A Voxelotor for Sickle Cell Anemia Patients at Highest Risk for Progression of Chronic Kidney Disease

This study is a single center, prospective exploratory pilot study of Sickle Cell Anemia (SCA) participants. The study will enroll patients with early stages of sickle cell nephropathy (Chronic Kidney Disease (CKD) stage 1 or 2) who are at the highest risk of CKD progression (presence of both hemoglobinuria and urine albumin concentration ≥ 30 mg/g creatinin

This study is a single center, prospective exploratory pilot study of Sickle Cell Anemia (SCA) participants, age ≥18 years, with SCA. The study will enroll patients with early stages of sickle cell nephropathy (Chronic Kidney Disease (CKD) stage 1 or 2) who are at the highest risk of CKD progression (presence of both hemoglobinuria and urine albumin concentration ≥ 30 mg/g creatinin

Eligibility Criteria:
Inclusion Criteria

1. Documentation of SCA genotype (HbSS or HbSβ0-thalassemia) may be based on history of laboratory testing or must be confirmed by laboratory testing during screening
2. Participants have had urine dipstick defined hemoglobinuria (positive for blood (+1 or higher) and ≤ 2 red blood cells per high power field) on 2 prior outpatient visits
3. Participants with albuminuria (urine albumin ≥ 30 mg/g creatinine) and an eGFR ≥ 60 mL/min/1.73m2 calculated using the CKD-EPI equation on 2 prior outpatient visits
4. Age ≥18 years
5. Hemoglobin (Hb) ≥ 5.5 and ≤ 10.0 g/dL during screening
6. For participants taking hydroxyurea (HU), the dose of HU (mg/kg) must be stable for at least 90 days prior to signing the ICF and with no anticipated need for dose adjustments or initiation during the study, in the opinion of the Investigator
7. Endari stable dose for one month.
8. For participants taking an angiotensin converting enzyme (ACE)-inhibitor or angiotensin receptor blocker, the dose must be stable for at least 90 days prior to signing the ICF and with no anticipated need for dose adjustments or initiation during the study, in the opinion of the Investigator
9. Participants, who if female and of child bearing potential, are using highly effective methods of contraception from study start to 30 days after the last dose of study drug, and who if male are willing to use barrier methods of contraception, from study start to 30 days after the last dose of study drug
10. Participant has provided documented informed consent (the informed consent form \[ICF\] must be reviewed and signed by each participant

Exclusion Criteria

1. Female who is breast feeding or pregnant
2. Patients who are receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or have received a RBC transfusion for any reason within 30 days of signing the ICF or at any time during the screening period
3. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days prior to signing the ICF (i.e., a vaso-occlusive event cannot be within 14 days prior to ICF)
4. Hepatic dysfunction characterized by alanine aminotransferase (ALT) \>4 × ULN
5. Participants with clinically significant bacterial, fungal, parasitic or viral infection which require therapy:

   * Participants with acute bacterial infection requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed
   * Participants with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive
6. Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the central laboratory) \< 60mL/min/1.732, on chronic dialysis, or have received a kidney transplantation
7. History of malignancy within the past 2 years prior to treatment Day 1 requiring chemotherapy and/or radiation (with the exception of local therapy for non-melanoma skin malignancy)
8. History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:

   * Unstable angina pectoris or myocardial infarction or elective coronary intervention
   * Congestive heart failure requiring hospitalization
   * Uncontrolled clinically significant arrhythmias
9. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable)
10. Participated in another clinical trial of an investigational agent (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational agent (or medical device)
11. Inadequate venous access as determined by the investigator/site staff
12. Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent
13. Receipt of erythropoietin or other hematopoietic growth factors within 28 days of signing ICF or anticipated need for such agents during the study