haptoglobin and LDH levels in patients will be assessed at every visit.


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Interference with serological testing
After injection of immunoglobulin the transitory rise of various passively transferred antibodies in 
the patient’s blood may result in misleading positive results in serological testing.
Passive transmission of antibodies to erythrocyte antigens, e.g. A, B, D may interfere with some 
serological tests for red cell antibodies for example the direct antiglobulin test (DAT), direct 
Coombs’ test.
Interaction with other medicinal products 
I10E may impair the efficacy of live attenuated virus vaccines for a period of up to 3 months. In the 
case of measles, this impairment may persist for up to 1 year.
Transmissible agents
Despite dedicated effective measures to prevent infections resulting from the use of plasma-derived 
products including selection of donors, screening of individual donations and plasma pools, as well 
as effective manufacturing steps for the inactivation/removal of viruses, the risk of transmitting 
infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and 
other pathogens. 
Patient serum reference samples will be drawn at the beginning and at the end of the study, and will
be kept for long term storage.
 3RWHQWLDOULVNVUHODWHGWRWKHVWXG\SURFHGXUHV
Blood sampling will be performed during this study in order to monitor the safety. Although this 
procedure represents an inconvenience for the patient, it does not constitute an additional significant 
risk.
There is a minor risk of haematoma from intravenous infusion of the study drug and from drawing 
blood. Slight pain at the injection site, feeling light-headed, bruising and, exceptionally, infection as 
well as bleeding from the site of the puncture may occur.
5LVNPLQLPLVDWLRQDFWLRQVWKURXJKRXWWKHSURWRFRO
Some adverse drug reactions may be related to the infusion flow rate. Patients will be closely 
monitored and carefully observed for any symptoms throughout the infusion periods. In the case of
AE, the infusion rate may be reduced or even stopped. Standard medical care should be 
implemented as necessary.
Potential complications will be avoided by ensuring that patients: 
x have an adequate hydration status prior to infusions of the study drug; 
x are not sensitive to human normal Ig by initially infusing the product slowly, starting at 
0.5 mL/kg/h during the first 30 minutes; 
x are carefully monitored for any symptoms throughout the infusion period and 30-45 minutes after 
the end of each infusion. An additional phone call at 4 days (+/- 1 day) from the Investigator or 
the Study Nurse to the patient is planned to ask if AEs or TAAEs are reported within 72 hours 
(+/- 1 day) after the end of each course; 
x Close Monitoring (vital signs, biological tests, haematological tests, physical examinations 
planed for each course to minimise these risks);
x Haematology (96h after the end of the first course): complete blood count + differentials, 
platelets count, MCV and haptoglobin; 


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x Biochemical (96h after the end of the first course): creatinine, glomerular filtration rate according 
to MDRD formula, total and free bilirubin tests (total bilirubin in all patients; if total bilirubin 
! ULN, free bilirubin will be assessed from the same blood sample, as total bilirubin); 
x D-Dimers, in case of suspected thrombus; 
x Reticulocytes and Direct Coombs test, in case of haemolysis based on biological tests (Hb, 
haptoglobin, LDH, total and free bilirubin levels (total bilirubin in all patients; if total bilirubin 
! ULN, free bilirubin will be assessed from the same blood sample, as total bilirubin). 
 %HQHILW5LVN%DODQFH
I10E have been developed by LFB and manufactured from plasma pools which are EMA certified. 
Marketing Authorization Application (MAA) was submitted in Intravenous Immunoglobulin (IVIg) 
Core Summary of Product Characteristics (SPC) indications through the Decentralized Procedure 
(DCP) in the following European Union Member States: Austria, Belgium, Czech Republic, 
Denmark, Finland, Germany, Greece, Hungary, Italy, Luxembourg, the Netherlands, Spain, 
Slovakia, Sweden, and the United Kingdom. The first marketing authorization was granted in the 
United Kingdom in August 2015, then in Denmark, Germany, Hungary, Belgium and Finland. 
This study is designed according to the currently accepted scheme of the standard of care of CIDP, 
based on the clinical guideline (EFNS/PNS CIDP Guideline 2010, First revision) which is in line 
with European countries’ recommendations and the recommendations of EMA.  
IVIg are used in CIDP patients and have shown a favorable benefit/risk balance.  
I10E has already been assessed in two pivotal studies: I10E-0718 and I10E-0719, respectively in 
PID and ITP, in 100 patients. Both studies concluded to a comparable safety profile with IVIg 
preparation. The I10E doses recommended in this protocol will not exceed those used in current 
medical practice in this indication, in the before-mentioned clinical trials. Participation in the study 
is not expected to induce significant additional risk for patients. 
$OWHUQDWLYHWKHUDSHXWLFPDQDJHPHQWKDQGOLQJHPHUJHQFLHV
x If allergic or anaphylactic-type reactions occur, the infusion must be stopped immediately and 
standard medical treatment must be implemented.
x In case of misuse and/or overdose, appropriate corrective actions should be promptly undertaken 
when possible. The patient should be followed-up until the assurance that no AE occurs is 
obtained. 
'HILQLWLRQDQGUHSRUWLQJRIVHULRXVDGYHUVHHYHQWV
 'HILQLWLRQRI$GYHUVH(YHQWDQG6HULRXV$GYHUVH(YHQW
An AE is any untoward medical occurrence in a patient or clinical investigation subject to whom a 
medicinal product is administered. The occurrence does not have necessarily a causal relationship 
with the treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding, for example), any symptom or disease, whether new or exacerbated, 
temporally associated with the use of a medicinal product, whether or not related to the 
investigational drug product.


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An AE, whether or not considered to be causally related to the investigational drug product, may be: 
x The deterioration of a pre-existing chronic disease or aggravation of a symptom or disease that 
was present at inclusion of the patient in the study. 
x A symptom or disease discovered after the start of the study even if it was probably present prior 
to the patient's inclusion. 
x Abnormal laboratory findings when they are considered as clinically significant by the 
Investigator.  
In case a vital sign shows a clinically significant abnormality, an AE should be reported (or the 
abnormal vital sign should be linked to an already reported AE). A serious AE is an AE that, at any 
time, fulfils one or more of the following criteria:
x results in death, 
x is life threatening (the patient was at risk of death at the time of the event; it does NOT refer to an 
event which hypothetically might have caused death if it were more severe),
x requires in-patient hospitalisation or prolongation of existing hospitalisation - hospitalisation 
required by the study will not be considered as an AE, 
x results in persistent or significant disability/incapacity (substantial disruption of a person’s ability 
to carry out normal life functions), 
x is a congenital anomaly/birth defect,
x is any important medical event that may not be immediately life threatening or result in death or 
hospitalisation but, based upon appropriate medical judgment, may endanger the patient or may 
require intervention to prevent one of the other outcomes listed in the definition above, and 
should also be reported in the same way as an SAE. Examples of such events are invasive or 
malignant cancers, intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalisation; or 
development of drug dependency or drug abuse. 
Distinction should be made between serious and severe AEs. Severity is a measure of intensity 
whereas seriousness is based on the outcome or the action criteria described above, for example, 
nausea that persists for several hours may be considered as severe, but not as an SAE. On the 
contrary, a cardiovascular event that causes limited degree of disability may be considered as not 
severe but would be recorded as an SAE. 
x Events initially reported as an AE may become serious. For example, diarrhoea may become 
debilitating and require hospitalisation or prolongation of hospitalisation and is then reported as 
an SAE.  
x Surgical intervention is not to be considered as a SAE but the medical condition requiring the 
surgery is to be reported as such. 
x If a medical condition known before the start of study treatment requires hospitalisation for 
planned surgical measures, it should not be considered as an AE. However, the medical condition 
should be reported in the medical history. 
x Occurrence of study drug misuse/abuse, overdose or drug dependency, whether or not associated 
to an adverse event, must be recorded, reported immediately to the Sponsor.  
 'HILQLWLRQRIVSHFLILFHYHQWVLQWKHVWXG\LIDSSOLFDEOH
A worsening of the CIDP will not be regarded as an AE (or a SAE) and will be recorded in specific 
eCRF forms. These data will be analysed as part as the efficacy assessment.


