Dose-Finding Study of SC411 in Children With Sickle Cell Disease

This Phase 2 study is to be conducted in two parts. Part A is a randomized, double-blind,
placebo-controlled, parallel-group, dose-finding study of SC411 in children with SCD. This
part of the study will consist of a screening period of up to 2 weeks, followed by an
eight-week treatment period. Part B is an optional 49-month open-label extension for patients
who have completed Part A.

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).