Please select the eligibility criteria that correspond to the clinical trial below.
Title: A PROSPECTIVE, MULTI-CENTER, PHASE II STUDY TO EVALUATE THE SAFETY AND EFFICACY OF ECULIZUMAB IN SUBJECTS WITH GUILLAIN-BARRÉ SYNDROME
Brief Summary: Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy that usually follows an antecedent infection and causes acute neuromuscular paralysis. GBS is currently classified into the two major subtypes: a classical demyelinating type and axonal variant type. Whereas in Europe and North America demyelinating GBS is the major subtype, in East Asia and Central and South America, axonal GBS is found in 30\~65% of patients. Although the pathophysiology of GBS has not been fully understood, major advances have been made in understanding the pathophysiology particularly for the axonal form of GBS. It is now established that axonal GBS is caused by molecular mimicry of human gangliosides by the Campylobacter jejuni lipo-oligosaccharides. Autoantibodies bind to GM1 or GD1a at the nodes of Ranvier, activate complements, and disrupt sodium channel clusters and axo-glial junctions, resulting in the nerve conduction failure and muscle weakness. C. jejuni infection induces production of antibodies, which cross-react with gangliosides on the human nerve axolemma, and activate the complements, resulting in formation of membrane attack complex (MAC). The pathology leads to axonal degeneration.

The standard treatments for GBS are plasma exchange and intravenous immunoglobulin and the disease progression reaches its nadir within 4 weeks. However, during the acute phase, 18-28 % of the patients require artificial ventilation and 4.1-6.3 % of the patients die of complications. Recovery takes several months or years, and 16.7-19.7 % of the patients still require aid to walk one year after onset. Because of such serious disability of GBS patients, an alternative novel therapy that can prevent death during acute phase or severe sequelae is needed.

Eculizumab is a humanized monoclonal antibody of murine anti-human C5 antibody and specifically binds to the final activation complement component C5 and inhibits MAC formation by suppressing the cleavage reaction of C5 into C5a and C5b. The efficacy of eculizumab against GBS has been shown in a model of axonal GBS. At present, there are no animal models of demyelinating GBS. However, autopsy studies have shown that C3d and C5b-9 (MAC) are deposited on the Schwan cells, and therefore eculizumab can be effective also for demyelinating GBS.

This clinical trial will be conducted to investigate the efficacy and safety of eculizumab for GBS to warrant future global clinical trials. Moreover, we also study the relationship between the efficacy and clinical subtypes of GBS, such as axonal or demyelinating form. Our trial will provide insights on whether the future global developmental plan should target the whole spectrum of GBS world-wide or focusing on Asia and South America.


Options:
A: Inclusion Criteria:

1. Male or female patients between ages from 12 and up to 18 years of age weighing ≥ 40 kg who have been diagnosed with Atypical Hemolytic-Uremic Syndrome (aHUS).
2. Patients must be receiving PT for aHUS and must be observed to receive ≥ 1 PT treatment every two weeks and no more than 3 PT treatments/week (at an unchanged frequency) for at least 8 weeks before the first dose of IP.
3. Platelet Count Pre-PT Baseline Set-Point (collected in the hours before the Qualifying PT Episode) is within 75% of the average of the pre-PT platelet counts collected at Screening and during the Observation Period.
4. Known complement regulatory protein genetic abnormality.
5. Lactate dehydrogenase (LDH) level at screening or at the onset of the current aHUS episode was ≥ ULN. If LDH is normal at screening, other markers indicative of ongoing hemolysis such as haptoglobin, schistocytes should be evaluated and discussed with Sponsor.
6. Creatinine level ≥ ULN for age.
7. Female patients of childbearing potential must be practicing an effective, reliable and medically approved contraceptive regimen during the entire duration of the study, including the follow-up period and for up to 5 months following eculizumab treatment discontinuation.
8. Patient's parents/legal guardian must be willing and able to give written informed consent and patient must be willing to give written informed assent (if applicable as determined by the IRB/IEC).
9. Able and willing to comply with study procedures.

Exclusion Criteria:

1. TTP, (defined as ADAMTS-13 activity \<5%) from an historical observation (prior to initiation of plasma therapy) or as tested at the screening visit by the central laboratory.
2. Malignancy within 5 years of screening.
3. Typical HUS (Shiga toxin +).
4. Known HIV infection.
5. Identified drug exposure-related HUS.
6. Infection-related HUS.
7. HUS related to bone marrow transplant.
8. HUS related to vitamin B12 deficiency.
9. Patients with a confirmed diagnosis of sepsis.
10. Presence or suspicion of active and untreated systemic bacterial infection that, in the opinion of the Investigator confounds an accurate diagnosis of aHUS or impedes the ability to manage the aHUS disease.
11. Pregnancy or lactation.
12. Unresolved meningococcal disease.
13. Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome.
14. Any medical or psychological condition that, in the opinion of the investigator, could increase the patient's risk by participating in the study or confound the outcome of the study.
15. Patients who have received previous treatment with eculizumab.
16. Patients receiving IVIg within 8 weeks or Rituximab therapy within 12 weeks of the screening visit.
17. Patients receiving other immunosuppressive therapies such as steroids, mTOR inhibitors or tacrolimus are excluded unless: \[1\] part of an established post-transplant anti-rejection regime, \[2\] patient has confirmed anti-CFH antibody requiring immunosuppressive therapy, and \[3\] dose of such medications have been unchanged for at least 4 weeks prior to the screening period and throughout the Obeservation Period or \[4\] patient is experiencing an acute aHUS relapse immediately after transplant.
18. Patients receiving Erythrocyte Stimulating Agents (ESAs) unless already on a stable dose for at least 4 weeks prior to the screening period or a washout period of at least 2 weeks from the last dose of ESA therapy.
19. Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedures beginning 4 weeks prior to screening and throughout the entire trial.
20. Hypersensitivity to eculizumab, to murine proteins, or to one of the excipients.
21. Patients between the ages from 12 and up to 18 years weighing \< 40 kg.
B: * Patients who have been diagnosed with GBS with reference to GBS NINDS(National Institute of Neurological Disorders and Stroke) diagnostic criteria and those who meet all the following inclusion criteria and do not fall under any of the exclusion criteria will be included in this trial.

Inclusion Criteria：

1. Subjects ≥ 18 years of age at the time of obtaining informed consent.
2. Patients with onset of muscular weakness due to GBS less than 2 weeks before the time of consent.
3. Patients unable to walk unaided for ≥5 meters (progressively deteriorating FG(Functional Grade)3 or FG 4-5).
4. Patients who are already on IVIg or deemed eligible for and who will start IVIg (Generally, administration of 400mg/kg over 5 days).
5. Patients who can start their first dose of eculizumab within 2 weeks from onset of weakness and before the end of the IVIg treatment period.
6. Female subjects of child bearing potential with a negative result in their pregnancy test. All subjects must be able to practice an effective, reliable, medically approved method of contraception during the IP(Intraperitoneal) administration period and up to 5 months after IP administration is ended.
7. Patients who can be hospitalized during IP administration period.
8. Patients who have signed the informed consent form.

Exclusion Criteria:

1. Patients who are being considered for or are already on plasmapheresis.
2. Patients who are pregnant or lactating.
3. Patients showing clear clinical evidence of peripheral polyneuropathy other than GBS, e.g. diabetic (except for mild sensory disturbance) or severe vitamin B1 deficiency related.
4. Patients who have received immunosuppressive treatment (e.g. azathioprine, cyclosporine, tacrolimus, or \>20 mg prednisolone daily) during the 4 weeks prior to providing consent.
5. Patients who are known to have severe concurrent disease (such as malignancy with uncontrolled primary tumors or metastatic lesions, severe cardiovascular disease, severe COPD(chronic obstructive pulmonary disease ), or TB).
6. Patients who are unable to comply with study procedures and the treatment regimen.
7. Patients who have received rituximab within 24 weeks prior to providing consent.
8. Patients with a history of or unresolved Neisseria meningitides.
9. Patients with active infectious diseases determined to be clinically severe by the principal investigator or sub-investigator that are not being appropriately treated with antibiotics.
10. Patients who that cannot be treated with antibiotic prophylaxis due to allergies.
11. Patients who are allergic to eculizumab.
12. Patients who are known to have or are suspected of having hereditary complement deficiencies.
13. Patients who have been administered another investigational product within 12 weeks prior to providing consent or are currently participating in another trial.
14. Patients with any condition that, in the opinion of the principal investigator or sub-investigator, could increase the patient's risk by participating in the study or confound the outcome of the study.
15. Patients who have a history of Eculizumab treatment for GBS.
C: Inclusion Criteria:

1. Male or female patients from 12 and up to 18 years weighing ≥ 40 kg who have been diagnosed with Atypical Hemolytic-Uremic Syndrome (aHUS).
2. Decrease in platelet count despite at least 4 plasma therapy (PT) treatments in the 1 week immediately prior to screening.

   1. Screening platelet count , \< 150 x10\^9/L and at least 25% lower than the average remission platelet count or
   2. If remission counts not available, platelet count at onset of the current aHUS episode must be ≤75x10\^9/L and platelet count at screening must be ≤ 100 x 10\^9/L despite PT treatment administration of at least 4 PT treatments in the 1 week immediately prior to screening
3. Known complement regulatory protein genetic abnormality
4. Lactate dehydrogenase (LDH) level ≥ ULN unless the patient has been receiving plasma exchange and LDH at the onset of the current aHUS episode was at least the ULN. If LDH is normal at screening, other markers indicative of ongoing hemolysis such as haptoglobin, schistocytes should be evaluated and discussed with Sponsor
5. Creatinine level ≥ ULN for age
6. Female patients of childbearing potential must be practicing an effective, reliable and medically approved contraceptive regimen during the entire duration of the study, including the follow-up period and for up to 5 months following of eculizumab treatment discontinuation.
7. Patient's parents/legal guardian must be willing and able to give written informed consent and patient must be willing to give written informed assent.
8. Able and willing to comply with study procedures.

Exclusion Criteria:

1. TTP, (defined as ADAMTS-13 activity \<5%) from an historical observation (prior to initiation of plasma therapy) or as tested at the screening visit by the central laboratory
2. Malignancy within 5 years of screening.
3. Typical HUS (Shiga toxin +).
4. Known HIV infection.
5. Identified drug exposure-related HUS.
6. Infection-related HUS.
7. HUS related to bone marrow transplant
8. HUS related to vitamin B12 deficiency
9. Renal function status requiring chronic dialysis
10. Patients with a confirmed diagnosis of sepsis
11. Presence or suspicion of active and untreated systemic bacterial infection that, in the opinion of the Investigator confounds an accurate diagnosis of aHUS or impedes the ability to manage the aHUS disease.
12. Pregnancy or lactation.
13. Unresolved meningococcal disease.
14. Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome.
15. Any medical or psychological condition that, in the opinion of the investigator, could increase the patient's risk by participating in the study or confound the outcome of the study.
16. Patients who have received previous treatment with eculizumab
17. Patients receiving IVIG within 8 weeks or Rituximab therapy within 12 weeks of screening.
18. Patients receiving other immunosuppressive therapies such as steroids, mTOR inhibitors or tacrolimus are excluded unless: \[1\] part of an established post-transplant anti-rejection regime, \[2\] patient has confirmed anti-CFH antibody requiring immunosuppressive therapy, and \[3\] dose of such medications have been unchanged for at least 4 weeks prior to the screening period or \[4\] patient is experiencing an acute aHUS relapse immediately after transplant
19. Patients receiving Erythrocyte Stimulating Agents (ESAs) unless already on a stable dose for at least 4 weeks prior to the screening period or a washout period of at least 2 weeks from the last dose of ESA therapy.
20. Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedures beginning 4 weeks prior to screening and throughout the entire trial.
21. Hypersensitivity to eculizumab, to murine proteins or to one of the excipients
22. Patients between ages from 12 and up to 18 years weighing \< 40 kg
D: Inclusion Criteria:

* Fulfil diagnostic criteria for GBS of National Institute of Neurological Disorders and Stroke (NINDS). Patients with Miller Fisher syndrome and all other variants of GBS, including overlap syndromes, can be included.
* Inclusion of all males and females of all ages, independent of disease severity and treatment
* Inclusion within two weeks of onset of weakness
* Inclusion of patients transferred from another hospital if the stay in the first hospital was less than one week
* Opportunity to conduct a follow-up of at least one year
* Informed consent of patient or, in case of children, of parents or legal guardians

Exclusion Criteria:

* There are no exclusion criteria

Answer: B