Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Finding Study and Open-Label Extension of SC411 in Children With Sickle Cell Disease
Brief Summary: This is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study of SC411 in children with sickle cell disease (SCD). The primary objective of the study is to evaluate the safety and tolerability of three different doses of SC411 compared to a placebo. All patients will undergo eight weeks of oral study treatment and a four-week safety follow-up period. Patients will be randomized to one of three dose levels of SC411 or placebo.


Options:
A: Inclusion Criteria:

* Patient is at least five years of age.
* Patient has been diagnosed with sickle cell anemia or sickle ß°-thalassemia (documented by hemoglobin electrophoresis).
* Patient has had at least two documented episodes of sickle cell crises within 12 months of the screening visit.
* If the patient has been treated with an anti-sickling agent within three months of the screening visit, the therapy must have been continuous for at least three months with the intent to continue for the duration of the study.
* Patient or the patient's legally authorized representative has given written informed consent.
* If the patient is a female of child-bearing potential, she agrees to avoid pregnancy during the study and is willing and agrees to practice a recognized form of birth control during the course of the study (e.g. barrier, birth control pills, abstinence).

Exclusion Criteria:

* Patient has a significant medical condition that required hospitalization (other than sickle cell crisis) within two months of the screening visit.
* Patient has prothrombin time INR \> 2.0.
* Patient has serum albumin \< 3.0 g/dl.
* Patient has received any blood products within three weeks of the Screening Visit.
* Patient has uncontrolled liver disease or renal insufficiency.
* Patient is pregnant or lactating or has the intention of becoming pregnant during the study (if female and of child-bearing potential).
* Patient is currently taking or has been treated with any form of glutamine supplement within 30 days of the screening visit.
* Patient has been treated with an experimental anti-sickling medication/ treatment within 30 days of the screening visit (with the exception of hydroxyurea in pediatric patients).
* Patient is currently taking or has been treated with an investigational drug within 30 days of the screening visit (with the exception of hydroxyurea in pediatric patients).
* Patient is currently enrolled in an investigational drug or device study and/or has participated in such a study within 30 days of the screening visit.
* There are factors that would, in the judgment of the investigator, make it difficult for the patient to comply with the requirements of the study.
B: Inclusion Criteria:

* Established diagnosis of H SS or S-beta thalassemia
* History of at least one vaso-occlusive pain event in the 12 months prior to study entry
* Regular compliance with comprehensive medical care
* In a steady disease state and not in the midst of any acute complication due to SCD at study entry

Exclusion Criteria:

* Inability to take or tolerate oral medications
* Liver dysfunction (i.e., SGPT level greater than or equal to two times the normal limit and albumin level less than or equal to 3.2 g/dL)
* Kidney dysfunction ( i.e., creatinine level greater than or equal to 1.2 mg/dL for children and greater than or equal to 1.4 mg/dL for adults)
* Allergy to arginine
* Pregnant
* Received a blood transfusion within the 90 days prior to study entry
* More than 10 hospital admissions for pain in the 12 months prior to study entry
* Daily use of opioids and experiencing unstable pain that interferes with work or daily routine
* Required more than 3 hospital admissions and more than 10 emergency department/day hospital visits in the 12 months prior to study entry
* Received treatment with hydroxyurea within the 90 days prior to study entry
* Received treatment with any investigational drug in the 90 days prior to study entry
C: Inclusion Criteria:

1. Aged greater than or equal to 5 years and less than or equal to 17 years at screening;
2. Has been diagnosed with SCD that includes the phenotypes HbSS, hemoglobin SC, and HbS/beta-thalassemia. Hemoglobin phenotyping must be previously documented by either hemoglobin high-performance liquid chromatography \[HPLC\] or electrophoresis at time of Screening. If a patient does not have documented hemoglobin phenotyping at the time of Screening, or has received a blood transfusion within the two months prior to the Screening Visit, hemoglobin phenotyping should be documented by hemoglobin HPLC;
3. Has had at least two and no more than ten documented episodes of clinical sickle cell crises within 12 months prior to the Screening Visit. A sickle cell crisis is defined as an episode of vaso-occlusive event:

   * Painful crisis defined as new onset of pain that lasts two or more hours for which there is no explanation other than vaso-occlusion, and which requires therapy with oral or parenteral opioids, non-steroidal anti-inflammatory drugs, or other analgesics prescribed by a healthcare provider in a medical setting such as a hospital, clinic, or emergency room visit, or documented telephone management (Ballas, 2010; Heeney, 2016; Jacob, 2005); and
   * Acute chest syndrome defined as acute illness characterized by a new segmental pulmonary infiltrate on a chest x-ray, and fever (greater than or equal to 38.5°C) or respiratory symptoms such as hypoxia, chest pain, tachypnea, wheezing, or cough (Ballas, 2010);
4. Is either not on hydroxyurea at the Screening Visit and does not plan on receiving it during the course of the first 12 weeks of the study (Part A), or has received hydroxyurea for a minimum of 6 months and, except for safety reasons, will remain on the same weight-based dose of hydroxyurea from screening throughout the duration of Part A of the study;
5. Parent or guardian is able to give written informed consent, and the potential pediatric patient is able to provide assent in a manner approved by the Institutional Review Board (IRB) and comply with the requirements of the study other than for safety reasons; and
6. If sexually active, agrees to use a reliable method of birth control (eg, barrier, birth control pills, abstinence) during the study and for one month following the last dose of study drug.