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 $GYHUVH(YHQWUHFRUGLQJDQGUHSRUWLQJ
3HULRGRI6HULRXV$GYHUVH(YHQW'DWD&ROOHFWLRQ
In order to ensure complete safety data collection, recording and reporting, all (S)AEs occurring 
during the study, i.e. after signature of the Informed Consent, must be recorded, even if no study 
drug was administered. These include all AEs occurring, recurring, or worsening after the signature 
of the informed consent. The period of observation for the study is from the screening visit to the 
end of study visit. 
If the Investigator becomes aware, after that period, of any unusual safety information or any safety 
information that appears to be drug related involving a patient who had participated in the study, 
even after the patient completes the study, he/she should contact the sponsor to determine how it 
should be documented and reported. 
5HFRUGLQJDQG'HVFULSWLRQRI6HULRXV$GYHUVH(YHQW
All AEs occurring after signature of the informed consent until the end of study visit will be 
recorded in the appropriate pages of eCRF, including AEs occurring during the screening period and 
before the first administration of study drug, other than baseline findings which will be recorded as 
medical history. 
Each individual AE is to be listed as a separate entry on the eCRF AE form. The Investigator will 
provide information on dates of onset and resolution, seriousness, severity, frequency, action(s) 
taken with regard to corrective therapy or to the study drug, outcome and relationship to the study 
drug. The Investigator must report to the Sponsor or its designee all AEs that occur during the study 
from the time the written informed consent is given until the EOS visit or premature termination, 
regardless of their relationship to the study drug. Apart from AEs clinically observed by the 
Investigator, the patient will be given the opportunity to report AEs spontaneously. A general 
prompt will also be given to detect AEs, e.g. “Did you experience any illness or unusual symptom
since your last visit?”
)ROORZXSRI$GYHUVH(YHQWV
All AEs and SAEs assessed as not related to study medication, including clinically significant 
laboratory tests or physical examination findings, must be followed until the event resolves, the 
condition stabilizes, the event is otherwise explained, or the final study visit occurs, whichever 
comes first. 
AEs or SAEs assessed as related to study drug will be followed for as long as necessary to 
adequately evaluate the subject’s safety, or until the event stabilizes, or the subject is lost to follow 
up. If resolved, a resolution date should be provided. 
The Investigator is responsible for ensuring that follow-up includes any supplemental investigations 
indicated to elucidate the nature and/or causality of the AE. This may include additional clinical 
laboratory testing or investigations, histopathological examinations, or consultation with other health 
care professionals as is practical.


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If a patient is withdrawn from study due to safety reasons, he/she should be followed until the event 
disappears, is otherwise explained or the patient’s condition has stabilised. 
Any patient who voluntarily withdraws from the study should be carefully questioned for the 
possible occurrence of an adverse event. Whenever possible, a patient should be followed through 
the last scheduled visit.
If no follow-up information can be provided after all efforts and attempts, the Investigator must 
document the outcome as “unknown” and provide a justification. 
 3URFHGXUHVIRUUHSRUWLQJ6HULRXV$GYHUVH(YHQWV3UHJQDQF\DQG
RYHUGRVHDEXVHPLVXVH
 6$(
The Sponsor or its representative must be informed immediately, and no later than 24 hours, of 
receipt of the SAE information by the site.
If one or more seriousness criteria is fulfilled, the Investigator must promptly forward to the Sponsor 
or its representative a duly completed “SERIOUS ADVERSE EVENT NOTIFICATION FORM”
provided by the Sponsor, even if the data are incomplete or if it is obvious that more data will be 
needed in order to draw any conclusions, but as soon as the minimum of following information is 
present: 
 identification of the notifying person, 
 identification of the clinical study, 
 identification of a patient (patient number and/or initials),
 description of the SAE and relationship to the study drug. 
After the initial SAE report, the Investigator is required to proactively follow each patient and to 
provide further information on the patient’s condition. The Investigator will ensure that follow-up 
includes any further investigations as may be indicated to elucidate the nature or the causality of the 
SAE. 
Supporting documentation (discharge summaries, all examinations carried out, etc.) will not be sent 
systematically, as all relevant information must appear and be summarized in the narrative of the 
SAE report. However, if judged important, the Investigator could send these documents or LFB 
could request them (all documents must be blinded with respect to the subject’s name). Any follow-
up information must be reported within the same timelines.






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6HFRQGDU\HIILFDF\DVVHVVPHQWV
Secondary assessments are: 
 Grip strength with the Martin vigorimeter in both hands; 
 Rasch-built Overall Disability Scale (R-ODS);
 Patient and Investigator Clinical Global Impression (CGI);
 Medical Research Council (MRC) 12 muscles sum score (0 to 5) and Rasch-modified MRC 
(0 to 3). 
Analyses and time of assessments are described in Section 12.9 Efficacy analysis.
 $VVHVVPHQWRI6DIHW\
The Investigator will ensure that all the AEs occurring during the study are identified and 
documented in the eCRF. The identification of AEs may come from various sources: 
x The Investigator or nurse may clinically observe an AE in the patient at hospital.
x The patient may spontaneously report an AE to Investigator or Nurse. 
x From baseline to EOS, the patient will have to document on a patient diary any AE that occurs 
outside the hospital. This diary will be verified at each visit by the investigator. The patient will 
be sensibilised to report carefully day and time of TAAEs. 
x At each visit the patient will be given a general prompt, e.g. “Did you experience any illness or 
unusual sign or symptom since your last visit?” in order to ensure that no AE has been forgotten. 
x Vitals signs, including systolic and diastolic blood pressures (mmHg), heart rate (beats/minute), 
and body temperature (°C) will be measured before each infusion, during infusion (30-45 min 
and 60-75 min after the infusion start) and 30-45 minutes after the end of infusion and will be 
recorded in the eCRF. Weight will also be recorded before each study drug course, as it is used to 
calculate the quantity of study drug to be infused.  
x Biological tests will be performed at the screening, before each study drug course, 4 days after 
the first study drug course and at the end of study assessment. Clinically significant abnormality 
in physical examination or biological tests performed at the screening as per study protocol will 
be regarded as a medical history.  
x The Investigator or a Study Nurse will call the patient 4 days after each treatment course in order 
to collect information about the possible occurrence of an AE after the patient has left the 
hospital. The purpose of this phone call is to ensure that all the temporally associated AEs 
(TAAEs) are tracked.
x If a TAAE is reported by the patient during the phone call, the Investigator will ask the patient 
additional information at the next visit. If relevant; the Investigator will report the TAAE in the 
eCRF.
It is the responsibility of the Investigator to collect all the relevant information regarding identified 
AEs.


