Conditions: Chronic Inflammatory Demyelinating Poly(Radiculo)Neuropathy
Keywords: Chronic Inflammatory Demyelinating Poly Neuropathy (CIDP)
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 142
Healthy volunteers: no

Brief summary:
Study to evaluate the Efficacy and Safety of Three Different Dosages of NewGam in Patients With Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy

Detailed description:
Prospective, Double-blind, Randomized, Multicenter Phase III Study Evaluating Efficacy and Safety of Three Different Dosages of NewGam in Patients With Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy ("ProCID trial")

Arms:
arm 1: All patients will receive a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (0.5g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days). arm 2: All patients will receive a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (1.0g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days). arm 3: All patients will receive a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (2.0g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days).

Interventions: intervention 1: NewGam
Intervention descriptions: intervention 1: In the Dose-evaluation Phase, all patients will receive a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (0.5, 1.0 or 2.0 g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days). If a patient is randomized to receive the low or medium NewGam dose, the same volume with the same infusion rate as would have been applied in case the patient would have been randomized to 2.0 g/kg NewGam will be used, thus supplemented with an authorized 0.9% w/v isotonic sodium chloride solution as appropriate and detailed in the following infusion bag split to maintain the blinding

Protocol document:
Prot_000.pdf: 
File Ref:
TITLE OF'TRIAL/STUDY:
EUDRACT NUMBER:
IND NUMBER:
SPONSOR:
PRODUCT:
REF'ERENCE THERAPY:
PROTOCOL AMENDMENT No. 02
NGAM-O8
PROSPECTIVE, DOUBLE-BLTND,
RANDOMI ZED, MULTICENTER PHASE III
STUDY EVALUATING EFFICACY AND SAFETY
OF THREE DIFFERENT DOSAGES OF NEWGAM
IN PATIENTS WITH CHRONIC
INFLAMMATORY DEMYELINATING
POLY(RADICULO)NEUROPATHY (ProCID Study)
20ls-005443-14
14096
Octapharma Pharmazeutika Produktionsges.m.b.H.,
Oberlaaer Strasse 235, A-1100 Vienna, Austria
Newgam 10%
Sodium chloride 0.9%;o wlv solution
APPROVED BY:
Octapharma Pharmazeutika ProduktionsgmbH
Oberlaaerstr. 235, A- I 100 Vienna, Austria
PROTOCOL Versions:
This document contains confldential and proprietary information of Octapharma. Copying or
distribution of this document is only permitted with the written permissbn of Octapharma. Any
commercialuse of the information is subjectto the perm ission of Octapharma and a lirense fee.
Version
Date
Description
Final Version 0l
17-Dec-2015
Submitted to the FDA
Version 02
28-Nov-2016
Implementation of changes as requested bv the FDA
Version 03
09-Mar-2017
Implementation of changes as requested by VHP
Version 04
08-Jun-201 8
Implementation of recommendation of the IDMC and
changes for clarifi cation.
OCTAPHARMA DocID 2790
Page I of6
08-Jun-201 8


Protocol Amendment #02 – NGAM-08 
 
CONFIDENTIAL  
 
 
 
 
OCTAPHARMA DocID 2790 
Page 2 of 6  
08-Jun-2018 
 
The following changes have been made to the sections of the Study Protocol below: Added 
text is underlined and bold and deleted text is double crossed out. Text not relevant for 
changes in the sections listed below is represented by [...]. 
 
MODIFICATON 1 
Description of change: 
Inclusion criteria 5 regarding age range of the patients was amended as per 
recommendation by the IDMC. 
 Study Outline,  Section 4.1 and 4.1.1: 
Inclusion Criteria 5 was amended as follows: 
“≥ 18 to < 80 years of age”” 
 
MODIFICATION 2 
Description of change: 
Exclusion criteria 10 regarding diabetic neuropathy was amended as per recommendation 
by the IDMC. 
 Study Outline and Section 4.1.1: 
Exclusion Criteria 10 was amended as follows:  
“10. Diabetic neuropathy, unless having a stable HbA1C in treated diabetic patients not 
exceeding the required normal values” 
 
MODIFICATION 3 
Description of the change: 
Clarification of Exclusion Criteria 20. 
 Study Outline and Section 4.1.1: 
Exclusion Criteria 20 was amended as follows:  
“20. History of severe hypersensitivity, e.g. anaphylaxis or severe systemic response, to 
immuno-globulin, blood or plasma derived products, or any component of NewGam” 
 
MODIFICATION 4 
Description of the change: 
Clarification regarding Patient Global Impression of Change. 
 Section 3.2: 
The wording regarding the Patients´Global Impression of Change was amended as follows: 
“(i.e., patients who decrease on whose overall status worsened according to the Patients' 
Global Impression of Change2 (PGIC).” 
 
 


Protocol Amendment #02 – NGAM-08 
 
CONFIDENTIAL  
 
 
 
 
OCTAPHARMA DocID 2790 
Page 3 of 6  
08-Jun-2018 
 
 
MODIFICATION 5 
Description of change: 
The wording regarding EVA bags was amended as follows: 
 Section 5.3: 
“After transfer and pooling into ethylene vinyl acetate (EVA) infusion bags, the medication” 
 Several times in section 5.3, 5.5, 5.6 and 5.8: 
” EVA infusion bags” 
 
MODIFICATION 6 
Description of change: 
The storage time of infusion bags was amended. 
 Section 5.6: 
“The EVA infusion bags can then be stored for up to 72 24 hours at +2°C to +8°C (36°F to 
46°F).” 
 
MODIFICATION 7 
Description of change: 
The questionnaire Patient Global Impression of Change was listed incorrectly at Visit 1 
(Screening Visit). 
 Section 6.1.1: 
The following questionnaire was listed incorrectly and was deleted:   
• PGIC scale 
 
MODIFICATION 8 
Description of change: 
No time window for blood sampling is required for this study and therefore was deleted 
from the table. 
 Section 6.1.5: 
Time point 
Time stated 
Tolerance 
Interval between visits 
3 weeks 
± 4 days 
Blood sampling 
before IMP administration 
≤ 60 minutes  
Vital signs 
before IMP administration 
≤ 60 minutes 
Vital signs 
after IMP administration 
≤ 60 minutes 


Protocol Amendment #02 – NGAM-08 
 
CONFIDENTIAL  
 
 
 
 
OCTAPHARMA DocID 2790 
Page 4 of 6  
08-Jun-2018 
 
 
MODIFICATION 9 
Description of change: 
No time window for blood sampling is required for this study and therefore was deleted 
from the table. 
 Section 7.3.4: 
Viral marker samples will be taken at screening, before the first NewGam infusion at 
screening at Visit 2 and at the termination visit. 


Protocol Amendment #02 - NGAM-08 
CONFIDENTIAL 
AGREEMENT: THESE SIGNATURES CONSTITUTE APPROVAL OF THIS 
PROTOCOL AMENDMENT AND PROVIDE THE NECESSARY ASSURANCE THAT 
THE STUDY WILL BE CONDUCTED ACCORDING TO ALL STIPULATIONS OF 
PROTOCOL AND AMENDMENTS. 
Authorised person for signing the Study Protocol and Protocol Amendments on 
behalf of the Sponsor and Sponsor's Medical Expert: 
International Medical Director 
on behalf of the Sponsor 
Octapharma Pharmazeutika Produktionsgesellschaft mbH 
Oberlaaerstr. 235, A-1100 Vienna, Austria 
Tel: 
, Fax: 
 
 
Manager Biometrics 
Signature 
Octapharma Pharmazeutika Produktionsgesellschaft mbH 
Oberlaaerstr. 235, A-1100 Vienna, Austria 
Tel: 
, Fax: 
 
OCT APHARMA DocID 2790 
Page 5of6 
Z2-JuN-2ort 
Date 
08-Jun-2018 


Protocol Amendment #02 - NGAM-08 
CONFIDENTIAL 
AGREEMENT: THESE SIGNATURES CONSTITUTE APPROVAL OF THIS 
PROTOCOL AMENDMENT AND PROVIDE THE NECESSARY ASSURANCE THAT 
THE STUDY WILL BE CONDUCTED ACCORDING TO ALL STIPULATIONS OF 
PROTOCOL AND AMENDMENTS. 
Authorised person for signing the Study Protocol and frotocol Amendments on 
behalf of the Sponsor and Sponsor's Medical Expert: 
l 
Signature of the Coordinating Investigator 
(N 
' ~.C.Dl'iiu19 
euro
e
ate 
University of Toronto 
Toronto General Hospital I UHN 
200 Elizabeth Street, SES-306 
Toronto, Ontario 
MSG 2C4 
OCT APHARMA DocID 2790 
Page 6of6 
08-Jun-2018 


oclqphormo
CLINICAL STUDY PROTOCOL
"pRospECTM, DOUBLE-BLIND, RANDOMTZED,
MULTICENTER PHASE III STUDY EVALUÄTING EFFICACY
AND SAFETY OF THREE DIFFERENT DOSAGES OF'
NEWGAM IN PATIENTS WITH CHRONIC INFLAMMATORY
DEMYELII\ATING POLY(RADICULO)NEUROPATHY''
(ProCID study)
Investigational Product:
Immune Globulin Intravenous, Human l0% (working
title "NewGam ,r)
Indication:
Chronic Inflammatory Demyelinating Poly(radiculo)-
neuropathy (CIDP)
Study Design:
Prospective, parallel group, double-blind, randomized,
multicenter phase III efficacy study
Sponsor:
Octapharma Pharmazeutika Produktionsges.m.b. H.
Oberlaaer Str.235, 1100 Vienna, Austria
Study Number:
NGAM-O8
EudraCT and/or
IND Number:
20Is-005443-14
BB-IND #14096
Development Phase
Phase III
Planned Clinical Start:
Quarter 12017
Planned Clinical End:
Quarter 4 2019
Date of Protocol:
08 June 201 8
Version
04
Co-ordinating Investigator:
, University
Toronto General Hospital / UHN
200 Elizabeth Street, 5ES-306
Toronto, Ontario M5G 2C4
This d ocu m ent contains con f ide ntial a nd p roprieta ry inf ormation of Octap harm a, Copying or
diEtribution of this docurnent is only pennitted with the written permission of Octapharma. Any
comm ercialuse of the information is subjectto the perm ission of Octapharma and a lire nse fee.
OgO-CS P - NGA M-08- VO4/DOC I D 2 7 89


 
 
i 
STUDY OUTLINE 
Name of Sponsor/Company: 
Octapharma Pharmazeutika Produktionsges.m.b.H., 1100 Vienna, AT 
Name of Investigational Product: 
NewGam 
Protocol Identification Code: 
NGAM-08 (ProCID) 
Name of Active Ingredient: 
Immunoglobulin Intravenous (human) 10% 
Date of Final Protocol: 
08-June-2018 
Title of Study:  
Prospective, Double-blind, Randomized, Multicenter Phase III Study Evaluating Efficacy 
and Safety of Three Different Dosages of NewGam in Patients With Chronic Inflammatory 
Demyelinating Poly(radiculo)neuropathy (“ProCID trial”) 
Indication: 
Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy (CIDP) 
Number of Study Centre(s): 
Approximately 45 selected study sites worldwide with focus on Eastern European countries. 
Study Duration: 
Q1 2017 to Q4 2019 
Development Phase: III 
Objectives: 
Primary: 
• To provide confirmatory data on the effect of 1.0 g/kg NewGam every three weeks 
in patients with active CIDP based on the percentage of responders at Week 24, 
which should corroborate the existing evidence on efficacy of IGIV in CIDP as 
known from published literature. 
Secondary: 
• To assess the effect of 0.5 g/kg and 2.0 g/kg NewGam every three weeks in 
patients with active CIDP based on the percentage of responders at Week 24 
compared to patients on 1.0 g/kg NewGam every three weeks  
• To evaluate the safety of NewGam administration using various dosages in 
patients with CIDP 
• To further evaluate the beneficial effect of three NewGam dosages in patients with 
CIDP by assessing different parameters/scores/scales 
Exploratory: 
• To assess the primary and secondary objectives at three weeks after having 
provided rescue medication (if applicable) 
• To further evaluate the beneficial effect of NewGam administration in patients 
with CIDP by additional assessments/scores including quality of life (QoL) 
measures 
Study Design: 
Prospective, parallel group, double-blind, randomized, multicenter phase III efficacy study 
 


 
 
ii 
Name of Sponsor/Company: 
Octapharma Pharmazeutika Produktionsges.m.b.H., 1100 Vienna, AT 
Name of Investigational Product: 
NewGam 
Protocol Identification Code: 
NGAM-08 (ProCID) 
Name of Active Ingredient: 
Immunoglobulin Intravenous (human) 10% 
Date of Final Protocol: 
08-June-2018 
Number of Patients: 
A minimum of 140 adult patients of both genders with definite or probable CIDP according 
to the EFNS/PNS Criteria are to be enrolled. Patients will be randomized 1:2:1 to receive 
either 0.5 g/kg or 1.0 g/kg or 2.0 g/kg NewGam for seven maintenance infusions at 3-week 
intervals during the Dose-evaluation Phase. 
Patient Selection Criteria: 
Inclusion Criteria: 
1. Patients with diagnosis of definite or probable CIDP according to the EFNS/PNS 
Guideline 2010; including patients with Multifocal Acquired Demyelinating 
Sensory And Motor Neuropathy (MADSAM) or pure motor CIDP  
2. Patients currently depending on treatment with immunoglobulins or corticosteroids 
3. Patients with active disease, i.e. not being in remission, who are progressive or 
relapsing prior to trial start or during the Wash-out Phase 
4. Weakness of at least 2 limbs 
5. ≥ 18 to < 80 years of age 
6. Adjusted INCAT disability score between 2 and 9 (with a score of 2 coming 
exclusively from leg disability) 
7. Voluntarily given, fully informed written consent obtained from patient before any 
study-related procedures are conducted 
Exclusion Criteria: 
1. Unifocal forms of CIDP 
2. Pure sensory CIDP 
3. MMN with conduction block 
4. Patients who previously failed immunoglobulin therapy 
5. Treatment with immunomodulatory/suppressive agents (cyclosporin, methotrexate, 
mitoxantrone, mycophenolate mofetil or azathioprine) during the six months prior 
to baseline visit 
6. Patients on or treated with rituximab, alemtuzumab, cyclophosphamide, or other 
intensive chemotherapeutic regimens, previous lymphoid irradiation or stem cell 
transplantation during the 12 months prior to baseline visit 
7. Respiratory impairment requiring mechanical ventilation 
8. Myelopathy or evidence of central nervous system demyelination or significant 
persisting neurological deficits from stroke, or central nervous system (CNS) trauma 
9. Clinical evidence of peripheral neuropathy from another cause such as 
a. connective tissue disease or systemic lupus erythematosus (SLE) 
b. HIV infection, hepatitis, Lyme disease 


 
 
iii 
Name of Sponsor/Company: 
Octapharma Pharmazeutika Produktionsges.m.b.H., 1100 Vienna, AT 
Name of Investigational Product: 
NewGam 
Protocol Identification Code: 
NGAM-08 (ProCID) 
Name of Active Ingredient: 
Immunoglobulin Intravenous (human) 10% 
Date of Final Protocol: 
08-June-2018 
c. cancer (with the exception of basal cell skin cancer) 
d. IgM paraproteinemia with anti-myelin associated glycoprotein antibodies 
10. Diabetic neuropathy 
11. Cardiac insufficiency (New York Heart Association [NYHA] 
III/IV), 
cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or 
advanced ischemic heart disease 
12. Severe liver disease (ALAT 3x > normal value) 
13. Severe kidney disease (creatinine 1.5x > normal value) 
14. Hepatitis B, hepatitis C or HIV infection 
15. Thromboembolic events: patients with a history of deep vein thrombosis (DVT) 
within the last year prior to baseline visit or pulmonary embolism ever; patients with 
susceptibility to embolism or DVT 
16. Body mass index (BMI) ≥40 kg/m2 
17. Patients with uncompensated hypothyroidism (abnormally high Thyroid-
Stimulating Hormone [TSH] and abnormally low Thyroxine [T4]) or known vitamin 
B12 deficiency if they don’t receive adequate substitution therapy 
18. Medical conditions whose symptoms and effects could alter protein catabolism 
and/or IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome) 
19. Known IgA deficiency with antibodies to IgA 
20. History of severe hypersensitivity, e.g. anaphylaxis or severe systemic response, to 
immuno-globulin, blood or plasma derived products, or any component of NewGam 
21. Known blood hyperviscosity, or other hypercoagulable states 
22. Use of other blood or plasma-derived products within three months prior to Visit 2 
23. Patients with a past or present history of drug abuse or alcohol abuse within the 
preceding five years prior to baseline visit 
24. Patients unable or unwilling to understand or comply with the study protocol 
25. Participation in another interventional clinical study with IMP treatment currently 
or during the three months prior to Visit 2 
26. Women who are breast feeding, pregnant, or planning to become pregnant, or are 
unwilling to use an effective birth control method (such as implants, injectables, 
combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence 
or vasectomized partner) while on study 
Test Product, Dose, Mode of Administration, and Batch Number(s): 
NewGam is a 10% human normal immunoglobulin, solvent/detergent (S/D) treated solution 
for intravenous infusion. To be stored and transported light-protected at + 2°C to + 8°C 


 
 
iv 
Name of Sponsor/Company: 
Octapharma Pharmazeutika Produktionsges.m.b.H., 1100 Vienna, AT 
Name of Investigational Product: 
NewGam 
Protocol Identification Code: 
NGAM-08 (ProCID) 
Name of Active Ingredient: 
Immunoglobulin Intravenous (human) 10% 
Date of Final Protocol: 
08-June-2018 
(36°F to 46°F) and brought to room or body temperature before use. NewGam must not be 
frozen. 
During the Dose-evaluation Phase, all patients will receive a loading dose of 2.0 g/kg 
NewGam followed by seven times maintenance dosage of 0.5, 1.0 or 2.0 g/kg they were 
randomized to (given at 3-week intervals). 
Duration of Treatment: 
The duration of the entire study for each patient will be between >9 and up to 39 weeks and 
consists of the following segments: approximately 3 weeks for Screening, up to 12 weeks 
for the Wash-out Phase and 24 weeks for the Dose-evaluation Phase (for patients who 
deteriorate at the end of the 12-week Wash-out Phase and who are continued responders 
during the Dose-evaluation Phase). The minimal duration could be >9 weeks after 
Screening (for patients in the 2.0 g/kg arm deteriorating after being only a few days in the 
Wash-out Phase and being stable until Week 6 or deteriorating by then as they will not 
receive rescue treatment but drop-out). Thus, the length of the Dose-evaluation Phase can 
vary between 6 and 24 weeks, while the length of the Wash-out Phase can vary between >0 
and 12 weeks. 
Reference Therapy, Dose, Mode of Administration, and Batch Number(s): 
N/A 
Study Outcome Parameters (Primary, Secondary and Exploratory Endpoints): 
Efficacy: 
Primary 
• Proportion of responders in the 1.0 g/kg NewGam arm at Week 24 (Termination Visit) 
relative to baseline (Week 0). A responder being defined as a patient with a decrease of 
at least 1 point on the adjusted INCAT disability score (a scale from 0 to 10, from 
healthy to unable to make any purposeful movements with arms and/or legs) 
Secondary 
• Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative 
to baseline compared to the 1.0 g/kg arm, based on the adjusted INCAT disability score 
• Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative 
to baseline at Week 0 compared to the 1.0 g/kg arm, based on the grip strength (Martin 
Vigorimeter) using the previously published minimum clinically important difference 
(MCID) cut-off of 8 kPa 
• Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative 
to baseline at Week 0 compared to the 1.0 g/kg arm, based on the I-RODS scores using 
the MCID concept related to the varying standard errors (MCID-SE) as recently 
demonstrated. 


 
 
v 
Name of Sponsor/Company: 
Octapharma Pharmazeutika Produktionsges.m.b.H., 1100 Vienna, AT 
Name of Investigational Product: 
NewGam 
Protocol Identification Code: 
NGAM-08 (ProCID) 
Name of Active Ingredient: 
Immunoglobulin Intravenous (human) 10% 
Date of Final Protocol: 
08-June-2018 
• Time to first confirmed worsening on the adjusted INCAT disability scale by at least 1 
point from the value at baseline (Week 0) 
• Mean change from baseline (Week 0) to Termination Visit in  
o grip strength of both hands (assessed by Martin Vigorimeter) 
o Inflammatory Rasch-built overall disability sum score (I-RODS using the concept 
of MCID-SE as recently reported; Appendix 1) and number of improvers 
o sum of the distal evoked amplitude of 4 right sided and 4 left sided motor nerves 
(peroneal, tibial, ulnar and median)  
o Pain Intensity Numeric Rating Scale (PI-NRS) 
• Time to first confirmed worsening on the I-RODS scale 
• Time to 1 point decrease (improvement of disability) in adjusted INCAT disability score 
• Time to decrease in I-RODS scores 
 
Exploratory 
• Mean change from baseline (Week 0) to Termination Visit in:  
o modified Fatigue Severity Scale (FSS; 7-item scale from 0-21 points; see Appendix 
2) 
o number of improvers by at least 4 points in the MRC sum score (according to the 
universal rule of minimal clinical important difference) 
o SF-36 Health Survey physical composite score (PCS), mental composite score 
(MCS) and their 8 health domains (see Appendix 3) 
o additional NCS analyses (e.g. individual nerve analysis) 
• Time to decrease in MRC sum score to or below baseline value after temporary 
improvement (increase) 
Safety (throughout the entire Wash-out and Dose-evaluation Phases): 
• Occurrence of all adverse events (AEs)  
• Short term tolerance parameters including vital signs  
• Physical/neurological examination 
• Laboratory parameters (hematology and clinical chemistry) and tests for viral safety  
Summary of Study Procedures and Statistical Analysis Plan: 
Study Procedures: 
Disability will be assessed by the adjusted INCAT score and the I-RODS at each visit. 
Pain will be assessed by the PI-NRS at each visit. 
Impairment will be assessed by the grip strength at each visit, MRC sum score and the 
modified FSS (Fatigue Scale) at Screening, Week 0, Week 12 and Termination Visit. 
Quality of life (SF-36) will be measured at Screening, Week 0, Week 12, and at Termination 
Visit. 


 
 
vi 
Name of Sponsor/Company: 
Octapharma Pharmazeutika Produktionsges.m.b.H., 1100 Vienna, AT 
Name of Investigational Product: 
NewGam 
Protocol Identification Code: 
NGAM-08 (ProCID) 
Name of Active Ingredient: 
Immunoglobulin Intravenous (human) 10% 
Date of Final Protocol: 
08-June-2018 
Electrophysiological measurements (nerve conduction studies) will be done at Screening, 
Week 0, Week 12, and at Termination Visit. 
Adverse events (AEs) and serious adverse events (SAEs) temporally associated with 
administration of IMP or saline solution will be collected throughout the entire study 
(starting with the Wash-out Phase for patients on IGIV) as well as pregnancies, drug 
overdose, interaction, medication error, lack of efficacy, and post-study SAEs. 
Laboratory safety tests (hematology and clinical chemistry) will be determined from blood 
samples taken at each visit. IgG level will be determined at each visit but Screening; viral 
markers will be determined at Screening, Week 0, and Termination Visit. Urinalysis will be 
performed at Screening and Termination Visit. 
Statistical Analysis: 
The primary endpoint will be evaluated by comparing the lower limit of the 95% Wilson-
Score confidence interval for the percentage of responders on the adjusted INCAT disability 
scale in the 1.0 g/kg dose group with a predefined threshold of 42%. 
The response rates in the alternative dose groups will be compared descriptively to the 1.0 
g/kg treatment group, and the confidence intervals for the differences will be presented. In 
addition, an exploratory logistic regression, that includes the pre-treatment as well as the 
dose group as predictor variables, will be conducted. The same model will also be used for 
secondary response variables (based on grip strength, or I-RODS scores). 
All other endpoints will be analyzed and presented in full detail by means of descriptive 
statistics, including summary and frequency tables, confidence intervals and graphs. 
A formal statistical analysis plan describing all details of the analyses to be performed will 
be prepared by the study statistician and approved by the Sponsor prior to unblinding and 
the start of the statistical analysis. 
The analysis of safety will be based on the safety set which includes all patients who 
received any study drug. The primary evaluation of efficacy endpoints will be based on the 
Full Analysis Set (intention-to-treat analysis). 
The study assessments and scheduled time points are summarized in the Flowchart overleaf:


Study Protocol 
CONFIDENTIAL 
Version 04
No. NGAM-08 (ProCID) 
08-June-2018
 
 
vii 
FLOWCHART 
 
 
Screening  
Wash-out 
Phase1 
Dose-evaluation Phase2 
 
Visit 1 
Week -15  
Week  
-12 to 0 
Visit 2 
Week 0  
Visit 3 
Week 3 
Visit 4 
Week 6 
Visit 5 
Week 9  
Visit 6 
Week 12 
Visit 7 
Week 15 
Visit 8 
Week 18 
 Visit 9 
Week 21 
Termination visit 
Week 24  
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
In-/Exclusion criteria 
X 
 
X 
 
 
 
 
 
 
 
 
Randomization/Enrollment 
 
 
X 
 
 
 
 
 
 
 
 
Concomitant medication 
 
X10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
 
X10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical/neurological 
examination 
X 
 
X 
 
 
 
X 
 
 
 
X 
ECG 
X 
 
 
 
 
 
 
 
 
 
 
Clinical chemistry3; 
Hematology4 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum IgG5 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis6 
X 
 
 
 
 
 
 
 
 
 
X 
Pregnancy test11 
X 
 
 
 
 
 
 
 
 
 
 
Viral marker7 
X 
 
X 
 
 
 
 
 
 
 
X 
PGIC scale 
 
 
X 
 
 
 
 
 
 
 
 
Adjusted INCAT score;  
I-RODS score,  PI-NRS 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Grip strength 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MRC sum score 
X 
 
X 
 
 
 
X 
 
 
 
X 
Modified FSS 
X 
 
X 
 
 
 
X 
 
 
 
X 
Nerve Conduction Studies 
X 
 
X 
 
 
 
X 
 
 
 
X 
SF-36 Health Survey 
X 
 
X 
 
 
 
X 
 
 
 
X 
Vital signs8; Weight 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Study drug infusion 
 
 
X9 
X 
X, [X12,13] 
X, [X12,13] 
X, [X12] 
X, [X12] 
X, [X12] 
X, [X12] 
 


Study Protocol 
CONFIDENTIAL 
Version 04
No. NGAM-08 (ProCID) 
08-June-2018
 
 
viii 
 
1 May last up to 12 weeks (until deterioration): Selection of active patients requiring treatment after dosage reduction 
2 Infusion visits take 2 days 
 
 
 
 
 
 
 
3 Clinical chemistry: Na+, K+, glucose, ALAT/ALT/GPT, ASAT/AST/GOT, LDH, total bilirubin, BUN (blood urea nitrogen) or urea, creatinine, albumin, serum IgG      
4 Hematology: Hematocrit, hemoglobin, CBC with differential 
 
 
 
5 Serum IgG to be determined prior to infusion   
6 Urinalysis: Protein, pH, glucose, ketones, leukocytes, hemoglobin and blood  
 
7 Viral Markers: HIV, HBV and HCV 
8 Vital signs: Pulse, blood pressure, respiratory rate and temperature   
 
 
9 Loading dose of 2.0 g/kg NewGam 
10 Only for patients on immunoglobulin treatment visiting the site for infusions  
 
 
 
11 Pregnancy test should only be done in women of childbearing potential (WOCBP). Pregnancy test is mandatory at Visit 1. At Visit 2, 3, 4, 5, 6, 7, 8, 9 and Termination 
Visit a pregnancy test should be performed only if required by local regulations. 
12   Two consecutive 3-weekly infusions of 2.0 g/kg NewGam only for patients on 0.5 or 1.0 g/kg NewGam who deteriorate after Week 3 and until Week 18  
13 Two consecutive 3-weekly infusions of 2.0 g/kg NewGam only for patients on 0.5 or 1.0 g/kg NewGam being stable by Week 6 


Study Protocol
No. NGAM-08 (ProCID)
CONFIDENTIAL
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PROTOCOL SIGNATURES
Signature of the Sponsor's Representative
This study is intended to be conducted in compliance with the protocol,
ICH-GCP E6 and the applicable regulatory requirements.
 
International Medical Director
on behalfofthe Sponsor
Octapharma Pharmazeutika Produktionsges.m.b. H.
Oberlaaer Str. 235
1100 Vienna
Austria
(a 6 .2r;'{
S
Date


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Signature of the Manager Biometrics
This study is intended to be conducted in compliance with the protocol,
ICH-GCP E6 and the applicable regulatory requirements.
 
 
ls*1rtu -zttt
Manager Biometrics 
Signature
Octapharma Pharmazeutika Produktionsges.m.b.H.
Oberlaaer Str. 235
1100 Vienna
Austria
Date
2


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Signature of the Coordinating Investigator 
This study is intended to be conducted in compliance with the protocol, 
ICH-GCP E6 and the applicable regulatory requirements. 
 
 
University of Toronto 
Toronto General Hospital I UHN 
200 Elizabeth Street, SES-306 
Toronto, Ontario MSG 2C4 
Signature 
:Iv»-& i.~ i.  e 
Date 
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TABLE OF CONTENTS 
STUDY OUTLINE ................................................................................................................... I 
FLOWCHART ..................................................................................................................... VII 
PROTOCOL SIGNATURES .................................................................................................. 1 
TABLE OF CONTENTS ......................................................................................................... 4 
LIST OF ABBREVIATIONS .................................................................................................. 8 
1 
INTRODUCTION .......................................................................................................... 10 
1.1 RATIONALE FOR CONDUCTING THE STUDY ................................................................... 11 
1.2 BENEFIT-RISK STATEMENT ........................................................................................... 12 
2 
STUDY OBJECTIVES .................................................................................................. 14 
2.1 PRIMARY OBJECTIVE ..................................................................................................... 14 
2.2 SECONDARY OBJECTIVES .............................................................................................. 14 
2.3 EXPLORATORY OBJECTIVES .......................................................................................... 14 
3 
INVESTIGATIONAL PLAN ........................................................................................ 15 
3.1 PRIMARY AND SECONDARY ENDPOINTS ........................................................................ 15 
3.1.1 Primary Endpoint ................................................................................................. 15 
3.1.2 Secondary Endpoints ............................................................................................ 15 
3.1.3 Exploratory Endpoints .......................................................................................... 16 
3.2 OVERALL STUDY DESIGN AND PLAN ............................................................................. 16 
3.3 DISCUSSION OF STUDY DESIGN AND CHOICE OF CONTROL GROUP(S) ........................... 19 
3.3.1 Study Design ......................................................................................................... 19 
3.3.2 Control Group(s) .................................................................................................. 20 
3.3.3 Target Parameters ................................................................................................ 20 
4 
STUDY POPULATION ................................................................................................. 21 
4.1 POPULATION BASE ........................................................................................................ 21 
4.1.1 Inclusion Criteria ................................................................................................. 21 
4.1.2 Exclusion Criteria ................................................................................................ 21 
4.2 PRIOR AND CONCOMITANT THERAPY ............................................................................ 22 
4.2.1 Prior Therapy ....................................................................................................... 22 
4.2.2 Permitted Concomitant Therapy .......................................................................... 23 
4.2.3 Forbidden Concomitant Therapy ......................................................................... 23 
4.3 ASSIGNMENT OF PATIENTS TO TREATMENT GROUPS ..................................................... 23 
4.4 WITHDRAWAL AND REPLACEMENT OF PATIENTS .......................................................... 24 
4.4.1 Premature Patient Withdrawal ............................................................................. 24 
4.4.2 Patient Replacement Policy .................................................................................. 25 
5 
INVESTIGATIONAL MEDICINAL PRODUCT(S) ................................................. 26 
5.1 TREATMENT COMPLIANCE ............................................................................................. 26 
5.1.1 Drug Dispensing and Accountability ................................................................... 26 


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5.1.2 Assessment of Treatment Compliance .................................................................. 26 
5.2 CHARACTERIZATION OF INVESTIGATIONAL PRODUCT(S) ............................................... 26 
5.3 PACKAGING AND LABELING .......................................................................................... 27 
5.4 CONDITIONS FOR STORAGE AND USE ............................................................................ 28 
5.5 DOSE AND DOSING SCHEDULE ...................................................................................... 28 
5.6 PREPARATION AND METHOD OF ADMINISTRATION ....................................................... 30 
5.7 TREATMENT DURATION ................................................................................................. 30 
5.8 BLINDING, EMERGENCY UNBLINDING AND BREAKING THE STUDY BLIND .................... 31 
5.9 SUBSEQUENT THERAPY ................................................................................................. 32 
5.10 RELEVANT PROTOCOL DEVIATIONS .............................................................................. 32 
6 
STUDY CONDUCT ....................................................................................................... 33 
6.1 OBSERVATIONS BY VISIT ............................................................................................... 33 
6.1.1 Screening (Visit 1; duration up to 21 days, i.e. Week -15 to -12) ........................ 33 
6.1.2 Procedures During the Wash-out Phase of the Study .......................................... 34 
6.1.3 Procedures During the Dose-evaluation Phase of the Study ............................... 34 
6.1.4 Procedures during the Rescue Treatment ............................................................ 37 
6.1.5 Interpretation of Time Windows in this Study ...................................................... 37 
6.2 DURATION OF STUDY .................................................................................................... 37 
6.2.1 Planned Duration for an Individual Patient ........................................................ 37 
6.2.2 Planned Duration for the Study as a Whole ......................................................... 37 
6.2.3 Premature Termination of the Study .................................................................... 38 
7 
ASSESSMENTS AND METHODS .............................................................................. 39 
7.1 BACKGROUND / BASELINE INFORMATION ..................................................................... 39 
7.2 EFFICACY ASSESSMENTS ............................................................................................... 39 
7.2.1 Assessments for Primary Efficacy Endpoints ....................................................... 39 
7.2.1.1 
Adjusted INCAT Score (Disability Score) ..............................................................39 
7.2.2 Assessments for Secondary Efficacy Endpoints ................................................... 39 
7.2.2.1 
I-RODS (Disability Scale) .......................................................................................39 
7.2.2.2 
Grip Strength (Muscle Strength)..............................................................................40 
7.2.3 Assessments of Exploratory Efficacy Endpoints ................................................... 40 
7.2.3.1 
MRC Sum Score (Impairment Scale) ......................................................................40 
7.2.3.2 
Modified FSS Scale (Fatigue Scale) ........................................................................40 
7.2.3.3 
Pain Intensity Numeric Rating Scale (Assessment of Pain) ....................................40 
7.2.3.4 
Nerve Conduction Studies (Electrophysiological Measurements) ..........................41 
7.2.3.5 
SF-36 Health Survey (Quality of Life Assessment) ................................................41 
7.3 SAFETY ASSESSMENTS .................................................................................................. 42 
7.3.1 Adverse Events ...................................................................................................... 42 
7.3.1.1 
Definitions ...............................................................................................................42 
7.3.1.2 
Collection .................................................................................................................42 
7.3.1.3 
Severity ....................................................................................................................43 
7.3.1.4 
Causality ..................................................................................................................43 
7.3.1.5 
Outcome ...................................................................................................................44 
7.3.1.6 
Action(s) taken .........................................................................................................44 
7.3.2 Serious Adverse Events ......................................................................................... 45 


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7.3.3 Laboratory Safety Tests ........................................................................................ 46 
7.3.4 Viral Safety Tests .................................................................................................. 46 
7.3.5 Vital Signs and Physical Examination ................................................................. 47 
7.3.6 Other Relevant Safety Information ....................................................................... 47 
8 
DATA HANDLING AND RECORD KEEPING ........................................................ 49 
8.1 DOCUMENTATION OF DATA ........................................................................................... 49 
8.1.1 Source Data and Records ..................................................................................... 49 
8.1.2 Electronic Case Report Forms ............................................................................. 49 
8.1.3 Changes to Case Report Form Data .................................................................... 49 
8.2 INFORMATION OF INVESTIGATORS ................................................................................. 50 
8.3 RESPONSIBILITIES .......................................................................................................... 50 
8.4 INVESTIGATOR’S SITE FILE ............................................................................................ 51 
8.5 PROVISION OF ADDITIONAL INFORMATION .................................................................... 51 
8.6 INDEPENDENT DATA MONITORING COMMITTEE ............................................................ 51 
8.7 STEERING COMMITTEE .................................................................................................. 51 
9 
STATISTICAL METHODS AND SAMPLE SIZE .................................................... 53 
9.1 DETERMINATION OF SAMPLE SIZE ................................................................................. 53 
9.2 STATISTICAL ANALYSIS ................................................................................................. 54 
9.2.1 Population for Analysis ........................................................................................ 54 
9.2.2 Efficacy Analysis Plan .......................................................................................... 55 
9.2.3 Safety Analysis Plan ............................................................................................. 56 
9.2.3.1 
Adverse Events ........................................................................................................56 
9.2.3.2 
Laboratory Safety Tests ...........................................................................................56 
9.2.3.3 
Viral Safety tests ......................................................................................................56 
9.2.3.4 
Vital Signs ...............................................................................................................57 
9.2.3.5 
Physical Examination ..............................................................................................57 
9.2.3.6 
Other Relevant Safety Information ..........................................................................57 
9.2.4 Handling of Missing Data .................................................................................... 57 
9.3 RANDOMIZATION / STRATIFICATION / CODE RELEASE .................................................. 57 
9.4 INTERIM ANALYSIS ........................................................................................................ 58 
10 ETHICAL / REGULATORY, LEGAL AND ADMINISTRATIVE ASPECTS ...... 59 
10.1 ETHICAL / REGULATORY FRAMEWORK .......................................................................... 59 
10.2 APPROVAL OF STUDY DOCUMENTS ............................................................................... 59 
10.3 PATIENT INFORMATION SHEET AND INFORMED CONSENT FORM ................................... 59 
10.4 PROTOCOL AMENDMENTS ............................................................................................. 59 
10.5 CONFIDENTIALITY OF PATIENTS’ DATA......................................................................... 60 
11 QUALITY CONTROL AND QUALITY ASSURANCE ........................................... 61 
11.1 PERIODIC MONITORING ................................................................................................. 61 
11.2 AUDIT AND INSPECTION................................................................................................. 61 
12 REPORTING AND PUBLICATION ........................................................................... 61 
12.1 CLINICAL STUDY REPORT.............................................................................................. 61 


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12.2 PUBLICATION POLICY .................................................................................................... 61 
13 LIABILITIES AND INSURANCE ............................................................................... 62 
14 REFERENCES ............................................................................................................... 63 
15 APPENDICES ................................................................................................................. 66 


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LIST OF ABBREVIATIONS 
ADR(s)  
Adverse Drug Reaction(s) 
AE(s) 
 
Adverse Event(s) 
ALAT  
Alanine Aminotransferase 
ANCOVA 
Analysis of Covariance  
ASAT  
Aspartate Aminotransferase 
CBC 
 
Complete Blood Count 
CIDP 
 
Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy 
CMAP  
Compound Muscle Action Potential 
CRO 
 
Contract Research Organization 
DM 
 
Diabetes Mellitus 
DMC 
 
Data Monitoring Committee 
DVT 
 
Deep Vein Thrombosis 
ECG 
 
Electrocardiogram 
e-CRF(s) 
electronic Case Report Form(s) 
EDC 
 
Electronic Data Capture 
EFNS 
 
European Federation of Neurological Societies 
EMG 
 
Electromyograph 
EVA 
 
Ethylene Vinyl Acetate 
FAS 
 
Full Analysis Set 
FDA 
 
Food and Drug Administration 
FSS 
 
Fatigue Severity Scale 
GBS 
 
Guillain-Barré Syndrome 
GCP 
 
Good Clinical Practice 
HBV 
 
Hepatitis B Virus 
HCV 
 
Hepatitis C Virus 
HIV 
 
Human Immunodeficiency Virus 
ICH 
 
International Conference on Harmonisation 
IEC 
 
Independent Ethics Committee 
IgA/G/M 
Immunoglobulin A/G/M 
IGIV 
 
Immunoglobulin Intravenous 
IMP 
 
Investigational Medicinal Product 
INCAT  
Inflammatory Neuropathy Cause and Treatment 
IND 
 
Investigational New Drug 
IRB 
 
Institutional Review Board 
I-RODS  
Inflammatory Rasch-built Overall Disability Scale 
ITT 
 
Intention-To-Treat 
IWRS 
 
 Interactive Web Recognition System 
K 
 
Kalium (Potassium) 
LDH 
 
Lactate Dehydrogenase 
MADSAM 
Multifocal Acquired Demyelinating Sensory And Motor Neuropathy 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMN 
 
Multifocal Motor Neuropathy 
MRC 
 
Medical Research Council 
Na 
 
Natrium (Sodium) 
NCS 
 
Nerve Conduction Studies 
PEX 
 
Plasma Exchange 
PI-NRS  
Pain Intensity Numeric Rating Scale 
PNS 
 
Peripheral Nerve Society 
PP 
 
Per-Protocol 
QoL 
 
Quality of Life 
S/D 
 
Solvent/Detergent 


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SAE(s)  
Serious Adverse Event(s) 
SF-36 
 
Short Form 36 Items Health Status 
SOP(s)  
Standard Operating Procedure(s) 
TEAE(s) 
Treatment Emergent Adverse Event(s) 
WOCBP 
Women of Childbearing Potential 


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1 
INTRODUCTION 
Since more than five decades immunoglobulins have been used to provide antibodies for the 
prevention of viral and bacterial diseases (replacement therapy) in immunocompromised 
patients. Within the last 25 years IGIV has been proven to be useful in a wide variety of clinical 
conditions other than replacement therapy of immunocompromised patients, in which IGIV 
exhibits an immunomodulatory effect. These include Idiopathic Thrombocytopenic Purpura 
(ITP), in children and adults at high risk of bleeding or prior to surgery to correct the platelet 
count, Kawasaki disease and Guillain-Barré syndrome (GBS). More recently, single IGIV 
brands have also been licensed for Multifocal Motor Neuropathy (MMN) and Chronic 
Inflammatory Demyelinating Poly(radiculo)neuropathy (CIDP). Experimental off-label use of 
IGIV mostly in other neurological and dermatological indications is widespread. 
NewGam is a newly developed 10% human normal immunoglobulin solution ready for 
intravenous administration (IGIV) developed by Octapharma. It is supplied as a ready to use 
liquid formulation.  
The NewGam manufacturing process achieves a significant viral reduction through a 
combination of two dedicated manufacturing process steps: solvent/detergent (S/D) treatment 
and nanofiltration (20 nm). Based on the combination of these two steps, NewGam complies 
with the latest international consensus on best practices for viral safety. The Source Q 
chromatography (ion-exchange chromatography) step in the NewGam process also contributes 
significantly to the viral safety of NewGam. The efficacy of the virus inactivation procedures 
has been extensively validated according to relevant international guidelines in place. Further 
information can be found in the current Investigator’s Brochure. ADRs reported for NewGam 
were similar in type and intensity to those reported with other IGIV preparations. NewGam is 
currently under review by the FDA and EMA. 
CIDP is a distinct acquired chronic progressive or relapsing and spontaneously remitting 
neuropathy characterized by progressive weakness, reduced or absent tendon reflexes and 
impaired sensation over more than a 2 months period. The weakness and sensory impairment 
are typically symmetrical and the weakness may be proximal or distal.[1] Approximately 4% 
to 17% of CIDP patients die from the disease usually as a consequence of respiratory failure or 
pulmonary embolism, whereas 50% require persistent treatment, and 13% are permanently 
disabled.[2] 
CIDP is divided into typical and atypical forms [3], and into those un-associated or associated 
with systemic diseases. These forms can be further divided into subgroups with symmetrical 
(classical), asymmetrical (MADSAM or Lewis-Sumner syndrome), pure motor, pure sensory, 
and mixed forms (modified according to [4]). 
CIDP is generally considered to be an autoimmune disease caused by the activation of 
autoimmune mechanisms although the triggering event(s) are unknown.[5] 
CIDP can be diagnosed throughout life, from early childhood (<1 year) to old age (>80 years). 
Nevertheless, on average the onset of disease is around the end of the fifth decade of life.[6] 
CIDP seems to affect more men than women.[7] Its prevalence given in literature has a range 
from 1.0 to 8.9 per 100,000, thus qualifying it as orphan disease.[8] 


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Various criteria for diagnosing CIDP for research studies have been published [9-11] but the 
most established and widely used are the European Federation of Neurological Sciences and 
Peripheral Nerve Society (EFNS/PNS) criteria.[12] Electrodiagnostic tests are mandatory for 
achieving a correct diagnosis. 
1.1 
Rationale for Conducting the Study 
In addition to its use for the treatment of primary and secondary immunodeficiencies, IGIV is 
increasingly used for immunomodulating therapy in the treatment of patients with a variety of 
autoimmune and inflammatory neurological disorders. 
IGIV is currently used as a standard treatment in patients with chronic inflammatory 
demyelinating neuropathies, for initiation therapy as well as for long-term treatment. However, 
clinical studies published so far focused on a loading dose of 2.0 g/kg IGIV and/or a standard 
maintenance dosage of 1.0 g/kg IGIV, without investigating different dosing response options. 
The ProCID study thus aims to confirm the published clinical results obtained with the 1.0 g/kg 
standard dose, and will in addition evaluate one higher and one lower dose, with the aim to 
offer CIDP patients a more adequately dosed and effective treatment policy. The safety and 
tolerability of the various dosages will also be investigated, since many patients need lifelong 
treatment.  
IGIV can be used for therapy of all different types of CIDP. Corticosteroids may worsen pure 
motor CIDP in which IGIV is recognized as the first-line treatment.[13,14] 
Corticosteroids were the first treatment introduced for CIDP.[15] Several non-randomized 
studies and one randomized study concluded that corticosteroids have a beneficial effect in 
CIDP.[16] The advantages of corticosteroids are their availability and low initial costs. 
Unfortunately, the doses needed are often large, treatment has to be prolonged for months or 
years and cushingoid and various other side effects are very common.[17] 
Plasma exchange (PEX) has been shown to be beneficial in two randomized trials.[18] The 
usefulness of PEX as a treatment for CIDP is limited by its inconvenience, requirement for 
hospital attendance and specially trained staff, and the occurrence of AEs. Complications, 
usually from the use of a central venous catheter, have been reported.[19] Therefore, PEX is 
now usually only considered as a third line therapy, if corticosteroids and IGIV do not prove to 
be effective.[20] 
Some patients do not respond or become refractory or intolerant to the above described 
conventional treatments. Over the years, small non-randomized studies have shown possible 
beneficial effects of various immunosuppressive agents. A Cochrane review concluded that 
there is insufficient evidence at present to decide whether these immunosuppressive drugs are 
beneficial in CIDP or may even cause demyelinating disease. It is difficult to prove beneficial 
effects of these newer treatments since they only have been administered to small groups of 
patients who are refractory to other treatments, and often in combination with other treatments. 
Various treatments for CIDP are described such as azathioprine, cyclosporine, 
cyclophosphamide, interferons, methotrexate, mycophenolate mofetil, rituximab and 
etanercept.[21] 


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Over the last 20 years, high-dose IGIV has become an effective and safe therapeutic option for 
CIDP in adults and the preferred treatment in children due to the ease of its application.[22,23] 
The placebo-controlled ICE study in 117 CIDP patients confirmed this short-term benefit and 
showed for the first time sustained benefit from maintenance treatment, leading to the approval 
for CIDP by various authorities.[24] Other IGIV brands have meanwhile also been licensed in 
European countries. 
The EFNS/PNS guidelines recommend that IGIV or corticosteroids should be considered for 
induction of treatment in CIDP in the presence of troublesome symptoms.[12] The authors 
recommend IGIV as an initial treatment in pure motor CIDP and PEX only in case of 
ineffectiveness of corticosteroids and IGIV. However, to date no study has been performed to 
systematically compare different IGIV dosage options in patients with CIDP. 
The rationale for conducting this study is to investigate the efficacy, safety and optimal dosage 
of NewGam in CIDP patients, and to confirm the efficacy results that were observed in 
published clinical studies in order to apply for market authorization of NewGam worldwide, 
including the US and the EU. The study will furthermore systematically investigate different 
dosages of IGIV in an uncontrolled trial. 
1.2 
Benefit-Risk Statement 
Currently, the optimal dosage of IGIV for treatment of CIDP patients is not known and has 
never been systematically examined. Historically, a dose of 1.0 g/kg has been used in the largest 
and longest placebo-controlled study that led to approval of the first IGIV for CIDP.[24] Later 
studies usually relied to this dosage scheme.[25] However, there may be additional benefits to 
individuals and society from this trial (ProCID: “Progress in CIDP”) in which the lack of dose 
response data in the literature will be addressed more extensively. There might be the possible 
benefit of a potential finding of this trial that a lower dose is beneficial for most patients 
resulting in less risk of adverse treatment effects for patients and lower costs for healthcare 
systems. On the other hand, it could also indicate that a higher dose might increase the number 
of patients who benefit from IGIV treatment, thus, reducing the number of non-responders. 
The risks of IGIV administration are well documented. In general, the incidence of AEs 
associated with IGIV tends to increase with the rate of infusion, and thus the recommended 
dosage, infusion rates, and monitoring procedures should be adhered to. Patients naïve to IGIV 
are at higher risk compared to those who are well maintained and on regular therapy. 
Patients with pre-existing risk factors for thrombotic events (such as advanced age, obesity, 
hypertension, diabetes mellitus and a history of vascular disease or thrombotic episodes, 
patients with acquired or inherited thrombophilic disorders, patients with prolonged periods of 
immobilization, severely hypovolemic patients, patients with diseases which increase blood 
viscosity) may be at risk.  
When medicinal products prepared from human blood or plasma are given to a patient, the 
transmission of infectious agents cannot be totally excluded. This applies also to hitherto 
unknown pathogens. However, specific virus inactivation procedures are implemented in the 
manufacturing process of NewGam which are described in detail in the Investigator's Brochure. 


