Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized, Multicenter, Double-blind, Placebo-controlled, Parallel-group Phase III Study to Investigate the Efficacy, Safety, and Tolerability of 2 Different Doses of IgPro20 (Subcutaneous Immunoglobulin) for the Treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) - the PATH Study
Brief Summary: This is a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group 3-arm study to investigate 2 different doses of subcutaneous (SC) IgPro20 compared with placebo for maintenance treatment of patients with CIDP.

Patients who received at lease 1 dose of intravenous immunoglobulin (IVIG) within 8 weeks before screening will be assessed during 4 separate study periods. Patients first undergo a Screening Period, followed by an IgG Dependency Test Period of up to 12 weeks to test for ongoing need of IgG. Those patients experiencing CIDP relapse during this test period will be administered a standardized IVIG regimen during an IVIG Re-stabilization Period. Patients with improved and maintained adjusted inflammatory neuropathy cause and treatment scale (INCAT) in the IVIG Re-stabilization Period will continue to the SC Treatment Period of the study. Patients entering the 24 week SC Treatment Period will be randomized to receive weekly infusions of 1 of 2 IgPro20 doses (0.2 or 0.4 g/kg body weight) or placebo.

The overall study duration is up to 52 weeks. Clinical outcomes will be assessed by the Inflammatory Neuropathy Cause and Treatment (INCAT) score, maximum grip strength, the Medical Research Council (MRC) sum score, the Rasch-built Overall Disability Scale (R-ODS), and electrophysiological evaluations.


Options:
A: Inclusion Criteria:

IVIG-untreated subjects:

* Either subjects with newly diagnosed CIDP (developing over at least 2 months) or subjects with an IVIG treatment interruption for at least 1 year with a progressive disease (deteriorating in the last 2 months) prior to enrolment.
* Actual diagnosis (including electrophysiology) of CIDP with progressive or relapsing dysfunction from motor and sensory or symmetric motor nerve only in at least 1 limb resulting from neuropathy. Criteria for definite or probable CIDP according to EFNS/PNS guideline.
* Age ≥18 years.
* Male or female.
* Written informed consent for study participation obtained before undergoing any study specific procedures.

IVIG-pretreated subjects:

* Being treated regularly with IVIG on a fixed cycle length of 2 to 6 weeks ± 5 days in the last 6 months, on a fixed dosage of ± 20 % in the last 6 months and deteriorating by at least 1 INCAT score point during the Washout Period of up to 10 weeks (except for an increase from 0 to 1 solely due to upper limb score).
* Historic diagnosis of CIDP with progressive or relapsing dysfunction from motor and sensory or symmetric motor nerve only in at least 1 limb resulting from neuropathy. Criteria for definite or probable CIDP according to EFNS/PNS guideline.
* Age ≥18 years.
* Male or female.
* Written informed consent for study participation obtained before undergoing any study specific procedures.

Exclusion Criteria:

* A motor syndrome that fulfils criteria for multifocal motor neuropathy (MMN) with conduction block (i.e., upper limb motor weakness without sensory deficit and with a 50% decrease in action potential amplitude or area on proximal compared with distal stimulation in motor nerves).
* CIDP with monoclonal gammopathy of uncertain significance (CIDP-MGUS) with anti-MGUS antibodies and patients with distal acquired demyelinating symmetric (DADS)neuropathy.
* Any disease (mainly neurological or chronic orthopedic) that may cause symptoms or may interfere with treatment or outcome assessments with the INCAT (e.g., diphtheria, drug or toxin exposure and diabetes mellitus likely to have caused the neuropathy, IgM paraproteinemia, familial neuropathy, borreliosis with radiculopathy, post-polio-syndrome,M. Parkinson, stroke).
* Current malignancy.
* History of cardiac insufficiency (New York Heart Association \[NYHA\] III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease, congestive heart failure or severe hypertension.
* History of thrombotic episodes (deep vein thrombosis, myocardial infarction, cerebrovascular accident).
* Migraine associated with IVIG infusion in the last 3 months prior to enrolment.
* Known allergic or other severe reactions to blood products including intolerability to previous IVIG (i.e. severe headache, hypersensitivity, intravascular hemolysis).
* Subjects with serum IgA level less than 50% of the lower normal limit.
* Known hyperprolinemia.
* Any condition (including alcohol, drug or medication abuse) that is likely to interfere with evaluation of the study product or satisfactory conduct of the study.
* Plasma exchange 3 months prior to enrolment.
* Treatment with immunomodulatory agents others than steroids, methotrexate or azathioprine (e.g. interferon, TNF-α inhibitors) within 6 months before enrolment.
* Treatment with rituximab in the 12 months before enrolment.
* Abnormal laboratory parameters: creatinine \> 1.5 times the upper normal limit (UNL), lactate dehydrogenase (LDH) \> 1.5 times the UNL, C-reactive protein (CRP) \> 1.5 times the UNL, hemoglobin (Hb) \< 10 g/dL.
* Ongoing HIV, hepatitis C and hepatitis B infection.
* Participation in another clinical study (or use of another investigational medicinal product \[IMP\]) within 3 months prior to enrolment
* Not able to comply with study procedures and treatment regimen.
* Employee at the study site, or spouse/partner or relative of any study staff (e.g., investigator, sub-investigators, or study nurse).
* Pregnancy or nursing mother.
* Intention to become pregnant during the course of the study.
* Female subjects of childbearing potential either not using, or not willing to use, a medically reliable method of contraception for the entire duration of the study, or not sexually abstinent for the entire duration of the study, or not surgically sterile.
B: Inclusion Criteria:

* Definite or probable CIDP according to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria 2010.
* An IVIG treatment during the last 8 weeks prior to enrollment.
* Age ≥18 years.
* Written informed consent for study participation obtained before undergoing any study-specific procedures.