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
'$7$0$1$*(0(17
 H&5)FRPSOHWLRQJXLGHOLQHV
The following is a general description of the eCRF completion guidelines for this study. For 
complete details please refer to the eCRF completion guidelines included in the eCRF.
,QWURGXFWLRQ
All of the information required to be reported to the Sponsor as per protocol will be transcribed in 
the eCRFs for each study patient. The eCRFs will be completed by the Investigator or any study 
centre staff designated by the Investigator. The access to the data at the clinical site will be restricted 
and monitored through the system software with its required log-in security procedures. The 
Investigator will be responsible for ensuring that data recorded in the eCRFs are complete, accurate 
and legible. All eCRFs should be filled in before review by the Monitor. 
*HQHUDOLQVWUXFWLRQV
2YHUYLHZ
eCRFs should be completed in English. 
All data will be recorded in the eCRFs. The eCRF is a web based application linked to a 
computerized system that allows creating, modifying, maintaining, archiving, retrieving, or 
transmitting data. 
Access to the eCRF must be limited to authorised individuals. In this way, each Investigator and 
each person, authorised to have access to the eCRF, will receive an individual user login and a 
unique password before the study start and after having completed a specific training. Different 
accesses will be limited according to individual profiles. Therefore individuals must only work 
under their own logins and passwords, and must not share these with others. The attributed password 
should be changed at the first log in. 
Individual training: 
It will be the responsibility of the Sponsor to organize an individual training and certification for all 
persons who will use the computerised system. In order to have their login and password, each 
person should perform this training. 
All data in the eCRFs must come from and be consistent with the source documents - i.e. patient’s 
file or medical records - except the neurological scales which are performed for the specific purpose 
of the study and for which source data worsheets will be provided as source documents. 
Source documents may therefore be:
 The patient’s medical file
 The nurse’s sheets
 Laboratories results sheets
 Specific worksheets provided for neurological scales assessment
 Any other document issued in the routine practice of healthcare and providing information on 
the medical status of the patient.
Any discrepancy between data in the eCRF and those in the source documents should be 
documented by the Investigator through a query. 


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3DWLHQWLGHQWLILFDWLRQ
Patients will be identified on each page of the eCRF by their patient number: patient number will be 
composed of 4 digit numbers (see Section 8.1.3 Patient allocation). Patients with screening failure 
will have an eCRF completed.
&RQILGHQWLDOLW\
Patient identity must be kept confidential and should not appear on any eCRF form or study-specific 
documents. 
H&5)&RPSOHWLRQ
The Investigators should complete the eCRF as soon as possible (within 5 days) after each patient’s 
visit. The Investigator or the delegated study site staff will complete all applicable forms in the 
eCRF. All data should be completed and missing data will be documented. 
Specific instructions for completing the eCRF will be detailed in a specific guide.
H&5)&RPSOHWLRQLQFDVHRIVFUHHQLQJIDLOXUHRUSUHPDWXUHZLWKGUDZDO
In case of a screening failure, the Investigator will complete the relevant forms of the eCRF, 
including AE page and concomitant medication page if applicable. 
In case of a premature withdrawal after the first study drug course, all study data available up to the 
point of withdrawal must be recorded on the eCRF, as well as any new AE or modifications to 
existing AEs and/or concomitant medications. The end of study assessment will also be completed. 
H&5)FRUUHFWLRQV
To ensure and to protect the authenticity, the integrity and the confidentiality of electronic records 
an audit trail will be integrated to the eCRF. All entries and all changes will be tracked in an audit 
trail. The audit trail is a secure, computer-generated, time-stamped system which independently 
records the date and time of operator entries and actions that create, modify or delete electronic 
records.
 H&5)DQG'DWD+DQGOLQJ
Data management will be carried out by a Contract Research Organisation (CRO) from electronic-
based CRF and in accordance with Good Clinical Practices (GCP see ICH-E6).
Throughout the study, the data will be stored in servers located in the United States of America. All 
transfers will be validated. 
Helpdesk services for all investigators and staff will be available 16/24 hours and 5/7 days. Training 
will be provided to the investigators and staff. 
The data handling documents, e.g. annotated eCRF, database structure, data entry manual, coding 
rules and computerized validation system, are defined in a Data Management Plan.  
The database and data entry screens will be created in software specifically designed for clinical 
data management in compliance with ICH-E6 requirements.
The tracking of the eCRF will be integrated to the computerized system. As soon as a patient has 
signed his informed consent, the Investigator will create the patient in the e-CRF and will complete 
the appropriate form(s).


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The consistency of data will be checked by computerised programs and related queries will be 
generated for resolution by the Investigator. In case of abnormality, Electronic Data Clarification 
Forms (DCFs) will be generated through the eCRF platform for resolution by the Investigator. 
Medical coding will be done using Medical Dictionary of Regulatory Activities (MedDRA) for all 
medical terms (medical history, AEs) and World Health Organisation (WHO) drug for all drug 
names (prior and concomitant medications). 
Quality controls to ensure the overall quality and consistency of the database and reconciliation of 
SAE reports with the Pharmacovigilance database will also be carried out.
At the end of the data handling process, a final data review meeting will be held in order to prepare 
the database lock. After database lock, data will be transferred into SAS format for the production of 
statistical analyses.
Data processing, from data capture through database lock, will be carried out in accordance with 
GCP-ICH-E6.

67$7,67,&6
 7ULDO2EMHFWLYHVDQG'HVLJQ
The main objective of this study is to assess the efficacy and the safety of I10E in CIDP patients. 
The design is a phase III, international, multicentre, single arm, open-label prospective study. 
 6WDWLVWLFDO$QDO\VLV3ODQ
This section is the basis for the Statistical Analysis Plan (SAP) of the study. 
The detailed technical aspects of the statistical analyses will be provided in the SAP. The SAP will 
possibly take protocol amendments into account and adapt to unexpected issues raised by the study
running and/or data that affect planned analyses in the protocol.  
Any changes from the protocol will be discussed in the clinical study report.
Prior to locking the database, a data review meeting will be planned in order to review individual 
data and validate the SAP.
 6DPSOH6L]H'HWHUPLQDWLRQ
The study is designed to demonstrate superiority of I10E to an historical control in terms of 
responder rate. The historical responder rate with placebo is estimated from the ICE study [10]. As a 
conservative estimate the upper boundary of the 95% confidence interval (CI) of the observed rate is 
used (observed rate 12/58 = 20.7%, 95% CI [11.2%, 33.3%]). Based on this historical placebo 
responder rate of 33.3% and a 60% responder rate with I10E, 38 evaluable patients are needed in 
order to obtain 90% power using an exact binomial test with a one-sided nominal level of 
significance D=2.5%. Presuming a 10% non-evaluable patients, 42 patients will be included in the 
study (around one third of all patients will be either Ig-naïve or relapsing Ig-pretreated).
 5DQGRPL]DWLRQ
Not applicable 


