Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Open-Label, Multi-Center Controlled Clinical Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant Atypical Hemolytic Uremic Syndrome (aHUS)
Brief Summary: The purpose of this study is to determine whether eculizumab is safe and effective in the treatment of adolescent patients with plasma therapy-resistant Atypical Hemolytic-Uremic Syndrome (aHUS).


Options:
A: 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
B: Criteria For Patient Cohort Originally Enrolled in ALXN1210-PNH-301 Study: Inclusion Criteria: 1. Male or female ≥18 years of age. 2. PNH diagnosis confirmed by documented by high-sensitivity flow cytometry. 3. Presence of 1 or more of the following PNH-related signs or symptoms within 3 months of screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia (hemoglobin \<10 gram/deciliter), history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or history of packed red blood cells (pRBC) transfusion due to PNH. 4. Lactate dehydrogenase (LDH) level ≥1.5 times the upper limit of normal at screening. 5. Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment. 6. Female participants of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab. 7. Willing and able to give written informed consent and comply with study visit schedule. Exclusion Criteria: 1. Treatment with a complement inhibitor at any time. 2. History of bone marrow transplantation. 3. Body weight \<40 kg. 4. Females who are pregnant, breastfeeding, or who have a positive pregnancy test at screening or Day 1. 5. Participation in another interventional clinical study or use of any experimental therapy within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater. 6. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the investigator or sponsor, would preclude participation. 7. Unstable medical conditions (for example, myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, coexisting chronic anemia unrelated to PNH). Eligibility Criteria For Roll-over Cohort: 1. All participants regardless of age, who are currently receiving ALXN1210 IV in an ongoing ALXN1210 study in patients with PNH 2. Participants must be willing and able to give written informed consent and to comply with all Extension study visits and procedures, including the use of any data collection device(s) to directly record patient data 3. Females of childbearing potential and male patients with female partners of childbearing potential must use highly effective contraception continuing until at least 8 months after the last dose of ravulizumab.
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:

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.

Answer: C