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The safety profile of NewGam is well characterized. For NewGam, the same type of adverse 
reactions has been seen as with other IGIV products. No new or unknown safety problems are 
expected to emerge which are not already described in the Investigator's Brochure. 
In terms of efficacy, it can reasonably be assumed that NewGam exhibits the same effectiveness 
as other IGIV brands. 


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2 
STUDY OBJECTIVES 
2.1 
Primary Objective 
• To provide confirmatory data on the effect of 1.0 g/kg NewGam every three weeks in 
patients with active CIDP based on the percentage of responders at Week 24, which 
should corroborate the existing evidence on efficacy of IGIV in CIDP as known from 
published literature. 
2.2 
Secondary Objectives 
• To assess the effect of 0.5 g/kg and 2.0 g/kg NewGam every three weeks in patients 
with active CIDP based on the percentage of responders at Week 24 compared to 
patients on 1.0 g/kg NewGam every three weeks  
• To evaluate the safety of NewGam administration using various dosages in patients 
with CIDP 
• To further evaluate the beneficial effect of three NewGam dosages in patients with 
CIDP by assessing different parameters/scores/scales 
2.3 
Exploratory Objectives 
• To assess the primary and secondary objectives at three weeks after having provided 
rescue medication (if applicable) 
• To further evaluate the beneficial effect of NewGam administration in patients with 
CIDP by additional assessments/scores, including quality of life (QoL) measures 
 


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3 
INVESTIGATIONAL PLAN 
3.1 
Primary and Secondary Endpoints 
3.1.1 Primary Endpoint 
• Proportion of responders in the 1.0 g/kg NewGam arm at Week 24 (Termination Visit) 
relative to baseline (Week 0). A responder being defined as a patient with a decrease 
of at least 1 point on the adjusted1 INCAT disability score (a scale from 0 to 10, from 
healthy to unable to make any purposeful movements with arms and/or legs)  
3.1.2 Secondary Endpoints 
Efficacy: 
• Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative 
to baseline at Week 0 compared to the 1.0 g/kg arm, based on the adjusted INCAT 
disability score 
• Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative 
to baseline at Week 0 compared to the 1.0 g/kg arm, based on the grip strength (Martin 
Vigorimeter) using the previously published minimum clinically important difference 
(MCID) cut-off of 8 kPa.[26] 
• Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative 
to baseline at Week 0 compared to the 1.0 g/kg arm, based on the I-RODS scores using 
the MCID concept related to the varying standard errors (MCID-SE) as recently 
demonstrated.[27]  
• Time to first confirmed worsening on the adjusted INCAT disability scale by at least 1 
point from the value at Baseline  
• Mean change from Baseline (Week 0) to Termination Visit in  
o grip strength of both hands (assessed by Martin Vigorimeter) Inflammatory Rasch-
built Overall Disability Sum Score (I-RODS using the concept of MCID-SE as 
recently reported; Appendix 1) and number of improvers 
o sum of the distal evoked amplitude of 4 right sided and 4 left sided motor nerves 
(peroneal, tibial, ulnar and median) 
o Pain Intensity Numeric Rating Scale (PI-NRS) 
• Time to first confirmed worsening on the I-RODS scale  
• Time to 1 point decrease (improvement of disability) in adjusted INCAT disability score 
• Time to decrease in I-RODS scores 
 
                                                 
 
1 The adjusted INCAT score is identical to the original INCAT disability score with the exception that upper 
extremity score changes from 0 (normal) to 1 (minor symptoms) or from 1 to 0 are excluded in determining the 
adjusted score, given that these changes are not considered clinically meaningful. 


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Safety:  
Throughout the entire 24-week Dose-evaluation Phase: 
• Occurrence of all adverse events (AEs)  
• Short term tolerance parameters including vital signs  
• Physical/neurological examination 
• Laboratory parameters (hematology and clinical chemistry) and tests for viral safety  
• Standard ECG (only at screening visit) 
3.1.3 Exploratory Endpoints 
Efficacy: 
Mean change from baseline (Week 0) to Termination Visit in:  
• modified Fatigue Severity Scale (FSS; 7-item scale from 0-21 points; see Appendix 2) 
• number of improvers by at least 4 points in the MRC sum score (according to the 
universal rule of MCID [28] at Week 12 or at time of rescue NewGam infusion [26]  
• SF-36 Health Survey physical composite score (PCS), mental composite score (MCS) 
and their 8 health domains (see Appendix 3) 
• additional NCS analyses (see Section 7.2.3.4)  
Time to decrease in MRC sum score [29] to or below baseline value after temporary 
improvement (increase) 
3.2 
Overall Study Design and Plan 
ProCID study is planned to start in Q1 2017 and be completed by Q4 2019, corresponding to a 
total duration of 30 months. The enrollment period is projected to last approximately 20 months. 
ProCID study will be a prospective, parallel group, double-blind, randomized, multicenter, 
Phase 3 study in a minimum of 140 adult patients of both genders with definite or probable 
CIDP according to the EFNS/PNS Criteria.[12] As CIDP is a rare disease, about 45 sites are 
projected to participate worldwide, with emphasis on Eastern European countries, and 
projecting about 3-4 patients for each study site.  
Data from the 1.0 g/kg arms in the ICE [24] and PRIMA [25] trials will be used as historical 
controls. 
Patients will be screened, and if eligible for this trial, their current medication will be reduced 
in a predefined standard manner (immunoglobulins: 25% at each sequential infusion or 
corticosteroids as per the discretion of the Investigator at a rate to expect study entry within 
6-12 weeks) for a maximum of 12 weeks. Only patients who deteriorated in this phase, i.e. 
active patients who demonstrate needing treatment (i.e., patients whose overall status worsened 
according to the Patients' Global Impression of Change2 (PGIC) scale PLUS are either 
increasing on the INCAT by at least 1 point OR decreasing at least 8 kPa on grip strength in 
                                                 
 
2 PGIC, a 7-point scale on which patients rate change in overall status since start of Wash-out Phase (1–3 = 
improved, 4 = no change, 5–7 = worsened). 


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one hand OR at least reaching the I-RODS MCID-SE cut-off of -1.96 or less), will be 
randomized 1:2:1 between three different maintenance dosages of 0.5 g/kg, 1.0 g/kg or 2.0 g/kg 
NewGam in the Dose-evaluation Phase.  
Patients not deteriorating in the 12-week Wash-out Phase will not be enrolled into the ProCID 
study as they are not having active disease. Their treating physician will decide when and which 
treatment will be started in these patients as part of the health system’s standard of care foreseen 
for CIDP patients. 
During the 24-week Dose-evaluation Phase all patients will first receive an initial loading dose 
of 2.0 g/kg NewGam, followed by 7 maintenance dosages of 0.5 g/kg, 1.0 g/kg or 2.0 g/kg 
NewGam every 3 weeks (± 4 days) as they were randomized to. Two different maintenance 
dosages of NewGam (a higher one of 2.0 g/kg and a lower one of 0.5 g/kg) applied in the Dose-
evaluation Phase will be compared with the standard dosing scheme of 1.0 g/kg every 3 weeks 
regarding efficacy and safety.  
Due to the opportunity to receive 2.0 g/kg NewGam twice as a rescue medication and to receive 
standard or higher IGIV doses, it is not expected that many patients drop out. Thus, patients 
dropping out will not be replaced in general, but are included in the sample size calculations. 
The end of the study is defined as the last visit of the last patient participating in the study. 
The graph overleaf shows the study design. 
 


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Graph 3.1: Scheme of Study Design  


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3.3 
Discussion of Study Design and Choice of Control Group(s) 
3.3.1 Study Design 
The design of this prospective, parallel group, randomized, double-blind multicenter study with 
three maintenance dosage groups in the Dose-evaluation Phase is appropriate to verify the 
clinical efficacy observed in published clinical studies, and to evaluate whether different 
dosages of NewGam could cause an effect in patients with definite or probable CIDP and 
whether there will be differences in efficacy compared to CIDP patients from the ICE [24] and 
PRIMA [25] studies. The study design includes all major scientific, state-of-the-art 
interventions with respect to assessment of the safety and efficacy of IGIV administration in 
CIDP patients. 
Previously, a meta-analysis of five double-blind randomized clinical trials with altogether 235 
patients has shown that infusing 2.0 g/kg IGIV once produces a significant improvement in 
disability lasting 2-6 weeks.[30-34] In the ICE trial [24] it was demonstrated that a dosage of 
1.0 g/kg IGIV administered at 3-week intervals (after a loading dose of 2.0 g/kg IGIV) was 
significantly superior to placebo also as long-term treatment. For maintenance therapy, a dosage 
of 0.4–1.0 g/kg IGIV is often administered at intervals varying from 2-8 weeks. Therefore, this 
ProCID study intends to compare three different, commonly used IGIV dosages: 0.5 g/kg (half 
of the standard maintenance dose), 1.0 g/kg (standard maintenance dose) or 2.0 g/kg (generally 
used loading dose as mentioned at the beginning of this paragraph). 
To our knowledge, currently only one randomized study has been published evaluating 
prospectively different IGIV dosages.[35] This trial in 59 CIDP and MMN patients (2:1 ratio) 
was not placebo-controlled, but used 0.25 g/kg IGIV as lowest dosage. The other two arms were 
1.0 g/kg and 2.0 g/kg IGIV. Patients were switched 9 weeks after first administration to the next 
higher dosage if they were non-responders and not already on the highest dosage.  
About half of the IGIV responders show a positive development after the initial 2.0 g/kg loading 
dose and the other half only after one or more additional 1.0 g/kg dose(s).[36] For comparability 
with the ICE trial results, the primary endpoint will be the proportion of responders to treatment, 
where response is defined as improvement of at least 1 point on the adjusted INCAT disability 
scale compared to baseline for those randomized to the 1.0 g/kg arm (the adjusted INCAT score 
is identical to the original INCAT disability score with the exception that upper extremity score 
changes from 0 (normal) to 1 (minor symptoms) or from 1 to 0 are excluded in determining the 
adjusted score, given that these changes are not considered clinically meaningful). Hence, a 
newer and better scale (I-RODS, [27]) will only be applied as secondary endpoint. In 
conformity with ICE and PRIMA studies, the primary endpoint will be assessed at Week 24, 
although the maximum response in the ICE study has been published to be after 10.2 weeks on 
average.[36] 
Patients eligible after screening will first enter a Wash-out Phase of up to 12 weeks or until 
deterioration (see Section 3.2), whatever comes first, in order to select active patients who are 
in need of treatment. Selected patients will subsequently enter the 24-week Dose-evaluation 
Phase. 
This Wash-out Phase and the 3-week interval between infusions have been chosen to make 
results comparable to the ICE and PRIMA studies.[24,25] It is in line with the “EFNS 
guidelines for the use of IGIV in treatment of neurological diseases”.[37] Therein it is 
recommended to reduce the dose in IGIV responders at intervals in order to discover whether 


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the patient still needs IGIV and what dosage is needed. The 3-week interval [±4 days] chosen 
is also in line with the general treatment practice to administer IGIV every 2-6 weeks. 
In the Dose-evaluation Phase, three NewGam dosages will be employed and the efficacy results 
of the higher (2.0 g/kg) and lower (0.5 g/kg) doses compared to the standard dose (1.0 g/kg) 
results to evaluate a potential linear dependency between dose and response. The responder 
rates under standard dose will be compared with the responder rates of the ICE and PRIMA 
studies. 
Risk minimization is achieved due to the introduction of a potential rescue treatment option: 
Two consecutive infusions of 2.0 g/kg NewGam at 3-week intervals [±4 days] for all patients 
in the 0.5 and 1.0 g/kg NewGam arms who are either stable at Week 6 or deteriorate after Week 
3 and before Week 18. The potential rescue treatment during the Dose-evaluation Phase 
provides the opportunity to assess if two high-dose courses of NewGam (2.0 g/kg) will convert 
previous non-responders (stable or deteriorating patients) in the low or medium NewGam 
dosage arms to responders. Patients in the 2.0 g/kg NewGam arm will drop-out if they are stable 
at Week 6 or deteriorating after Week 3 and before Week 21. 
Measures will be taken to ensure that the sponsor, the evaluating Investigator and all parties 
involved in the conduct of the trial will remain blinded. 
3.3.2 Control Group(s) 
Since the placebo-controlled ICE study, which confirmed the beneficial results from earlier 
trials that were much smaller and shorter in duration, led to the licensure of the Gamunex IGIV 
brand in the US, it is not ethically justified to conduct additional large placebo-controlled 
studies with other IGIV brands. Further, with corticosteroids and plasma exchange there are 
also different treatment options available that have proven beneficial for this chronic disease 
[16,18], and Investigators and patients would be reluctant to participate. One higher (2.0 g/kg) 
and one lower (0.5 g/kg) dosage of NewGam serve as the study’s internal control with the lower 
dose being putatively not sufficient for certain patients to remain stable or improve, thus 
mimicking a placebo arm to some extent. 
The responder rates (improvement in adjusted INCAT score at Week 24) from the ICE and 
PRIMA studies will be used to compare the rates found in ProCID. Both used the current 
standard dose of 1.0 g/kg IGIV every 3 weeks that is also used in ProCID for the evaluation of 
the primary endpoint. 
3.3.3 Target Parameters 
Because of the pleiotropic mechanisms of action of polyvalent immunoglobulin preparations, 
the exact mode(s) of action that lead(s) to the beneficial effects of IGIV in CIDP patients is/are 
not yet fully understood. Potential mechanisms of IGIV include blocking of antibodies, B-cells, 
T-cells, and macrophages at multiple sites, neutralization of activated complement, modulation 
of pro-inflammatory cytokines, and influence on cell migration, thus resulting in 
immunomodulation. The current hypothesis assumes that multiple effects of IGIV act in concert 
to evoke the beneficial effects seen in patients with neuro(auto)immunological diseases. 
The chosen safety parameters are commonly used to obtain safety information on IGIV 
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4 
STUDY POPULATION 
4.1 
Population Base 
Male or female patients of ≥ 18 to < 80 years of age with documented diagnosis of CIDP by a 
neurologist specialized/experienced in neuromuscular diseases will be enrolled in this study. 
Eligible patients need to fulfill the definite or probable EFNS/PNS criteria for CIDP [12] and 
must have an adjusted INCAT disability score between 2 and 9. 
4.1.1 Inclusion Criteria 
Patients who meet all of the following criteria are eligible for the study: 
1. Patients with diagnosis of definite or probable CIDP according to the EFNS/PNS 
Guideline 2010 [12]; including patients with Multifocal Acquired Demyelinating 
Sensory And Motor Neuropathy (MADSAM) or pure motor CIDP  
2. Patients currently depending on treatment with immunoglobulins or corticosteroids 
3. Patients with active disease, i.e. not being in remission, who are progressive or relapsing 
prior to trial start or during the Wash-out Phase 
4. Weakness of at least 2 limbs 
5. ≥ 18 to < 80 years of age 
6. Adjusted INCAT disability score between 2 and 9 (with a score of 2 coming exclusively 
from leg disability) 
7. Voluntarily given, fully informed written consent obtained from patient before any 
study-related procedures are conducted 
4.1.2 Exclusion Criteria 
Patients who do meet any of the following criteria are not eligible for the study: 
1. Unifocal forms of CIDP 
2. Pure sensory CIDP  
3. MMN with conduction block [12] 
4. Patients who previously failed immunoglobulin treatment 
5. Treatment with immunomodulatory/suppressive agents (cyclosporin, methotrexate, 
mitoxantrone, mycophenolate mofetil or azathioprine) during the six months prior to 
baseline visit 
6. Patients on or treated with rituximab, alemtuzumab, cyclophosphamide, or other 
intensive chemotherapeutic regimens, previous lymphoid irradiation or stem cell 
transplantation during the 12 months prior to baseline visit 
7. Respiratory impairment requiring mechanical ventilation 
8. Myelopathy or evidence of central nervous system demyelination or significant 
persisting neurological deficits from stroke, or central nervous system (CNS) trauma 
9. Clinical evidence of peripheral neuropathy from another cause such as 
a. connective tissue disease or systemic lupus erythematosus (SLE) 
b. HIV infection, hepatitis, Lyme disease 
c. cancer (with the exception of basal cell skin cancer) 


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d. IgM paraproteinemia with anti-myelin associated glycoprotein antibodies 
10. Diabetic neuropathy 
11. Cardiac insufficiency (New York Heart Association [NYHA] III/IV), cardiomyopathy, 
significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic 
heart disease  
12. Severe liver disease (ALAT 3x > normal value) 
13. Severe kidney disease (creatinine 1.5x > normal value) 
14. Hepatitis B, hepatitis C or HIV infection 
15. Thromboembolic events: patients with a history of deep vein thrombosis (DVT) within 
the last year prior to baseline visit or pulmonary embolism ever; patients with 
susceptibility to embolism or DVT 
16. Body mass index (BMI) ≥40 kg/m2 
17. Patients with uncompensated hypothyroidism (abnormally high Thyroid-Stimulating 
Hormone [TSH] and abnormally low Thyroxine [T4]) or known vitamin B12 deficiency 
if they don’t receive adequate substitution therapy 
18. Medical conditions whose symptoms and effects could alter protein catabolism and/or 
IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome) 
19. Known IgA deficiency with antibodies to IgA 
20. History of severe hypersensitivity, e.g. anaphylaxis or severe systemic response, to 
immuno-globulin, blood or plasma derived products, or any component of NewGam 
21. Known blood hyperviscosity, or other hypercoagulable states 
22. Use of other blood or plasma-derived products within three months prior to Visit 2 
23. Patients with a past or present history of drug abuse or alcohol abuse within the 
preceding five years prior to baseline visit 
24. Patients unable or unwilling to understand or comply with the study protocol 
25. Participation in another interventional clinical study with IMP treatment currently or 
during the three months prior to Visit 2 
26. Women who are breast feeding, pregnant, or planning to become pregnant, or are 
unwilling to use an effective birth control method (such as implants, injectables, 
combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or 
vasectomized partner) while on study 
4.2 
Prior and Concomitant Therapy 
Details of any prior (up to 12 months before screening for all CIDP related treatments; up to 
3 months for all others) and concomitant medication (drug and non-drug therapy, such as 
physical therapy taken throughout the study) must be recorded in the source documentation and 
the electronic case report form (e-CRF). 
4.2.1 Prior Therapy 
Prior treatment with first-line CIDP therapies (IGIV or corticosteroids) is required (at least 
3 months on stable dosage). 


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Treatment with azathioprine is permitted if patients have been taking it for ≥12 months prior to 
Visit 2 (Baseline) on a stable dose: such patients should continue taking the same dose during 
the trial. 
Patients should not require the use of pre-medication for IGIV infusions to treat tolerability 
problems of IGIVs. 
Medications not particularly permitted or forbidden have to be evaluated by the Investigator 
under consideration of possible interactions with the presumed mode of action of IGIV products 
in CIDP. 
4.2.2 Permitted Concomitant Therapy 
Mild forms of pain can be treated with acetaminophen, if required. 
Corticosteroids (prednisolone or equivalent) ≤ 20 mg/day or equivalent (i.e., ≤ 40 mg every 
2 days) on a stable dose during the Dose-Evaluation-Phase are permitted for patients with prior 
corticosteroid therapy. 
4.2.3 Forbidden Concomitant Therapy 
Corticosteroids may not be given as a pre-treatment to alleviate potential tolerability problems. 
Administration of any other blood or plasma-derived product is forbidden and should only be 
given for emergency reasons. Patients will be withdrawn from the study if immunoglobulin 
preparations other than NewGam are administered. 
• Corticosteroids (prednisolone or equivalent) > 20 mg/day or equivalent (i.e., > 40 mg 
every 2 days) 
• PEX 
• Cyclosporin, methotrexate, mitoxantrone, mycophenolate mofetil and interferon or 
other immunosuppressive or immunomodulatory drugs 
• Rituximab, alemtuzumab, cyclophosphamide or other chemotherapeutic regimens 
• Any experimental treatment 
• Regulatory Authorities discourage the use of pre-medication in clinical trials designed 
to evaluate the safety of biologic products, except in cases where such pre-medication 
is important to the safety of the trial patients. Therefore any routine pre-medication to 
alleviate potential tolerability problems is disallowed. However, patients who 
experience 2 consecutive infusion-related AEs that are likely to be prevented by pre-
medication are permitted to receive antipyretics, antihistamines, or antiemetic drugs. 
Non-steroidal anti-inflammatory drugs (NSAIDs) can affect renal function and should 
be avoided. 
NewGam must not be mixed with other medicinal products; a separate intravenous line should 
be used in such cases. 
4.3 
Assignment of Patients to Treatment Groups 
For each patient screened, the Investigator or designee will enter the center number and the 
month and year of birth into an interactive web response system (IWRS) or another comparable 
electronic system. The IWRS will allocate the next available screening ID, ensuring that 


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screening IDs are assigned sequentially per center. The screening ID will be a 6-digit number 
with the first two digits being the country code (e.g. “49” for Germany), the next two digits 
identifying the center (01, 02, …) and the last two digits the sequence number assigned by the 
IWRS (01, 02, …) for each site continuously. Leading zeros will be used for center and patient 
numbers below 10. The second patient screened at center 4 in Germany would e.g. be identified 
as 490402.  
The Investigator will enter the information – month and year of birth and the associated 
screening ID – into the confidential patient identification list. 
If the patient qualifies, randomization will be done centrally through the IWRS after 
deterioration, i.e., at start of the Dose-evaluation Phase, after all inclusion and exclusion criteria 
have been checked again and the patient is still found eligible. The IWRS will ensure balance 
of allocation by means of a stratified block design, using the treatment before enrollment 
(immunoglobulin or corticosteroids treatment) as strata. The fact that a patient has been 
randomized will be reported immediately and automatically by the system to the Investigator, 
the contract research organization (CRO) and the sponsor. The result of randomization, i.e. the 
treatment group assignment, will however only be reported to the hospital pharmacist or 
designee by a dedicated email that no other trial personnel will have access to. 
The patient will be identified by the previously assigned screening ID throughout the trial, no 
additional patient or randomization number will be used. 
No randomization results will be transmitted to the sponsor to comply with the double-blind 
character of this study. The responsible monitor will be informed of new patients enrolled 
automatically by the IWRS system via email.  
Under no circumstances are patients who enroll in the study permitted to re-enroll. 
4.4 
Withdrawal and Replacement of Patients 
4.4.1 Premature Patient Withdrawal 
For any discontinuation after study entry, the Investigator will obtain all the required details 
and document the reason(s) for discontinuation in the CRF. If the reason for withdrawal of a 
patient is an AE, the main specific event or laboratory test will be recorded in the CRF, and the 
Investigator will make thorough efforts to clearly document the outcome. 
Patients have the right to withdraw from the study at any time for any reason, without the need 
to justify their decision. The Investigator also has the right to withdraw patients from the study 
in case of AEs, poor compliance, or other reasons. Since an excessive rate of withdrawal can 
render the study non-interpretable, the unnecessary withdrawal of patients must be avoided. 
Should a patient decide to withdraw, the Investigator will make the best efforts to complete and 
report the observations. The Investigator will document the reason(s) for withdrawal of each 
patient in the electronic Case Report Form (eCRF). 
Patients who terminate the study prematurely are drop-outs. The Investigator has to organize 
the pre-termination visit.  
Reasons for premature termination of patients may be: 
• Withdrawal of patient’s consent (e.g. due to ineffective therapy in case of deterioration) 
• Pregnant patients will be immediately excluded from the study 


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• Investigator’s opinion that the patient may be severely harmed if he/she continues trial 
participation, namely by the treatment and procedures according to the study protocol 
• Occurrence of a disease which interferes with the study treatment or represents an 
exclusion criterion 
• Administration of IGIV other than NewGam. 
4.4.2 Patient Replacement Policy 
Only in case of a withdrawal portion in excess of 10%, patients will be replaced, unless the 
planned number of patients in the respective dose group has been achieved already. A 
replacement patient will be assigned to the same treatment group as the withdrawn patient. 
Patients withdrawn from the study because of safety reasons will not be replaced. 


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5 
INVESTIGATIONAL MEDICINAL PRODUCT(S) 
5.1 
Treatment Compliance 
5.1.1 Drug Dispensing and Accountability 
Any IMP provided to the site will be accounted for. This includes IMP received at the site and 
IMP dispensed to patients. 
NewGam will be delivered to the participating centers/pharmacists by the Sponsor or designee. 
A Drug Inventory and Dispensing Log will be kept current by the Investigator/pharmacist, 
detailing the dates and quantities of IMP received and dispensed to each patient and the 
remaining quantity.  
The inventory and dispensing log will be available to the unblinded monitor to verify drug 
accountability during the study.  
Unused IMP can be destroyed at the study site or returned to the Sponsor for destruction. 
Destruction can be initiated only after accountability has been verified and fully reconciled by 
the monitor and after the Sponsor has granted written approval of destruction. Empty or 
partially used bottles should be destroyed at the study site following local policies after the peel-
off label has been removed and stuck to the drug accountability form. 
When saline has been used for patients on low or medium IGIV dosage, the product name and 
batch number have to be recorded on the drug accountability form in addition to the tear-off 
label of the NewGam bottle. 
5.1.2 Assessment of Treatment Compliance 
All patients will be infused at the study site under the surveillance of authorized study 
personnel. Infusion details will be documented together with the batch number(s) on the drug 
accountability form kept by the pharmacist or designee, which will be checked regularly by the 
unblinded monitor. 
5.2 
Characterization of Investigational Product(s) 
NewGam is a 10% IGIV ready for intravenous administration. NewGam is made from a pool 
of at least 1000 donations of human fresh-frozen plasma per batch. During the manufacturing 
process of NewGam, significant viral reduction is obtained via a combination of S/D treatment 
and 20 nm nanofiltration. In addition, the Source Q chromatography (ion-exchange 
chromatography) step in the NewGam manufacturing process contributes significantly to the 
viral safety of NewGam. The S/D method is highly effective against enveloped viruses, while 
the 20 nm nanofiltration is effective against both, enveloped and non-enveloped viruses. A 
further phenomenon which contributes to the viral safety of NewGam is neutralization by the 
present antibodies. The efficacy of the virus inactivation procedures has been extensively 
validated according to relevant international guidelines in place. The composition with the most 
important ingredients and the biochemical characteristics are summarized in the Investigators’ 
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5.3 
Packaging and Labeling 
NewGam is delivered as ready-to-use solution in glass bottles. 
Each NewGam bottle will be labeled as follows: 
 
EU Master Label – NewGam: 
FOR CLINICAL TRIAL USE ONLY 
Study: NGAM-08 
NewGam 
Unit size: ______ mL 
 
1 mL contains: 100 mg protein of which ≥ 95% is human normal immunoglobulin. 
Infusion solution for intravenous administration. 
To be stored at +2°C to +8°C and protected from light. Must not be frozen. 
Must be inspected visually for particulate matter and discoloration prior to administration. Do not 
use non-homogenous solutions or those that have a deposit. 
To be warmed up to room or body temperature before use. 
Dosage: see study protocol Section 5.5  
EudraCT number: 2015-005443-14 
Investigator:   _________________________________________________ 
Sponsor: OCTAPHARMA PPG, Oberlaaer Str. 235, 1100 Vienna, Austria, Tel: 
 
CRO:   _________________________________________________ 
Batch no.: ______________ 
Expiration date: __________________ 
Final labeling will be in compliance with the national requirements of each country where the 
study will be conducted. 
After transfer and pooling into infusion bags, the medication (NewGam or 0.9% saline solution) 
will be blinded with an overpouch and re-labelled. The following labels will be used for sending 
the medication from the pharmacy/clinic to the ward: 
 
 
 
 
 
 
 
 
 


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EU Master Label – Overpouch for infusion bags: 
FOR CLINICAL TRIAL USE ONLY 
Study: NGAM-08 
NewGam OR Sodium Chloride 0.9% w/v solution 
 
 
Volume: ______ mL 
 
1 mL contains: 100 mg protein of which ≥ 95% is human normal immunoglobulin OR sodium 
chloride 0.9% w/v solution. 
Infusion solution for intravenous administration. 
To be stored at +2°C to +8°C (see study protocol Section 5.4). Must not be frozen. 
To be warmed up to room temperature before use. 
Dosage: see study protocol Section 5.5 
Pat. number: |__|__|__|__|__|       Infusion week:  |____|  Bag number: |__| of |__| 
Date and time of preparation: __________________ 
Use by (date and time): __________________ 
Any unused solution residues or waste material to be disposed according to local requirements at 
the study site. 
EudraCT number: 2015-005443-14 
Investigator:   _________________________________________________ 
Sponsor: OCTAPHARMA PPG, Oberlaaer Str. 235, 1100 Vienna, Austria, Tel: 
 
CRO:   _________________________________________________ 
Final labeling will be in compliance with the national requirements of each country where the 
study is to be conducted. 
5.4 
Conditions for Storage and Use 
NewGam should be stored and transported light-protected at +2°C to +8°C (36°F to 46°F) and 
must not be frozen. 
NewGam must not be used after its expiration date. 
Authorized personnel at the individual study centers/pharmacies will ensure that the IMPs are 
stored under appropriate conditions with restricted access and in compliance with national 
regulations. 
5.5 
Dose and Dosing Schedule 
NewGam is available in glass bottles with different volumes of human immunoglobulin. Glass 
bottles of different content should be combined in order to reach the required amount of IgG 
(split into infusions of 0.5 g/kg and 1.0 g/kg to maintain blinding). The total amount per patient 
should be dosed exactly. Partially used bottles must be discarded. 
All patients should be clinically assessed for being adequately hydrated prior to infusion.  
In the Dose-evaluation Phase, all patients will receive a loading dose of 2.0 g/kg Newgam 
(administered over two consecutive days), followed by seven infusions of the maintenance dose 
the patient has been randomized to (0.5, 1.0 or 2.0 g/kg NewGam), also administered over two 
consecutive days every 3 weeks (±4 days). If a patient is randomized to receive the low or 
medium NewGam dose, the same volume with the same infusion rate as would have been 
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supplemented with an authorized 0.9% w/v isotonic sodium chloride solution as appropriate 
and detailed in the following infusion bag split to maintain the blinding: 
Treatment Arms 
Infusion Bag Content 
 
Day 1 
Day 2* 
0.5 g/kg NewGam 
0.5 g/kg NewGam + 
0.5 g/kg saline 
1.0 g/kg saline 
1.0 g/kg NewGam 
0.5 g/kg NewGam + 
0.5 g/kg NewGam 
1.0 g/kg saline 
2.0 g/kg NewGam 
0.5 g/kg NewGam + 
0.5 g/kg NewGam 
1.0 g/kg NewGam 
* Volume of Day 2 may be split up using 2 bags 
The following infusion schedule must be adhered to in the Dose-evaluation Phase [all doses per 
kg body weight; rescue treatment only for patients who had been on 0.5 or 1.0 g/kg NewGam 
before, patients on 2.0 g/kg before will drop-out]: 
 
1. Patients deteriorating* after Week 3 and before Week 6 or being stable** at Week 6 
Week 0 
Week 3 
Week 6 
Week 9 
Week 12 
2.0 g 
(LD) 
0.5g 
1.0 g 
2.0 g (RT) 2.0 g (RT) 
EOS  
2.0 g 
EOS 
 
 
 
2. Patients deteriorating* after Week 6 and before Week 9 
Week 0 
Week 3 
Week 6 
Week 9 
Week 12 
Week 15 
2.0 g 
(LD) 
0.5g 
1.0 g 
0.5g 
1.0 g 
2.0 g (RT) 2.0 g (RT) 
EOS 
2.0 g 
2.0 g 
EOS 
 
 
 
3. Patients deteriorating* after Week 9 and before Week 12 
Week 0 
Week 3 
Week 6 
Week 9 
Week 12 
Week 15 
Week 18 
2.0 g 
(LD) 
0.5g 
1.0 g 
0.5g 
1.0 g 
0.5g 
1.0 g 
2.0 g (RT) 2.0 g (RT) 
EOS 
2.0 g 
2.0 g 
2.0 g 
EOS 
 
 
 
4. Patients deteriorating* after Week 12 and before Week 15 
Week 0 
Week 3 
Week 6 
Week 9 
Week 12 
Week 15 
Week 18 
Week 21 
2.0 g 
(LD) 
0.5g 
1.0 g 
0.5g 
1.0 g 
0.5g 
1.0 g 
0.5g 
1.0 g 
2.0 g (RT) 2.0 g (RT) 
EOS 
2.0 g 
2.0 g 
2.0 g 
2.0 g 
EOS 
 
 
 
5. Patients deteriorating* after Week 15 and before Week 18 
Week 0 
Week 3 
Week 6 
Week 9 
Week 12 
Week 15 
Week 18 
Week 21 
Week 24 
2.0 g 
(LD) 
0.5g 
1.0 g 
0.5g 
1.0 g 
0.5g 
1.0 g 
0.5g 
1.0 g 
0.5g 
1.0 g 
2.0 g (RT) 2.0 g (RT) 
EOS 
2.0 g 
2.0 g 
2.0 g 
2.0 g 
2.0 g 
EOS 
 
 
LD – Loading Dose, RT – Rescue Treatment, EOS – End-of-Study-Visit 
*   = adjusted INCAT disability score increase of at least 1 point 
** = adjusted INCAT disability score remains unchanged 


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5.6 
Preparation and Method of Administration 
All NewGam or saline vials/bottles necessary to achieve the calculated amount according to the 
body weight of the patient must be pooled by the hospital pharmacist or designee in three 
separate infusion bags to be administered at 2 consecutive days. NewGam must not be mixed 
with other medicinal products or saline - the saline solution may be administered after 
NewGam in the same intravenous line. For other IV products a separate IV line must be used. 
The preparation should be performed under aseptic conditions using a sterile bench, as 
described in the manual handed out to the hospital pharmacist or designee. The infusion bags 
can then be stored for up to 24 hours at +2°C to +8°C (36°F to 46°F). IMP prepared without 
the use of a laminar air flow must be administered within 3-4 hours after preparation.  
Each bottle of NewGam must be examined visually by the pharmacist or designee for 
particulate matter and discoloration prior to pooling. Non-homogenous solutions or those that 
have a deposit must not be pooled. The same procedures should be performed also for saline. 
The infusion bags must be allowed to warm to room or body temperature prior to infusion. The 
same holds true for saline for patients on the low and medium (standard) NewGam dosages. 
Patients must be monitored and carefully observed for any symptoms throughout the infusion 
period and at least 1 hour thereafter.  
The special warnings and precautions for use (see Investigator's Brochure) of NewGam must 
be respected. 
The initial infusion rate will be 0.01 mL/kg/min (60 mg/kg/hr) for the first 30 minutes; if 
tolerated, advanced to 0.02 mL/kg/min (120 mg/kg/hr) for the next 30 minutes; if tolerated, 
advanced to 0.04 mL/kg/min (240 mg/kg/hr) for the next 30 minutes; if tolerated, advanced to 
0.08 mL/kg/min (480 mg/kg/hr) for the next 30 minutes and, if tolerated, advanced to 0.12 
mL/kg/min (720 mg/kg/hr) for the remainder of the infusion. From the third infusion on, the 30 
minutes interval for the 0.02 to 0.08 mL/kg/min infusion rates may be shortened to 15 minutes 
as per the discretion of the investigator. 
If AEs occur during infusion, the rate is to be reduced to half the rate at which the event 
occurred, or the infusion interrupted until symptoms subside. The infusion may then be resumed 
at a rate tolerated by the patient. 
5.7 
Treatment Duration 
In the Dose-evaluation Phase, all patients will receive a loading dose of 2.0 g/kg NewGam 
followed by seven times the dosage they were randomized to (0.5, 1.0 or 2.0 g/kg NewGam). 
Patients in the 0.5 and 1.0 g/kg NewGam arms being clinically stable until Week 6 (i.e. with 
unchanged adjusted INCAT disability score compared to baseline) will receive further infusions 
of 2.0 g/kg NewGam at Week 6 and 9, still keeping the blind. Patients who deteriorate (i.e. with 
increase in adjusted INCAT disability score of at least 1 point) after Week 3 and before Week 
18 will receive two infusions of 2.0 g/kg NewGam at the next two consecutive 3-week intervals 
(earliest at Week 6 and latest at Week 21). Afterwards they will continue with the regular 
termination visit. Patients deteriorating after Week 18 will drop-out and have their Termination 
Visit at Week 21; patients deteriorating after Week 21 will drop-out and have their Termination 
Visit at Week 24. 


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5.8 
Blinding, Emergency Unblinding and Breaking the Study Blind 
The Investigators will be provided with an unblinding procedure to disclose the actual treatment 
of a particular patient in case of medical emergency. Blinding in individual patients should not 
be broken only in case of a serious adverse event or unexpected ADR, when knowledge of the 
type of the administered IMP is required for therapeutic decisions regarding this event. 
However the decision and the responsibility to break the treatment code in emergency situations 
resides solely with the investigator. In the event of medical emergency to keep subject safety, 
the investigator is able to unblind a patient immediately by accessing the IWRS system without 
needing a PIN code and without needing to contact any third party. 
To maintain blinding in the Dose-evaluation Phase, infusions will be given in three infusion 
bags (corresponding to a volume of 0.5 g/kg, 0.5 g/kg and 1.0 g/kg NewGam or saline). Thus, 
the old label will be discarded together with the vial/bottle, and a new label will be fixed onto 
an opaque overpouch by the hospital pharmacist or designee. The order of the infusion bags 
will be added on the label: on Day 1 of an infusion visit the NewGam infusion bag 
(corresponding to 0.5 g/kg NewGam) comes first, then the second infusion bag (corresponding 
to 0.5 g/kg NewGam or matching saline) and last, at the following Day 2, the large infusion bag 
(corresponding to 1.0 g/kg NewGam or matching saline). Volume of Day 2 may be split up 
using two infusion bags instead of one. 
An overpouch (normally used for light protection) will be put over each infusion bag to 
maintain blinding. The new labels will be identical for both, NewGam and saline, so that the 
content of the bags is only known to the unblinded hospital pharmacist or designee. An example 
of this label can be found above in Section 5.3.  
The hospital pharmacist or designee will send the 3 infusion bags per patient (potentially 
already fixed to the opaque infusion line) to the ward on the corresponding days. At the ward, 
the infusions will be given according to the order stated on the label (“1 of 3”, “2 of 3”, on Day 
1 and “3 of 3” on Day 2). To further assure the double-blind character of this study, the 
physician or designee who applies the medication to the patient will not be involved in any 
other evaluations other than drawing blood samples or checking for vital signs, i.e. will not be 
involved in any patient ratings (e.g. INCAT, I-RODS, NCS, grip strength). In parallel, all 
Investigators for the electrophysiological or neurological evaluations will not be involved in 
the application of the medication. 
Blinding of the patient: The patient will be blinded to the medication throughout the entire 
study. Because of the opaque (non-transparent) infusion line and overpouches, the patient will 
not be able to see the medication he/she is treated with.  
Therefore, patients deteriorating (increase in adjusted INCAT disability score of at least 1 point) 
in the 0.5 and 1.0 g/kg NewGam arms after Week 3 and before Week 18 or remaining stable 
(unchanged adjusted INCAT disability score from baseline) by Week 6, and thus receiving 2 
additional treatments with 2.0 g/kg NewGam, will continue with all study procedures as 
described in this protocol and will remain blinded as no serious safety issues are expected 
related to these procedures for patients continuing with NewGam treatment, while patients on 
2.0 g/kg NewGam will drop-out if they deteriorate or are stable at Week 6. 
The local study file will contain code break envelopes (or detailed instructions for the electronic 
equivalent thereof). If paper envelopes are used, the monitor will check the envelopes at each 
visit. Any breaking of the blind has to be documented with date, time, person, and reason. 


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The Investigator has to notify the Sponsor as soon as possible about the unblinding of a patient. 
5.9 
Subsequent Therapy 
In case a patient decides to withdraw from the study or is withdrawn by the Investigator, he/she 
may continue with the treatment he/she has received before study participation or with another 
standard of care. 
5.10 Relevant Protocol Deviations 
Deviations from the protocol should not occur. If deviations occur, the Investigator should 
promptly inform the Monitor and the implication of the deviation must be reviewed and 
discussed. Any deviation must be documented, stating the reason and date, the action taken, 
and the impact for the patient and/or the trial. The documentation must be kept in the 
Investigator’s Trial File and the Sponsor’s file. 
Examples of relevant protocol deviations that will be addressed are: 
• Patients who entered the study even though they did not satisfy the entry criteria 
• Patients who developed withdrawal criteria during the study 
• Patients who received the wrong treatment or incorrect dose 
• Patients who received an excluded concomitant treatment (e.g. IGIV other than NewGam). 
In case of any major protocol deviations or violations the Investigator and Octapharma will 
decide on the further participation of the patient in this study, after having discussed all relevant 
aspects.  
A list of all included patients with all deviations from the intended study procedures and other 
criteria that may affect the patient's validity for statistical analysis will be prepared upon clinical 
completion of the study. This will then be discussed by a panel consisting of the clinical project 
manager, a medical expert of the Sponsor, the data manager, the study biometrician and the 
Steering Committee. This panel will decide upon the membership of the patient in the ITT and 
PP efficacy and safety populations for statistical analysis. 


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6 
STUDY CONDUCT  
A signed informed consent form must be available before the start of screening activities. 
The schedule of all visits is applicable for all patients of all treatment arms. 
6.1 
Observations by Visit 
6.1.1 Screening (Visit 1; duration up to 21 days, i.e. Week -15 to -12) 
Patients have to be informed about the study details and have to give their written informed 
consent. Prior to treatment initiation, patients will have to be screened for eligibility (inclusion 
and exclusion criteria). This includes general physical/neurological examination, vital signs and 
medical history assessment. Also, electrophysiological recordings (NCS of 4 right sided and 4 
left-sided motor nerves) to confirm the diagnosis of definite or probable CIDP will be done as 
part of the in-/exclusion criteria evaluation. Women of childbearing potential (WOCBP) must 
have a negative pregnancy test to be eligible for the study. At Visit 2, 3, 4, 5, 6, 7, 8, 9 and 
Termination Visit a pregnancy test should be performed only if required by local requirements.  
If feasible, screening should be completed within three weeks. However, screening results 
should be available as soon as possible but might take up slightly longer until also the results 
of the centrally evaluated NCS (by 
) become available. Based on 
the screening results, the patients’ eligibility for the study is determined, and a patient could 
proceed with the Wash-out Phase, if he/she is eligible. 
Screening failures will be entered into the eCRF. 
The following assessments will be performed during screening: 
• Obtaining voluntarily given, written (signed and dated) informed consent 
• Medical history and prior/concomitant medication 
• Physical/neurological examination 
• Vital signs (including body weight and height) 
• Inclusion and exclusion criteria 
• Standard ECG  
• Urinalysis  
• Blood sample (5 mL) for viral markers 
• Blood samples (10 mL) for safety laboratory (hematology and clinical chemistry) 
• Pregnancy test 
• Grip strength  
• Adjusted INCAT disability score 
• I-RODS 
• MRC sum score 
• Modified FSS 
• PI-NRS 
• NCS 
• SF-36 


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6.1.2 Procedures During the Wash-out Phase of the Study  
Eligible patients will have to enter a Wash-out Phase of up to 12 weeks, i.e., they have to 
decrease their current medication (immunoglobulins or corticosteroids; see Section 3.2). In this 
Phase the medication will successively be reduced until the patient deteriorates.  
For patients on corticosteroids, no scheduled or required study evaluations/visits will take place 
during the Wash-out Phase. However the patients must inform the investigator whenever they 
notice any symptom of disease worsening at any time during the Wash-out Phase and must 
come to the site for assessment of deterioration. If deterioration cannot be confirmed, the Wash-
out Phase will continue. 
Patients on immunoglobulin treatment will have to visit the study site (e.g. IGIV every three 
weeks) for their infusions. Thus, from these patients concomitant medications and AEs will be 
recorded. 
6.1.3 Procedures During the Dose-evaluation Phase of the Study 
Only patients who deteriorate during the Wash-out Phase (active patients) will visit the study 
site and enter the Dose-evaluation Phase after randomization. All other patients who do not 
have active disease will not be eligible for enrollment into ProCID and will discuss their further 
treatment possibilities with their treating physician. 
Visit 2 (Week 0; up to 12 weeks after Screening end; Baseline for Dose-evaluation Phase) 
All patients who deteriorate during the Wash-out Phase will be rechecked for eligibility and, if 
positive, will be treated with 2.0 g/kg NewGam. At this time they will also be randomized to 
one of three NewGam dosages employed. The following assessments will be performed: 
Before infusion: 
• Physical/neurological examination 
• Confirm eligibility (in-/exclusion criteria) 
• Randomization and enrollment 
• Blood sample (5 mL) for viral markers 
• Blood samples (15 mL) for safety laboratory (serum IgG, hematology and clinical 
chemistry) 
• Grip strength  
• Adjusted INCAT disability score 
• I-RODS 
• MRC sum score 
• Modified FSS 
• PI-NRS 
• NCS 
• PGIC scale 
During and after infusion: 
• Administration/Infusion of IMP (2.0 g/kg NewGam) 
• SF-36 (during infusion) 


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• Vital signs (including body weight) before, at least once during and after infusion 
• Monitoring of adverse events (AEs) 
• Documentation of concomitant medication 
Visits 3, 4, and 5 (Week 3, 6, and 9) 
The following assessments will be performed: 
Before infusion: 
• Blood sample(s) (15 mL) for safety laboratory (serum IgG, hematology and clinical 
chemistry) 
• Grip strength  
• Adjusted INCAT disability score 
• I-RODS  
• PI-NRS 
During and after infusion: 
• Administration/Infusion of IMP (0.5, 1.0 or 2.0 g/kg NewGam) 
• Vital signs before, at least once during and after infusion 
• Monitoring of adverse events (AEs) 
• Documentation of concomitant medication 
Visit 6 (Week 12) 
The following assessments will be performed:  
Before infusion: 
• Physical/neurological examination 
• Blood samples (15 mL) for safety laboratory (serum IgG, hematology and clinical 
chemistry) 
• Grip strength  
• Adjusted INCAT disability score 
• I-RODS 
• MRC sum score 
• Modified FSS 
• PI-NRS 
• NCS 
During and after infusion: 
• Administration/Infusion of IMP (0.5, 1.0 or 2.0 g/kg NewGam) 
• SF-36 (during infusion) 
• Vital signs (including body weight) before, at least once during and after infusion 
• Monitoring of adverse events (AEs) 
• Documentation of concomitant medication 


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Visits 7, 8 and 9 (Week 15, 18 and 21) 
The following assessments will be performed: 
Before infusion: 
• Blood sample(s) (15 mL) for safety laboratory (serum IgG, hematology and clinical 
chemistry) 
• Grip strength  
• Adjusted INCAT disability score 
• I-RODS 
• PI-NRS 
During and after infusion: 
• Administration/Infusion of IMP (0.5, 1.0 or 2.0 g/kg NewGam) 
• Vital signs before, at least once during and after infusion 
• Monitoring of adverse events (AEs) 
• Documentation of concomitant medication 
End of Study (Final) Examination 
The final examination is performed three weeks after the last IMP administration (regularly at 
Visit 10 scheduled for Week 24 for responders), which can be either the last dose as 
randomized, or the last rescue dose. 
The following investigations will be performed: 
• Physical/neurological examination 
• Blood sample (5 mL) for viral markers 
• Blood samples (15 mL) for safety laboratory (serum IgG, hematology and clinical 
chemistry) 
• Urinalysis  
• Grip strength  
• Adjusted INCAT disability score 
• I-RODS 
• MRC sum score 
• Modified FSS 
• PI-NRS 
• NCS 
• SF-36 
• Monitoring of adverse events (AEs) 
• Documentation of concomitant medication 


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After the Final Examination, the clinical study is considered completed for the patient. No 
further study-related assessments will be performed, unless safety concerns (e.g., ongoing AEs) 
require follow-up. 
6.1.4 Procedures during the Rescue Treatment 
This section is only applicable for patients in the 0.5 and 1.0 g/kg NewGam arms, namely 
a) for patients deteriorating after Week 3 and before Week 18 or 
b) for patients being stable until Week 6 
Depending on the time point when deterioration is detected or at Week 6 for patients remaining 
stable, the Rescue Treatment is initiated. 
During the Rescue Treatment patients receive two doses of 2.0 g/kg NewGam in a 3-week 
interval; first dose at the visit when the deterioration is detected, or at the visit in Week 6 for 
patients remaining stable, the second dose three weeks later. 
Please refer to Section 5.5 for an overview on dosing if a Rescue Treatment is required. 
Visit procedures at the Rescue Treatment follow essentially the same process as described for 
corresponding visits. 
Three weeks after the second rescue dose the study termination visit is performed. 
6.1.5 Interpretation of Time Windows in this Study 
For this study the following time windows apply: 
Time point 
Time stated 
Tolerance 
Interval between visits 
3 weeks 
± 4 days 
Vital signs 
before IMP administration 
≤ 60 minutes 
Vital signs 
after IMP administration 
≤ 60 minutes 
6.2 
Duration of Study 
6.2.1 Planned Duration for an Individual Patient 
The duration of the entire study for each patient will be between >9 and up to 39 weeks and 
consists of the following: approximately 3 weeks for Screening, up to 12 weeks for the Wash-
out Phase and 24 weeks for the Dose-evaluation Phase (for patients who deteriorate at the end 
of the 12-week Wash-out Phase and who are continued responders during the Dose-evaluation 
Phase). The minimal duration could be >9 weeks after Screening (for patients in the 2.0 g/kg 
arm deteriorating after being only a few days in the Wash-out Phase and being stable until Week 
6 or deteriorating by then as they will not receive rescue treatment but drop-out). Thus, the 
length of the Dose-evaluation Phase can vary between 6 and 24 weeks, while the length of the 
Wash-out Phase can vary between >0 and 12 weeks. 
6.2.2 Planned Duration for the Study as a Whole 
The study will be considered completed, when all patients have completed the study termination 
visit.  