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 3URWRFRO'HYLDWLRQVDQG$QDO\VLV6HWV
All deviations from protocol definitions will be listed and defined as major or minor deviations in 
the SAP.
The definition of analysis sets is as follows: 
 Total Treated Set (TTS): all patients who received at least one administration of study drug.  
 Full Analysis Set (FAS): all TTS patients having an available assessment of the primary 
efficacy endpoint. 
 Per Protocol Set (PPS): all FAS patients without any major deviations from protocol.
The TTS will be used for the analysis of safety data.
The FAS will be used for the primary analysis of efficacy data and the PPS to test its robustness.  
 *HQHUDOUXOHVIRUKDQGOLQJRIPLVVLQJRULQFRQVLVWHQWGDWD
No general rules for the replacement of missing data are planned. Every effort should be made to 
collect the study parameters over the study period.
 'HPRJUDSKLFDQGEDVHOLQHFKDUDFWHULVWLFV
All baseline characteristics and baseline efficacy variables will be summarised using descriptive 
statistics on relapsing Ig-pretreated patients, Ig-naive patients and overall. All summary tables will 
describe the variables according to their nature: 
 Categorical variables (binary, nominal and ordinal) will be summarised by contingency tables 
(frequencies and percentage),
 Quantitative variables will be summarised by their mean, standard deviation, median, 
minimum and maximum values.
3UHYLRXV7UHDWPHQWV
All previous treatments will be classified using the ATC codes and summarised.
 6WXG\GUXJDQGFRQFRPLWDQWWUHDWPHQWV
All variables will be summarised for the subgroups of relapsing Ig-pretreated patients and Ig-naïve 
patients as well as overall. 
([WHQWRI([SRVXUH
The duration of treatment exposure will be assessed as from the first day of study drug
administration to the EOS assessment. 
The number of infusions, cumulative dose (g and g/kg), volume infused, duration of infusion, 
infusion rate (initial rate and maximum rate) will be described using descriptive statistics. The 
treatment exposure will also be listed for each patient.  
7UHDWPHQW&RPSOLDQFH
The following compliance criteria will be described:


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 Prescribed course dosage included in the ranges allowed by the protocol 
 Course frequency included in the ranges allowed by the protocol 
 Courses administered at each visit.
 Ratio administered dose / prescribed dose within 20%. 
&RQFRPLWDQW7UHDWPHQW
All concomitant treatments as defined in Section 7.2 Concomitant medication will be classified 
using the ATC codes and summarised.  
 (IILFDF\$QDO\VLV
All efficacy endpoints will be analysed overall and by subgroups of relapsing Ig-pretreated patients 
and Ig-naive patients.
3ULPDU\(IILFDF\9DULDEOHV
'HVFULSWLRQRIWKHSULPDU\HIILFDF\YDULDEOHV
The primary efficacy endpoint will be the responder rate at EOS visit.
Responder patients are defined as patients with a decrease of at least 1 point in the adjusted INCAT 
disability score between baseline and the EOS visit.
If a patient is treated with a not-allowed treatment during the study period, then all efficacy variables 
measured after the intake of these not-allowed treatments will be censored for the efficacy analyses.
+\SRWKHVLV7HVWDQG3ULPDU\$QDO\VLV0RGHO
The responder rate will be tested against the historical responder rate of 33.3% with a one-sided 
Clopper-Pearson test (exact binomial test) at the nominal level of significance of 2.5%.  
The null and alternative hypotheses are as follows:
H0: S(I10E)
d33.3% 
Ha: SI10E)
!33.3%
The proportion of responders and the associated 95% confidence interval will be estimated using a 
Clopper-Pearson method. The primary analysis will be performed on the FAS.  
+DQGOLQJRI0LVVLQJ'DWD
The primary analysis of the primary criterion will be done using the baseline and last available 
assessment of the adjusted INCAT disability score after the first study drug administration. If the 
score at EOS visit is missing, then the Last Observation Carried Forward (LOCF) approach will be 
applied and the last available adjusted INCAT disability score will replace the missing value at EOS 
visit. Other imputation methods might be defined in the SAP for the purpose of sensitivity analyses. 
3URJQRVWLFIDFWRUVDQGFRYDULDWHV
No prognostic factors will be used in the statistical model.


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2WKHUDQDO\VHVIRUWKHSULPDU\YDULDEOH
The analysis of the primary criterion will be repeated on the PPS as sensitivity analyse.  
Other sensitivity analyses might be defined in the SAP.
6HFRQGDU\HIILFDF\YDULDEOHV
'HVFULSWLRQRIVHFRQGDU\HIILFDF\YDULDEOHV
x Responder rate at 12 weeks. 
x Time to response.  
x Percentage of patients at 12 weeks and EOS visit with no change in CIDP treatment. 
x Changes from baseline to 12 weeks and EOS visit in the following scores: 
 Adjusted INCAT disability score; 
 Grip strength with the Martin vigorimeter in both hands; 
 Rasch-built Overall Disability Scale (R-ODS);
 Patient and Investigator Clinical Global Impression (CGI);
 Medical Research Council (MRC) 12 muscles sum score (0 to 5) and Rasch-modified MRC (0 
to 3). 
$QDO\VLVRIVHFRQGDU\HIILFDF\YDULDEOHV
All parameters as well as the change from baseline will be summarised using Hodges-Lehmann 
point estimates and corresponding confidence intervals. Time to response will be analysed using a 
Kaplan-Meier method.
If a patient is treated with a not-allowed treatment during the study period (Plasma exchange, blood 
products or derivatives other than the study drug, immunomodulatory/immunosuppressant agents, 
corticotherapy, if administred with an increasing dosage or introduced orally or systematically at a 
dose higher than 10 mg daily prednisolone or equivalent), then all adjusted INCAT disability scores 
measured after the intake of these not-allowed treatments will be censored for the efficacy analyses.
A LOCF approach will be used to handle the missing data of secondary endpoints. All details to 
handling of missing data will be provided in the SAP. 
The 12-week and the EOS visit values will be compared to the baseline value using appropriate 
statistical tests. A significance level of 5% (two-sided) will be applied. 
The adjusted INCAT disability score will additionally be presented graphically over the patients’ 
follow-up during the study.  
 6DIHW\$QDO\VLV
All safety analyses will be performed on the subgroups of relapsing Ig-pretreated patients and Ig-
naive patients as well as overall. 


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
$GYHUVHHYHQWV
All AE will be classified using MedDRA including Lowest Level Terms (LLT), Preferred Terms 
(PT) and System Organ Class (SOC).
TEAEs defined as AEs occurring after the start of the 1st study drug administration will be analysed. 
Other AEs will only be listed.
The absolute number of TEAEs as well as the number of patients with at least one TEAE will be 
tabulated by SOC and PT. Patients with SAEs, drug-related AEs will be analysed by SOC and PT. 
The duration of the TEAE and the time between the last administration of study drug and the onset 
of the TEAE will be calculated.
TAAEs will be analysed by patients and infusions. 

9LWDOVLJQV
Vitals signs, including body temperature (in °C), heart rate (in beats/minute) and systolic and 
diastolic blood pressures (in mmHg), will be measured before each infusion, during infusion 
(30-45 min and 60-75 min after the beginning of infusion) and 30-45 minutes after the end of 
infusion for all visits. Descriptive statistics will be performed. 
All abnormalities in vital signs, clinically significant or not, will be listed.

/DERUDWRU\GDWD
Laboratory data will be assessed at screening, before each study drug course, after the 1st study drug
course, and at the EOS visit. Shift tables will be produced by study drug courses and baseline. 
Descriptive statistics will be performed. All abnormalities, clinically significant or not will be listed. 
 ([SORUDWRU\$QDO\VLV
The following exploratory endpoints will be analysed: 
 Anti-CNTN1 and anti-NF155 antibodies titers at screening and EOS visit.  
 FcJRIIB B cells marker levels at visits V2, V3 and V4.  
 BAFF and complement components (C3 and C4 antigens, CH50) at visits V2, V3, V4 and 
EOS visit.
 Serum total IgG trough levels before each study drug administration. 
 Change from baseline to EOS visit in nerve conduction velocities, distal latencies, amplitude 
of the negative phase of compound muscle action potentials and F wave for the following 
peripheral nerves: median nerve, ulnar nerve and deep fibular nerve (F wave assessed on ulnar 
nerve only). 
 Change from baseline to EOS visit in nerve maximal/minimal cross section area (CSA), intra-
nerve and inter-nerve variability and ultrasound (USG) immune-related classification (see 
Section 1.4.4 Peripheral nerve ultrasonography) in the following peripheral nerves: median 
nerve, ulnar nerve, fibular nerve and sural nerve. 
All exploratory variables will be described in summary tables. The relationship between these 
variables and clinical response will be explored and detailed in the SAP.  


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
678'<5(3257
A clinical study report will be prepared in accordance with the ICH-E3 guidelines by the Sponsor. 
Within 1 year after the end of the study, the Sponsor will provide the Health Authorities with the full 
study report or summary. Only the Sponsor is entitled to make the study report available to the 
Authorities.
Neither the complete report nor any part of the study report should be used without the approval of 
the Sponsor. 

&21),'(17,$/,7<$1'38%/,&$7,21
 3DWLHQWFRQILGHQWLDOLW\
Patient data will be kept strictly confidential and patient anonymity will be protected by using 
number codes. 
The Sponsor or its representative(s) and the Health Authorities are obligated to respect medical 
secrecy and to refrain from divulging any personal patient information they might fortuitously be 
aware of.
 8VHRILQIRUPDWLRQ
The Investigator shall not divulge unpublished data or information related to the study provided by 
the Sponsor, including but not limited to the study protocol, eCRFs, assay methods and scientific 
data, to any third party without written approval from the Sponsor. 
In addition, any new information that may become available during the course of the study shall be 
considered as confidential and shall not be used for any purpose other than the performance of the 
clinical study.
The study data are the property of the Sponsor. The Investigator and any of the research staff shall 
obtain written approval from the Sponsor prior to the publication/communication of the results of 
any work carried out during or in relation to the study. 
Publication and/or communication of the results of the clinical study will be of a cooperative nature 
involving authors representing the Sponsor, the Investigators and the scientific committee. 
The Sponsor reserves the right to request modification of the content and/or timing of any 
publication or presentation if a patent application, an existing patent or other proprietary rights may 
be jeopardized. 
Authorship of any publication related to the study and the order of presentation of the authors’ 
names shall be approved by the Sponsor. The Sponsor shall not use an Investigator’s name in any 
publication without his/her written permission and vice versa. 


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03 May 2017, incorporated the amendment N°3
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
$5&+,9,1*
The Investigators should retain all essential study-related documents, i.e. documents which permit 
evaluation of the conduct of a study and the quality of the data produced, in accordance with the 
applicable regulatory requirements of his/her country. These essential documents include but are not 
limited to signed protocol, eCRFs, medical records, laboratory reports, informed consent forms, 
drug disposition records, safety reports, information regarding participants who discontinued, and 
other relevant documents and data. 
The study-related documents should be kept together in the Investigator site file provided to the 
Investigator by the Sponsor. 
Sufficient information about the identity of all study patients, e.g. name, medical records number, 
patient number and study number, should be retained by the Investigator so that any Sponsor 
representatives, auditors or inspectors may access this information when required. 
The investigator must retain all records until at least 2 years after the last approval of a marketing 
application in an ICH region for the Study Drug for the indication which is being investigated, or 
40 years after the database locked, whichever is longer, or longer if required by specific local 
requirements.  
The Investigator will contact the Sponsor for authorization prior to the destruction of any study 
records or in the event of accidental loss or destruction of any of them.  
The Investigator will also notify the Sponsor should he/she relocate or move the study-related files 
to a location other than that specified in the Sponsor’s study master file. 
All records should be kept in a secure area. However, in the cases of audit or inspection, they should 
be rapidly made available.


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03 May 2017, incorporated the amendment N°3
Page 75/90

5(63216,%,/,7,(62)3$57,&,3$176
 5HVSRQVLELOLWLHVRIWKH,QYHVWLJDWRUV
The Investigators will conduct the study in accordance with Good Clinical Practices, all applicable 
laws in the country where the study is conducted and in accordance with this study protocol. 
The responsibilities of the Investigators are summarised below but not limited to: 
x 3DWLHQWLQIRUPDWLRQDQGFRQVHQW
Prior to undertaking any study-related procedure, it is the responsibility of the Investigator, or a 
formal designee, to provide each patient and/or a legal representative/witness, with relevant, 
comprehensive, verbal and written information, including the written information which received 
approval or a favourable opinion from the IEC/IRB and the Health Authorities.
Signed informed consent must be obtained prior to undertaking any study-related procedure. 
Obtaining of consent and how it was obtained must be described and documented in the patient’s 
file.
x ,QIRUPDWLRQRQWKHRYHUDOOUHVXOWVRIWKHVWXG\
Pursuant to the French “Patient’s rights” law adopted on 9 August 2004, the Investigator must 
provide any patient who so requests it with the overall results of the study, once it is completed.
The Sponsor will provide the Investigator with the overall results beforehand.
The Investigator should document in the patient’s file the fact that the information has been 
provided. 
x ,QIRUPDWLRQWRRWKHUSUDFWLWLRQHUVLIUHOHYDQW
In agreement with the patient, the Investigator will formally inform other practitioners of the
patient’s participation in the study, to avoid any interference or bias in the conduct of the study. 
x ,QGHSHQGHQW(WKLFV&RPPLWWHH,(&
In accordance with local regulations, the Investigator may be required to interface with the 
IRB/IEC.
x $GYHUVHHYHQWV
The investigator is responsible for ensuring adequate safety monitoring and follow-up of the 
study patients.
The Investigator must report and handle any serious and non-serious adverse event, whether 
clinically observed or spontaneously reported by the patient, using concise medical terminology 
in accordance with Section 9 of the protocol. 
x 'DWDUHFRUGLQJ
It is the Investigator’s responsibility to ensure, on an on-going basis, completion and validation of 
all case report forms as well as study-related supportive data. eCRFs must be signed by the 
Investigator. If the Investigator formally delegates completion of the eCRFs, the Investigator 
nevertheless has the final responsibility for signing the eCRFs to certify the accuracy and 
reliability of the data recorded therein.


