Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3 Study to Evaluate the Safety and Efficacy of OMS721 for the Treatment of Atypical Hemolytic Uremic Syndrome (aHUS) in Adults and Adolescents
Brief Summary: The purpose of this study is to evaluate the platelet count change from baseline and safety of OMS721 in adults and adolescents with atypical hemolytic uremic syndrome (aHUS). The study will also evaluate pharmacokinetics (PK), pharmacodynamics (PD), and anti-drug antibody response (ADA).


Options:
A: Inclusion Criteria:

* Competent to provide informed consent, or if a minor, have at least one parent or legal guardian to provide informed consent with written assent from the subject.
* Are at least 12 years old at screening (Visit 1).
* Have a clinically diagnosis of primary atypical hemolytic uremic syndrome (aHUS), with ADAMTS13 activity greater than 5% in plasma.
* Plasma therapy-resistant aHUS patients must have a screening platelet count less than 150,000/uL, evidence of microangiopathic hemolysis, and serum creatinine greater than upper limit of normal.
* Plasma therapy-responsive aHUS patients must have documented history of requiring plasma therapy to prevent aHUS exacerbation and received plasma therapy at least once every 2 weeks at an unchanged frequency for at least 8 weeks before first dose of OMS721.

Exclusion Criteria:

* Have STEC-HUS, a direct positive Coombs test, history of hematopoietic stem cell transplant, and/or HUS from an identified drug.
* History of vitamin B12 deficiency-related HUS, systemic lupus erythematosus, and/or antiphospholipid syndrome.
* Active cancer or history of cancer (except non-melanoma skin cancers) within 5 years of screening.
* Have been on hemodialysis or peritoneal dialysis for greater than or equal to 12 weeks.
* Have an active systemic bacterial or fungal infection requiring systemic antimicrobial therapy (prophylactic antimicrobial therapy administered as standard of care is allowed).
* Baseline resting heart rate less than 45 beats per minute or greater than 115 beats per minute.
* Baseline QTcF greater than 470 milliseconds.
* Have malignant hypertension (diastolic blood pressure \[BP\] greater than 120 mm Hg with bilateral hemorrhages or "cotton-wool" exudates on funduscopic examination).
* Have a poor prognosis with a life expectancy of less than three months in the opinion of the Investigator.
* Are pregnant or lactating.
* Have received treatment with an investigational drug or device within four weeks prior to screening.
* Have abnormal liver function tests defined as ALT or AST \> five times ULN.
* Have HIV infection.
* History of cirrhosis of the liver.
* Have previously completed treatment in an OMS721study.
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:

1. Patient's parent/legal guardian must have been willing and able to give written informed consent and the patient must have been willing to give written informed assent (if applicable as determined by the central IRB/IEC).
2. Pediatric patients with aHUS: Patients could have been newly diagnosed, or with previously diagnosed disease, or post-kidney transplant with the disease.
3. Patients one month to 18 years and body weight ≥ 5kg.
4. Platelet count at screening and baseline visit must have been below lower limit of normal (\<LLN). If screening visit and baseline visit are combined into one day, an additional platelet count value obtained at least 24 hours before screening/baseline sample must also be \<LLN.
5. Exhibited signs or symptoms of hemolysis at start of current aHUS event (i.e., lactate dehydrogenase (LDH) ≥1.5 x Upper Limit of Normal \[ULN\] and hemoglobin ≤LLN), fragmented RBC with a negative Coombs test.
6. Serum Creatinine level ≥97 percentile for age at screening (patients requiring dialysis for acute renal failure are also eligible).
7. Patients with aHUS due to complement regulatory protein genetic abnormality or anti-complement factor antibody or those in whom known etiologies of hemolytic uremic syndrome (HUS) have been ruled out as confirmed in the Exclusion Criteria.
8. Patients must have been vaccinated against N. meningitidis, pneumococcus and haemophilus (per the vaccine label) at least 14 days prior to study drug initiation or otherwise be protected by prophylactic antibiotics. Patients under age two years were to receive antibiotic prophylaxis throughout the treatment period.
9. Female patients of childbearing potential (female patients who have achieved menarche) must have been 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, patients must have agreed to continue to use adequate contraception methods for up to five months following discontinuation of eculizumab treatment.
10. Able and willing to comply with study procedures

Exclusion:

Any of the following was regarded as a criterion for exclusion from the study:

1. Known familial ADAMTS-13 deficiency (ADAMTS-13 \<5%).
2. Shiga toxin E.coli-related hemolytic uremic syndrome (STEC-HUS \[known Shiga toxin + E.coli\]).
3. History of malignancy within five years of screening.
4. Known human immunodeficiency virus (HIV) infection.
5. Identified drug exposure-related HUS.
6. Infection-related HUS.
7. HUS related to bone marrow transplant (BMT).
8. HUS related to vitamin B12 deficiency.
9. Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome.
10. Plasma Therapy for \>5 weeks prior to enrollment.
11. Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for end-stage renal disease \[ESRD\]).
12. Patients with a confirmed diagnosis of sepsis defined as positive blood cultures within seven days of the screening visit and not treated with antibiotics to which the organism is sensitive.
13. 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.
14. Pregnancy or lactation.
15. History of meningococcal/pneumococcal/gonococcal disease.
16. 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.
17. Patients receiving chronic intravenous immunoglobulin (IVIg) within eight weeks unless for unrelated medical condition (e.g., Hypogammaglobinemia), or chronic Rituximab therapy within 12 weeks of the screening visit.
18. Patients receiving other immunosuppressive therapies such as steroids, mTOR inhibitors, calcineurin inhibitors (e.g., cyclosporine or tacrolimus are excluded unless: \[1\] part of an established post-transplant anti-rejection regime, or \[2\] patient has confirmed anti-Complement Factor antibodies antibody requiring immunosuppressive therapy or \[3\] steroids are being used for a condition other than aHUS (example asthma).
19. Participation in any other investigational drug trial or device trial, or procedures beginning four weeks prior to screening and throughout the entire trial
20. Prior use of eculizumab, hypersensitivity to eculizumab, to murine proteins or to one of the excipients.
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: A