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The study as a whole should be completed within 30 months. The estimated start of the study 
(enrollment of first patient) is Q1 2017 with the estimated end of the study (last visit of last 
patient) being Q4 2019. The enrollment period is projected to last approximately 20 months. 
6.2.3 Premature Termination of the Study 
Both the Investigator and the Sponsor reserve the right to terminate the study at any time. 
Should this be necessary, the procedures will be arranged on an individual study basis after 
review and consultation by both parties. In terminating the study, the Sponsor and the 
Investigator will ensure that adequate consideration is given to the protection of the patients' 
interests. 
Regulatory authorities and IECs/IRBs should be informed according to national regulations. 
Early termination of the study as a whole or center-wise may apply for the following reasons: 
Clinical Study: 
At any time the study as a whole will be terminated prematurely if: 
• New toxicological or pharmacological findings or safety reports invalidate the earlier 
positive benefit-risk-assessment. 
Study Centre: 
At any time the study can be terminated at an individual center if: 
• The center cannot comply with the requirements of the protocol. 
• The center cannot comply with ICH-GCP E6 standards. 
• The center’s first patient is not recruited by 24 weeks after initiation of the center. 
• The required recruitment rate is not met. 
Should the study be prematurely terminated, all study materials (including IMP etc.) must be 
returned to the Sponsor. 


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7 
ASSESSMENTS AND METHODS 
7.1 
Background / Baseline Information 
The following information will be captured at Screening and upon enrollment: 
Demographics: including gender, age, weight and height (calculated Body Mass Index [BMI]), 
and ethnic origin. 
Relevant medical and neurological history: obtained by interviewing the patient and by 
performing a physical examination. 
Previous and concomitant medication: obtained by interviewing the patient and retrieving the 
Patients Global Impression of Change (PGIC) 
Disease status: obtained by adjusted INCAT disability score, I-RODS (disability score), grip 
strength (measured by Martin Vigorimeter), MRC sum score (impairment scale), modified FSS 
(fatigue scale), PI-NRS (pain score), NCS (electrophysiological recordings) 
Quality of Life: assessed by SF-36 
7.2 
Efficacy Assessments 
All participating centers will be trained by a third party in the assessment of the following 
efficacy endpoints: 
• Nerve Conduction Studies (NCS) by 
  
• Adjusted INCAT disability scale, I-RODS, modified FSS, PI-NRS, MRC sum score and 
grip strength by 
. 
7.2.1 Assessments for Primary Efficacy Endpoints 
7.2.1.1 Adjusted INCAT Score (Disability Score) 
Functional disability will be assessed by an adjusted INCAT disability score at each visit. The 
adjusted score is identical to the INCAT disability score with a range from 0 (no disability) to 
10 (maximum disability), except for the exclusion of changes in upper limb function from 0 
(normal) to 1 (minor symptoms) or from 1 to 0, because these changes were judged by the 
regulatory authorities as not being clinically significant in the patients in the recently published 
ICE trial. However, all other 1-point steps in either the arm or the leg scale represented clinically 
meaningful changes in disability. The original INCAT disability score has an arm and a leg 
grade, both with a score range from 0 to 5.[38] 
7.2.2 Assessments for Secondary Efficacy Endpoints 
7.2.2.1 I-RODS (Disability Scale) 
A great variety of disability scales have been applied as primary outcome measures in immune-
mediated neuropathy trials. The recently developed patient-reported Inflammatory Rasch-built 
Overall Disability Sum Score (I-RODS) using the concept of minimum clinically important 
differences using the individually obtained standard errors (MCID-SE) as reported very 
recently [27,39], which is the first outcome measure that captures activity and participation 
limitations in patients with immune-mediated neuropathies, will be employed in this study. The 


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I-RODS fulfils all modern clinimetric requirements and its use is therefore suggested in future 
clinical trials in these conditions.[27] Patients’ dynamics will be captured using the MCID-SE 
concept as previously described. 
7.2.2.2 Grip Strength (Muscle Strength) 
Grip strength of both hands (assessed by the best of 3 attempts with a Martin Vigorimeter, a 
hand-held dynamometer to measure grip strength) will be determined at each visit. This tool 
has demonstrated to be more sensitive than the INCAT score in detecting significant 
improvement or deterioration.[40] 
7.2.3 Assessments of Exploratory Efficacy Endpoints 
All the exploratory parameters are commonly used in studies of this kind and also in daily 
clinical practice. 
7.2.3.1 MRC Sum Score (Impairment Scale) 
The MRC sum score is an impairment scale that assesses motor impairment and is widely used 
in patients suffering from peripheral neuropathies.  
The MRC sum score is a summation of the MRC grades (range 0–5) given in full numbers of 
the following muscle pairs: upper arm abductors, elbow flexors, wrist extensors, hip flexors, 
knee extensors, and foot dorsal flexors.[41] The MRC sum score ranges from 0 (“total 
paralysis”) to 60 (“normal strength”). The individual MRC grades range from 0 = no movement, 
1 = flicker, 2 = movement in the absence of gravity, 3 = movement against gravity, 4 = 
movement against gravity and resistance and 5 = full movement. Recently, the ability of 
physicians to differentiate between the various MRC has been examined and a proposed Rasch-
built 4-grades modified version has been proposed, since physicians demonstrated having great 
difficulty differentiating between the various grades. However, as part of the current study, 
extensive training will be given providing > 100 illustrative pictures standardizing the 
assessment of MRC grades. [29] Both, the traditional and newly proposed grades will be 
assessed as part of the current study. 
7.2.3.2 Modified FSS Scale (Fatigue Scale) 
Fatigue is a major disabling complaint in patients with immune-mediated neuropathies like 
CIDP.[42] The 9-item Fatigue Severity Scale (FSS) has been used to assess fatigue in these 
conditions, despite having limitations due to its classic test theory construct. The authors were 
able to construct a 7-item linearly weighted Rasch-built modified FSS scale for proper 
assessment of fatigue in future studies in patients with immune-mediated neuropathies. The use 
of its sum score (ranging from 0 [no fatigue] to 21 [most severe fatigue]) is suggested, since the 
data also fit the rating scale model.[43] 
A research manual will be provided to all participating centers presenting elegantly the various 
parts of the selected measures. 
7.2.3.3 Pain Intensity Numeric Rating Scale (Assessment of Pain) 
The Pain Intensity Numeric Rating Scale (PI-NRS, a numeric scale where 0 = no pain and 
10 = worst possible pain) is an 11–point scale for patient self-reporting of pain. 


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7.2.3.4 Nerve Conduction Studies (Electrophysiological Measurements) 
A pre-specified secondary endpoint in the study will be the change from baseline to the last 
measurement in the sum of the distal evoked amplitude of 4 right sided and 4 left sided motor 
nerves (peroneal, tibial, ulnar and median). All additional NCS analyses are considered 
exploratory (e.g. individual nerve analysis).  
Electromyograph (EMG) will not be performed. 
The NCS will be conducted in a standardized fashion, and a central neurology core laboratory 
will monitor the NCS for quality control.  
The electrophysiological core lab has developed a standard electrophysiological operations 
manual (SOM) for each study site. All methodological details such as filter settings, rules for 
supramaximal stimulation, gain and sweep speed settings for tracing measurement, etc. are 
outlined comprehensively in the SOM. 
Motor nerve studies: The median motor nerve will be tested using stimulation at the wrist and 
elbow; the ulnar motor nerve will be tested using stimulation at the wrist and below the elbow; 
the peroneal motor nerve will be tested using stimulation at the ankle and below the fibular 
head; and the tibial motor nerve will be tested using stimulation at the ankle. F-wave latencies 
will be tested in all nerves with a minimum of 10 stimulations.  
Parameters measured for the motor responses will include distal and proximal onset latency, 
amplitude (baseline-to-peak), velocity, duration (from the onset of the waveform to the return 
to baseline), area (calculated by the computer), and F-wave latency.  
All original nerve conduction tracings will be reviewed in a blinded fashion by the core 
electrophysiology laboratory for all pertinent information and for adherence to the standardized 
measures set out in the study protocol and in the study operations manual provided to each 
study site. Prior to enrolling patients with CIDP, each study site will perform nerve conduction 
testing on two healthy controls (one man and one woman). All nerves will be tested on each 
control subject during two separate visits to ensure technical reliability. Commercially available 
EMG equipment will be employed as long as required functions were part of the equipment 
(e.g., hard copy tracings and averaging capabilities). Motor calibrations will be performed at 
the beginning of each set of NCS for each patient. Limb temperatures will be recorded on the 
original tracings before and after the study, and temperature control equipment (warming water 
bath, heating pads, heating blanket, or radiant lamp) will be used for NCS to ensure a minimum 
temperature of 32°C over digit 2 and 31°C on the toe. Careful attention to distance 
measurements is mandated, and standardized stimulation sites for each nerve are employed by 
all Investigators. Approval of each site’s reference (control) NCS will be in place prior to testing 
of any patient with CIDP in the study.  
7.2.3.5 SF-36 Health Survey (Quality of Life Assessment) 
The SF-36 Health Survey generic health survey will be used for assessing quality of life 
(www.sf-36.org/; www.qualitymetric.com). The SF-36 is a multi-purpose, short-form health 
survey with only 36 questions. It yields an 8-scale profile of functional health and well-being 
scores as well as psychometrically-based physical and mental health summary measures and a 
preference-based health utility index. The SF-36 is the most widely evaluated generic patient 
assessed health outcome measure being used in more than 200 diseases and conditions. It has 
been validated in multiple diseases and languages and has been used successfully in more than 


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600 randomized clinical trials reported in over 240 scientific and medical journals. The SF-36 
has been proven responsive in 44 disease conditions and is accepted by the FDA as proof of 
benefit for improved functioning and other patient-reported outcomes. The SF-36 is available 
in 103 language translations. 
The SF-36 has mental (4) and physical (4) component subscales. All 8 individual subscales will 
be measured but the principal analysis will be on the physical component summary score which 
is expected to be the most relevant for this patient population. 
7.3 
Safety Assessments 
Any of the following drug safety information shall be collected: 
Adverse events (AEs) and serious adverse events (SAEs) temporally associated with 
administration of IMP or saline solution (definitions and reporting requirements see Sections 
7.3.1 and 7.3.2) 
Pregnancies, drug overdose, interaction, medication error, lack of efficacy, post-study SAEs 
(see Section 7.3.6) 
7.3.1 Adverse Events 
7.3.1.1 Definitions 
Adverse event (AE): An AE is any untoward medical occurrence in a study patient receiving 
an IMP and which does not necessarily have a causal relationship with this treatment. An AE 
can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of an IMP, whether or not 
related to the IMP. 
Adverse drug reaction (ADR): An ADR is any noxious and unintended response to an IMP 
related to any dose. The phrase “response to an IMP” means that a causal relationship between 
the IMP and an AE carries at least a reasonable possibility, i.e., the relationship cannot be ruled 
out. 
Other significant AEs: Any marked laboratory abnormalities or any AEs that lead to an 
intervention, including withdrawal of drug treatment, dose reduction or significant additional 
concomitant therapy. 
Withdrawal due to AE/ADR: AE/ADR leading to discontinuation of treatment with IMP. Any 
such events will be followed up by the Investigator until the event is resolved or until the 
medical condition of the patient is stable. All follow-up information collected will be made 
available to the Sponsor. 
7.3.1.2 Collection 
The condition of the patient will be monitored throughout the study. At each visit, whether 
scheduled or unscheduled, AEs will be elicited using a standard non-leading question such as 
“How have you been since the last visit / during the previous study period?” In addition, the 
patient diaries (if applicable) will be checked by the Investigator for any documented event. 
Any AE or ADR which occurs during the study will be noted in detail on the appropriate pages 
of the eCRF. If the patient reports several signs or symptoms, which represent a single 


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syndrome or diagnosis, the latter should be recorded in the eCRF. The Investigator responsible 
will grade the severity of all AEs or ADRs (mild, moderate or severe), the seriousness (non-
serious or serious) and causality, as defined below (Sections 7.3.1.3, 7.3.1.4 and 7.3.2). The 
Sponsor is responsible to assess the expectedness of each ADR (expected or unexpected), as 
defined below (Section 7.3.1.4). 
In the event of clinically significant abnormal laboratory findings, the tests will be repeated and 
followed-up until they have returned to normal and/or an adequate explanation is available. 
Diseases, signs and symptoms and/or laboratory abnormalities already existing before the first 
administration of IMP are not considered as AEs when observed at a later stage unless they 
represent an exacerbation in intensity or frequency (worsening). 
The Investigator responsible should always provide detailed information concerning any 
abnormalities and the nature of, and reasons for any necessary action(s), as well as any other 
observations or comments, which are useful for the interpretation and understanding of the 
patients’ AEs or ADRs. 
7.3.1.3 Severity 
The intensity/severity of all AEs will be graded as follows: 
• mild: an AE, usually transient, which causes discomfort but does not interfere with the 
patient’s routine activities; 
• moderate: an AE which is sufficiently discomforting to interfere with the patient’s 
routine activities; 
• severe: an AE which is incapacitating and prevents the pursuit of the patient’s routine 
activities. 
Grading of an AE is up to the medical judgment of the Investigator and will be decided on a 
case by case basis. 
7.3.1.4 Causality 
The relationship of AEs to the administered IMP will be assessed by the Investigator: 
• probable: reports including good reasons and sufficient documentation to assume a 
causal relationship, in the sense of plausible, conceivable, likely, but not necessarily 
highly probable. A reaction that follows a reasonable temporal sequence from 
administration of the IMP; or that follows a known or expected response pattern to the 
suspected medicine; or that is confirmed by stopping or reducing the dosage of the 
medicine and that could not reasonably be explained by known characteristics of the 
patient’s clinical state. 
• possible: reports containing sufficient information to accept the possibility of a causal 
relationship, in the sense of not impossible and not unlikely, although the connection is 
uncertain or doubtful, for example because of missing data or insufficient evidence. A 
reaction that follows a reasonable temporal sequence from administration of the IMP; 
that follows a known or expected response pattern to the suspected medicine; but that 
could readily have been produced by a number of other factors. 
• unlikely: reports not following a reasonable temporal sequence from IMP 
administration. An event which may have been produced by the patient’s clinical state 
or by environmental factors or other therapies administered. 


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• not related (unrelated): events for which sufficient information exists to conclude that 
the etiology is unrelated to the IMP. 
• unclassified: reports which for one reason or another are not yet assessable, e.g. because 
of outstanding information (can only be a temporary assessment). 
Classification of ADRs: 
ADRs will be classified by the Sponsor as either expected or unexpected: 
• expected: an ADR that is listed in the current edition of the Investigator's Brochure (or 
other reference safety information). 
• unexpected: an ADR that is not listed in the current edition of the Investigator's 
Brochure or other reference safety information, or that differs because of greater severity 
or greater specificity. 
7.3.1.5 Outcome 
The outcome of all reported AEs has to be documented as follows: 
1. recovered, resolved 
2. recovering, resolving 
3. not recovered, not resolved 
4. recovered, resolved with sequelae 
5. fatal 
6. unknown 
NOTE: A patient’s death per se is not an event, but an outcome. The event which resulted in 
patient’s death must be fully documented and reported, even in case the death occurs within 4 
weeks after IMP treatment end, and without respect of being considered treatment-related or 
not. 
7.3.1.6 Action(s) taken 
AEs requiring action or therapy must be treated with recognized standards of medical care to 
protect the health and well-being of the patient. Appropriate resuscitation equipment and 
medicines must be available to ensure the best possible treatment in an emergency situation. 
The action taken by the Investigator must be documented: 
a) 
in general 
- 
none 
- 
medication (other than IMP) or other (e.g., physical) therapy started 
- 
test performed 
- 
other (to be specified) 


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b) 
on IMP 
- 
none 
- 
product withdrawn 
- 
dose reduced 
- 
dose increased 
The Investigator will follow-up each AE until it is resolved or until the medical condition of 
the patient is stable, and all relevant follow-up information will be reported to the Sponsor. 
7.3.2 Serious Adverse Events 
A serious AE (SAE) is any untoward medical occurrence that at any dose: 
• results in death, 
• is life-threatening, 
• requires hospitalization or prolongation of existing hospitalization, 
• results in persistent or significant disability/incapacity, 
• is a congenital anomaly/birth defect, 
• is another important medical event. 
NOTE: The term "life-threatening" refers to an event in which the patient was — in the view 
of either the reporting Investigator or the Sponsor — at immediate 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. 
Medical judgment should be exercised in deciding whether an adverse event/reaction is serious 
in other situations: Important AEs/ADRs that are not immediately life-threatening or do not 
result in death or hospitalization but may jeopardize the patient or may require intervention to 
prevent one of the other outcomes listed in the definitions above, should also be considered 
serious.  
In addition, although not classified under the seriousness criteria, all suspected transmissions 
of an infectious agent should be reported as SAE. A suspected virus transmission means that 
virus antigen has been detected in the patient. A passive transmission of antibodies alone does 
not constitute a suspected virus transmission. 
SAE reporting timelines 
All SAEs, whether suspected to be related to study treatment or not, are to be reported by 
telephone, fax or e-mail immediately to the Clinical Project Manager or designee.  
Contact details will be communicated at the study initiation visit. 
An Octapharma "Serious Adverse Event Report" must be completed and submitted within 
24 hours after recognition of the event. 


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All SAEs should additionally be reported to 
Octapharma’s Central Drug Safety Unit: 
OCTAPHARMA Pharmazeutika Produktionsges.m.b.H. 
Oberlaaer Strasse 235, 1100 Vienna, Austria 
Fax: 
 
E-mail: 
 
24 hours emergency telephone number:  
Europe: 
 
USA: 
 
Waiver from SAE reporting requirement: 
These exceptions/waivers include surgeries that are elective or planned before study entry, 
hospitalization because of study-related procedures or prolongation of the existing 
hospitalizations due to economic or social reasons, but not medical reasons. These should not 
be considered as SAEs. 
7.3.3 Laboratory Safety Tests 
Laboratory determinations will be done at a central laboratory. 
The following parameters will be investigated during the study period as specified in Section 
6.1 “Observations by visit”: 
Clinical chemistry: Na+ (sodium), K+ (potassium), glucose, ALAT/ALT/GPT (alanine 
aminotransferase), ASAT/AST/GOT (aspartate aminotransferase), LDH, total bilirubin, BUN 
(blood urea nitrogen), creatinine, albumin 
Hematology: hematocrit, hemoglobin, complete blood count (CBC) with differential 
(erythrocytes/RBC, leukocytes/WBC, neutrophils, eosinophils, basophils, lymphocytes, 
monocytes, platelets)  
Serum IgG 
Urinalysis: protein, pH, glucose, ketones, leukocytes, hemoglobin and blood will be tested in 
urine by dipstick test (middle stream urine will be used) 
Pregnancy test: Urine pregnancy test; if positive, a serum pregnancy test will be performed at 
central laboratory. 
Blood sampling will take place prior to infusion of NewGam. The methods used for each 
parameter and the normal ranges of each determination will be provided in the Clinical Study 
Report. 
7.3.4 Viral Safety Tests 
Viral marker samples will be taken at screening, before the first NewGam infusion at Visit 2 
and at the termination visit. Viral safety will be determined by serology tests for HIV, HBV and 
HCV at the central laboratory.  
A screening and termination visit retention sample will be collected and stored frozen at ≤-70°C 
at the central laboratory for possible future testing.  


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7.3.5 Vital Signs and Physical Examination 
To evaluate short-term tolerance, close monitoring of vital signs including pulse and respiratory 
rate, blood pressure and body temperature will be performed at time points specified in Section 
6.1. Measurements will be carried out before the start of each infusion, at least once during each 
infusion, and up to 1 hour after end of infusion. Hemodynamic changes may occur during IGIV 
infusion and minor changes in pulse and blood pressure are frequent. For this reason, only 
changes in vital signs considered clinically significant by the Investigator are to be reported as 
AEs. In case fever occurs, temperature will be measured every morning until the body 
temperature is normalized. Fever will be defined as a body temperature >37.8 °C orally, >38.2 
°C rectally, >38 °C axillary, >38.2 °C tympanic, and has to be documented as an AE. 
Weight will be recorded at each infusion visit and reported to the pharmacist or designee as it 
is needed for the preparation of the next study medication dosage by the unblinded pharmacist 
or designee 3 weeks later. Height will be measured at baseline. 
7.3.6 Other Relevant Safety Information 
Post study related safety reports: 
Any SAE which occurs up to four weeks after the last IMP administration should be reported 
by the Investigator to the Sponsor if the Investigator becomes aware of it. Proactive monitoring 
for post study SAEs is not required. 
If a post study SAE is identified, the Investigator should complete an SAE form. Relation to 
the clinical study should be stated on the report. 
If a patient dies within 4 weeks after the last IMP administration, this should be reported as 
well, regardless of being considered treatment-related or not.  
Pregnancies: 
Every effort will be made to avoid a pregnancy during the use of an IMP. WOCBP using an 
acceptable effective contraceptive method during the study will be enrolled.  
WOCBP is defined as fertile woman, following menarche and until becoming post-menopausal 
unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral 
salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 
12 months without an alternative medical cause.  
Acceptable effective contraceptive measures include the following: 
• combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation (oral, intravaginal, transdermal) 
• progestogen-only hormonal contraception associated with inhibition of ovulation (oral, 
injectable, implantable)  
• progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mode of action 
• intrauterine device 
• intrauterine hormone-releasing system 
• bilateral tubal occlusion 
• vasectomised partner 


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• sexual abstinence 
• male or female condom with or without spermicide 
• cap, diaphragm or sponge with spermicide 
Pregnancies occurring during the study (fetal exposure to the IMP) need to be reported.  
In case of pregnancy during the study the Investigator is asked to complete the pregnancy 
notification form and to send it (by fax) to the CPM or designee. 
Follow-up information on the outcome of both mother and fetus will be requested by a Sponsor 
representative. 
Overdose, interaction, misuse, medication error and lack of efficacy: 
The following safety relevant information should be reported as an AE or, if the reaction fulfils 
one of the criteria for seriousness, as a SAE. 
Drug overdose: 
An overdose is a deliberate or inadvertent administration of a treatment at a dose higher than 
that specified in the protocol, and higher than the known therapeutic dose and of clinical 
relevance. The reaction must be clearly identified as an overdose. 
Interaction: 
A drug interaction is a situation in which a substance/medicinal product affects the activity of 
an IMP, i.e., the effects are increased or decreased, or they produce an effect that none of the 
products exhibits on its own. The reaction must be clearly identified as drug interaction. 
Misuse: 
Misuse is the deliberate administration or use of the medicinal product outside its described 
indication or outside the current state of the art medical practice (off-label-use). The reaction 
must be clearly identified as misuse. 
Medication error: 
Medication error involves the inadvertent administration or unintended use of a medicinal 
product which may be caused by the naming, presentation of pharmaceutical form/packaging, 
instructions for use/labelling. The reaction must be clearly identified as a medication error. 
 


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8 
DATA HANDLING AND RECORD KEEPING 
8.1 
Documentation of Data 
8.1.1 Source Data and Records 
Source data are defined as all the information related to clinical findings, observations, or other 
activities in the study, written down in original records or certified copies of original records 
allowing reconstruction and evaluation of the clinical study. 
The Investigator will maintain adequate source records (e.g., case histories or patient files for 
each patient enrolled). Source records should be preserved for the maximum period of time 
required by local regulations. 
For each patient enrolled, the Investigator will indicate in the source records that the patient 
participates in this study. 
All data entered into the eCRF must be supported by source data in the patient records with the 
exceptions listed in Section 8.1.2. 
The Investigator will permit study-related monitoring, audit(s), IEC/IRB review(s) and 
regulatory inspection(s), by providing direct access to source data/records. 
The Investigator may authorize site staff (e.g., sub-Investigators, nurses) to enter study data into 
the eCRF. This must be documented in the „Delegation of Authority Log“, signed by the 
Investigator. 
8.1.2 Electronic Case Report Forms 
For each patient enrolled, an electronic CRF (eCRF) will be completed within the Electronic 
Data Capture (EDC) system and approved by the Investigator or an authorized sub-Investigator.  
Study site staff (e.g. research nurse) will be responsible for entering patient data into the 
validated EDC system. All site personnel will be trained on the EDC system and study specific 
eCRFs prior to receiving access to the live database for data entry. The site is also provided 
with the approved eCRF Completion Guidelines which will assist in data entry and data 
issues/questions. The site will be notified once the database is active to begin data entry. 
Additional site training may be provided as refreshers throughout the study, if needed. All 
persons allowed to enter or change eCRF data must appear on the delegation of authority log. 
8.1.3 Changes to Case Report Form Data 
Monitors will perform source data verification (SDV) as defined for the study. 
If any errors or discrepancies in the eCRFs are found during data entry or review, discrepancies 
will be generated programmatically within the EDC system, and ‘manual’ queries will be 
generated by either a monitor or Data Management.  
Discrepancies and queries can only be corrected by the Investigator(s) or other authorized site 
personnel. An audit trail documents all changes to the data over the entire study period. If the 
reason for a change is not obvious, a comment must be supplied within the query’s response, 
stating the reason for the change, prior to closing. The study monitor should provide guidance 
to Investigator(s) and the Investigator(s)’ designated representatives on making such 
corrections.  


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Once queries have been resolved by the site staff, the resolutions are assessed by Data 
Management. If the query response provided confirms the data as correct, the discrepancy will 
be closed. If the response does not adequately address the question raised, a new query will be 
issued for further clarification. 
Manual checks are performed and programs are run throughout the study until the data is clean 
and the database is ready for lock. All discrepancies will be resolved prior to database lock. 
There will be a final run of the programmed checks to ensure all discrepancies are closed out, 
SDV will be confirmed as complete by the monitor, and all eCRFs will be approved by the 
Investigator prior to database lock. 
8.2 
Information of Investigators 
An Investigator’s Brochure will be handed out to the Investigator before the start of the study. 
This Brochure contains all information in the Sponsor’s possession necessary for the 
Investigator to be fully and accurately informed about the safety of the IMP under evaluation 
and the respective benefit-risk ratio. 
The Investigator’s Brochure will be updated by the Sponsor at regular intervals and in case new 
information concerning the IMP becomes available. 
The Investigators will be informed about the methods for rating relevant study outcomes and 
for completing CRFs in order to reduce discrepancies between participating Investigators and 
study sites. 
The Investigator will be kept informed of important data that relate to the safe use of the IMP 
as the study proceeds. 
8.3 
Responsibilities 
The Sponsor provides the study medication (NewGam). In this role, the Sponsor can be 
contacted in case of medical issues and is responsible for the assessment of the reported SAEs 
as well as for the further distribution to the relevant regulatory authorities.  
The Co-ordinating Investigator of this study is 
  
The Principal Investigator is accountable for the conduct of the clinical study. Responsibilities 
may be delegated to appropriately qualified persons.   
A „Delegation of Authority Log“ will be filled in and signed by the Principal Investigator. In 
accordance with this authority log, study site staff (e.g., sub-Investigators, nurses) is authorized 
to perform tasks relating to the study. 
Monitoring will either be done by the Sponsor or by a subcontractor (to be appointed later). 
Study data management and statistics and EDC system will be delegated under an agreement 
of transfer of responsibilities to an external CRO and/or third party vendor. All Octapharma 
procedures and policies have to be met by this CRO/third party vendor, discrepancies or 
exceptions are to be approved by Octapharma's Manager of Biometrics. 
An Independent Data Monitoring Committee (IDMC) will be installed to observe the safety 
throughout the trial. The detailed obligations and procedures will be laid down in a written 
procedure provided by the Sponsor. 


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All laboratory tests (hematology, clinical chemistry, virology and urinalysis) will be done 
centrally. 
NCS will be centrally reviewed by 
. 
All parties involved in the study are responsible to comply with local and international 
obligations, regulatory requirements and duties in accordance with local laws, ICH-GCP E6 
and GLP guidelines, SOPs and other applicable regulations. 
8.4 
Investigator’s Site File 
At each study site, the Investigator is responsible for maintaining all records to enable the 
conduct of the study to be fully documented. Essential documents as required by ICH-GCP E6 
guidelines and regulations (e.g., copies of the protocol, study approval letters, all original 
informed consent forms, a blank print-out of the e-CRF, drug dispensing and accountability 
logs, correspondence pertaining to the study, etc.) should be filed accurately and kept by the 
Investigator for the maximum period of time required by local regulations. 
The Investigator is responsible for maintaining a confidential patient identification code list, 
which provides the unique link between named source records and eCRF data for the Sponsor. 
The Investigator must arrange for the retention of this confidential list for the maximum period 
of time required by local regulations. 
No study document should be destroyed without prior written agreement between the 
Investigator and the Sponsor. Should the Investigator elect to assign the study documents to 
another party, or move them to another location, the Sponsor must be notified in writing. 
8.5 
Provision of Additional Information 
On request, the Investigator will supply the Sponsor with additional data relating to the study, 
or copies of relevant source records, ensuring that the patient’s confidentiality is maintained. 
This is particularly important when errors in data transcription are encountered. In case of 
particular issues or governmental queries, it is also necessary to have access to the complete 
study records, provided that the patient’s confidentiality is protected in accordance with 
applicable regulations. 
8.6 
Independent Data Monitoring Committee 
An Independent Data Monitoring Committee (IDMC) will be established by the Sponsor. The 
IDMC will be composed of recognized experts in the field of peripheral neuropathy who are 
not actively recruiting patients. 
The IDMC will review relevant data periodically during the study and will give advice on the 
continuation, modification or termination of the study. A written study specific procedure will 
define in detail the composition, responsibilities and procedures of the IDMC. 
8.7 
Steering Committee 
A Steering Committee will be established to medically/scientifically advice and guide the 
Sponsor during the study progress. The Steering Committee will be responsible for overall 
study overview, may give recommendations for protocol amendments after discussion with the 
Sponsor and may be involved in publication writing together with the DMC members and Co-


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ordinating Investigator. It will consist of at least three national coordinating investigators and/or 
internationally well-known CIDP experts with experience in conducting clinical trials.  
 


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9 
STATISTICAL METHODS AND SAMPLE SIZE 
The statistical analysis will be delegated under an agreement of transfer of responsibilities to 
an external CRO. All Octapharma procedures and policies have to be met by this CRO. 
Discrepancies or exceptions are to be approved by the Sponsor's Manager of Biometrics. 
9.1 
Determination of Sample Size 
The sample size calculation is based on the proportion of responders in the 1.0 g/kg dose group. 
This dose regimen is the currently most commonly used for maintenance IGIV doses in CIDP. 
Recent experiences with this dosing regimen are available from the ICE study [24] and the 
PRIMA trial.[25] In both of these studies, the lower confidence limit of the 95% Wilson-Score 
confidence interval for the proportion of responders (R) was 42% if rounded to the nearest 
integer, and thus we have also chosen 42% as the threshold for the following pair of hypotheses 
for evaluation of the primary endpoint: 
H0: R < 0.42 
H1: R ≥ 0.42 
This will be tested by comparing the lower limit of the 95% Wilson-Score confidence interval 
for the observed proportion of responders with the pre-defined threshold of 0.42. 
We estimate the true percentage of responders in CIDP patients treated with NewGam as 60%. 
This corresponds to the 60.7% of responders observed in the PRIMA study, but is higher than 
the outcome in the ICE (54.2%), that in the opinion of many experts underestimates the true 
percentage of responders. 
We applied these parameters to a computer simulation realized in SAS to determine the 
statistical power associated with various group sizes: 
 


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To achieve a power of at least 80%, a minimum of 62 evaluable patients in the 1.0 g/kg dose 
group will be needed; to account for possible dropouts we plan to enroll 70 patients into this 
group. 
In order to allow for the comparison between dose groups, ProCID will enroll half of the eligible 
patients in the standard dose arm (1.0 g/kg NewGam) and the other half into the lower and 
higher dose arms (0.5 g/kg and 2.0 g/kg NewGam), resulting in a total of 124 evaluable patients, 
and an enrollment target of 140 patients overall (ratio: 1:2:1 for 0.5 g/kg, 1.0 g/kg, and 2.0 g/kg, 
respectively). 
9.2 
Statistical Analysis 
A formal statistical analysis plan describing all details of the analyses to be performed will be 
prepared by the study statistician and approved by the Sponsor prior to unblinding and the start 
of the statistical analysis. 
Data tabulations will comprise the results for the different dose groups and for the whole 
analysis set whenever appropriate. Evaluation of primary and secondary endpoints will be 
presented for each randomization stratum (prior treatment with Immunoglubulins or 
Corticosteroids) separately to facilitate the identification of noteworthy differences in the 
clinical responses between these two groups.  No further subgroup analyses are pre-specified 
for this study, but the different CIDP variants eligible for enrollment, such as Multifocal 
Acquired Demyelinating Sensory And Motor Neuropathy (MADSAM) or pure motor CIDP, 
will be compared with respect to dose group, INCAT score and proportion of response as well. 
If indicated by the data, further comparisons between these CIDP variants will be added post-
hoc.  
9.2.1 Population for Analysis 
The following populations will be considered for the statistical analysis: 
The safety set (SAF) will include all randomized patients who received at least part of one 
infusion of IMP. 
The full analysis set (FAS) is defined according to the intention-to-treat principle, and will 
include all patients of the SAF who satisfy all major entry criteria – in particular the diagnosis 
of CIDP – and for whom any data was collected post infusion of IMP. Every treated subject 
will be considered in the analysis according to his randomized treatment/dose assignment. 
The per-protocol set (PPS) – being a subset of the FAS — will exclude patients with significant 
protocol deviations, which may have an impact on the evaluation of the primary study outcome 
parameter(s). This is the set of patients who participated in the study as intended and for whom 
the primary efficacy endpoint can be evaluated as planned. 
All protocol deviations documented during the conduct of the study or identified at the data 
review process prior to DB lock will be reviewed and classified with respect to its effect on the 
planned analysis. Only protocol violations with the potential to significantly affect the study 
results or to invalidate the interpretation of the data obtained will lead to exclusion of patients 
from the PPS. This classification of protocol violations is the joint responsibility of the clinical 
study manager, the study statistician, and Octapharma’s responsible medical expert, and will 
be performed and documented before the database is locked, the data is unblinded, and the 
statistical analyses are performed. 


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Protocol deviations to be considered will include (but are not limited to): 
• Deviations of the study entry criteria 
• Administration of any other blood or plasma-derived product or of any other 
immunoglobulin preparations 
• Any prohibited concomitant medication 
• Failure to attend two scheduled consecutive visits OR three or more scheduled visits 
during the study for reasons other than clinical reasons 
The analysis of safety will be based on the safety set. 
The evaluation of primary objective(s) will be performed for the FAS (intention-to-treat 
analysis) and for the PPS (per-protocol analysis). The ITT analysis is considered to be the most 
relevant, and will be presented first in the statistical report. 
The evaluation of secondary objectives will be performed for the FAS, and in addition for the 
PPS in case the two populations differ by more than 5% 
9.2.2 Efficacy Analysis Plan 
Efficacy will be evaluated by a variety of commonly used parameters to assess the severity and 
progression of CIDP, with the adjusted INCAT disability score being the most important 
parameter. The primary efficacy endpoint will thus be the proportion of responders in the 
1.0 g/kg NewGam arm, where a responder is defined as a patient with a decrease of at least 1.0 
point on the adjusted INCAT disability score at Week 24 relative to Baseline. 
Confirmatory statistical testing of the primary endpoint will be done by constructing the 95% 
Wilson-Score confidence interval for the proportion of responders, and comparing the lower 
confidence limit with the predefined threshold of 0.42. This corresponds to a one-sided test of 
the following pair of hypotheses at the α=0.025 confidence level. 
H0: R < 0.42 
H1: R ≥ 0.42 
Where R is the proportion of responders i.e. the number of patients in the FAS who are 
responders according to the abovementioned definition, divided by the total number of patients 
in the FAS. 
This evaluation will also be presented for the PPS to assess the robustness of the primary study 
endpoint with respect to protocol violations. 
To assess and compare the effectiveness of the different dose groups, these will be presented 
side-by-side in descriptive statistics, including the 95% confidence intervals for the proportion 
of responders. In addition the response rates in the alternative dose groups will be compared 
descriptively to the 1.0 g/kg treatment group by presenting the confidence intervals for the 
differences; furthermore an exploratory logistic regression, that includes the pre-treatment as 
well as the dose group as predictor variables, will be conducted. 
All efficacy endpoints detailed in Sections 3.1.2 and 3.1.3 will be summarized by means of 
descriptive statistics, presented graphically as appropriate, and listed in full detail. Tables and 
graphs will allow for direct comparison of the different dose groups whenever feasible. A 
similar logistic regression as for the primary endpoint will also be used for the secondary 
response variables (based on grip strength or I-RODS scores). 


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9.2.3 Safety Analysis Plan 
The safety analysis will comprise descriptive statistics, tabulations and listings of all treatment 
emergent adverse events (TEAEs), safety laboratory results, viral markers, vital signs, physical 
examination findings, and any other relevant safety information as detailed in Section 7.3. 
9.2.3.1 Adverse Events 
All reported AEs will be coded according to Medical Dictionary for Regulatory Activities 
(MedDRA). 
An AE is defined as treatment-emergent, if first onset or worsening is after start of the first IMP 
administration. Only TEAEs are accounted for in the analysis. 
A TEAE will be considered to be temporally associated with the infusion (or ‘infusional’) if it 
starts during or within 72 hours of the end of the infusion. 
Incidences of TEAEs will be given as numbers and percentages of patients and infusions with: 
• Any TEAE 
• Any serious TEAE 
• Any TEAE probably or possibly related to the trial drug 
• Any severe TEAE 
• Number of infusional TEAEs  
• Number and percentage of infusions temporally associated with one or more TEAE 
• Any withdrawal due to TEAE 
• Any significant TEAE (see Section 7.3.1.1) 
• Any TEAE by MedDRA Preferred Term (PT) 
• Any TEAE by MedDRA System Organ Class (SOC) 
Summary tables for TEAEs will be given by System Organ Class (SOC) and Preferred Term 
(PT). Additionally, TEAEs will be summarized by severity and relationship to study treatment. 
All TEAEs for each patient, including multiple occurrences of the same event, will be listed in 
full detail, including reported term, MedDRA PT and SOC, onset, duration, time to the AE 
occurrence from last dose, causality, dosage, severity, seriousness and actions taken. 
Narratives will be prepared describing each death, other SAEs, and other significant TEAEs 
that are judged to be of special interest because of clinical importance. 
9.2.3.2 Laboratory Safety Tests 
The safety laboratory data (Clinical chemistry, hematology, and urinalysis) will be converted 
to standard units during the data management process. The laboratory data will be listed with 
suitable flags indicating abnormal values (L=Lower than reference range, H=Higher than 
reference range) and clinical significance as judged by the investigator whenever available. 
Summary statistics for the laboratory values as well as their changes from baseline at each time 
point will be tabulated. 
9.2.3.3 Viral Safety tests 
All viral marker results will be listed, and shift tables will be used to identify any possible 
seroconversion during the course of the study. 


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9.2.3.4 Vital Signs 
Vital signs parameters will be summarized by visit, using the standard set of summary statistics 
for both, absolute values and changes from baseline. 
9.2.3.5 Physical Examination 
Shift tables will be used to identify changes in the assessments between visits. New or worsened 
symptoms/findings will be listed individually. 
9.2.3.6 Other Relevant Safety Information 
All additional safety information collected in the study will be listed and reviewed. If judged to 
be of relevance, narratives will be prepared to describe any such results in full detail. 
9.2.4 Handling of Missing Data 
In general, missing data will not be imputed, and all data derivations will be based on observed 
values only. Only in case of missing body weight, the last available weight measurement will 
be used for calculating the dose per kg bodyweight (last observation carried forward). 
If missing values occur in the confirmatory analysis of the primary endpoint in the FAS, they 
will be imputed by worst observed values, i.e. the patient concerned will be analyzed as non-
responder. 
9.3 
Randomization / Stratification / Code Release 
All patients still qualified to participate in the study at Visit 2 will be randomized to one of the 
three treatment arms by an electronic IWRS tool. The randomization will apply a randomization 
ratio of 1:2:1 with respect to the dosage groups of 0.5, 1.0, and 2.0 g/kg of NewGam by means 
of a stratified block design, using the treatment before enrollment (immunoglobulin or 
corticosteroids treatment) as strata and a fixed block size. This will ensure the desired overall 
randomization ratio and avoid random differences between the dosage groups with respect to 
the CIDP treatment used prior to enrollment into the ProCID study. 
The randomization scheme will only be available to the statisticians responsible for creating it, 
and the programmer implementing the scheme into the IWRS system. No information on 
treatment assignment will be communicated to the sponsor or any CRO personnel responsible 
for the conduct of the study or the analysis of data. 
The result of randomization, i.e. the treatment group assignment of individual patients will only 
be reported to the hospital pharmacist or designee by a dedicated email that no other trial 
personnel will have access to. 
Blinding will not be broken while the study is ongoing, unless in case of medical emergencies 
as described in Section 5.8. Only after completion of all procedures related to data cleaning, the 
medical review of the data, the finalization of the statistical analysis plan, the agreement on the 
final patient disposition, and the formal database lock the blind will be broken and the individual 
treatment assignment will be added to the clinical database for analysis. 
 


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9.4 
Interim Analysis 
No interim analysis is planned.  


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10 ETHICAL / REGULATORY, LEGAL AND ADMINISTRATIVE ASPECTS 
10.1 Ethical / Regulatory Framework 
This study will be conducted in accordance with the ethical principles laid down in the 
Declaration of Helsinki. The study protocol and any subsequent amendment(s) will be 
submitted to an Independent Ethics Committee (IEC) / Institutional Review Board (IRB) and 
to the Regulatory Authority. The study will be conducted in compliance with the protocol, ICH-
GCP E6 regulations and applicable regulatory requirements. 
The regulatory application or submission for regulatory approval will be made by the Sponsor 
or designated third party (e.g. CRO) as required by national law and in accordance with 
FDA/Regulatory Authority regulations. 
10.2 Approval of Study Documents 
The study protocol, a sample of the patient information and informed consent form, any other 
materials provided to the patients, and further requested information will be submitted by the 
Sponsor or the Investigator to the appropriate IEC/IRB and the Regulatory Authority. The study 
approval letter must be available before any patient is exposed to a study-related procedure. 
The Sponsor, the Investigator and any third party (e.g., CRO) involved in obtaining approval, 
must inform each other in writing that all ethical and legal requirements have been met before 
the first patient is enrolled in the study. 
10.3 Patient Information Sheet and Informed Consent Form 
The Investigator will obtain freely given written consent from each patient after an appropriate 
explanation of the aims, methods, anticipated benefits, potential hazards and any other aspect 
of the study which is relevant to the patient’s decision to participate. An English master version 
of the patient information sheet and the informed consent form will be translated into local 
languages. The informed consent form must be signed, with name and date and time noted by 
the patient, before the patient is exposed to any study-related procedure, including screening 
tests for eligibility. 
The Investigator will explain that the patients are completely free to refuse to enter the study or 
to withdraw from it at any time, without any consequences for their further care and without 
the need to justify. The Investigator will complete the informed consent section of the CRF for 
each patient enrolled. 
Each patient will be informed that his/her medical (source) records may be reviewed by the 
study monitor, a quality assurance auditor or a health authority inspector, in accordance with 
applicable regulations, and that these persons are bound by confidentiality obligations. 
10.4 Protocol Amendments 
Any prospective change to the protocol will be agreed between the Investigator (Co-ordinating 
Investigator in multicenter studies) and the Sponsor prior to its implementation. Any such 
amendments will be submitted to the IEC/IRB(s) and/or competent authority responsible as 
required by applicable regulations. IEC/IRB(s) approval will at a minimum be requested for 
any change to this protocol which could affect the safety of the patients, the objective/design of 


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the study, any increase in dosage or duration of exposure to the IMP, an increase in the number 
of patients treated, the addition of a new test or procedure, or the dropping of a test intended to 
monitor safety. 
10.5 Confidentiality of Patients’ Data 
The Investigator will ensure that the patient's confidentiality is preserved. In eCRFs or any other 
documents submitted to the Sponsor, the patients will not be identified by their names, but by 
a unique patient number. Documents not for submission to the Sponsor, i.e., the confidential 
patient identification code list, original consent forms and source records will be maintained by 
the Investigator in strict confidence. 


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11 QUALITY CONTROL AND QUALITY ASSURANCE 
11.1 Periodic Monitoring 
The monitor will contact and visit the Investigator periodically to review all study-related 
source data/records, verify the adherence to the protocol and the completeness, correctness and 
accuracy of all eCRF entries compared to source data. The Investigator will co-operate with the 
monitor to ensure that any discrepancies identified are resolved. 
For this study, the first monitoring visit shall take place shortly after the inclusion of the first 
patient. Thereafter, monitoring frequency will depend on study progress, but is expected to be 
every 10 to 12 weeks depending on the sites’ performance and recruitment rate. 
The monitor must be given direct access to source documents (original documents, data and 
records). Direct access includes permission to examine, analyze, verify and reproduce any 
records and reports that are important to the evaluation of the clinical study. Source data will 
be available for all data in the eCRFs, including all laboratory results. 
11.2 Audit and Inspection 
The Investigator will make all study-related source data and records available to a qualified 
quality assurance auditor mandated by the Sponsor, or to IEC/IRB/regulatory inspectors, after 
reasonable notice. The main purposes of an audit or inspection are to confirm that the rights 
and welfare of the patients have been adequately protected, and that all data relevant for the 
assessment of safety and effectiveness of the IMP have been reported to the Sponsor. 
12 REPORTING AND PUBLICATION 
12.1 Clinical Study Report 
A clinical study report (CSR; in accordance with relevant guidelines and Sponsor’s SOPs) will 
be prepared by the Sponsor or designee after the completion of the study. The Co-ordinating 
Investigator will approve the final study report after review. 
12.2 Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is 
envisaged by an Investigator, the Investigator agrees to inform the Sponsor and to submit all 
manuscripts or abstracts to the Sponsor prior to submission to an editorial board or scientific 
review committee. This will allow the Sponsor to protect proprietary information and to provide 
comments based on information that may not yet be available to the Investigator. 
In accordance with standard editorial and ethical practice, the Sponsor will support publication 
of multicenter studies only in their entirety and not as individual center data. Authorship will 
be determined by mutual agreement. 


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13 LIABILITIES AND INSURANCE 
In order to cover any potential damage or injury occurring to a patient in association with the 
IMP or the participation in the study, the Sponsor will contract insurance in accordance with 
local regulations. 
The Investigator is responsible for dispensing the IMP according to this protocol, and for its 
secure storage and safe handling throughout the study. 


