Anemia, Sickle Cell, Sickle Cell Anemia, Sickle Cell Disease, Sickle Cell Disorders, To Assess the Safety and Tolerabiltiy of an Amino Acid Composition in Subjects With Sickle Cell Disease
Conditions
Keywords
Amino Acid, Food Study
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTAXA4010
The study will initiate with approximately eight (8) adult subjects (≥18 y/o) with SCD (Cohort 1). Each subject will receive AXA4010 twice a day (BID) for 12 weeks. Safety and tolerability will be monitored, and study procedures will be performed. Analysis of safety, tolerability and laboratory assessments at week 12 would be performed. Based on the 12-week observations from at least three subjects in Cohort 1, subsequent Cohorts 2 and 3 in Part II may be initiated.
Sponsors
Axcella Health, Inc
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Study Product-Emergent Adverse Events [Safety and Tolerability ] | Baseline to Week 12 | Incidence of study product emergent adverse events (AEs) and serious adverse events (SAEs) |
Secondary
| Measure | Time frame |
|---|---|
| Change in Lactate Dehydrogenase (LDH) | Baseline to Week 12 |
| Change Indirect Bilirubin | Baseline to Week 12 |
| Change Absolute Reticulocyte Count | Baseline to Week 12 |
| Changes in Renal and Cerebral blood flow via MRI (in Adult Cohort 2 Only) | Baseline to Week 12 |
Countries
United States
Outcome results
None listed