Exclusion Criteria:

1. Has a significant medical condition that required hospitalization (other than sickle cell crisis) within two months of the Screening Visit;
2. Has a known allergy or hypersensitivity to fish or shellfish;
3. Has a known allergy or hypersensitivity to soy;
4. Is planning to initiate, terminate, or alter the dosing of hydroxyurea during the first 12 weeks of the study, other than for safety reasons;
5. Has chronic daily use (more than 30 consecutive days during the last six months prior to enrollment) of opioid analgesia for any reason;
6. Has a diagnosis of chronic pain or chronic pain syndrome (eg, chronic pain from the repeated vaso-occlusive events, chronic pain from avascular necrosis);
7. Has a history of Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C infection;
8. Has a history of documented episode(s) of priapism within 12 months of the Screening Visit;
9. Has a history of atrial or ventricular arrhythmia;
10. Has an international normalized ratio (INR) \>2.0, or is on regular anticoagulation therapy, or has a history of a known bleeding diathesis;
11. Has thrombocytopenia (platelets less than 80,000) or is on chronic acetylsalicylic acid therapy;
12. Has increased risk of stroke: documented abnormal or "high conditional" transcranial Doppler (TCD) mean velocity (TCD V) by STOP criteria (Adams, 1998) within the preceding year or has a history of known cerebrovascular disease:

    * "High conditional" = TCD V greater than or equal to 185 to 199 cm/sec, or TCDi V greater than or equal to 170 to 184 cm/sec, or TCD maximum V greater than or equal to 250 cm/sec; or
    * Abnormal = TCD V greater than or equal to 200 cm/sec, or abnormal high TCDi V greater than or equal to 185 cm/sec, or TCD maximum V greater than or equal to 250 cm/sec;
13. Has received a blood transfusion or exchange transfusion in the three months prior to the Screening Visit;
14. Has renal insufficiency (creatinine greater than 1.5 times upper limit of normal \[ULN\], or requiring peritoneal dialysis or hemodialysis);
15. Has liver dysfunction (ALT greater than 2.0 times ULN);
16. Has other concomitant chronic medical or psychiatric condition that, in the opinion of the Investigator, would compromise participation in the study or confound the evaluation of the study outcome;
17. Is pregnant or lactating or has the intention of becoming pregnant during the study (if a female of child-bearing potential or partner of a patient participating in the study);
18. Is currently taking, or has been treated with, any form of omega-3 fatty acid or fish oil supplement within 30 days of the Screening Visit or during the course of the study;
19. Has been treated with an experimental anti-sickling medication/treatment within 30 days of the Screening Visit or during the course of the study;
20. Is currently taking or has been treated with any investigational drug for any disease within 30 days of the Screening Visit or during the course of the study;
21. Is currently enrolled in an investigational drug or device study and/or has participated in such a study within 30 days of the Screening Visit or during the course of the study; or
22. There are factors that would, in the judgment of the Investigator, make it difficult for the patient to comply with the requirements of the study (eg, inability to swallow capsules due to past history of stroke, or poor compliance).
D: Inclusion Criteria:

Subjects who meet all of the following criteria are eligible for enrollment into the study:

* Participant has signed the informed consent/assent with parent signing informed consent as age appropriate.
* Established diagnosis of HbSS or HbSβo Thal.
* History of ≥3 vasocclusive pain events in preceding 12 months.
* Regular compliance with comprehensive care.
* Aged 10 years or greater and less than 20 years.
* At enrollment, subject should be in his/her steady or baseline state.

Exclusion Criteria

* Subjects with Hb levels \<5.5gm/dL.
* Inability to take or tolerate oral medications.
* Poor compliance with previous treatment regimens.
* Hepatic dysfunction (SGPT also known as ALT \>2X upper limit of normal or conjugated bilirubin \>2X the patients baseline within the last 6 weeks).
* Renal dysfunction (A creatinine level within the past 6 weeks of ≥ 1.0mg/dL for children and ≥ 1.2mg/dL for a subject ≥ 18 years of age).
* Allergy to fish or shell fish.
* Triglyceride levels \<80mg/dL.
* Pregnancy.
* Chronic Transfusion Therapy.
* Transfusion within the last 30 days.
* Persistent pain from sickle-complications (e.g. avascular necrosis).
* A vasocclusive pain episode lasting longer than 2 weeks or \>12 pain episodes in preceding year.
* Daily narcotic usage.
* Treatment with any investigational drug or regular fish oil supplementations in last 60 days.
* Currently receiving another investigational agent, or on such an agent with the last 60 days.
* Dosage changes in preceding 3 months if on hydroxyurea.
* Bleeding disorder or patient on concomitant anti-coagulation.
* Conditional or abnormal TCD result or stroke.
* Other chronic illness that could adversely affect subjects performance such as HIV or TB.
* Children in Care (CiC): A child in care is a child who has been placed under the control or protection of an agency, organization, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation.

Answer: C