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Page 76/90
x 5HFRUGUHWHQWLRQ
To enable inspections and audits from Health Authorities or the Sponsor, the Investigator agrees 
to keep records, including the identity of all participating patients, i.e. sufficient information to 
link records, all original signed informed consent forms and detailed records of treatment 
disposition. An electronic copy of eCRFs will be provided by the Sponsor to be retained and 
archived at site. The Investigator should maintain a site file with all essential documents.
See also Section 15 Archiving 
x 8VHRIVWXG\UHODWHGLQIRUPDWLRQ
The Investigator is obligated to provide the Sponsor with complete test results and all data 
derived from the study. 
Only the Sponsor may make information available to physicians, Health Authorities and/or 
patients enrolled in the study, except as required by local regulations. 
x 6WXG\GUXJ
Responsibility for study drug accountability at the study centre rests with the Investigator or with 
the institution, depending on local regulations. 
x 4XDOLW\FRQWURO
The Investigator and the relevant personnel should be available during monitoring visits and 
possible audits or inspections and ensure that sufficient time is devoted to the process. 
The Investigator guarantees the Sponsor or its representative and appropriate Health Authorities 
direct access to source documents.
x 6WXG\GLVFRQWLQXDWLRQ
Should the Health Authorities or the Sponsor decide to discontinue the study prematurely for any 
reason, the Investigator must promptly, contact all participating patients so they can be 
appropriately followed-up. All study supplies must be collected and all electronic case report 
forms must be completed as fully as possible. 
x /LDELOLW\DQGLQVXUDQFH
Liability and insurance provisions for this study are set out in separate agreements. 
x 'HOHJDWLRQRI,QYHVWLJDWRUGXWLHV
The Investigator can delegate tasks to the research team but he/she remains responsible for 
coordinating and informing his/her staff about the protocol and the possible changes made to it. 
The Investigator should ensure that all persons assisting with the study are adequately qualified, 
and are informed about the study protocol, any amendments to the protocol, the study treatments, 
and their study-related duties and functions. 
The Investigator should maintain a list of appropriately qualified persons to whom significant 
study-related duties will be delegated. The list is to be kept up-to-date.
The Investigator should supply a dated and signed, up-to-date curriculum vitae (CV) in English, 
together with a list of his/her collaborators responsible for the operational conduct of the study. 
These collaborators should also provide a recent dated and signed English version of their CVs. 


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Page 77/90
x 6WXG\DJUHHPHQWGLVFRQWLQXDWLRQ
During the study, if events such as retirement, promotion or relocation prevent the Investigator 
from conducting the study as agreed, the Investigator should appropriately transfer his/her 
responsibilities, knowledge and documents to another willing individual, with the agreement of 
the Sponsor. Study specific contracts must be signed between the Sponsor and the newly assigned 
person. 
 5HVSRQVLELOLWLHVRIWKHPRQLWRU
Instructions for monitoring will be developed in a monitoring plan. 
The responsibilities of the study Monitor are defined in ICH-E6, Chapter 5. The Monitor, who is 
mandated by the Sponsor, must ensure that the study is conducted in accordance with Good Clinical 
Practice guidelines and all applicable local laws, and that the rights, the security and the well-being 
of the patients are respected.
During the conduct of the study, the Monitor reports any deviations or persistent poor compliance 
with the study requirements and the Sponsor makes decisions about appropriate corrective actions. 
x &RPPXQLFDWLRQ
The Monitor is the main line of communication between the Investigator and the Sponsor. 
x 7UDLQLQJ
The Monitor must present the protocol and all procedures related to the study during the study 
set-up visit and provide the Investigator with case report form completion guidelines. 
x &RPSOLDQFH
During periodic monitoring visits at mutually convenient times, the Monitor has the 
responsibility of assessing the progress of the study, of checking that the informed consent forms 
have been signed, of ensuring adhesion to and compliance with the study protocol and other 
study-related documents, and of ensuring the accuracy and completeness of the eCRFs.
Inconsistencies in the study records are to be resolved.
x 6RXUFHGDWDYHULILFDWLRQ
The Monitor will perform source document verification and validation and request clarification to 
ensure the accuracy, completeness and reliability of data.
x 6WXG\GUXJ
The Monitor must ensure that study drug handling is properly carried out and documented. 
He/she must ensure that the investigator file is up-to-date with regard to essential documents. 
 5HVSRQVLELOLWLHVRIWKHGDWDPDQDJHU
The LFB Data Manager is responsible for the management of clinical data from data entry to 
database lock.


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Page 78/90

(7+,&6$1'5(*8/$725<&216,'(5$7,216
The current study is to be conducted in accordance with globally accepted standards of Good 
Clinical Practice (ICH-E6), European Directive 2001/20/EC, and the revised version of the 
Declaration of Helsinki set out in the European Directive, as well as with applicable local 
requirements.
In France, this study will be conducted in accordance with the Code de la Santé Publique CSP.  
The protocol will be submitted to the Health Authorities and a properly constituted Ethics 
Committee (EC) for formal approval of the study conduct in accordance with local regulations.  
The study may not begin until the protocol has received written approval from the Health 
Authorities in accordance with local requirements.
In accordance with specific local requirements, the Investigator may be responsible for submitting 
the protocol and any amendments to the local EC. A copy of the decision letter, a list and versions of 
documents submitted, the list of EC members and their affiliation should be provided by the 
Investigator to the Sponsor. 
During the study, the Sponsor should promptly notify the Investigators, Health Authorities and EC 
of any relevant information that could affect the safety of patients and could impact on the conduct 
of the study. 
x 3HUVRQDO'DWD3URWHFWLRQ
For biomedical research in France: The Sponsor attests his conformity regarding the Personal Data 
Protection French requirements ("Méthodologie de Réference MR001" updated in October 2010). 
x ,QVXUDQFH
The Sponsor certifies substracting a contract of public liability insurance to provide patients with 
compensation for any injury, including the consequences of administration of the investigational 
product and of the study procedures.
In case of injury or disability resulting from participation in the study, the patient is requested to 
promptly inform the Investigator responsible for the study. 
x ,QGHPQLW\
Participation in this study will not entail any financial compensation to patient.
x &KDQJHVWRWKHSURWRFRO
The Sponsor will not assume any responsibility or liability resulting from implementation of 
unapproved deviations or changes.
The only circumstance in which an amendment may be initiated prior to approval by the Health 
Authorities is where the change is necessary to eliminate apparent immediate hazards to the patients. 
In this event, the Investigator must notify the Sponsor and if applicable the EC, in writing within 5 
working days after implementation.


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03 May 2017, incorporated the amendment N°3
Page 79/90

$8',7$1',163(&7,21
An audit/inspection may be carried out by qualified Sponsor staff, by subcontracted auditors or by 
representatives of national or foreign Health Authorities to ensure that the study is conducted as per 
protocol and in accordance with regulatory requirements, and to ensure the validity of the data. 
Participation in this study implies acceptance to cooperate in any potential audit/inspection.
The audit/inspection may consist of an inspection of the premises and equipment together with 
verification of the study documents and data. 
The investigational team must be available for inspection or audit. 
When the Sponsor or the Investigator is informed that an inspection is to be performed, the other 
party must be informed immediately.
Audits/inspection may take place after the end of the study. 


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
5()(5(1&(6
1
Lunn MP, Manji H, Choudhary PP, Hughes RA, Thomas PK. Chronic inflammatory 
demyelinating polyradiculoneuropathy: a prevalence study in south east England. J 
Neurol Neurosurg Psychiatry. 1999; 66(5):677-80. 
2
Laughlin RS, Dyck PJ, Melton LJ 3rd, Leibson C, Ransom J, Dyck PJ. Incidence 
and prevalence of CIDP and the association of diabetes mellitus. Neurology. 2009; 
73(1):39-45. 
3
Gaebel K, Blackhouse G, Campbell K, Robertson D, Xie F, Assasi N, Chalk C, 
Levine M, Goeree R. Intravenous immunoglobulin for the treatment of chronic 
inflammatory demyelinating polyradiculoneuropathy: A systemic review and meta-
analysis. Open Medicine. 2010; 4(3):154-166. 
4
European Federation of Neurological Societies/Peripheral Nerve Society Guideline 
on management of chronic inflammatory demyelinating polyradiculopathy: report of 
a joint task force of the European Federation of Neurological Societies and the 
Peripheral Nerve Society – First revision. J Peripher Nerv Syst. 2010; 15:1-9. 
5
Van den Bergh PY, Piéret F. Electrodiagnostic criteria for acute and chronic 
inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve. 2004; 
29(4):565-74. 
6
Hughes R. Chronic inflammatory demyelinating polyradiculoneuropathy. J Clin 
Immunol. 2010 Apr 15. 
7
Vlam L, van der Pol WL, Cats EA, Straver DC, Piepers S, Franssen H, van den Berg 
LH. Multifocal motor neuropathy: diagnosis, pathogenesis and treatment strategies.
Nat Rev Neurol. 2011 Nov 22; 8(1):48-58. 
8
Austin JH. Recurrent polyneuropathies and their corticosteroid treatment; with five-
year observations of a placebo-controlled case treated with corticotrophin, cortisone, 
and prednisone. Brain. 1958; 81(2):157-92. 
9
Patwa HS, Chaudhry V, Katzberg H, Rae-Grant AD, So YT. Evidence-based 
guideline: Intravenous immunoglobulin in the treatment of neuromuscular disorders. 
Neurology 2012; 78:1009-1015. 
10
Eftimov F, Winer JB, Vermeulen M, de Haan R, van Schaik IN. Intravenous 
immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy. 
Cochrane Database Syst Rev. 2009; 21(1):CD001797. 


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03 May 2017, incorporated the amendment N°3
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11
Hughes RA, Donofrio P, Bril V, Dalakas MC, Deng C, Hanna K, Hartung HP, Latov 
N, Merkies IS, van Doorn PA; ICE Study Group; Intravenous immune globulin 
(10% caprylate-chromatography purified) for the treatment of chronic inflammatory 
demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-
controlled trial. Lancet Neurol. 2008; 7(2):136-44. Erratum in: Lancet Neurol. 2008; 
7(9):771. 
12
Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory 
diseases with intravenous immune globulin. N Engl J Med. 2001; 345:747-755. 
13
Tackenberg B, Jelcic I, Baerenwaldt A, Oertel WH, Sommer N, Nimmerjahn F, 
Lünemann JD. Impaired inhibitory Fcgamma receptor IIB expression on B cells in 
chronic inflammatory demyelinating polyneuropathy. Proc Natl Acad Sci U S A. 
2009 Mar 24; 106(12):4788-92. 
14
EMA/CHMP/BPWP/94038/2007 rev.4. Guideline on the clinical investigation of 
human normal immunoglobulin for intravenous administration (IVIg). July 2010. 
15
Querol, L., G.Nogales-Gadea, R.Rojas-Garcia, E.Martinez-Hernandez, J.Diaz-
Manera, X.Suarez-Calvet, M.Navas, J.Araque, E.Gallardo, and I.Illa. 2013. 
Antibodies to contactin-1 in chronic inflammatory demyelinating polyneuropathy. 
Ann.Neurol. 73:370-380. 
16
Nimmerjahn, F. and J.V.Ravetch. 2008. Fcgamma receptors as regulators of immune 
responses. Nat.Rev.Immunol. 8:34-47). 
17
Nimmerjahn, F. and J.D.Lunemann. 2011. Expression and function of the inhibitory 
Fcgamma-receptor in CIDP. J.Peripher.Nerv.Syst. 16 Suppl 1:41-44. 
18
Tackenberg, B., I.Jelcic, A.Baerenwaldt, W.H.Oertel, N.Sommer, F.Nimmerjahn, 
and J.D.Lunemann. 2009. Impaired inhibitory Fc
฀5,,% H[SUHVVLRQ RQ % FHOOV LQ
chronic inflammatory demyelinating polyneuropathy. Proc.Natl.Acad.Sci.U.S.A 
106:4788-4792.| UA $ 
19
Tackenberg B., F.Nimmerjahn, and J.D.Lunemann. 2010. Mechanisms of IVIg 
efficacy in chronic inflammatory demyelinating polyneuropathy. J.Clin.Immunol. 30 
Suppl 1:S65-S69. 
20
Bick S., M.Tschernatsch, A.Karg, V.Fuehlhuber, T.E.Trenczek, K.Faltermeier, 
H.Hackstein, M.Kaps, and F.Blaes. 2013. Intravenous immunoglobulin inhibits 
BAFF production in chronic inflammatory demyelinating polyneuropathy - a new 
mechanism of action? J.Neuroimmunol. 256:84-90. 
21
Jacob S. and Y.A.Rajabally. 2009. Current proposed mechanisms of action of 
intravenous immunoglobulins in inflammatory neuropathies. Curr.Neuropharmacol. 
7:337-342. 
22
Durandy A. et al, Intravenous immunoglobulins – understanding properties and 
mechanisms. Clin Exp Immunol. 2009 December; 158(Suppl 1): 2–13. 


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03 May 2017, incorporated the amendment N°3
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23
Goedee HS, Brekelmans GJ, Visser LH. Multifocal enlargement and increased 
vascularization of peripheral nerves detected by sonography in CIDP: A pilot study. 
Clin Neurophysiol 2014; 125:154–159. 
24
Imamura K, Tajiri Y, Kowa H, Nakashima K. Peripheral nerve hypertrophy in 
chronic 
inflammatory 
demyelinating 
polyradiculoneuropathy 
detected 
by 
ultrasonography. Intern Med 2009; 48:581–582. 
25
Zaidman CM, Al-Lozi M, Pestronk A. Peripheral nerve size in normals and patients 
with polyneuropathy: an ultrasound study Muscle Nerve. 2009 Dec;40(6):960-6; 
Muscle Nerve. 2012 Aug;46(2):270-5).
26
Matsuoka N, Kohriyama T, Ochi K, Nishitani M, Sueda Y, Mimori Y, Nakamura S, 
Matsumoto M. Detection of cervical nerve root hypertrophy by ultrasonography in 
chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol Sci. 2004 
Apr 15;219(1-2):15-21. 
27
Taniguchi N, Itoh K, Wang Y, et al. Sonographic detection of diffuse peripheral 
nerve hypertrophy in chronic inflammatory demyelinating polyradiculoneuropathy. J 
Clin Ultrasound 2000; 28:488–491. 
28
Padua L, Granata G, Sabatelli M, Inghilleri M, Lucchetta M, Luigetti M, Coraci D, 
Martinoli C, Briani C. Heterogeneity of ultrasound pattern in CIDP patients. Clin 
Neurophysiol. 2014 Jan; 125(1):160-5. doi: 10.1016/j.clinph.2013.07.023. Epub 
2013 Oct 5. 
29
Won SJ, Kim BJ, Park KS, Kim SH, Yoon JS. Measurement of cross-sectional area 
of 
cervical 
roots 
and 
brachial 
plexus 
trunks. 
Muscle 
Nerve; 
Doi: 
10.1002/mus.23503. Epub 2012 Jun 22. 
30
Padua L, Martinoli C, Pazzaglia C, Lucchetta M, Granata G, Erra C, Briani C. Intra- 
and internerve cross-sectional area variability: new ultrasound measures. Muscle 
Nerve. 2012 May; 45(5):730-3. Doi:10.1002/mus.23252. 
31
Kersanoudis A, Klasing A, Behrendt V, Gold R, Yoon MS. Intra-and internerve 
cross-sectional area variability: new ultrasound measures. Muscle Nerve. 2013 Jan; 
47(1):146-7. Doi: 10.1002/mus/23520. Epub 2012 Nov 21. 
32
Hughes R, Bensa S, Willison H, Van den Bergh P, Comi G, Illa I, Nobile-Orazio E, 
van Doorn P, Dalakas M, Bojar M, Swan A; Inflammatory Neuropathy Cause and 
Treatment (INCAT) Group. Randomised controlled trial of intravenous 
immunoglobulin versus oral Prednisolone in chronic inflammatory demyelinating 
polyradiculoneuropathy. Ann Neurol 2001; 50(2):195-201. 
33
Van van Nes SI, Vanhoutte EK, van Doorn PA, Hermans M, Bakkers M, Kuitwaard 
K, Faber CG, Merkies IS, on behalf of the PeriNomS study group. Rasch-built 
Overall Disability Scale (R-ODS) for immune-mediated peripheral neuropathies. 
Neurology 2011 Jan 25; 76(4):337-45. 






