CIDP: Study to Evaluate Safety and Efficacy of Three Different Dosages of NewGam in Patients With Chronic Inflammatory Demyelinating Poly (Radiculo) Neuropathy

• Sponsor: Octapharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02638207
• Collaborator: (none)
• Enrollment: 142
• Locations: 26
• Arms: 3
• Actual Duration (Months): 23.3
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Inflammatory Demyelinating Poly(Radiculo)Neuropathy	Drug: NewGam	Phase 3

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")

Study Design

• Study Type: Interventional
• Actual Enrollment: 142 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Sep 27, 2017
• Actual Primary Completion Date: Sep 5, 2019
• Actual Study Completion Date: Sep 5, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 0.5 g/kg NewGam 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).	Drug: NewGam; 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; Other Names: Panzyga
Experimental: 1.0 g/kg NewGam 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).	Drug: NewGam; 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; Other Names: Panzyga
Experimental: 2.0 g/kg NewGam 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).	Drug: NewGam; 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; Other Names: Panzyga

Outcome Measures

Primary Outcome Measures

1. Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score [at Week 24]

   Efficacy - 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 Inflammatory Neuropathy Cause and Treatment (INCAT) disability score (a scale from 0 to 10, from healthy to unable to make any purposeful movements with arms and/or legs)

Secondary Outcome Measures

1. Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score [at Week 24]

   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 Inflammatory Neuropathy Cause and Treatment (INCAT) disability score

2. Grip Strength Score [at Week 24]

   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 kilopascal (kPa)

3. Inflammatory Rasch-built Overall Disability Scale (I-RODS Score) [at Week 24]

   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 Inflammatory Rasch-built overall disability scale (I-RODS Score) using the MCID concept related to the varying standard errors (MCID-SE) as recently demonstrated

4. Worsening in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score [Week 24]

   Time to first confirmed worsening on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale by at least 1 point from the value at baseline (Week 0)

5. Mean Change in Grip Strength [Up to 24 weeks]

   Mean change from baseline (Week 0) to Termination Visit in grip strength of both hands (assessed by Martin vigorimeter). The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point.

6. Inflammatory Rasch-built Overall Disability Scale (I-RODS) [Up to 24 weeks]

   Mean change from baseline (Week 0) to Termination Visit in Inflammatory Rasch-built overall disability sum score (I-RODS using the concept of MCID-SE as recently reported) and number of improvers. The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. A scale from 0 to 48, from "Not possible to perform" to "Possible without any difficulty". Higher values represent a better outcome.

7. Motor Nerves [Up to 24 weeks]

   Mean change from baseline (Week 0) to Termination Visit in sum of the distal evoked amplitude of 4 right sided and 4 left sided motor nerves (peroneal, tibial, ulnar and median). The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point.

8. Mean Change in Pain Intensity Numerical Rating Scale (PI-NRS Scale) [Up to 24 weeks]

   Mean change from baseline (Week 0) to Termination Visit in Pain Intensity Numeric Rating Scale (PI-NRS). The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. 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. A higher value represents a worse outcome.

9. Worsening on the Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale) [24 weeks]

   Time to first confirmed worsening on the I-RODS scale. The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. A scale from 0 to 48, from "Not possible to perform" to "Possible without any difficulty". Higher values represent a better outcome. Worsening is determined using the concept of MCID (minimum clinically important difference) using the individually obtained standard errors (MCID-SE).

10. 1 Point Decrease in the INCAT Disability Score [24 weeks]

    Time to 1 point decrease (improvement of disability) in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score

11. Decrease in Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale) [24 weeks]

    Time to decrease in Inflammatory Rasch-built overall disability scale (I-RODS) scores

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with diagnosis of definite or probable Chronic inflammatory demyelinating polyneuropathy (CIDP) according to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) Guideline 2010 [van den Bergh et al., 2010]; including patients with Multifocal Acquired Demyelinating Sensory And Motor Neuropathy (MADSAM) or pure motor Chronic inflammatory demyelinating polyneuropathy (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 Inflammatory Neuropathy Cause and Treatment (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 Chronic inflammatory demyelinating polyneuropathy (CIDP)

2. Pure sensory Chronic inflammatory demyelinating polyneuropathy (CIDP)

3. Multifocal motor neuropathy (MMN) with conduction block [van den Bergh et al., 2010]

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

10. connective tissue disease or systemic lupus erythematosus (SLE)

11. HIV infection, hepatitis, Lyme disease

12. cancer (with the exception of basal cell skin cancer)

13. IgM paraproteinemia with anti-myelin associated glycoprotein antibodies

14. Diabetic neuropathy

15. Cardiac insufficiency (New York Heart Association [NYHA] III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease

16. Severe liver disease (ALAT 3x > normal value)

17. Severe kidney disease (creatinine 1.5x > normal value)

18. Hepatitis B, hepatitis C or HIV infection

19. 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 deep vein thrombosis (DVT)

20. Body mass index (BMI) ≥40 kg/m2

21. Patients with uncompensated hypothyroidism (abnormally high Thyroid-Stimulating Hormone [TSH] and abnormally low Thyroxine [T4]) or known vitamin B12 deficiency if patients don't receive adequate substitution therapy

22. Medical conditions whose symptoms and effects could alter protein catabolism and/or Immunoglobulin G (IgG) utilization (e.g. protein-losing enteropathies, nephrotic syndrome)

23. Known Immunoglobulin A (IgA) deficiency with antibodies to Immunoglobulin A (IgA)

24. History of severe hypersensitivity, e.g. anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products, or any component of NewGam

25. Known blood hyperviscosity, or other hypercoagulable states

26. Use of other blood or plasma-derived products within three months prior to Visit 2

27. Patients with a past or present history of drug abuse or alcohol abuse within the preceding five years prior to baseline visit

28. Patients unable or unwilling to understand or comply with the study protocol

29. Participation in another interventional clinical study with investigational medicinal product (IMP) treatment currently or during the three months prior to Visit 2

30. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MHAT Puls EOOD	Blagoevgrad		Bulgaria	2700
2	St. Naum Hospital	Sofia		Bulgaria	1797
3	Toronto General Hospital	Toronto	Ontario	Canada	M5G 2C4
4	Octapharma Research Site	Montréal		Canada	H3A2B4
5	Outpatient Clinic of Neurology	Hradec Králové		Czechia	500 03
6	Regional Hospital Pardubice	Pardubice		Czechia	532 03
7	Thomayer Faculty Hospital	Prague		Czechia	140 00
8	University Medical Center Goettigen	Goettigen		Germany	37075
9	Jahn Ferenc Del Pesti Korhaz	Budapest		Hungary	1204
10	Szegedi Tudományegyetem ÁOK Neurológiai Klinika	Szeged		Hungary	6725
11	Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Klinika Neurologii	Lublin		Poland	20-954
12	Wojewodzki Szpital Specjalistyczny W Olsztynie	Olsztyn		Poland	10-561
13	Uniwersytecki Szpital Kliniczny	Wrocław		Poland	50-556
14	Theo Health S.R.L.	Braşov		Romania	500091
15	Institutul Clinic Fundeni	Bucharest		Romania	022328
16	Spitalul Clinic Judetean de Urgenta "Sf.Apostol Andrei" Constanta	Constanţa		Romania	900591
17	Republican Clinical Neurological Centre	Kazan'		Russian Federation	420021
18	Neurology Research Centre	Moscow		Russian Federation	125367
19	Nizhny Novgorod Regional Clinical Hospital N.A. N.A.Semashko	Nizhny Novgorod		Russian Federation	603126
20	National Medical Research Centre of Psychiatry and Neurology n.a. V.M.Bekhterev	Saint Petersburg		Russian Federation	192019
21	City Multifield Hospital #2	Saint Petersburg		Russian Federation	194354
22	Ivano Frankivsk National Medical University	Ivano-Frankivs'k		Ukraine	76008
23	National Medical Academy Of Postgraduate Education Named After P.L. Shupyk	Kyiv		Ukraine	4112
24	Volyn Regional Clinical Hospital	Luts'k		Ukraine	4300
25	Vinnytsia National Medical University	Vinnytsia		Ukraine	21005
26	Municipal Institution Zaporizhzhya Regional Clinical Hospital	Zaporizhzhya		Ukraine	69600

Sponsors and Collaborators

• Octapharma

Investigators

• Study Director: Wolfgang Frenzel, MD, Octapharma

Study Documents (Full-Text)

• Study Protocol - Jun 8, 2018
• Statistical Analysis Plan - Jun 6, 2019

More Information

Publications

None provided.

• Responsible Party: Octapharma
• ClinicalTrials.gov Identifier: NCT02638207
• Other Study ID Numbers: NGAM-08
• First Posted: Dec 23, 2015
• Last Update Posted: Feb 16, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Octapharma: Chronic Inflammatory Demyelinating Poly Neuropathy (CIDP)
• Additional relevant MeSH terms: Peripheral Nervous System Diseases

Study Results

Participant Flow

Arm/Group Title	0.5 g/kg NewGam	1.0 g/kg NewGam	2.0 g/kg NewGam
Arm/Group Description	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).	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).	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).
Period Title: Overall Study
STARTED	35	69	38
COMPLETED	28	61	34
NOT COMPLETED	7	8	4

Baseline Characteristics

Arm/Group Title	0.5 g/kg NewGam	1.0 g/kg NewGam	2.0 g/kg NewGam	Total
Arm/Group Description	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).	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).	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).	Total of all reporting groups
Overall Participants	35	69	38	142
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.49 (14.449)	56.32 (14.616)	58.05 (13.764)	55.84 (14.398)
Sex: Female, Male (Count of Participants)
Female	13 37.1%	31 44.9%	14 36.8%	58 40.8%
Male	22 62.9%	38 55.1%	24 63.2%	84 59.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	35 100%	69 100%	38 100%	142 100%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	84.09 (16.511)	81.74 (16.333)	77.68 (75.50)	81.23 (79.00)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	173.46 (9.506)	172.81 (8.304)	171.61 (9.030)	172.65 (8.770)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.92 (4.873)	27.27 (4.588)	26.33 (5.231)	27.18 (4.837)

Outcome Measures

1. Primary Outcome

Title	Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score
Description	Efficacy - 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 Inflammatory Neuropathy Cause and Treatment (INCAT) disability score (a scale from 0 to 10, from healthy to unable to make any purposeful movements with arms and/or legs)
Time Frame	at Week 24

Outcome Measure Data

Analysis Population Description

Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.

Arm/Group Title	1.0 g/kg NewGam
Arm/Group Description	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).
Measure Participants	69
Number [proportion of subjects]	.7971

2. Secondary Outcome

Title	Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score
Description	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 Inflammatory Neuropathy Cause and Treatment (INCAT) disability score
Time Frame	at Week 24

Outcome Measure Data

Analysis Population Description

Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.

Arm/Group Title	0.5 g/kg NewGam	1.0 g/kg NewGam	2.0 g/kg NewGam
Arm/Group Description	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).	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).	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).
Measure Participants	34	69	36
Number [Proportion of responders]	.6471	.7971	.9167

3. Secondary Outcome

Title	Grip Strength Score
Description	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 kilopascal (kPa)
Time Frame	at Week 24

Outcome Measure Data

Analysis Population Description

Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.

Arm/Group Title	0.5 g/kg NewGam	1.0 g/kg NewGam	2.0 g/kg NewGam
Arm/Group Description	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).	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).	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).
Measure Participants	34	69	36
Number [Proportion of responders]	.5588	.6522	.8333

4. Secondary Outcome

Title	Inflammatory Rasch-built Overall Disability Scale (I-RODS Score)
Description	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 Inflammatory Rasch-built overall disability scale (I-RODS Score) using the MCID concept related to the varying standard errors (MCID-SE) as recently demonstrated
Time Frame	at Week 24

Outcome Measure Data

Analysis Population Description

Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.

Arm/Group Title	0.5 g/kg NewGam	1.0 g/kg NewGam	2.0 g/kg NewGam
Arm/Group Description	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).	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).	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).
Measure Participants	34	69	36
Number [Proportion of responders]	.3824	.5507	.7222

5. Secondary Outcome

Title	Worsening in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score
Description	Time to first confirmed worsening on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale by at least 1 point from the value at baseline (Week 0)
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

There was only 1 patient with worsening (in the 1.0 g/kg group), thus an analysis of the time to first worsening was not possible.

Arm/Group Title	0.5 g/kg NewGam	1.0 g/kg NewGam	2.0 g/kg NewGam
Arm/Group Description	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).	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).	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).
Measure Participants	34	69	36
Median (95% Confidence Interval) [days]	NA	NA	NA

6. Secondary Outcome

Title	Mean Change in Grip Strength
Description	Mean change from baseline (Week 0) to Termination Visit in grip strength of both hands (assessed by Martin vigorimeter). The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.

Arm/Group Title	0.5 g/kg NewGam	1.0 g/kg NewGam	2.0 g/kg NewGam
Arm/Group Description	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).	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).	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).
Measure Participants	34	69	36
Dominant Hand	23.91 (25.290)	19.38 (20.377)	26.06 (25.030)
Non-dominant Hand	23.94 (24.600)	17.43 (19.916)	24.53 (22.247)

7. Secondary Outcome

Title	Inflammatory Rasch-built Overall Disability Scale (I-RODS)
Description	Mean change from baseline (Week 0) to Termination Visit in Inflammatory Rasch-built overall disability sum score (I-RODS using the concept of MCID-SE as recently reported) and number of improvers. The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. A scale from 0 to 48, from "Not possible to perform" to "Possible without any difficulty". Higher values represent a better outcome.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.

Arm/Group Title	0.5 g/kg NewGam	1.0 g/kg NewGam	2.0 g/kg NewGam
Arm/Group Description	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).	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).	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).
Measure Participants	34	69	36
Mean (Standard Deviation) [score on a scale]	11.38 (12.485)	10.32 (10.836)	13.86 (11.981)

8. Secondary Outcome

Title	Motor Nerves
Description	Mean change from baseline (Week 0) to Termination Visit in sum of the distal evoked amplitude of 4 right sided and 4 left sided motor nerves (peroneal, tibial, ulnar and median). The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.

Arm/Group Title	0.5 g/kg NewGam	1.0 g/kg NewGam	2.0 g/kg NewGam
Arm/Group Description	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).	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).	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).
Measure Participants	34	68	36
Mean (Standard Deviation) [mV]	2.16 (6.332)	2.69 (6.688)	3.93 (9.298)

9. Secondary Outcome

Title	Mean Change in Pain Intensity Numerical Rating Scale (PI-NRS Scale)
Description	Mean change from baseline (Week 0) to Termination Visit in Pain Intensity Numeric Rating Scale (PI-NRS). The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. 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. A higher value represents a worse outcome.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.

Arm/Group Title	0.5 g/kg NewGam	1.0 g/kg NewGam	2.0 g/kg NewGam
Arm/Group Description	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).	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).	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).
Measure Participants	34	69	36
Mean (Standard Deviation) [score on a scale]	-2.29 (3.040)	-2.19 (2.907)	-2.17 (3.256)

10. Secondary Outcome

Title	Worsening on the Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale)
Description	Time to first confirmed worsening on the I-RODS scale. The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. A scale from 0 to 48, from "Not possible to perform" to "Possible without any difficulty". Higher values represent a better outcome. Worsening is determined using the concept of MCID (minimum clinically important difference) using the individually obtained standard errors (MCID-SE).
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

There was 1 patient with worsening in the 0.5 g/kg group and 2 in the 1.0 g/kg group; an analysis of the time to first worsening was not possible

Arm/Group Title	0.5 g/kg NewGam	1.0 g/kg NewGam	2.0 g/kg NewGam
Arm/Group Description	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).	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).	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).
Measure Participants	34	69	36
Median (95% Confidence Interval) [days]	NA	NA	NA

11. Secondary Outcome

Title	1 Point Decrease in the INCAT Disability Score
Description	Time to 1 point decrease (improvement of disability) in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.

Arm/Group Title	0.5 g/kg NewGam	1.0 g/kg NewGam	2.0 g/kg NewGam
Arm/Group Description	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).	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).	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).
Measure Participants	34	69	36
Median (95% Confidence Interval) [days]	22.0	26.0	23.0

12. Secondary Outcome

Title	Decrease in Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale)
Description	Time to decrease in Inflammatory Rasch-built overall disability scale (I-RODS) scores
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.

Arm/Group Title	0.5 g/kg NewGam	1.0 g/kg NewGam	2.0 g/kg NewGam
Arm/Group Description	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).	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).	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).
Measure Participants	34	69	36
Median (95% Confidence Interval) [days]	NA	NA	NA

Adverse Events

Time Frame	Up to 36 weeks
Adverse Event Reporting Description	An AE is any untoward medical occurrence in a patient receiving an IMP and which does not have to have a causal relationship with treatment. At each visit AEs will be elicited using a standard non-leading question like "How have you been since the last visit / during the previous study period?" Patient diaries will also be checked. Safety Data Set (SDS): The SDS was based on all randomized patients who received at least part of one infusion of IMP. Therefore n=142 for the SDS.
Arm/Group Title	NGAM 0.5 g/kg		NGAM 1.0 g/kg		NGAM 2.0 g/kg		Total
Arm/Group Description	NGAM 0.5 g/kg		NGAM 1.0 g/kg		NGAM 2.0 g/kg		Total of all three treatment arms.
All Cause Mortality
	NGAM 0.5 g/kg		NGAM 1.0 g/kg		NGAM 2.0 g/kg		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		1/69 (1.4%)		1/38 (2.6%)		2/142 (1.4%)
Serious Adverse Events
	NGAM 0.5 g/kg		NGAM 1.0 g/kg		NGAM 2.0 g/kg		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/35 (2.9%)		4/69 (5.8%)		1/38 (2.6%)		6/142 (4.2%)
Cardiac disorders
Cardio-respiratory Arrest	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Ear and labyrinth disorders
Deafness unilateral	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Gastrointestinal disorders
Vomiting	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Infections and infestations
Osteomyelitis	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Pneumonia	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Encephalitis	0/35 (0%)	0	0/69 (0%)	0	1/38 (2.6%)	1	1/142 (0.7%)	1
Musculoskeletal and connective tissue disorders
Osteonecrosis	1/35 (2.9%)	1	0/69 (0%)	0	0/38 (0%)	0	1/142 (0.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Nervous system disorders
Headache	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Other (Not Including Serious) Adverse Events
	NGAM 0.5 g/kg		NGAM 1.0 g/kg		NGAM 2.0 g/kg		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/35 (57.1%)		45/69 (65.2%)		24/38 (63.2%)		88/142 (62%)
Blood and lymphatic system disorders
Leukopenia	1/35 (2.9%)	2	5/69 (7.2%)	5	0/38 (0%)	0	6/142 (4.2%)	7
Anaemia	0/35 (0%)	0	2/69 (2.9%)	2	1/38 (2.6%)	2	3/142 (2.1%)	4
Thrombocytopenia	0/35 (0%)	0	2/69 (2.9%)	2	0/38 (0%)	0	2/142 (1.4%)	2
Eosinophilia	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Lymphadenitis	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Neutropenia	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Thrombocytosis	1/35 (2.9%)	1	0/69 (0%)	0	0/38 (0%)	0	1/142 (0.7%)	1
Cardiac disorders
Tachycardia	1/35 (2.9%)	1	2/69 (2.9%)	4	1/38 (2.6%)	1	4/142 (2.8%)	6
Bradycardia	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Left atrial dilatation	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Left ventricular hypertrophy	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Ear and labyrinth disorders
Tinnitus	0/35 (0%)	0	0/69 (0%)	0	1/38 (2.6%)	1	1/142 (0.7%)	1
Eye disorders
Conjunctival oedema	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Gastrointestinal disorders
Nausea	1/35 (2.9%)	1	1/69 (1.4%)	2	3/38 (7.9%)	5	5/142 (3.5%)	8
Diarrhoea	0/35 (0%)	0	2/69 (2.9%)	2	2/38 (5.3%)	2	4/142 (2.8%)	4
Vomiting	0/35 (0%)	0	1/69 (1.4%)	2	1/38 (2.6%)	1	2/142 (1.4%)	3
Abdominal pain	0/35 (0%)	0	1/69 (1.4%)	2	0/38 (0%)	0	1/142 (0.7%)	2
Abdominal pain lower	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Abdominal pain upper	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Dysphagia	1/35 (2.9%)	1	0/69 (0%)	0	0/38 (0%)	0	1/142 (0.7%)	1
Gastrooesophageal reflux disease	1/35 (2.9%)	1	0/69 (0%)	0	0/38 (0%)	0	1/142 (0.7%)	1
Hiatus hernia	1/35 (2.9%)	1	0/69 (0%)	0	0/38 (0%)	0	1/142 (0.7%)	1
General disorders
Pyrexia	3/35 (8.6%)	4	6/69 (8.7%)	6	2/38 (5.3%)	3	11/142 (7.7%)	13
Chills	3/35 (8.6%)	4	3/69 (4.3%)	3	1/38 (2.6%)	1	7/142 (4.9%)	8
Influenza like illness	0/35 (0%)	0	3/69 (4.3%)	3	0/38 (0%)	0	3/142 (2.1%)	3
Asthenia	0/35 (0%)	0	1/69 (1.4%)	1	1/38 (2.6%)	1	2/142 (1.4%)	2
Chest pain	0/35 (0%)	0	1/69 (1.4%)	1	1/38 (2.6%)	1	2/142 (1.4%)	2
Catheter site pain	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Chest discomfort	0/35 (0%)	0	0/69 (0%)	0	1/38 (2.6%)	2	1/142 (0.7%)	2
Infusion site coldness	0/35 (0%)	0	1/69 (1.4%)	2	0/38 (0%)	0	1/142 (0.7%)	2
Infusion site discomfort	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Oedema peripheral	0/35 (0%)	0	0/69 (0%)	0	1/38 (2.6%)	1	1/142 (0.7%)	1
Peripheral swelling	0/35 (0%)	0	0/69 (0%)	0	1/38 (2.6%)	1	1/142 (0.7%)	1
Hepatobiliary disorders
Autoimmune hepatitis	1/35 (2.9%)	1	0/69 (0%)	0	0/38 (0%)	0	1/142 (0.7%)	1
Gallbladder disorders	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Infections and infestations
Nasopharyngitis	1/35 (2.9%)	1	2/69 (2.9%)	2	2/38 (5.3%)	2	5/142 (3.5%)	5
Respiratory tract infection viral	1/35 (2.9%)	1	2/69 (2.9%)	2	1/38 (2.6%)	1	4/142 (2.8%)	4
Urinary tract infection	1/35 (2.9%)	1	2/69 (2.9%)	2	1/38 (2.6%)	1	4/142 (2.8%)	4
Eczema infected	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Infective exacerbation of bronchiectasis	0/35 (0%)	0	1/69 (1.4%)	2	0/38 (0%)	0	1/142 (0.7%)	2
Influenza	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Pharyngitis	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Sinusitis	0/35 (0%)	0	0/69 (0%)	0	1/38 (2.6%)	1	1/142 (0.7%)	1
Upper respiratory tract infection	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Viral pharyngitis	1/35 (2.9%)	1	0/69 (0%)	0	0/38 (0%)	0	1/142 (0.7%)	1
Viral upper respiratory tract infection	0/35 (0%)	0	0/69 (0%)	0	1/38 (2.6%)	1	1/142 (0.7%)	1
Injury, poisoning and procedural complications
Contusion	0/35 (0%)	0	0/69 (0%)	0	1/38 (2.6%)	1	1/142 (0.7%)	1
Fall	0/35 (0%)	0	0/69 (0%)	0	1/38 (2.6%)	1	1/142 (0.7%)	1
Laceration	1/35 (2.9%)	1	0/69 (0%)	0	0/38 (0%)	0	1/142 (0.7%)	1
Ligament injury	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Investigations
Blood pressure increased	3/35 (8.6%)	7	6/69 (8.7%)	7	0/38 (0%)	0	9/142 (6.3%)	14
Body temperature increased	2/35 (5.7%)	2	4/69 (5.8%)	7	3/38 (7.9%)	3	9/142 (6.3%)	12
Blood lactate dehydrogenase increased	0/35 (0%)	0	5/69 (7.2%)	5	0/38 (0%)	0	5/142 (3.5%)	5
Heart rate decreased	0/35 (0%)	0	2/69 (2.9%)	2	1/38 (2.6%)	1	3/142 (2.1%)	3
Transaminases increased	1/35 (2.9%)	1	2/69 (2.9%)	2	0/38 (0%)	0	3/142 (2.1%)	3
Alanine aminotransferase increased	0/35 (0%)	0	2/69 (2.9%)	3	0/38 (0%)	0	2/142 (1.4%)	3
Aspartate aminotransferase increased	0/35 (0%)	0	2/69 (2.9%)	3	0/38 (0%)	0	2/142 (1.4%)	3
Blood uric acid increased	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Fibrin D dimer increased	0/35 (0%)	0	0/69 (0%)	0	1/38 (2.6%)	1	1/142 (0.7%)	1
Haemoglobin decreased	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Weight decreased	1/35 (2.9%)	1	0/69 (0%)	0	0/38 (0%)	0	1/142 (0.7%)	1
Metabolism and nutrition disorders
Dehydration	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Diabetes mellitus inadequate control	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Dyslipidaemia	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Electrolyte imbalance	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Type 2 diabetes mellitus	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/35 (0%)	0	4/69 (5.8%)	4	2/38 (5.3%)	2	6/142 (4.2%)	6
Pain in extremity	1/35 (2.9%)	1	2/69 (2.9%)	2	0/38 (0%)	0	3/142 (2.1%)	3
Arthralgia	0/35 (0%)	0	0/69 (0%)	0	1/38 (2.6%)	1	1/142 (0.7%)	1
Nervous system disorders
Headache	1/35 (2.9%)	1	9/69 (13%)	11	8/38 (21.1%)	12	19/142 (13.4%)	25
Somnolence	2/35 (5.7%)	3	0/69 (0%)	0	1/38 (2.6%)	1	3/142 (2.1%)	4
Dizziness	1/35 (2.9%)	1	0/69 (0%)	0	1/38 (2.6%)	1	2/142 (1.4%)	2
Tension headache	0/35 (0%)	0	1/69 (1.4%)	4	1/38 (2.6%)	3	2/142 (1.4%)	7
Carpal tunnel syndrome	0/35 (0%)	0	0/69 (0%)	0	1/38 (2.6%)	1	1/142 (0.7%)	1
Neuralgia	0/35 (0%)	0	0/69 (0%)	0	1/38 (2.6%)	1	1/142 (0.7%)	1
Paraesthesia	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Restless legs syndrome	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Renal and urinary disorders
Micturition urgency	0/35 (0%)	0	0/69 (0%)	0	1/38 (2.6%)	1	1/142 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/35 (0%)	0	1/69 (1.4%)	1	1/38 (2.6%)	1	2/142 (1.4%)	2
Dyspnoea	0/35 (0%)	0	0/69 (0%)	0	1/38 (2.6%)	1	1/142 (0.7%)	1
Tachypnoea	0/35 (0%)	0	1/69 (1.4%)	4	0/38 (0%)	0	1/142 (0.7%)	4
Skin and subcutaneous tissue disorders
Dermatitis allergic	4/35 (11.4%)	4	5/69 (7.2%)	10	4/38 (10.5%)	5	13/142 (9.2%)	19
Skin exfoliation	1/35 (2.9%)	1	2/69 (2.9%)	3	1/38 (2.6%)	1	4/142 (2.8%)	5
Urticaria	3/35 (8.6%)	4	0/69 (0%)	0	0/38 (0%)	0	3/142 (2.1%)	4
Pruritus	0/35 (0%)	0	0/69 (0%)	0	2/38 (5.3%)	3	2/142 (1.4%)	3
Rash	0/35 (0%)	0	1/69 (1.4%)	1	1/38 (2.6%)	5	2/142 (1.4%)	6
Seborrhoeic dermatitis	1/35 (2.9%)	1	0/69 (0%)	0	1/38 (2.6%)	1	2/142 (1.4%)	2
Decubitis ulcer	0/35 (0%)	0	1/69 (1.4%)	1	0/38 (0%)	0	1/142 (0.7%)	1
Dermatitis atopic	0/35 (0%)	0	0/69 (0%)	0	1/38 (2.6%)	1	1/142 (0.7%)	1
Erythema	1/35 (2.9%)	2	0/69 (0%)	0	0/38 (0%)	0	1/142 (0.7%)	2
Rash erythematous	1/35 (2.9%)	1	0/69 (0%)	0	0/38 (0%)	0	1/142 (0.7%)	1
Vascular disorders
Hypertension	0/35 (0%)	0	3/69 (4.3%)	3	0/38 (0%)	0	3/142 (2.1%)	3
Hypotension	1/35 (2.9%)	1	0/69 (0%)	0	0/38 (0%)	0	1/142 (0.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.