Exclusion Criteria:

* Any polyneuropathy of other causes
* Any other disease (mainly neurological or chronic orthopedic) that has caused neurological symptoms or may interfere with treatment or outcome assessments
* Severe diseases and conditions that are likely to interfere with evaluation of the study product or satisfactory conduct of the study
* History of thrombotic episodes within the 2 years prior to enrolment
* Known allergic or other severe reactions to blood products including intolerability to previous IVIG
C: Inclusion Criteria:

* Documented diagnosis of CIDP must be made by a neurologist specializing/experienced in neuromuscular diseases based on: a) Progressive or relapsing motor and sensory dysfunction of more than one limb resulting from neuropathy over the 2 months prior to the date informed consent is obtained, and b) Cerebrospinal fluid (CSF) less than 50 white cells/µl since CIDP diagnosis (CSF testing studies are NOT mandatory)
* Fulfillment of INCAT neurophysiological criteria for focal demyelinating polyradiculoneuropathy
* Overall INCAT score between 2-9 and significant disability in upper or lower limb function in at least 2 limbs. (An INCAT score of 2 must be exclusively from leg disability to qualify.)

Exclusion Criteria:

* Treatment with IGIV or plasma within 3 months prior to entry
* Steroids (Prednisolone or equivalent) \> 10 mg/day or equivalent (i.e., \> 20 mg every 2 days) during the last 3 months prior to entry
* Treatment with immunomodulatory/immunosuppressive agents (azathioprin, tacrolimus,cyclosporin, Muromonab-CD3 (OKT3), any interferon), previous lymphoid irradiation or prior treatment with cyclophosphamide, methotrexate, mitoxantrone or any other immunosuppressant drug within the past 6 months prior to entry
* Concomitant use of supplements containing any amount of fish oil within 30 days prior to entry
* Respiratory impairment requiring mechanical ventilation
* Myelopathy or evidence of central demyelination or persisting neurological deficits from stroke, central nervous system (CNS) trauma or peripheral neuropathies of other cause which include diabetes mellitus (defined as a history of type 1 or type 2 diabetes with fasting plasma glucose ≥ 7.0 mmol/L), uremic, toxic and familial neuropathies
* Pure motor syndrome fulfilling criteria for multifocal motor neuropathy with conduction block. Lower motor neuron disorder with motor weakness in an upper limb, without sensory deficit and with proximal conduction block (50% decrease in amplitude/area with proximal distal stimulation ) in motor nerves and normal sensory nerve conduction studies.
* Clinical or known evidence of associated systemic diseases that might cause neuropathy, including but not limited to connective tissue disease, HIV infection, hepatitis, Lyme disease, cancer (with the exception of benign skin cancer), Castleman's disease and systemic lupus erythematosus, diabetes mellitus (defined as a history of type 1 or type 2 diabetes with fasting plasma glucose ≥ 7.0 mmol/L), a malignant plasma cell dysplasia, immunoglobulin M (IgM) paraproteinemia, and amiodarone therapy.
* History of anaphylaxis or severe systemic response to immunoglobulin or with a blood product.
* Cardiac insufficiency (NYHA III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease, or history of congestive heart failure, severe hypertension (diastolic pressure \>120 mmHg or systolic \>170 mmHg).
* Females who are pregnant, breast feeding, or if of childbearing potential, unwilling to practice adequate contraception throughout the study.
* Known hyperviscosity.
* History of renal insufficiency or serum creatinine levels \> 221 µmol/L (2.5 mg/dL).
* Known selective immunoglobulin A (IgA) deficiency.
* Other investigational drugs received within the 30 days prior to entry
* Conditions whose symptoms and effects could alter protein catabolism and/or immunoglobulin G (IgG) utilization (e.g. protein-losing enteropathies, nephrotic syndrome).
* Known hypercoagulable state.
* Mentally challenged adult subjects who cannot give independent informed consent.
* Subjects with uncompensated hypothyroidism (abnormally high thyroid-stimulating hormone (TSH) and abnormally low T4) or vitamin B12 deficiency (abnormally low) within the last 3 months prior to entry.
D: 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

   1. connective tissue disease or systemic lupus erythematosus (SLE)
   2. HIV infection, hepatitis, Lyme disease
   3. cancer (with the exception of basal cell skin cancer)
   4. 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 deep vein thrombosis (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 patients don't receive adequate substitution therapy
18. Medical conditions whose symptoms and effects could alter protein catabolism and/or Immunoglobulin G (IgG) utilization (e.g. protein-losing enteropathies, nephrotic syndrome)
19. Known Immunoglobulin A (IgA) deficiency with antibodies to Immunoglobulin A (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 investigational medicinal product (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

Answer: B