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If Yes, ask: $UH\RXDEOHWRZDVKDQGEUXVK\RXUKDLU"  
If they cannot either wash or brush their hair the task is prevented. If they do not usually wash or 
brush their hair, they should be asked if they think they could, if required. If there is doubt, ask them 
to mime the tasks.
,V\RXUDELOLW\WRXVHDNQLIHDQGIRUNRUVSRRQWRJHWKHUDIIHFWHG"
If Yes, ask: $UH\RXDEOHWRXVHDNQLIHDQGIRUNRUVSRRQWRJHWKHU"
If patients do not use a knife and fork, ask about their usual eating implements (e.g. spoon, 
chopsticks).The task is considered as affected if the patient can use cutlery to eat their food but has 
difficulty. The activity is prevented if the patient cannot use their cutlery to eat. If adapted cutlery is 
used the task should be considered affected.  
,V\RXUDELOLW\WRKDQGOHVPDOOFRLQVDIIHFWHG"
If Yes ask: $UH\RXDEOHWRKDQGOHVPDOOFRLQV"
If there is doubt, ask them to show you how they take coins out of a purse or pocket and put them 
back.
If all the previous activities are prevented, ask: 
&DQ\RXPRYHHLWKHUKDQGRUDUPDWDOO"
If necessary, ask the patient to show you the movement. Score “Yes” if any voluntary movement is 
observed. 
/(**5$'(
Ask: 'R\RXKDYHGLIILFXOW\ZDONLQJ"
Difficulty walking may include difficulty walking long distances, fatigue or unsteadiness. 
If Yes ask: 'R\RXXVXDOO\ZDONRXWGRRUVZLWKDLG"
Could be the aid of another person, or the aid of stick(s), crutch(es), arm(s). 
If Yes ask:
'R\RXXVXDOO\ZDONRXWGRRUVZLWKXQLODWHUDOVXSSRUWVWLFNVLQJOHFUXWFKRQHDUP"
'R\RXXVXDOO\ZDONRXWGRRUVZLWKELODWHUDOVXSSRUWVWLFNVFUXWFKHVIUDPHWZRDUPV"
If the patient does not usually walk outdoors (is chairbound), ask: 
$UH\RXDEOHWRVWDQGDQGZDONDIHZVWHSVZLWKKHOS"
If necessary ask them to show how they stand and walk with help. 
0HGLFDO5HVHDUFK&RXQFLO05&VFDOHDQGVXPVFRUH
MRS sum score is a scale that assesses motor impairment.
7DEOH±05&VFDOH
The patient is investigated in sitting position and/or lying supine. 
0 = No visible contraction 
1 = Visible contraction without movement of the limb (not existent for hip flexion) 
2 = Movement of the limb but not against gravity 
3 = Movement against gravity over (almost) the full range* 


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03 May 2017, incorporated the amendment N°3
Page 86/90
4 = Movement against gravity and resistance 
5 = Normal 
The muscle groups (right and left) assessed in the measurement of the MRC-sum score are the 
following: 
Upper limbs: 
 Shoulder abduction *  
 Elbow flexion  
 Wrist extension  
Lower limbs: 
 Hip flexion
 Knee extension  
 Ankle dorsal flexion
For each muscle group, a standardised joint / limb position, as well as the point at which counter-
force is administered will be pre-defined and taken when assessing muscle strength. 
This scale yields the so-called ''MRC-sum score", ranging from 0 (paralysis) to 60 (normal strength).  
)RUVKRXOGHUDEGXFWLRQLVFRQVLGHUHGDGHTXDWHDQGIRUKLSIOH[LRQWRTXDOLI\IRUDVFRUHRI






LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03 May 2017, incorporated the amendement N°3
Page 89/90
(IILFDF\LQGH[&*,(
Rate this item on the basis of drug effect only.
Select the terms which best describe the degrees of therapeutic effect and side effects and record the number 
in the box where the two items intersect.
7KHUDSHXWLFHIIHFW
6LGHHIIHFWV
1RQH
'RQRW
VLJQLILFDQWO\
LQWHUIHUHZLWK
SDWLHQW¶V
IXQFWLRQLQJ
6LJQLILFDQWO\
LQWHUIHUHV
ZLWK
SDWLHQW¶V
IXQFWLRQLQJ
2XWZHLJKV
WKHUDSHXWLFHIIHFW
0DUNHG
Vast improvement. Complete 
or nearly complete remission 
of all symptoms
01
02
03
04
0RGHUDWH
Decided improvement. Partial 
remission of symptoms
05
06
07
08
0LQLPDO
Slight which doesn’t alter 
status of care of patient
09
10
11
12
8QFKDQJHGRU
ZRUVH
13
14
15
16
Not assessed = 
00
*ULSVWUHQJWK
The Martin vigorimeter, a portable dynamometer have been developed to measure grip strength, 
although, strictly speaking, it measures the air pressure in the bulb and not the force. The pressure in 
the bulb is registered on a manometer via a rubber junction tube and expressed in kiloPascals (kPa). 
Reference values for this instrument have been provided for right-handed healthy individuals [35]. 
The vigorimeter has demonstrated good responsiveness, even as early as at 3 weeks of IVIg 
therapies in patient with CIDP [35] [36]. 
Grip strength measure with the Martin Vigorimeter in both hands will be used to assess the efficacy 
of I10E. 
Grip strength reflecting distal strength and upper limb function, is a prognostic indicator of clinical 
and functional recovery and is useful in monitoring the effect of treatment. 
The medium size bulb will be used. Three tests will be performed and the best of the three recorded. 


LFB Biotechnologies – Protocol I10E-1302- Version 6.0 dated 03 May 2017, incorporated the amendement N°3
Page 90/90
)LJXUH±0DUWLQYLJRULPHWHU
Grip strength will be assessed 3 times in alternating order for both dominant and non-dominant 
hands.