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

A Pilot Study of 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

Study Overview

• Status: Terminated
• Conditions: Sickle Cell Disease; Sickle Cell Nephropathy
• Intervention / Treatment: Drug: Voxelotor

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Voxelot; Voxelotor 1500mg once a day	Drug: Voxelotor; Voxelotor 1500mg once a day
Other: Standard of Care (SOC); Observational while receiving SOC	Drug: Voxelotor; Voxelotor 1500mg once a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in albuminuria in voxelotor-treated SCA patients compared to the observation patients by a one-sided test	Albuminuria will be analyzed comparing the mean values from the Week 47 and 48 visits to the mean values from the baseline and screening visits	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values in albuminuria	Proportion of subjects achieving a 25% decline in albuminuria in the voxelotor-treated group compared to the observation group	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values in kidney function measure	24 hour urine protein	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values in In kidney function measure	24 hour urine eGFR	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values in kidney function measure	24 hour urine albumin concentration	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values in kidney function measure	24 hour serum creatinine	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values in Kidney function measure	24 hour serum cystatin C	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values in Kidney function measure	24 hour serum BUN	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values in Kidney function measure	CKD stage	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney function measure	24 hour urine retinol binding protein	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney function measure	24 hour urine β2 microglobulin	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney function measure	Plasma cell-free hemoglobin	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney function measure	Urine hemoglobin	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney function measure	Urine dipstick-defined hemoglobinuria)	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values markers of hemolysis	Lactate dehydrogenase (LDH)	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values markers of hemolysis	Aspartate aminotransferase (AST)	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values markers of hemolysis	Indirect bilirubin	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values markers of hemolysis	Reticulocyte%	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values markers of hemolysis	Hemoglobin concentration	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney injury biomarker	Urine nephrin	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney injury biomarker	Urine podocalyxin	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney injury biomarker	Urine KIM-1	48weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney injury biomarker	Urine NGAL	48 weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values oxidative injury biomarker	Serum Methylenedioxyamphetamine (MDA)	48weeks
Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values oxidative injury biomarker	Serum 8-OHd	48 weeks

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Collaborators: Global Blood Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2021
• Primary Completion (Actual): October 7, 2024
• Study Completion (Actual): October 7, 2024

Study Registration Dates

• First Submitted: April 2, 2020
• First Submitted That Met QC Criteria: April 3, 2020
• First Posted (Actual): April 6, 2020

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: March 31, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Genetic Diseases, Inborn; Hematologic Diseases; Renal Insufficiency; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Anemia, Sickle Cell; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: 2020-0047

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No