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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04335721
Recruitment Status : Not yet recruiting
First Posted : April 6, 2020
Last Update Posted : June 1, 2020
Sponsor:
Collaborator:
Global Blood Therapeutics
Information provided by (Responsible Party):
Santosh L Saraf, University of Illinois at Chicago

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Sickle Cell Nephropathy Drug: Voxelotor Phase 1 Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 6 participants will take voxelotor 1500mg once a day 6 participants will be observed while receiving standard of care (SOC)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Voxelotor for Sickle Cell Anemia Patients at Highest Risk for Progression of Chronic Kidney Disease
Estimated Study Start Date : June 2020
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Voxelot
Voxelotor 1500mg once a day
Drug: Voxelotor
Voxelotor 1500mg once a day

Standard of Care (SOC)
Observational while receiving SOC
Drug: Voxelotor
Voxelotor 1500mg once a day




Primary Outcome Measures :
  1. Change in albuminuria in voxelotor-treated SCA patients compared to the observation patients by a one-sided test [ Time Frame: 48 weeks ]
    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


Secondary Outcome Measures :
  1. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values in albuminuria [ Time Frame: 48 weeks ]
    Proportion of subjects achieving a 25% decline in albuminuria in the voxelotor-treated group compared to the observation group

  2. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values in kidney function measure [ Time Frame: 48 weeks ]
    24 hour urine protein

  3. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values in In kidney function measure [ Time Frame: 48 weeks ]
    24 hour urine eGFR

  4. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values in kidney function measure [ Time Frame: 48 weeks ]
    24 hour urine albumin concentration

  5. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values in kidney function measure [ Time Frame: 48 weeks ]
    24 hour serum creatinine

  6. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values in Kidney function measure [ Time Frame: 48 weeks ]
    24 hour serum cystatin C

  7. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values in Kidney function measure [ Time Frame: 48 weeks ]
    24 hour serum BUN

  8. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values in Kidney function measure [ Time Frame: 48 weeks ]
    CKD stage

  9. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney function measure [ Time Frame: 48 weeks ]
    24 hour urine retinol binding protein

  10. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney function measure [ Time Frame: 48 weeks ]
    24 hour urine β2 microglobulin

  11. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney function measure [ Time Frame: 48 weeks ]
    Plasma cell-free hemoglobin

  12. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney function measure [ Time Frame: 48 weeks ]
    Urine hemoglobin

  13. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney function measure [ Time Frame: 48 weeks ]
    Urine dipstick-defined hemoglobinuria)

  14. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values markers of hemolysis [ Time Frame: 48 weeks ]
    Lactate dehydrogenase (LDH)

  15. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values markers of hemolysis [ Time Frame: 48 weeks ]
    Aspartate aminotransferase (AST)

  16. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values markers of hemolysis [ Time Frame: 48 weeks ]
    Indirect bilirubin

  17. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values markers of hemolysis [ Time Frame: 48 weeks ]
    Reticulocyte%

  18. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values markers of hemolysis [ Time Frame: 48 weeks ]
    Hemoglobin concentration

  19. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney injury biomarker [ Time Frame: 48 weeks ]
    Urine nephrin

  20. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney injury biomarker [ Time Frame: 48 weeks ]
    Urine podocalyxin

  21. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney injury biomarker [ Time Frame: 48weeks ]
    Urine KIM-1

  22. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values kidney injury biomarker [ Time Frame: 48 weeks ]
    Urine NGAL

  23. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values oxidative injury biomarker [ Time Frame: 48weeks ]
    Serum Methylenedioxyamphetamine (MDA)

  24. Change from the average of the Screening and Baseline values to the Week 47 and Week 48 values oxidative injury biomarker [ Time Frame: 48 weeks ]
    Serum 8-OHd



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04335721


Contacts
Layout table for location contacts
Contact: Santosh Saraf, MD 312-996-5680 ssaraf@uic.edu)
Contact: Charity Ball, RN 312-996-2937 chball@uic.edu

Sponsors and Collaborators
University of Illinois at Chicago
Global Blood Therapeutics
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Responsible Party: Santosh L Saraf, Principal Investigator, University of Illinois at Chicago
ClinicalTrials.gov Identifier: NCT04335721    
Other Study ID Numbers: 2020-0047
First Posted: April 6, 2020    Key Record Dates
Last Update Posted: June 1, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Kidney Diseases
Renal Insufficiency, Chronic
Anemia, Sickle Cell
Anemia
Hematologic Diseases
Urologic Diseases
Renal Insufficiency
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn