Study of the Efficacy and Safety of Immune Globulin Intra... | NCT02176863

ID	Type	Description	Link
2013-004503-39	EudraCT Number

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Stage 1 Arm 1: 2 g/kg Flebogamma® 5% DIF	Experimental	Participants received Flebogamma® 5% DIF 2 g/kg of body weight administered via intravenous (IV) infusion over 2 consecutive days (Flebogamma® 5% DIF 1 g/kg infused on Day 1, followed by Flebogamma® 5% DIF 1 g/kg infused on Day 2) every 4 weeks for 52 weeks.	Biological: Flebogamma® 5% DIF
Stage 1 Arm 2: 1 g/kg Flebogamma® 5% DIF	Experimental	Participants received Flebogamma® 5% DIF 1 g/kg of body weight administered via IV infusion on Day 1, followed by 20 mL/kg of matching placebo administered on a separate day, for a total dosing period of 2 consecutive days, every 4 weeks for 52 weeks. The order of 1 g/kg Flebogamma® 5% DIF or matching placebo was randomly determined for each participant and was the same for the participant for all infusion visits during the treatment period.	Biological: Flebogamma® 5% DIF Drug: Placebo
Stage 1 Arm 3: Placebo	Placebo Comparator	Participants received matching placebo at a total dose of 40 mL/kg of body weight administered via IV infusion over 2 consecutive days. On Day 1, a dose of 20 mL/kg of matching placebo was given, followed by the second dose of 20 mL/kg of matching placebo on Day 2, administered every 4 weeks for 52 weeks.	Drug: Placebo
Stage 2 Arm 1: 1 g/kg Flebogamma® 5% DIF	Experimental	Participants received Flebogamma® 5% DIF 1 g/kg of body weight administered via IV infusion on Day 1, followed by 20 mL/kg of matching placebo administered on a separate day, for a total dosing period of 2 consecutive days, every 4 weeks for 52 weeks. The order of 1 g/kg of Flebogamma® 5% DIF or matching placebo was randomly determined for each participant and was the same for the participant for all infusion visits during the treatment period.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Flebogamma® 5% DIF	Biological	Human plasma-derived immunoglobulin	Stage 1 Arm 1: 2 g/kg Flebogamma® 5% DIF Stage 1 Arm 2: 1 g/kg Flebogamma® 5% DIF

Measure	Description	Time Frame
Change From Baseline in Physical Performance Assessed by Two-Minute Walk Distance (2MWD) Test	The 2MWD was used to assess physical performance by measuring the distance that a participant can quickly walk at a self-preferred speed on an indoor flat, hard surface 30 m (100-ft) hallway in a period of 2 minutes. A positive change from baseline indicates improvement (i.e. a patient can walk farther). Increase in distance walked (in meters) indicates improvement.	Baseline to Week 52

Measure	Description	Time Frame
Change From Baseline in Pain Using Visual Analogue Scale (VAS) of Pain	VAS is a participant self-reported pain scale used to evaluate the pain level in a 24 hours period. The scale consists of a 100 millimeters (mm) scale where 100 mm stands for the worst imaginable pain and zero stands for no pain. Higher scores indicate severe pain. A negative change from baseline indicates improvement. LS mean and 95% (CI) were based on MMRM method.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participants with Body Mass Index less than 35 kg/m^2.
Participants who meet the clinical criteria for diagnosis of PPS as set by March-of-Dimes.
Participants who are ambulatory or are able to walk with a cane or other aids or use a wheelchair (but they are not wheelchair-bound).
Participants who have at least 2 newly weakened muscle groups due to PPS (as defined by medical history), with at least 1 of them in a lower extremity, and having a Medical Research Council (MRC) scale score greater than 3 at the Manual Muscle Testing (MMT) performed by the independent assessor at the Screening Visit (SV).
Female of child-bearing potential must have a negative test for pregnancy (Human chorionic gonadotropin (HCG)-based assay).
Female of child-bearing potential and their sexual partners have agreed to practice contraception using a method of proven reliability (i.e., hormonal methods; barrier methods; intrauterine devices methods) to prevent a pregnancy during the course of the clinical trial.
Participants must be willing to comply with all aspects of the clinical trial protocol, including blood sampling and long-term storage of extra samples for the entire duration of the study.
Participants who are able to walk a 2MWD of at least 50 meters at the SV and Enrollment Visit/Infusion Visit 1 (EV/IV1)
Participants who are able to walk a consistent baseline 2 MWD, that is, the difference in 2MWD between the SV and EV/IV1 is not more than 10%.

Exclusion Criteria:

Participants who have received human normal immune globulin treatment given by intravenous, subcutaneous, or intramuscular route within the last 3 years.
Participants who are not ambulatory (wheelchair-bound individuals).
Participants with poor venous access.
Participants with intractable pain requiring narcotics or other psychotropic drugs.
Participants with a history of anaphylactic reactions or severe reactions to any blood-derived product.
Participants with a history of intolerance to any component of the investigational products, such as sorbitol.
Participants receiving corticosteroids, except for those who are taking inhaled corticosteroids for asthma.
Participants with a documented diagnosis of hyper viscosity or hypercoagulable state or thrombotic complications to polyclonal intravenous immunoglobulin (IVIG) therapy in the past.
Participants with a history of recent (within the last year) myocardial infarction, stroke, or uncontrolled hypertension.
Participants who suffer from congestive heart failure, embolism, or electrocardiogram changes indicative of unstable angina or atrial fibrillation.
Participants with a history of chronic alcoholism or illicit drug abuse (addiction) in the preceding 12 months prior to the SV.
Participants with active psychiatric illness that interferes with compliance or communication with health care personnel.
Participants with depression with scores >30 as assessed by the Center for Epidemiologic Studies Depression (CESD) validated scale.
Females who are pregnant or are nursing an infant child.
Participants with any medical condition which makes clinical trial participation unadvisable or which is likely to interfere with the evaluation of the study treatment and/or the satisfactory conduct of the clinical trial according to the Investigator's judgment.
Participants currently receiving, or have received within 3 months prior to the SV, any investigational medicinal product or device.
Participants who are unlikely to adhere to the protocol requirements, or are likely to be uncooperative, or unable to provide a storage serum/plasma sample prior to the first investigational drug infusion.
Participants with known selective Immune globulin A class (IgA) deficiency and serum antibodies anti-IgA.
Participants with renal impairment (i.e., serum creatinine exceeds more than 1.5 times the upper limit of normal [ULN]) for the expected normal range for the testing laboratory).
Participants with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels exceeding more than 2.5 times the ULN.
Participants with hemoglobin levels <10 g/dL, platelets levels <100,000 /mm^3, white blood cells count <3.0 k/µL, and erythrocyte sedimentation rate >50 mm/h or twice above normal.
Participants with known seropositive to Hepatitis C virus (HCV), Human immunodeficiency virus-1 (HIV-1) and/or Human immunodeficiency virus-2 (HIV-2).
Participants with a history of intolerance to fructose.

Name	Affiliation	Role
Marinos Dalakas, MD	Coordinating Investigator	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Washington University		St Louis	Missouri	63110	United States
SUNY Upstate Medical University

ID	Title	Description
FG000	Stage 1 Arm 1: 2 g/kg Flebogamma® 5% DIF	Participants received Flebogamma® 5% DIF 2 g/kg of body weight administered via intravenous (IV) infusion over 2 consecutive days (Flebogamma® 5% DIF 1 g/kg infused on Day 1, followed by Flebogamma® 5% DIF 1 g/kg infused on Day 2) every 4 weeks for 52 weeks.
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 7, 2022	Nov 20, 2025

Arm/Group Information

ID	Title	Description
BG000	Stage 1 Arm 1: 2 g/kg Flebogamma® 5% DIF	Participants received Flebogamma® 5% DIF 2 g/kg of body weight administered via intravenous (IV) infusion over 2 consecutive days (Flebogamma® 5% DIF 1 g/kg infused on Day 1, followed by Flebogamma® 5% DIF 1 g/kg infused on Day 2) every 4 weeks for 52 weeks.
BG001	Stage 1 Arm 2: 1 g/kg Flebogamma® 5% DIF	Participants received Flebogamma® 5% DIF 1 g/kg of body weight administered via IV infusion on Day 1, followed by 20 mL/kg of matching placebo administered on a separate day, for a total dosing period of 2 consecutive days, every 4 weeks for 52 weeks. The order of 1 g/kg Flebogamma® 5% DIF or matching placebo was randomly determined for each participant and was the same for the participant for all infusion visits during the treatment period.
BG002	Stage 1 Arm 3: Placebo	Participants received matching placebo at a total dose of 40 mL/kg of body weight administered via IV infusion over 2 consecutive days. On Day 1, a dose of 20 mL/kg of matching placebo was given, followed by the second dose of 20 mL/kg of matching placebo on Day 2, administered every 4 weeks for 52 weeks.
BG003	Stage 2 Arm 1: 1 g/kg Flebogamma® 5% DIF	Participants received Flebogamma® 5% DIF 1 g/kg of body weight administered via IV infusion on Day 1, followed by 20 mL/kg of matching placebo administered on a separate day, for a total dosing period of 2 consecutive days, every 4 weeks for 52 weeks. The order of 1 g/kg of Flebogamma® 5% DIF or matching placebo was randomly determined for each participant and was the same for the participant for all infusion visits during the treatment period.
BG004	Stage 2 Arm 2: Placebo	Participants received matching placebo at a total dose of 40 mL/kg of body weight administered via IV infusion over 2 consecutive days. On Day 1, a dose of 20 mL/kg of matching placebo was given, followed by the second dose of 20 mL/kg of matching placebo on Day 2, administered every 4 weeks for 52 weeks.
BG005	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Physical Performance Assessed by Two-Minute Walk Distance (2MWD) Test

The 2MWD was used to assess physical performance by measuring the distance that a participant can quickly walk at a self-preferred speed on an indoor flat, hard surface 30 m (100-ft) hallway in a period of 2 minutes. A positive change from baseline indicates improvement (i.e. a patient can walk farther). Increase in distance walked (in meters) indicates improvement.

ITT population included all participants who were randomized.

Posted

Mean

Standard Deviation

meters (m)

Baseline to Week 52

ID	Title	Description
OG000	Stage 1 Arm 1: 2 g/kg Flebogamma® 5% DIF	Participants received Flebogamma® 5% DIF 2 g/kg of body weight administered via intravenous (IV) infusion over 2 consecutive days (Flebogamma® 5% DIF 1 g/kg infused on Day 1, followed by Flebogamma® 5% DIF 1 g/kg infused on Day 2) every 4 weeks for 52 weeks.
OG001	Stage 1 Arm 2: 1 g/kg Flebogamma® 5% DIF	Participants received Flebogamma® 5% DIF 1 g/kg of body weight administered via IV infusion on Day 1, followed by 20 mL/kg of matching placebo administered on a separate day, for a total dosing period of 2 consecutive days, every 4 weeks for 52 weeks. The order of 1 g/kg Flebogamma® 5% DIF or matching placebo was randomly determined for each participant and was the same for the participant for all infusion visits during the treatment period.
OG002	Stage 1 Arm 3: Placebo	Participants received matching placebo at a total dose of 40 mL/kg of body weight administered via IV infusion over 2 consecutive days. On Day 1, a dose of 20 mL/kg of matching placebo was given, followed by the second dose of 20 mL/kg of matching placebo on Day 2, administered every 4 weeks for 52 weeks.
OG003	Stage 2 Arm 1: 1 g/kg Flebogamma® 5% DIF	Participants received Flebogamma® 5% DIF 1 g/kg of body weight administered via IV infusion on Day 1, followed by 20 mL/kg of matching placebo administered on a separate day, for a total dosing period of 2 consecutive days, every 4 weeks for 52 weeks. The order of 1 g/kg of Flebogamma® 5% DIF or matching placebo was randomly determined for each participant and was the same for the participant for all infusion visits during the treatment period.
OG004	Stage 2 Arm 2: Placebo	Participants received matching placebo at a total dose of 40 mL/kg of body weight administered via IV infusion over 2 consecutive days. On Day 1, a dose of 20 mL/kg of matching placebo was given, followed by the second dose of 20 mL/kg of matching placebo on Day 2, administered every 4 weeks for 52 weeks.

Units	Counts
Participants	OG00042 OG00142 OG00242 OG003

Title

Denominators

Categories

Baseline

Title	Measurements
	OG000109.03± 30.564 OG001112.55± 27.987 OG002105.86± 31.942 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG002 OG003 OG004		Posch and Bauer Method		0.0469	The overall adjusted p-value for the selected dose of Flebogamma® 5% DIF vs placebo was calculated from the p-values of both Stage 1 and Stage 2 by Posch & Bauer for testing the equality of means between the selected dose and placebo.													Superiority

Secondary

Change From Baseline in Pain Using Visual Analogue Scale (VAS) of Pain

VAS is a participant self-reported pain scale used to evaluate the pain level in a 24 hours period. The scale consists of a 100 millimeters (mm) scale where 100 mm stands for the worst imaginable pain and zero stands for no pain. Higher scores indicate severe pain. A negative change from baseline indicates improvement. LS mean and 95% (CI) were based on MMRM method.

ITT population included all participants who were randomized. As pre-specified in SAP, the analyses was performed over the two stages combined, using the placebo and selected dose of Flebogamma® 5% DIF treatment groups.

Posted

Least Squares Mean

95% Confidence Interval

millimeter (mm)

Baseline to Week 52

ID	Title	Description
OG000	Flebogamma® 5% DIF 1 g/kg	Participants received Flebogamma® 5% DIF 1 g/kg of body weight administered via IV infusion on Day 1 followed by 20 mL/kg of matching placebo administered on a separate day, for a total dosing period of 2 consecutive days every 4 weeks for 52 weeks during Stage 1 and then every 4 weeks for 52 weeks during Stage 2 of the study. The order of 1 g/kg of Flebogamma® 5% DIF was randomly determined for each participant and was the same for the participant for all infusion visits during the treatment period.
OG001	Placebo	Participants received matching placebo at a total dose of 40 mL/kg of body weight administered via IV infusion over 2 consecutive days. On Day 1, a dose of 20 mL/kg of matching placebo was given, followed by the second dose of 20 mL/kg of matching placebo on Day 2, administered every 4 weeks for 52 weeks during Stage 1 and then every 4 weeks for 52 weeks during Stage 2 of the study.

Secondary

Change From Baseline in Health-Related Quality of Life (HRQoL) Assessed by Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) Physical Component Summary (PCS)

HRQoL SF-36 is participant self-reported survey.It yields 8-scale profile of functional health and well-being as well as physical and mental health summary measures. It consists of the subscales:physical functioning,limitations due to physical health,body pain,general health,vitality,social functioning,emotional problems, and mental health. Each domain score ranges from 0(worst) to 100(best),higher scores reflect better functional status.PCS is a subscale score & give broader metric of physical HRQoL.PCS score ranges from 0 to 100 and is computed such that mean score of 50 corresponds to the general US population.Based on norm-based scoring,scores above 50 is better-than-average health & below 50 is below-average health.Higher scores represents better physical health.Positive change from baseline indicates improvement.LS mean and 95% CI were based on MMRM.

Posted

Least Squares Mean

95% Confidence Interval

Score on a scale

Baseline to Week 52

ID	Title	Description
OG000	Flebogamma® 5% DIF 1 g/kg	Participants received Flebogamma® 5% DIF 1 g/kg of body weight administered via IV infusion on Day 1 followed by 20 mL/kg of matching placebo administered on a separate day, for a total dosing period of 2 consecutive days every 4 weeks for 52 weeks during Stage 1 and then every 4 weeks for 52 weeks during Stage 2 of the study. The order of 1 g/kg of Flebogamma® 5% DIF was randomly determined for each participant and was the same for the participant for all infusion visits during the treatment period.

Secondary

Change From Baseline in Endurance Assessed by Six-Minute Walk Distance (6MWD) Test

The 6MWD was used to assess physical performance by measuring the distance that a patient can quickly walk at maximal speed on a flat, hard surface 30 m (100-ft) hallway in a period of 6 minutes. A positive change from baseline indicates improvement (i.e., a patient can walk farther). Increase from baseline in distance walked (in meters) indicated improvement. LS mean and 95% CI were based on MMRM method.

Posted

Least Squares Mean

95% Confidence Interval

meters (m)

Baseline to Week 52

ID	Title	Description
OG000	Flebogamma® 5% DIF 1 g/kg	Participants received Flebogamma® 5% DIF 1 g/kg of body weight administered via IV infusion on Day 1 followed by 20 mL/kg of matching placebo administered on a separate day, for a total dosing period of 2 consecutive days every 4 weeks for 52 weeks during Stage 1 and then every 4 weeks for 52 weeks during Stage 2 of the study. The order of 1 g/kg of Flebogamma® 5% DIF was randomly determined for each participant and was the same for the participant for all infusion visits during the treatment period.
OG001	Placebo	Participants received matching placebo at a total dose of 40 mL/kg of body weight administered via IV infusion over 2 consecutive days. On Day 1, a dose of 20 mL/kg of matching placebo was given, followed by the second dose of 20 mL/kg of matching placebo on Day 2, administered every 4 weeks for 52 weeks during Stage 1 and then every 4 weeks for 52 weeks during Stage 2 of the study.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment	EG0001 affected42 at risk EG0010 affected75 at risk EG0020 affected74 at risk
Hypertension	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0010 affected75 at risk EG0022 affected74 at risk
Miscarriage of partner	Social circumstances	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0010 affected75 at risk EG0021 affected74 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0011 affected75 at risk EG0020 affected74 at risk
Diagnostic procedure	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0011 affected75 at risk EG0020 affected74 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0010 affected75 at risk EG0021 affected74 at risk
Bone fissure	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0010 affected75 at risk EG0021 affected74 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0011 affected75 at risk EG0020 affected74 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0011 affected75 at risk EG0020 affected74 at risk
Myocardial infarction	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected42 at risk EG0010 affected75 at risk EG0020 affected74 at risk
Meningism	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0011 affected75 at risk EG0020 affected74 at risk
Syncope	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0010 affected75 at risk EG0021 affected74 at risk
Vertigo positional	Ear and labyrinth disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0011 affected75 at risk EG0020 affected74 at risk
Food poisoning	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0010 affected75 at risk EG0021 affected74 at risk
Pancreatitis chronic	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0010 affected75 at risk EG0021 affected74 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0010 affected75 at risk EG0021 affected74 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0011 affected75 at risk EG0020 affected74 at risk
Herpes zoster	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0010 affected75 at risk EG0021 affected74 at risk
Pneumonia	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0010 affected75 at risk EG0022 affected74 at risk
Prostate infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0011 affected75 at risk EG0020 affected74 at risk
Pyelonephritis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected42 at risk EG0010 affected75 at risk EG0020 affected74 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vertigo	Ear and labyrinth disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected42 at risk EG0013 affected75 at risk EG0024 affected74 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0017 affected75 at risk EG0028 affected74 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00011 affected42 at risk EG00113 affected75 at risk EG0024 affected74 at risk
Vomiting	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0006 affected42 at risk EG0015 affected75 at risk EG0023 affected74 at risk
Chills	General disorders	MedDRA 26.0	Systematic Assessment	EG0008 affected42 at risk EG00115 affected75 at risk EG0022 affected74 at risk
Fatigue	General disorders	MedDRA 26.0	Systematic Assessment	EG00014 affected42 at risk EG00122 affected75 at risk EG00220 affected74 at risk
Influenza like illness	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG00110 affected75 at risk EG0023 affected74 at risk
Infusion site swelling	General disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected42 at risk EG0012 affected75 at risk EG0024 affected74 at risk
Non-cardiac chest pain	General disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected42 at risk EG0014 affected75 at risk EG0021 affected74 at risk
Oedema peripheral	General disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected42 at risk EG0013 affected75 at risk EG0028 affected74 at risk
Pain	General disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected42 at risk EG0015 affected75 at risk EG0021 affected74 at risk
Pyrexia	General disorders	MedDRA 26.0	Systematic Assessment	EG0008 affected42 at risk EG00113 affected75 at risk EG0021 affected74 at risk
Cystitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected42 at risk EG0012 affected75 at risk EG0024 affected74 at risk
Influenza	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0004 affected42 at risk EG0019 affected75 at risk EG0022 affected74 at risk
Nasopharyngitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0004 affected42 at risk EG0018 affected75 at risk EG00211 affected74 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 affected42 at risk EG0013 affected75 at risk EG0024 affected74 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0002 affected42 at risk EG0015 affected75 at risk EG0028 affected74 at risk
Blood pressure increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0018 affected75 at risk EG0020 affected74 at risk
Fibrin D dimer increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0003 affected42 at risk EG0015 affected75 at risk EG0025 affected74 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0008 affected42 at risk EG00112 affected75 at risk EG00212 affected74 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0005 affected42 at risk EG0018 affected75 at risk EG0026 affected74 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected42 at risk EG0012 affected75 at risk EG0024 affected74 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0006 affected42 at risk EG00110 affected75 at risk EG0023 affected74 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0014 affected75 at risk EG0022 affected74 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected42 at risk EG00110 affected75 at risk EG0025 affected74 at risk
Dizziness	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected42 at risk EG0014 affected75 at risk EG00213 affected74 at risk
Headache	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG00027 affected42 at risk EG00139 affected75 at risk EG00223 affected74 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected42 at risk EG0014 affected75 at risk EG0023 affected74 at risk
Migraine	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected42 at risk EG0015 affected75 at risk EG0021 affected74 at risk
Paraesthesia	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0015 affected75 at risk EG0024 affected74 at risk
Device dislocation	Product Issues	MedDRA 26.0	Systematic Assessment	EG0003 affected42 at risk EG0011 affected75 at risk EG0020 affected74 at risk
Insomnia	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0014 affected75 at risk EG0020 affected74 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0004 affected42 at risk EG0013 affected75 at risk EG0021 affected74 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0004 affected42 at risk EG0011 affected75 at risk EG0023 affected74 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0014 affected75 at risk EG0022 affected74 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected42 at risk EG0014 affected75 at risk EG0020 affected74 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected42 at risk EG0014 affected75 at risk EG0021 affected74 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected42 at risk EG0014 affected75 at risk EG0021 affected74 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected42 at risk EG0017 affected75 at risk EG0023 affected74 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected42 at risk EG00111 affected75 at risk EG0020 affected74 at risk
Hypertension	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0007 affected42 at risk EG00112 affected75 at risk EG0028 affected74 at risk
Phlebitis	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected42 at risk EG0013 affected75 at risk EG0020 affected74 at risk

ID	Term
D011051	Poliomyelitis
D009187	Myelitis
D002494	Central Nervous System Infections
D007239	Infections
D004769	Enterovirus Infections
D010850	Picornaviridae Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D020966	Muscular Disorders, Atrophic
D009135	Muscular Diseases
D009140	Musculoskeletal Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D013118	Spinal Cord Diseases
D019636	Neurodegenerative Diseases
D000090862	Neuroinflammatory Diseases
D009468	Neuromuscular Diseases

ID	Term
D005719	gamma-Globulins
D016756	Immunoglobulins, Intravenous

ID	Term
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D007074	Immunoglobulin G
D007132	Immunoglobulin Isotypes
D000906	Antibodies

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Flebogamma® 5% DIF 2 g/kg	Participants received Flebogamma® 5% DIF 2 g/kg of body weight administered via intravenous (IV) infusion over 2 consecutive days (Flebogamma® 5% DIF 1 g/kg infused on Day 1, followed by Flebogamma® 5% DIF 1 g/kg infused on Day 2) every 4 weeks for 52 weeks.	42	3	42	36	42
EG001	Flebogamma® 5% DIF 1 g/kg	Participants received Flebogamma® 5% DIF 1 g/kg of body weight administered via IV infusion on Day 1 followed by 20 mL/kg of matching placebo administered on a separate day, for a total dosing period of 2 consecutive days every 4 weeks for 52 weeks during Stage 1 and then every 4 weeks for 52 weeks during stage 2 of the study. The order of 1 g/kg of Flebogamma® 5% DIF was randomly determined for each participant and was the same for the participant for all infusion visits during the treatment period.	75	7	75	71	75
EG002	Placebo	Participants received matching placebo at a total dose of 40 mL/kg of body weight administered via IV infusion over 2 consecutive days. On Day 1, a dose of 20 mL/kg of matching placebo was given, followed by the second dose of 20 mL/kg of matching placebo on Day 2, administered every 4 weeks for 52 weeks during Stage 1 and then every 4 weeks for 52 weeks during stage 2 of the study.	74	9	74	60	74