Please select the eligibility criteria that correspond to the clinical trial below.
Title: N/A
Brief Summary: Protocol is intended to characterize the overall safety and tolerability of eculizumab in this population.


Options:
A: Inclusion Criteria:

1. Male or female ≥ 12 years of age and weighing ≥ 40 kg at the time of consent.
2. Evidence of thrombotic microangiopathy, including low platelet count, hemolysis (breaking of red blood cells inside of blood vessels), and decreased kidney function.
3. Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study drug. Participants who received a meningococcal vaccine less than 2 weeks before initiating ravulizumab treatment must have received treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Participants who had not been vaccinated prior to initiating ravulizumab treatment should have received prophylactic antibiotics prior to and for at least 2 weeks after meningococcal vaccination. Participants \< 18 years of age must have been vaccinated against haemophilus influenzae type b and streptococcus pneumoniae according to national and local vaccination schedule guidelines.
4. Female participants of childbearing potential and male participants with female partners of childbearing potential had to use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.

Exclusion Criteria:

1. A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency (activity \< 5%).
2. Shiga toxin-related hemolytic uremic syndrome.
3. Positive direct Coombs test.
4. Pregnancy or breastfeeding.
5. Identified drug exposure-related hemolytic uremic syndrome (HUS).
6. Bone marrow transplant/hematopoietic stem cell transplant within last 6 months prior to start of Screening.
7. HUS related to known genetic defects of cobalamin C metabolism.
8. Systemic sclerosis (scleroderma), systemic lupus erythematosus, or antiphospholipid antibody positivity or syndrome.
9. Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for end-stage kidney disease).
B: Inclusion Criteria:

Complement Inhibitor Treatment Naïve:

1. Participants from birth up to \<18 years of age and weighing ≥5 kilograms (kg) at the time of consent.
2. Participants had not been previously treated with complement inhibitors.
3. Evidence of thrombotic microangiopathy (TMA), including low platelet count, hemolysis (breaking of red blood cells inside of blood vessels), and decreased kidney function.
4. Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae type b.
5. Female participants of childbearing potential and male participants with female partners of childbearing potential must have used highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.

Eculizumab Experienced:

1. Participants between 12 and \<18 years of age (non-Japanese sites) or \<18 years of age (Japanese sites) who had been treated with eculizumab according to the labelled dosing recommendation for aHUS for at least 90 days prior to screening.
2. Participants with documented diagnosis of aHUS.
3. Participants with clinical evidence of response to eculizumab indicated by stable TMA parameters at screening.
4. Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae type b.
5. Females of childbearing potential and male participants with female partners of childbearing potential must have used highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.

Exclusion Criteria:

1. Known familial or acquired ADAMTS13 ("a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13") deficiency (activity \<5%).
2. Known Shiga toxin-related hemolytic uremic syndrome.
3. Positive direct Coombs test.
4. Females who planned to become pregnant during the study or were currently pregnancy or breastfeeding.
5. Identified drug exposure-related hemolytic uremic syndrome.
6. Bone marrow transplant/hematopoietic stem cell transplant within the last 6 months prior to the start of screening.
7. Hemolytic uremic syndrome related to known genetic defects of cobalamin C metabolism.
8. Known systemic sclerosis (scleroderma), systemic lupus erythematosus, or antiphospholipid antibody positivity or syndrome.
9. Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for end-stage kidney disease.
10. For eculizumab-experienced participants, prior use of complement inhibitors other than eculizumab.
11. For eculizumab-experienced participants, any known abnormal TMA parameters within 90 days prior to screening.
C: Inclusion Criteria:

1. All patients with diagnosis of aHUS who have been receiving eculizumab by personal importation (specific eligibility criteria below do not apply) Or,
2. Patients with current clinical manifestations of aHUS who meet the following criteria:

   1. Patient with diagnosis of aHUS with or without an identified complement regulatory protein genetic abnormality or anti-complement factor antibody and for whom other known etiologies of hemolytic uremic syndrome (HUS) have been ruled out as confirmed in the Exclusion Criteria
   2. Patient (and legal guardian if patient is not an adult) willing and able to give written informed consent and assent (or verbal assent if patient is unable to read or write)
   3. Patient at least 1 month of age and body weight ≥5 kg
   4. Platelet count at screening \< lower limit of normal (LLN)
   5. Signs or symptoms of hemolysis (i.e., lactate dehydrogenase (LDH) ≥ 1.5x upper limit of normal (ULN) and Hemoglobin ≤ LLN) at start of current aHUS event
   6. Serum Creatinine (SrCr) level ≥ ULN at screening (patient requiring dialysis for acute renal failure also eligible)
   7. Female patient of childbearing potential practicing an effective, reliable and medically approved contraceptive regimen during the entire duration of the study, including the Follow-up Period. At the time of the last follow-up visit, patient must agree to continue to use adequate contraception methods for up to 5 months following discontinuation of eculizumab treatment
   8. Able and willing to comply with study procedures

Exclusion Criteria:

Shiga-toxin producing E. coli-HUS (STEC-HUS; shiga-toxin and/or STEC positive) History of malignancy within 5 years of screening Known human immunodeficiency virus (HIV) infection Identified drug exposure-related HUS Infection-related HUS HUS related to bone marrow transplant (BMT) HUS related to vitamin B12 deficiency Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for end-stage renal disease (ESRD)) Patients with a confirmed diagnosis of sepsis defined as positive blood cultures within 7 days of the screening visit and not treated with antibiotics to which the organism is sensitive 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 Pregnancy or lactation Unresolved systemic meningococcal disease Any medical or psychological condition that, in the opinion of the investigator, could increase patient's risk by participating in the study or confound the outcome of the study Patients receiving chronic intravenous immunoglobulin (IVIG) within 8 weeks unless for unrelated medical condition (e.g., hypogammaglobulinemia) or chronic rituximab therapy within 12 weeks of the screening visit Patients receiving other immunosuppressive therapies such as steroids, calcineurin inhibitors (mTOR), (e.g., cyclosporine or tacrolimus) are excluded unless: \[1\] part of an established post-transplant anti-rejection regimen, or \[2\] patient has confirmed anti-Complement Factor Antibodies requiring immunosuppressive therapy or \[3\] steroids are used for a condition other than aHUS (e.g., asthma) Prior eculizumab use, hypersensitivity to eculizumab, to murine proteins or to one of the excipients Inclusion in any other investigational intervention trial except this study
D: Inclusion Critera:

1. Male or female patients' ≥18 years of age 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 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. Able to give written informed consent.
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 Observation 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.

Answer: C