This is an open-label study to understand the safety and tolerability of AXA4010, a novel composition of amino acids in adult and adolescent subjects with sickle cell disease over 12 weeks. The study also assesses the effects of this amino acid composition on the structure and function of the vascular system. Physiological effects on structure and function will be assessed by Magnetic Resonance Imaging (MRI) to assess blood flow in the brain and kidneys and the 6-Minute walk with pulse oximetry. Changes in blood biomarkers of inflammation will also be assessed.

Inclusion Criteria:

• Willing to participate in the study and provide written informed consent

• Male and female adolescent (ages 12 to 17 inclusive) and adult (≥ 18 years of age) subjects with a prior medically documented diagnosis of sickle cell disease (SS or β0 thalassemia)

• For Cohort 2 adult subjects only, a Screening cerebral blood flow/ velocity by transcranial doppler (TCD) should be >110 cm/sec

• Subjects must show active hemolysis at the time of screening based on each of the following parameters:

  • Lactate dehydrogenase (LDH) ≥ 2x above upper limits of normal (ULN) of the age- and gender-appropriate ranges
  • Indirect bilirubin > 2x of the age- and gender-appropriate ULN
  • Absolute reticulocyte counts > 2x of the age- and gender-appropriate ULN

• Able to ambulate (without assistance or walkers etc.) in a 6- minute walk test

Exclusion Criteria:

• Ten (10) or more Vascular-Occlusive Crisis (VOC)s that required hospital or emergency room (ER) visits within the past 12 months
• Any clinically significant changes abnormalities on the screening 12-lead ECG
• Estimated glomerular filtration rate <60mL/min/1.73m2 appropriately corrected
• Hemoglobin (Hb) ≤6.0 g/dL at Screening
• Subjects on chronic transfusion regimens, or who received a transfusion within the last 2 months prior to screening
• Experienced VOC or any other sickle crises (eg acute chest syndrome, splenic sequestration, dactylitis, stroke) within the last 2 months prior to Screening
• Current or history of significant alcohol consumption
• Other poorly controlled medical conditions as judged by the Investigator
• Known sensitivity and/or history of clinically significant food intolerance/allergies to proteins (including whey, soy, casein, amino acids, etc.)
• Unable or unwilling to adhere to contraception requirements
• Any contraindications to an MRI scan for Cohort 2 only
• Any other condition that, in the opinion of the Investigator, renders the subject at risk for compliance, compromises the well-being of the subject, or hinders study completion