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14 REFERENCES 
 
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van den Bergh PYK, Hadden RDM, Bouche P, Cornblath DR, Hahn A, Illa I, et al. European 
Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of 
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Donaghy M, Mills KR, Boniface SJ, Simmons J, Wright I, Gregson N, et al. Pure motor 
demyelinating neuropathy: deterioration after steroid treatment and improvement with 
intravenous immunoglobulin. JNeurolNeurosurgPsychiatry. 1994;57(7):778-83. 
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Busby M, Donaghy M. Chronic dysimmune neuropathy. A subclassification based upon the 
clinical features of 102 patients. JNeurol. 2003;250(6):714-24. 
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Austin  JH. Recurrent polyneuropathies and their corticosteroid treatment; with five-year 
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Hughes RA, Mehndiratta MM. Corticosteroids for chronic inflammatory demyelinating 
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Van den Bergh PY. Intravenous immunoglobulin (IVIG) in the treatment of chronic 
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Mehndiratta MM, Hughes RAC, Pritchard J. Plasma exchange for chronic inflammatory 
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Couriel D, Weinstein R. Complications of therapeutic plasma exchange: a recent assessment. 
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Koller H, Kieseier BC, Jander S, Hartung HP. Chronic inflammatory demyelinating 
polyneuropathy. New England Journal of Medicine. 2005;352(13):1343-56. 
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Kuitwaard K, van Doorn PA. Newer therapeutic options for chronic inflammatory 
demyelinating polyradiculoneuropathy. Drugs. 2009;69(8):987-1001. 
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Simmons Z, Wald JJ, Albers JW. Chronic inflammatory demyelinating polyradiculoneuropathy 
in children: I. Presentation, electrodiagnostic studies, and initial clinical course, with 
comparison to adults. Muscle Nerve. 1997;20(8):1008-15. 
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Simmons Z, Wald JJ, Albers JW. Chronic inflammatory demyelinating polyradiculoneuropathy 
in children: II. Long-term follow-up, with comparison to adults. Muscle Nerve. 
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Hughes RA, Donofrio P, Bril V, Dalakas MC, Deng C, Hanna K, et al. Intravenous immune 
globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory 
demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. 
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Leger JM, De Bleecker JL, Sommer C, Robberecht W, Saarela M, Kamienowski J, et al. 
Efficacy and safety of Privigen((R)) in patients with chronic inflammatory demyelinating 
polyneuropathy: results of a prospective, single-arm, open-label Phase III study (the PRIMA 
study). J PeripherNervSyst. 2013;18(2):130-40. 
26. 
Merkies IS, van Nes SI, Hanna K, Hughes RA, Deng C. Confirming the efficacy of intravenous 
immunoglobulin in CIDP through minimum clinically important differences: shifting from 
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Draak THP, Vanhoutte EK, van Nes SI, Gorson KC, van der Pol WL, Notermans NC, et al. 
Changing outcome in inflammatory neuropathies: Rasch-comparative responsiveness. 
Neurology. 2014;83(23):2124-32. 
28. 
Sloan JA. Assessing the minimally clinically significant difference: scientific considerations, 
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Vanhoutte EK, Faber CG, van Nes SI, Jacobs BC, van Doorn PA, van KR, et al. Modifying the 
Medical Research Council grading system through Rasch analyses. Brain. 2012;135(Pt 5):1639-
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30. 
Eftimov F, Winer JB, Vermeulen M, de HR, van S, I. Intravenous immunoglobulin for chronic 
inflammatory demyelinating polyradiculoneuropathy. The Cochrane database of systematic 
reviews. 2013;12:CD001797. 
31. 
van Doorn PA, Brand A, Strengers PF, Meulstee J, Vermeulen M. High-dose intravenous 
immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy: a double-
blind, placebo-controlled, crossover study. Neurology. 1990;40(2):209-12. 
32. 
Vermeulen M, van Doorn PA, Brand A, Strengers PF, Jennekens FG, Busch HF. Intravenous 
immunoglobulin 
treatment 
in 
patients 
with 
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inflammatory 
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polyneuropathy: a double blind, placebo controlled study. JNeurolNeurosurgPsychiatry. 
1993;56(1):36-9. 
33. 
Hahn AF, Bolton CF, Zochodne D, Feasby TE. Intravenous immunoglobulin treatment in 
chronic inflammatory demyelinating polyneuropathy. A double-blind, placebo-controlled, 
cross-over study. Brain. 1996;119 ( Pt 4):1067-77. 
34. 
Mendell JR, Barohn RJ, Freimer ML, Kissel JT, King W, Nagaraja HN, et al. Randomized 
controlled 
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polyradiculoneuropathy. Neurology. 2001;56(4):445-9. 
35. 
Kubori T, Mezaki T, Kaji R, Kimura J, Hamaguchi K, Hirayama K, et al. [The clinical 
usefulness of high-dose intravenous immunoglobulin therapy for chronic inflammatory 
demyelinating polyneuropathy and multifocal motor neuropathy]. No To Shinkei. 
1999;51(2):127-35. 
36. 
Latov N, Deng C, Dalakas MC, Bril V, Donofrio P, Hanna K, et al. Timing and Course of 
Clinical Response to Intravenous Immunoglobulin in Chronic Inflammatory Demyelinating 
Polyradiculoneuropathy. Arch Neurol. 2010;67(7):E1-E6. 


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37. 
Elovaara I, Apostolski S, Van DP, Gilhus NE, Hietaharju A, Honkaniemi J, et al. EFNS 
guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases: 
EFNS task force on the use of intravenous immunoglobulin in treatment of neurological 
diseases. European Journal of Neurology. 2008;15(9):893-908. 
38. 
Hughes R, Bensa S, Willison H, Van den BP, Comi G, Illa I, et al. Randomized controlled trial 
of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory 
demyelinating polyradiculoneuropathy. AnnNeurol. 2001;50(2):195-201. 
39. 
Vanhoutte EK, Faber CG, van Nes SI, Cats EA, van der Pol WL, Gorson KC, et al. Rasch-built 
Overall Disability Scale for Multifocal motor neuropathy (MMN-RODS(©) ). Journal of the 
peripheral nervous system : JPNS. 2015;20(3):296-305. 
40. 
Vanhoutte EK, Latov N, Deng C, Hanna K, Hughes RA, Bril V, et al. Vigorimeter grip strength 
in CIDP: a responsive tool that rapidly measures the effect of IVIG - the ICE study. European 
journal of neurology : the official journal of the European Federation of Neurological Societies. 
2012:doi:10.1111/j.468-331.2012.03851.x. 
41. 
Kleyweg RP, van der Meche FG, Schmitz PI. Interobserver agreement in the assessment of 
muscle strength and functional abilities in Guillain-Barre syndrome. Muscle Nerve. 
1991;14(11):1103-9. 
42. 
Merkies IS, Schmitz PI, Samijn JP, van der Meche FG, van Doorn PA. Fatigue in immune-
mediated polyneuropathies. European Inflammatory Neuropathy Cause and Treatment 
(INCAT) Group. Neurology. 1999;53(8):1648-54. 
43. 
van Nes SI, Vanhoutte EK, Faber CG, Garssen M, van Doorn PA, Merkies ISJ, et al. Improved 
fatigue assessment in immune-mediated neuropathies: the modified Rasch-built fatigue severity 
scale. J Peripheral Nervous System. 2009;14:268-78. 
 


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15 APPENDICES 
 
Appendix 1: Inflammatory Rasch-built overall disability sum score (I-RODS) 
Appendix 2: Modified Fatigue Severity Scale (FSS) 
Appendix 3: SF-36 Health Survey 
 
 

SAP_001.pdf: 
ocfophormo
Statistical Analysis Plan
Protocol version this
SAP is based upon
Version 04 {dated 08-JUN-2018)
Approved by
090-SAP-NcAM-08 Fina103_2019-06-0G.docx Doc tD 2969
This document contains confidentialandproprietary information of Octapharma,Copying or
distribution of this document is only pennitted with the written perm ission of Octapharma. Any
comm ercial u re of the inf ormation is iubj€ctto the perm iss ion of Octapharma and a lice n re fee,
Study lD
Study title
Study phase
NGAM-08
Prospective, Double-Blind, Randomized, Multicenter
Phase lll study Evaluating Efficacy and safety of Three
Different Dosages of Newgam in patients with chronic
lnflammatory Demyelinating poly(Radicu to)Neuropathy
(ProClD study)
lil
Document author
Document version
Supersedes
Effective date
Doc lD
I
I
Ma nager Biometrics, Octapharma
Final 03
2.4
06-Jun-2019
2959
Name
Function, affiliation
Date and signature
IT
Manager Biometrics, Octapharma
rI
lnternational Medical Director, Octapharm
Principal statistician, I 
I
L/28


Statistical Analysis Plan for NGAM-08 
 
 
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Document History 
Version 
Date 
Author 
Description 
Final v1 
17-Dec-2015 
 
New document 
Final v2 
16-Dec-2016 
 
Incorporation of protocol changes based on FDA 
feedback to protocol version 1. Specifications with 
respect to the randomization strata. 
Final v3 
06-Jun-2019 
 
Incorporation of protocol changes (v4) 
Details added on planned statistical analyses: 
Primary endpoint: Logistic regression 
Secondary endpoints: ANCOVA for changes from 
baseline in I-RODS total score; grip strength;  MRC 
sums score; FSS total score; NCS measurements; 
QoL scores; ANCOVA models will be used for 
LSMEANS calculation (+95% CI) in various 
subgroups  
Logistic regression for responses based on I-RODS; 
based on grip strength; based on MRC sum score 
For INCAT disability total score and PI-NRS 95% 
confidence intervals for the median are added. 
Kaplan-Meier analysis for time-to response 
variables 
Deterioration after Wash-out/during dose 
evaluation added 
Abbreviations 
AE 
Adverse Event 
 
ITT 
Intention-To-Treat 
BMI 
Body Mass Index 
 
I-RODS 
Inflammatory Rasch-built Overall Disability 
Scale 
CI 
Confidence Interval 
 
IWRS 
Interactive Web Response System 
CIDP 
Chronic Inflammatory Demyelinating 
Poly(Radiculo)Neuropathy 
 
MADSAM 
Acquired Demyelinating Sensory And Motor 
Neuropathy 
CSR 
Clinical Study Report 
 
MCS 
Mental Composite Score 
DB 
Database 
 
MedDRA 
Medical Dictionary for Regulatory Activities 
ECG 
Electrocardiogram 
 
MRC 
Medical Research Council 
(e)CRF 
(Electronic) Case Report Form 
 
NAT 
Nucleic Acid Test 
EFNS 
European Federation of Neurological Societies  
NCS 
Nerve Conduction Studies 
FAS 
Full Analysis Set 
 
PCS 
Physical Composite Score 
FDA 
Food and Drug Administration 
 
PNS 
Peripheral Nerve Society 


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FSS 
Fatigue Severity Scale 
 
PP 
Per Protocol 
GCP 
Good Clinical Practice 
 
PT 
Preferred Term 
HBV 
Hepatitis B Virus 
 
QoL 
Quality of Life 
HCV 
Hepatitis C Virus 
 
SAP 
Statistical Analysis Plan 
HIV 
Human Immunodeficiency Virus 
 
SOC 
System Organ Class 
ICH 
International Conference on Harmonisation 
 
TEAE 
Treatment Emergent Adverse Event 
IgG 
Immunoglobulin G 
 
 
 
IGIV 
Intravenous Immunoglobulin 
 
 
 
IMP 
Investigational Medicinal Product 
 
 
 
INCAT 
Inflammatory Neuropathy Cause and 
Treatment 
 
 
 


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Table of Contents 
1. 
Preface ............................................................................................................................................. 6 
2. 
Purpose ............................................................................................................................................ 7 
3. 
Study Objectives and Endpoints ...................................................................................................... 8 
3.1. 
Study Objectives ...................................................................................................................... 8 
3.1.1. 
Primary Objective ............................................................................................................ 8 
3.1.2. 
Secondary Objectives ...................................................................................................... 8 
3.1.3. 
Exploratory Objectives .................................................................................................... 8 
3.2. 
Study Endpoints (Target Variables) ......................................................................................... 8 
3.2.1. 
Primary Target Variables ................................................................................................. 8 
3.2.2. 
Secondary and Exploratory Target Variables .................................................................. 9 
4. 
Study Methods .............................................................................................................................. 11 
4.1. 
Overall Study Design and Plan ............................................................................................... 11 
4.2. 
Selection of Study Population ............................................................................................... 12 
5. 
Sequence of Planned Analyses ...................................................................................................... 13 
5.1. 
Interim Analyses .................................................................................................................... 13 
5.2. 
Final Analyses and Reporting ................................................................................................ 13 
6. 
Sample Size Determination ........................................................................................................... 14 
6.1. 
Patient Replacement Policy ................................................................................................... 15 
6.2. 
Premature Termination of the Study .................................................................................... 15 
7. 
Analysis Populations ...................................................................................................................... 16 
7.1. 
Subgroups .............................................................................................................................. 16 
8. 
General Issues for Statistical Analysis ........................................................................................... 17 
8.1. 
Analysis Software .................................................................................................................. 17 
8.2. 
Withdrawals .......................................................................................................................... 17 
8.3. 
Handling of Missing Data....................................................................................................... 17 
8.4. 
Derived and Computed Variables ......................................................................................... 18 
9. 
Study Subjects and Demographics ................................................................................................ 20 
9.1. 
Disposition of Subjects and Withdrawals .............................................................................. 20 
9.2. 
Protocol Deviations ............................................................................................................... 20 
9.3. 
Demographics and Other Baseline Characteristics ............................................................... 20 
9.4. 
Measurement of Treatment Compliance .............................................................................. 21 
10. Efficacy Analysis............................................................................................................................. 22 
10.1. Primary Efficacy Variable Analysis ......................................................................................... 22 
10.2. Secondary and Exploratory Efficacy Variable Analysis .......................................................... 23 
11. Safety and Tolerability Analyses .................................................................................................... 24 
11.1. Adverse Events ...................................................................................................................... 24 
11.2. Laboratory Safety Tests ......................................................................................................... 25 
11.3. Viral Markers ......................................................................................................................... 25 
11.4. Vital Signs .............................................................................................................................. 25 
11.5. Physical Examination ............................................................................................................. 25 
12. Reporting Conventions .................................................................................................................. 26 


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12.1. General Reporting Conventions ............................................................................................ 26 
12.2. Population Summary Conventions ........................................................................................ 26 
13. Tables, Listings and Figures ........................................................................................................... 28 
 
 
 
 


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1. Preface 
This Statistical Analysis Plan (SAP) describes the planned analysis and reporting for Octapharma 
protocol NGAM-08 (the ProCID study): 
Prospective, Double-Blind, Randomized, Multicenter Phase III Study Evaluating Efficacy and Safety of 
Three Different Dosages of Newgam in Patients With Chronic Inflammatory Demyelinating 
Poly(Radiculo)Neuropathy 
This phase III study is conducted to assess efficacy and safety of three different dosages of Newgam in 
adult patients with a documented diagnosis of CIDP, who fulfill the definite or probable EFNS/PNS 
criteria for CIDP, and who have an adjusted INCAT disability score between 2 and 9. 
The structure and content of this SAP provides sufficient detail to meet the requirements identified by 
the FDA and International Conference on Harmonization (ICH) of Technical Requirements for 
Registration of Pharmaceuticals for Human Use: Guidance on Statistical Principles in Clinical Trials1.  
The following documents were reviewed in preparation of this SAP: 
• 
Clinical Study Protocol NGAM-08, Version 04 
The reader of this SAP is encouraged to also read the clinical protocol for details on the planned 
conduct of this study. Operational aspects related to collection and timing of planned clinical 
assessments are not repeated in this SAP unless relevant to the planned analyses. 
                                                          
1 International Conference on Harmonization. (1998). Guidance on Statistical Principles. ICH Topic E9 (Statistical 
Principles for Clinical Trials) (p. 37). London: International Conference on Harmonization. 


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2. Purpose 
This SAP outlines all statistical analyses to be performed on data collected in study NGAM-08, and the 
resulting output that will be compiled to support the completion of the Clinical Study Report (CSR). 
The planned analyses identified in this SAP will be included in regulatory submissions and/or future 
manuscripts. Exploratory analyses not necessarily identified in this SAP may be performed to support 
the clinical development program. Any post-hoc or unplanned analyses performed that are not 
identified in this SAP will be clearly identified in the respective CSR. 
The statistical output provided to the medical writer of the CSR will closely follow the ICH guideline for 
industry on topic E3 (Structure and Content of Clinical Study Reports2) to facilitate the subsequent 
compilation of the CSR. 
This statistical output will consist of tables, figures and listings, including 
• 
Tables, figures and listings used or referenced in, or appended to the CSR as detailed in the 
remainder of this SAP (section 14 of the CSR) 
o Demographic data summary figures and tables 
o Efficacy data summary figures and tables 
o Safety data summary figures and tables 
• 
Listings provided as appendices to the CSR 
o Patient data listings (section 16.2 of the CSR) 
o Individual patient data listings (section 16.4 of the CSR) will be covered by inclusion of 
SAS datasets into the electronic submission to the authorities 
A detailed list of all tables, figures and listings will be supplied in a separate document later when all 
feedback from authorities will be available. 
                                                          
2 International Conference on Harmonization. (1996). Structure and Content of Clinical Study Reports. Structure 
and Content of Clinical Study Reports (Guideline for Industry) (S. 37). London: International Conference on 
Harmonization. 


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3. Study Objectives and Endpoints 
3.1. 
Study Objectives  
3.1.1. 
Primary Objective 
• 
To provide confirmatory data on the effect of 1.0 g/kg NewGam every three weeks in patients 
with active CIDP based on the percentage of responders at Week 24, which should corroborate 
the existing evidence on efficacy of IGIV in CIDP as known from published literature. 
3.1.2. 
Secondary Objectives 
Secondary objectives are 
• 
To assess the effect of 0.5 g/kg and 2.0 g/kg NewGam every three weeks in patients with active 
CIDP based on the percentage of responders at Week 24 compared to patients on 1.0 g/kg 
NewGam every three weeks 
• 
To evaluate the safety of NewGam administration using various dosages in patients with CIDP 
• 
To further evaluate the beneficial effect of three NewGam dosages in patients with CIDP by 
assessing different parameters/scores/scales 
3.1.3. 
Exploratory Objectives 
• 
To assess the primary and secondary objectives at 3 weeks after having provided rescue 
medication (if applicable) 
• 
To further evaluate the beneficial effect of NewGam administration in patients with CIDP by 
additional assessments/scores including quality of life (QoL) measures 
3.2. 
Study Endpoints (Target Variables) 
3.2.1. 
Primary Target Variables 
The primary (efficacy) endpoint is the proportion of responders in the 1.0 g/kg NewGam arm at Week 
24. 
A responder is defined as a patient with a decrease of at least 1 point on the adjusted INCAT disability 
score relative to baseline (week 0). 
The adjusted INCAT (Inflammatory Neuropathy Cause and Treatment) disability score is a measure of 
activity limitation ranging from 0 (healthy) to 10 (unable to make any purposeful movements with arms 
and/or legs), and is frequently used as a primary endpoint in CIDP trials. Participants in study NGAM-
08 are required to have an adjusted INCAT disability score between 2 and 9 at study entry. 
The proportion of responders will be calculated as (# of responders) / (# of patients in analysis set) and 
presented together with the two-sided 95% Wilson-score confidence interval (CI). 
In case the primary endpoint can’t be evaluated for a patient due to missing data, this patient will be 
considered as non-responder in the intent-to-treat (ITT) analysis based on the full analysis set (FAS), 
whereas the same patient would be excluded from the per-protocol (PP) analysis. 
 
 


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3.2.2. 
Secondary and Exploratory Target Variables 
• 
Efficacy 
o Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 
relative to baseline at Week 0 compared to the 1.0 g/kg arm, based on the adjusted 
INCAT disability score 
o Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 
relative to baseline at Week 0 compared to the 1.0 g/kg arm, based on the grip 
strength (Martin Vigorimeter) using the previously published minimum clinically 
important difference (MCID) cut-off of 8 kPa 
o Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 
relative to baseline at Week 0 compared to the 1.0 g/kg arm, based on the I-RODS 
scores using the MCID concept related to the varying standard errors (MCID-SE) as 
recently demonstrated (please refer to protocol) 
o Time to first confirmed worsening on the adjusted INCAT disability scale by at least 1 
point or more from the value at Baseline 
o Mean change from Baseline (Week 0) to Termination Visit in  
 
grip strength of both hands (assessed by Martin Vigorimeter) 
 
Inflammatory Rasch-built overall disability sum score (I-RODS using the 
concept of MCID-SE as recently reported; Appendix 1) and number of 
improvers 
 
sum of the distal evoked amplitude of 4 right sided and 4 left sided motor 
nerves (peroneal, tibial, ulnar and median) 
 
Pain Intensity Numeric Rating Scale (PI-NRS) 
o Time to first confirmed worsening on the I-RODS scale  
o Time to 1 point decrease (improvement of disability) in adjusted INCAT disability score 
o Time to decrease in I-RODS scores 
o Mean change from baseline (Week 0) to Termination Visit in:  
 
modified Fatigue Severity Scale (FSS) 
 
SF-36 Health Survey physical composite score (PCS), mental composite score 
(MCS) and their 8 health domains 
 
Additional nerve conduction studies (NCS) analyses (e.g. individual nerve 
analysis) 
o For MRC the following will be done: 
 
Time to decrease in MRC sum score to or below baseline value after temporary 
improvement (increase)  
 
mean change from baseline (Week 0) to Week 12 and to Termination Visit 
 
number of improvers by at least 4 points from baseline (Week 0) to Week 12 
and to Week 24  
 
• 
Safety:  
o Throughout the entire 24-week Dose-evaluation Phase: 
o Occurrence of all adverse events (AEs)  
o Short term tolerance parameters including vital signs  
o Physical/neurological examination 


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o Laboratory parameters: Serum IgG, hematology, clinical chemistry, urinalysis, 
pregnancy test, and tests for viral safety 


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4. Study Methods 
4.1. 
Overall Study Design and Plan 
Study NGAM-08 is designed as a prospective, double-blind, randomized, multicenter phase III study. 
The rationale for conducting this study is to confirm the published clinical results obtained with the 1.0 
g/kg dosing in order to apply for market authorization of NewGam, and to evaluate different dosing 
options on both sides of the standard dose with respect to efficacy and safety. 
Patients will be screened for eligibility and, if eligible, thereafter have to decrease their current 
medication (Immunoglobulins by 25% from infusion to infusion or corticosteroids as per the discretion 
of the Investigator at a rate to expect study entry within 6-12 weeks) for a maximum of 12 weeks 
(Wash-out Phase). Only patients who deteriorate in this phase, i.e. active patients who need 
treatment, will be randomized 1:2:1 between three different dosages of NewGam (0.5 g/kg, 1.0 g/kg 
or 2.0 g/kg NewGam), and enter the Dose-Evaluation Phase. 
The two allowed types of treatment prior to enrollment – Immunoglobulins or Corticosteroids – will 
be considered as strata in a stratified block design randomization with fixed block size. An electronic 
IWRS tool will be used to realize the randomization ratio of 1:2:1 with respect to the dosage groups, in 
each of the strata independently.  
During the 24-week Dose-evaluation Phase all patients will first receive an initial loading dose of 2.0 
g/kg NewGam, followed by 7 maintenance dosages of 0.5 g/kg, 1.0 g/kg or 2.0 g/kg NewGam every 3 
weeks as they were randomized to. 
Patients not deteriorating in the 12-week Wash-out Phase will not be enrolled into the ProCID study 
as they are not having active CIDP. 
In addition the following rescue treatment option will be available: two consecutive infusions of 2.0 
g/kg NewGam at 3-week intervals for all patients in the 0.5 and 1.0 g/kg NewGam arms who are either 
stable at Week 6 or deteriorate after Week 3 and before Week 18. Patients in the 2.0 g/kg NewGam 
arm will drop-out if they are stable at Week 6 or deteriorating after Week 3 and before Week 21. 
 


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4.2. 
Selection of Study Population 
The study population consists of patients of both sexes, ≥ 18 years of age, with documented diagnosis 
of CIDP by a neurologist specialized/experienced in neuromuscular diseases. Eligible patients need to 
fulfill the definite or probable EFNS/PNS criteria for CIDP, and have to have an adjusted INCAT disability 
score between 2 and 9 at screening (a score of 2 has to be exclusively from leg disability). 
Please refer to the protocol for the complete list of all eligibility criteria. 


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5. Sequence of Planned Analyses 
5.1. 
Interim Analyses 
No interim analysis is planned in this study. 
5.2. 
Final Analyses and Reporting 
Once the last patient has completed the study, data validation will be completed and the database will 
be locked according to the applicable standard operating procedures. This process includes (blinded) 
data review, medical coding and review, the identification and classification of any protocol deviations 
as detailed in section 7, and thus the patient disposition with respect to the analysis populations. After 
completion of all these procedures and the finalization of the statistical analysis plan, the formal 
database lock can be conducted. Only after that the blind will be broken, and the individual treatment 
assignment will be added to the clinical database for analysis. 
All final, planned, analyses identified in the protocol and in the SAP will then be performed.  
Key statistics and study results will be made available to the study team following database lock and 
prior to completion of the final CSR by means of tables, figures and listings. 
Any, post-hoc, exploratory analyses completed to support planned study analyses, which were not 
identified in the final SAP, will be documented and reported in appendices to the CSR. Any results from 
these unplanned analyses will also be clearly identified in the text of the CSR. 


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6. Sample Size Determination 
The sample size calculation is based on the proportion of responders in the 1.0 g/kg dose group. This 
dose regimen is the currently most commonly used for maintenance IGIV doses in CIDP. Recent 
experiences with this dosing regimen are available from the ICE study and the PRIMA trial (please refer 
to the protocol for more details). In both of these studies, the lower confidence limit of the 95% Wilson-
Score confidence interval for the proportion of responders (R) was 42% if rounded to the nearest 
integer, and thus we have also chosen 42% as the threshold for the following pair of hypotheses for 
evaluation of the primary endpoint: 
H0: R < 0.42 
H1: R ≥ 0.42 
This will be tested by comparing the lower limit of the 95% Wilson-Score confidence interval for the 
observed proportion of responders with the pre-defined threshold of 0.42. 
We estimate the true percentage of responders in CIDP patients treated with NewGam as 60%. This 
corresponds to the 60.7% of responders observed in the PRIMA study, but is higher than the outcome 
in the ICE (54.2%), that in the opinion of many experts underestimates the true percentage of 
responders. 
We applied these parameters to a computer simulation realized in SAS to determine the statistical 
power associated with various group sizes: 
 
To achieve a power of at least 80%, a minimum of 62 evaluable patients in the 1 g/kg dose group will 
be needed; to account for possible dropouts we plan to enroll 70 patients into this group. 
In order to allow for the comparison between dose groups, we plan to enroll half the same number of 
patients also into the other groups (0.5 g/kg and 2.0 g/kg), resulting in a total of 124 evaluable patients, 
and an enrollment target of 140 patients overall. 
 


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6.1. 
Patient Replacement Policy 
Only in case of a withdrawal portion in excess of 10%, patients will be replaced, unless the planned 
number of patients in the respective dose group has been achieved already. A replacement patient 
will be assigned to the same treatment group as the withdrawn patient. 
Patients withdrawn from the study because of safety reasons will not be replaced. 
6.2. 
Premature Termination of the Study 
If early termination of the study becomes necessary, the sponsor and the investigator will ensure that 
adequate consideration is given to the protection of the patients' interests. Premature termination will 
be notified in accordance with applicable regulatory requirements. Early termination might concern 
the study as a whole or individual centers. In any case the blind will be maintained until all database 
locking procedures are completed and the database has been locked; this includes finalization of the 
statistical analysis plan, which will be adapted to cover any issues arising from the premature 
termination. 
 


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7. Analysis Populations 
The following populations will be considered for the statistical analysis: 
The safety set (SAF) will include all randomized patients who received at least part of one infusion of 
IMP. 
The full analysis set (FAS) is defined according to the intention-to-treat principle, and will include all 
patients of the SAF for whom any data was collected post infusion of IMP. Every treated subject will 
be considered in the analysis according to his randomized treatment/dose assignment. 
The per-protocol set (PPS) – being a subset of the FAS — will exclude patients with significant protocol 
deviations, which may have an impact on the evaluation of the primary study outcome parameter(s). 
This is the set of patients who participated in the study as intended and for whom the primary efficacy 
endpoint can be evaluated as planned. 
All protocol deviations documented during the conduct of the study or identified at the data review 
process prior to DB lock will be reviewed and classified as minor or major and with respect to its effect 
on the planned analysis. Only major protocol deviations with the potential to significantly affect the 
study results or to invalidate the interpretation of the data obtained will lead to exclusion of patients 
from the PP set. This classification of protocol deviations is the joint responsibility of the clinical study 
manager, the study statistician, and Octapharma’s responsible medical expert, and will be performed 
and documented before the database is locked and the statistical analyses are performed. 
The analysis of safety will be based on the safety set. 
The evaluation of primary objective(s) will be performed for the FAS (intention-to-treat analysis) and 
for the PPS (per-protocol analysis). The ITT analysis is considered to be the most relevant, and will be 
presented first in the statistical report. 
The evaluation of secondary objectives will be performed for the FAS, and in addition for the PPS in 
case the two populations differ by more than 5%. 
7.1. 
Subgroups 
In addition to combined presentations over all strata, evaluation of the primary endpoint will be 
presented for each randomization stratum (prior treatment with Immunoglobulins or Corticosteroids) 
separately to facilitate the identification of noteworthy differences in the clinical responses between 
these two groups.  
The different CIDP variants eligible for enrollment, such as Multifocal Acquired Demyelinating Sensory 
And Motor Neuropathy (MADSAM) or pure motor CIDP, will be compared with respect to dose group 
and proportion of response as well.  
Additional analyses, such as logistic regression or ANCOVA, will be deployed for primary and secondary 
endpoints to further examine differences between subgroups in an exploratory manner. The ANCOVA 
models will also be used for least square means calculation including 95% confidence intervals in 
various subgroups (see section 10.2). 


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8. General Issues for Statistical Analysis 
Descriptive summaries will be presented for each of the primary, secondary and exploratory variables. 
In general, summaries will be completed for all patients overall and by dose group, and the data will 
be presented by means of standard summary statistics according to the different types of data: 
• 
Binary data (whether or not an event has occurred): counts and proportions 
• 
Count data (the frequency of an event in a set time period): rate (count per unit time) 
• 
Continuous data (measurements on a continuous scale, including quasi-continuous variables): 
arithmetic mean, standard deviation, median, minimum, maximum 
• 
Scales data (Ordinal and Non-ordinal): absolute and relative frequencies 
• 
Time-to-event data (how long it takes to observe the outcome of interest: time to event or last 
evaluation (censored data in case patients are lost to follow-up) and event rate). These 
parameters might not be tabulated separately, but can be included as an inset into a Kaplan-
Meier plot of the product-limit survival function estimates. 
 
Additional descriptive and exploratory statistics, such as geometric means, quartiles or confidence 
intervals, are included as appropriate. If not mentioned otherwise, confidence intervals are to be 
understood as two-sided, 95% confidence intervals. 
In general the denominator for calculating percentages will be the total number of patients in the 
analysis population unless otherwise specified. 
8.1. 
Analysis Software 
Statistical analyses will be performed using SAS Software version 9.1 or later. 
8.2. 
Withdrawals 
Patients who withdraw from the study prematurely will be considered in all data presentations for 
which they contribute data; in particular patients who fail to perform an INCAT evaluation at week 24 
will be considered to be non-responders in the analysis of the primary endpoint in the FAS. 
8.3. 
Handling of Missing Data 
In general, missing data will not be imputed, and all data derivations will be based on observed values 
only; exceptions are:  
In case of missing body weight, the last available weight measurement will be used for calculating the 
dose per kg bodyweight (last observation carried forward (LOCF)). 
Because the overall disability sum score (I-RODS) cannot be calculated if not all activities are evaluated, 
missing items will be replaced by the latest available score of the same activity (LOCF). 
If missing values occur in the confirmatory analysis of the primary endpoint in the FAS, they will be 
imputed by worst observed values, i.e. the patient concerned will be analyzed as non-responder. 
No analyses of the patterns of missing data will be done. 
For adverse events the following will be applied: 
An Adverse Event (AE) is defined as treatment-emergent, if first onset or worsening is after start of the 
first infusion of NewGam. 
If the start date and time of an AE are partially or completely missing, the AE will be assumed to be 
treatment-emergent if it cannot be definitely shown that the AE did not occur or worsen after start of 
the first infusion of NewGam. Missing dates and times will not be replaced. 


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For medications the following will be applied: A medication will be assumed to be concomitant if it 
cannot be definitely shown that the medication was not administered after start of the first infusion 
of NewGam. Missing dates will not be replaced. 
8.4. 
Derived and Computed Variables 
The following derived and computed variables have been initially identified as important for the 
analysis of the primary and secondary target variables. It is expected that additional variables will be 
required. The SAP will not be amended for additional variables that are not related to the primary 
target or key secondary target variables. Any additional derived or computed variables will be 
identified and documented in the SAS programs that create the analysis files. If the SAP is not 
amended, further derivations related to primary and secondary target variables will be described in 
the CSR. 
• 
Body Mass Index: BMI = (Body weight) / Height2 
[Unit: kg/m2] 
• 
Response based on the adjusted INCAT disability score: 
Yes, if [Score at week 24] ≤ [Score at Week 0] - 1 and patient did not receive rescue 
treatment; No otherwise (including patients discontinued before week 24 and patients 
receiving rescue treatment) 
The same definition will be applied to other visits than week 24 to allow for an analysis 
of the time to first response. Time to first response will be censored at start date of 
rescue medication if a patient received rescue medication and did not show a response 
before. In case a patient did not show any response until termination visit and did not 
receive rescue medication, time to first response will be censored at termination visit. 
• 
Worsening with respect to INCAT disability score: 
Worsening occurs if a patient score increases to at least 1 point above the Week 0 
value. 
• 
Response based on grip strength (Martin Vigorimeter): 
Evaluate both hands. Yes, if [Strength at Week 24] ≥ [Strength at Week 0] + 8kPa in the 
dominant or the non-dominant hand and patient did not receive rescue treatment; No 
otherwise (including patients discontinued before week 24 and patients receiving 
rescue treatment). 
• 
Response/Worsening based on the I-RODS score: 
The individual Minimally Clinically Important Difference (MCID)-related SE (MCID-SE) 
score is derived for each visit and patient individually, and categorized as follows: 
MCID-SE ≥ 1.96 
clinically important improvement 
0 < MCID-SE < 1.96 
clinically unimportant improvement 
MCID-SE = 0 
no change 
-1.96 < MCID-SE < 0 
clinically unimportant deterioration 
MCID-SE ≤ -1.96 
clinically important deterioration 
The individual MCID-SE values are computed through the Rasch person location values 
(logits) R associated with the I-RODS Summed Raw Scores as follows: 


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Overall patient response is defined as follows: 
Yes, if clinically important improvement (i.e. MCID-SE ≥ 1.96) at week 24 and patient 
did not receive rescue treatment; No otherwise (including patients discontinued 
before week 24 and patients receiving rescue treatment). 
• 
Response based on the original MRC sum score [at Week 24] : 
Yes, if increase from Week 0 by at least 4 points and patient did not receive rescue 
treatment; No otherwise (including patients discontinued before week 24 and patients 
receiving rescue treatment) 
An analogue definition will be applied for response at Week 12. 
Worsening based on the original MRC sum score: 
Decrease to or below baseline value after temporary improvement by at least 4 points. 
Patients who did not temporarily improve by at least 4 points will be excluded from 
the analysis of time to first worsening. 
• 
Changes from baseline to termination visit in scales/scores: 
When calculating those changes, values under rescue treatment will not be taken into 
account. Changes will be calculated to last value before start of rescue treatment. 
• 
MRC sum score: 
Though mentioned in the protocol, a modified version of the MRC sum score will not 
be calculated, as this modified version could not be established in other studies. 
• 
NCS measurements: 
The following variables will be calculated from NCS measurements: 
o Sum of all distal amplitudes: the sum will be calculated from 4 nerves, both right and 
left sides, for a total of 8 amplitudes. The distal sites are the ankle (lower limbs, 
peroneal and tibial nerves) and wrist (upper limbs, ulnar and median nerves). 
o Sum of the proximal amplitudes: this will be a total sum of 6 parameters, as no 
proximal amplitude was measured for the tibial nerve. Proximal sites are at the fibular 
head (lower limb peroneal nerve) and elbow (upper limbs). 
o Sum of conduction velocities (6 in total, as no conduction velocity was measured for 
tibial nerve) 
o Sum of durations – distal locations (8 in total) 
o Sum of areas – distal locations (8 in total) 
For the last three variables, in case the result is NR (No response) in the data set, the worst 
value in the data set for the corresponding parameter and for the respective nerve will be 
used. Worst value is the highest value for durations, lowest value for area and lowest value 
for conduction velocity. 


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9. Study Subjects and Demographics 
9.1. 
Disposition of Subjects and Withdrawals 
All patients enrolled in the study will be accounted for. Descriptive summaries of population data will 
be provided overall, by randomization stratum, and by dose group; these will include 
• 
The frequency and percent of patients in each analysis population, sex and age distribution 
• 
The disposition of patients (including number of patients enrolled, number of patients 
randomized, number of patients treated, number of completers) 
• 
study withdrawals by reason of withdrawal 
9.2. 
Protocol Deviations 
Protocol deviations will be documented throughout the study, and checked for on complete data for 
each patient by manual review as well as by electronic validation checks. 
The final decision regarding inclusion/exclusion of patients from the analysis sets will be taken based 
on protocol adherence reports during data review meetings before database lock, data release and 
analysis, applying the definitions in section 7. 
Major protocol deviations will be summarized by type of deviation and by dose group. Individual 
patients with these protocol deviations will be listed. 
9.3. 
Demographics and Other Baseline Characteristics 
Descriptive summaries of the demographic and other baseline characteristics will be completed for 
the populations specified below, overall and by dose group. Some particular tables will be repeated 
also by randomization stratum and/or by CIDP variant. Baseline tables include: 
• 
Demographics (SAF, FAS, PP) 
 Age, Gender, Race/Ethnicity, Height, Weight, BMI 
These parameters will also be summarized by investigational site 
• 
Medical History (SAF) 
Medical history will be coded with the Medical Dictionary for Regulatory Activities (MedDRA, 
according to the version specified in the Data Management Plan). Incidences of findings in 
medical history will be summarized by MedDRA system organ class (SOC) and preferred term 
(PT)  
• 
Prior and Concomitant Medications (SAF) 
Medications will be coded using the WHO Drug Dictionary (according to the version specified 
in the Data Management Plan). Incidences of prior and concomitant medications will be 
summarized by ATC level 2 and ATC level 4 
• 
Screening Physical Examination 
• 
ECG at screening 
• 
Disease status (FAS) at screening: 
Adjusted INCAT disability score, I-RODS disability score, grip strength, MRC sum score, modified 
FSS (fatigue scale), NCS (electrophysiological recordings) 
• 
Deterioration after the wash-out phase: 


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Any deterioration after the wash-out phase will be listed. The frequencies of deteriorations 
after the wash-out phase will be presented by dose group and category (Patients´ Global 
Impression of Change, adjusted INCAT disability score, grip strength, I-RODS) as well as in total.  
9.4. 
Measurement of Treatment Compliance 
The following parameters will be listed and summarized per patient and/or per infusion: 
• 
Body weight 
• 
Actual dose (total and per kg body weight, based on the latest available weight measurement) 
• 
Total dose of NewGam administered 
• 
Total number of infusions administered 
• 
Total volume of solution administered 
• 
Infusion times 
• 
Overall amount of product administered (only included in data listings) 
• 
Infusion rates 
Deviations from the planned treatment schedule will be summarized by counting the number of 
infusions that deviate from the scheduled intervals by more than 4 days, and by listing all cases with 
more than 4 days deviation individually. 


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10. 
Efficacy Analysis 
The primary objective of this study is to confirm the efficacy of NewGam in patients with CIDP that 
were observed in published clinical studies by evaluating the proportion of responders in the 1.0 g/kg 
dose group. 
This study will furthermore compare all efficacy endpoints between the different dosing groups. 
 Formal planned analyses are described below. It may be necessary for additional exploratory analyses 
to be performed after the results from the planned analysis are completed; in this case full details of 
additional analyses will be given in the CSR. 
The evaluation of the primary endpoint will be performed for the FAS and for the PPS. The evaluation 
of secondary endpoints will be performed for the FAS, and in addition for the PPS in case the two 
populations differ by more than 5%. The FAS analysis is considered to be the primary assessment of 
efficacy, and will be presented first in the report. 
10.1. 
Primary Efficacy Variable Analysis 
The primary efficacy variable is the proportion of responders in the 1.0 g/kg NewGam arm at Week 24 
(Termination Visit) relative to baseline (Week 0). A responder being defined as a patient with a 
decrease of at least 1 point on the adjusted INCAT disability score. 
Confirmatory statistical testing of the primary endpoint will be done by constructing the 95% Wilson-
Score confidence interval for the proportion of responders, and comparing the lower confidence limit 
with the predefined threshold of 0.42. This corresponds to a one-sided test of the following pair of 
hypotheses at the α=0.025 confidence level. 
H0: R < 0.42 
H1: R ≥ 0.42 
Where R is the proportion of responders i.e. the number of patients in the FAS who are responders 
according to the abovementioned definition, divided by the total number of patients in the FAS. 
This evaluation will also be presented for the PPS to assess the robustness of the primary study 
endpoint with respect to protocol deviations. 
To assess and compare the primary efficacy endpoint also between the different dose groups, and also 
between the randomization strata (by dose group and over all dose groups) the proportion of 
responders will be presented side-by-side, including the 95% confidence intervals. 
The time to first response and time to first worsening will be examined and presented by means of a 
Kaplan-Meier analysis. 
Additional analyses, such as logistic regression- will be deployed to further examine any noteworthy 
differencesin an exploratory manner. The logistic regression model for analysis of response will include 
dose group, randomization stratum and CIDP variant (typical vs. atypical) as factors and baseline score 
as covariate. Odds ratios will be calculated to compare response rates between the factor levels, these 
will be presented together with 95% confidence intervals. 
Moreover the proportion of responders after having provided rescue medication will be calculated 
with respect to all patients who received rescue medication and will be presented by dose group and 
overall, together with 95% confidence intervals.   


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10.2. 
Secondary and Exploratory Efficacy Variable Analysis 
All efficacy endpoints detailed in section 3.2 will be summarized by means of descriptive statistics, 
presented graphically as appropriate, and listed in full detail. Tables and graphs will allow for direct 
comparison of the different dose groups. If data are tabulated by dose group, the presentations will 
also include a total category, summarizing the data of all subjects in any of the dose groups. Tables for 
changes from baseline will include 95% confidence intervals of the mean for continuous secondary 
endpoints (I-RODS total score; grip strength;  MRC sum score; FSS total score; NCS measurements; QoL 
scores) and 95% confidence intervals for the median for ordinal scales (INCAT disability sore, PI-NRS), 
calculated with PROC univariate option CIQUANTDF. 
Similar analyses as for the primary endpoint will be performed for response variables defined based 
on secondary endpoints (I-RODS, grip strength, MRC sum score). These will include analysis of response 
rates and 95% confidence intervals, logistic regression models using the same factors as for the primary 
endpoint, Kaplan-Meier analyses for time to response and time to first worsening and response rates 
after having provided rescue medication. 
Moreover, ANCOVA models will be applied for continuous secondary endpoints (I-RODS total score; 
grip strength; MRC sums score; FSS total score; NCS measurements; QoL scores). These ANCOVA 
models for changes from baseline to end of study will include dose group, randomization stratum and 
CIDP variant as factors and baseline value of the score/measurement as covariate. ANCOVA models 
will be used for calculation of least square means in various subgroups as well as for calculation of 
difference in least square means between the factor levels. All least square means will be presented 
together with 95% confidence intervals. 
Any deterioration during the dose evaluation phase will be listed. Moreover, deteriorations during 
dose evaluation will be presented by dose group and by their effect on subject disposition 
(discontinuation, rescue medication). 
 


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11. 
Safety and Tolerability Analyses 
The analysis of safety assessments in this study will be presented for the SAF. 
11.1. 
Adverse Events 
All reported AEs will be coded according to MedDRA. 
An Adverse Event (AE) is defined as treatment-emergent, if first onset or worsening is after start of the 
first infusion of NewGam. Only treatment-emergent AEs (TEAE) are accounted for in the analysis. 
A TEAE will be considered to be temporally associated with the infusion (or ‘infusional’) if it starts 
during or within 72 hours of the end of the infusion. 
All treatment-emergent AEs for each patient, including multiple occurrences of the same event, will 
be listed in full detail, including reported term, MedDRA preferred term and system organ class, onset, 
duration, time to the AE occurrence from last dose, causality, dosage, severity, seriousness and actions 
taken.  
For each dose group and for the study as a whole the following will be given: 
• 
Total number of TEAEs reported 
• 
Number of temporally associated TEAEs 
• 
Number and percentage of infusions temporally associated with one or more TEAE 
• 
Number of temporally associated TEAEs divided by the total number of infusions 
 
On a per patient basis the incidence of TEAEs will be summarized by system organ class, preferred term 
and maximum severity. If a patient experiences an adverse event more than once the event at the 
most severe occurrence will be considered. Patients will be included only once under each system 
organ class and only once in the overall totals under the most severe event occurrence. 
TEAEs will be summarized by strongest relationship to study medication by system organ class and 
preferred term. If a patient experiences an adverse event more than once the event most related to 
study medication will be considered. Patients will be included only once under each system organ class 
and only once in the overall totals under the most related to study medication occurrence. 
Incidences of TEAEs (given as the number and percentage of patients) will be summarized overall and 
for each dose group as follows: 
• 
Any TEAE 
• 
Any serious TEAE 
• 
Any TEAE probably or possibly related to the trial drug 
• 
Any severe TEAE 
• 
Any withdrawal due to TEAE 
• 
Any significant TEAE 
• 
Any TEAE by MedDRA System Organ Class (SOC) and MedDRA Preferred Term (PT) 
 
Significant AEs fulfill at least one of the following criteria:  
• 
any concomitant medication or therapy started due to the AE 
• 
Study treatment was stopped/withdrawn or dose changed 
 


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Narratives will be prepared describing each death, each other serious AE and those of the other 
significant AEs that are judged to be of special interest because of clinical importance . 
 
11.2. 
Laboratory Safety Tests 
The safety laboratory data (Clinical chemistry, hematology, and urinalysis) will be converted to 
standard units during the data management process. The laboratory data will be listed with suitable 
flags indicating abnormal values (L=Lower than reference range, H=Higher than reference range) and 
clinical significance as judged by the investigator whenever available. 
Summary statistics for the laboratory values as well as their changes from baseline at each time point 
will be tabulated 
Summary statistics for the laboratory values as well as their changes from baseline at each time will be 
tabulated for all laboratory parameters. 
11.3. 
Viral Markers 
Viral marker samples will be taken before the first NewGam infusion at screening and at the (early) 
termination visit. All viral marker results will be listed with suitable flags indicating positive results, and 
shift tables will be used to identify any possible seroconversion during the course of the study. 
11.4. 
Vital Signs 
To evaluate short-term tolerance, vital signs will be monitored at all visits, including measurements 
before, at least once during and after infusion. Vital signs parameters will be summarized by visit and 
measurement time, using the standard set of summary statistics for both absolute values and changes 
from baseline. For pulse, respiratory rate, blood pressure and body temperature the baseline value is 
the pre-infusion measurement, whereas the weight measurements will be compared to the weight at 
screening. 
Fever is defined as a body temperature >37.8 °C orally, >38.2 °C rectally, >38 °C axillary, >38.2 °C 
tympanic, and has to be documented as an AE. 
Height is measured at baseline only, as is the standard ECG. 
11.5. 
Physical Examination 
A general physical examination will be performed at the screening visit, and relevant findings will be 
documented; the physical examination will be repeated at visits 2, 6, and at the end of study. 
Changes in results of physical examination will be summarized by body system and visit. Any clinically 
relevant worsening from the baseline status will be documented as an AE. 
 
 


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12. 
Reporting Conventions 
The following reporting conventions will be adopted for the presentation of study data. These 
conventions will enhance the review process and help to standardize presentation with common 
notations. 
12.1. 
General Reporting Conventions 
• 
All tables and data listings will be developed in landscape orientation, unless presented as part 
of the text in a CSR. 
• 
Figures will in general also be presented in landscape orientation, unless presented as part of 
the text in a CSR. 
• 
Legends will be used for all figures with more than one variable or item displayed. 
• 
Figures will be in black and white, unless color figures have been identified as useful for 
discriminating presentation in the figure. Lines in figures should be wide enough to view the 
line after being photocopied. 
• 
Specialized text styles, such as bolding, italics, borders, shading, superscripted and subscripted 
text will not be used in tables, figures and data listings unless they add significant value to the 
table, figure, or data listing. 
• 
Only standard keyboard characters should be used in tables and data listings. Special 
characters, such as non-printable control characters, printer specific, or font specific 
characters, will not be used on a table, figure, or data listing. Hexadecimal character 
representations are allowed (e.g., μ, α, β). 
• 
The ICH numbering convention is to be used for all tables, figures and data listings. 
• 
All footnotes will be left justified and placed at the bottom of a page. Footnotes must be 
present on the page where they are first referenced. Footnotes should be used sparingly and 
must add value to the table, figure, or data listing. If more than four footnote lines are planned 
then a cover page may be used to display footnotes. 
• 
Missing values for both numeric and character variables will be presented as blanks in a table 
or data listing. A zero (0) may be used if appropriate to identify when the frequency of a 
variable is not observed. 
• 
All date values will be presented as DDMMMYYYY (e.g., 29AUG2001) format. 
• 
All observed time values will be presented using a 24-hour clock HH:MM format (e.g. 15:26). 
• 
Time durations will be reported in HH:MM notation. The use of decimal notation to present 
(display) time durations should be avoided (e.g. 0.083h = 5min) unless it is necessary to show 
the computation of time differences in a table, figure, or data listing, in which case both 
notations may be used to display the time duration. 
• 
All tables, figures and data listings will have the name of the program, and a date stamp on the 
bottom of each output. 
12.2. 
Population Summary Conventions 
• 
Population(s) represented on the tables or data listings will be clearly identified in the title as 
“Population: <name of population>” where <name of population> is any of the analysis 
population names or abbreviations defined in section 7 (safety analysis set (SAF), full analysis 
set (FAS or ITT), per-protocol set (PPS). 


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• 
Sub-population(s) or special population(s) descriptions will provide sufficient detail to ensure 
comprehension of the population (e.g., ITT Females, Per-Protocol Males >60 years of age) used 
for analysis in a table or figure. 
• 
Population sizes may be presented for each treatment or dosing category as totals in the 
column header as (N=xxx), where appropriate. 
• 
Population sizes shown with summary statistics are the samples sizes (n) of patients with non-
missing values. 
• 
All population summaries for continuous variables will include: N, mean, SD, median, minimum 
and maximum. 
• 
All percentages are rounded and reported to a single decimal point (xx.x%). 
 


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13. 
 Tables, Listings and Figures 
To be supplied in a separate document later when all feedback from authorities will be available.