Voxelotor Sickle Cell Exercise Study

The Effect of Voxelotor on Exercise Capacity of Youths With Sickle Cell Anemia

This study is a pilot, open-label, single-arm study to evaluate the effect of the sickle cell medication voxelotor on exercise capacity, as measured by cardiopulmonary exercise testing (CPET) in patients 12 years of age and older with sickle cell anemia (SCA).

Study Overview

• Status: Completed
• Conditions: Sickle Cell Anemia
• Intervention / Treatment: Drug: Voxelotor

Detailed Description

This study will assess exercise capacity by cardiopulmonary exercise testing (CPET) before and after 8 weeks of voxelotor therapy.

Patients with genetically severe forms of sickle cell disease, including Hgb SS, Hgb S beta 0 thalassemia, Hgb SC Harlem, etc., age 12 or older, with stable Hgb and Hgb F will be recruited. Enrolled subjects will have study labs drawn, undergo baseline CPET in the exercise lab, then take voxelotor 1500mg daily for 2 months, followed by repeat study labs and a second CPET. Each subject's CPET results before and after voxelotor will be compared, and the study labs before and after voxelotor will be compared. Each subject will be compared to him/herself.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Pediatric Specialist of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, age > 12 years
4. In good general health as evidenced by medical history and diagnosed with a genetically severe form of sickle cell anemia (Hgb SS, Hgb S beta 0 thalassemia, Hgb SCHarlem, and others)
5. Patients who are on Hydroxyurea need to be on a stable dose for at least 3 months without anticipated change in dosing until the study is completed.
6. Ability to take oral medication and willingness to adhere to daily voxelotor and 2 CPETs at scheduled intervals.
7. For females of reproductive potential who are sexually active: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 30 days after the end of study.
8. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner

Exclusion Criteria:

1. Patients on chronic transfusions or who received a transfusion within last 8 weeks
2. Patients who had hospitalization for vaso-occlusive crisis or acute chest syndrome within 30 days prior to informed consent/assent.
3. Patients who have screening alanine aminotransferase (ALT) > 4X upper limit of normal
4. Patients who suffer from physical inactivity attributable to clinically significant musculoskeletal, cardiovascular, or respiratory comorbidities
5. Patients already taking commercially available voxelotor
6. Prior hypersensitivity to voxelotor or excipients.
7. Pregnant patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: voxelotor; Voxelotor 1500mg daily orally	Drug: Voxelotor; daily voxelotor 1500mg oral medication; Other Names: GBT440, Oxbryta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak oxygen consumption (VO2)	Change in peak oxygen consumption (VO2) measured in CPET after voxelotor treatment	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Biochemical markers of red cell sickling: Hemoglobin	Measured before and after treatment with voxelotor.	8 weeks
Change in Biochemical markers of red cell sickling: Reticulocyte Count	Measured before and after treatment with voxelotor.	8 weeks
Change in Biochemical markers of red cell sickling: Bilirubin	Measured before and after treatment with voxelotor.	8 weeks
Change in Biochemical markers of red cell sickling: Lactate Dehydrogenase (LDH)	Measured before and after treatment with voxelotor.	8 weeks
Change in Biochemical markers of red cell sickling: Haptoglobin	Measured before and after treatment with voxelotor.	8 weeks
Change in Biochemical markers of red cell sickling: % Fetal Hemoglobin expressing cells	Measured before and after treatment with voxelotor.	8 weeks
Change in Biochemical markers of red cell sickling: P50 oxygen dissociation	Measured before and after treatment with voxelotor.	8 weeks
Change in Biochemical markers of red cell sickling: Point of Sickling (POS)	Measured before and after treatment with voxelotor.	8 weeks
Change in Biochemical markers of red cell sickling: Dense Cells	Measured before and after treatment with voxelotor.	8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
HRQOL: Patient's Global Impression of Change (PGIC)	Health-related quality of life (HRQoL) as assessed by patient reported outcome via Patient's Global Impression of Change (PGIC) at end of treatment study visit. The PGIC asks patients to rate their overall improvement relative to their baseline state at the beginning of the study on a 7-point scale.; No change (or condition has got worse); Almost the same, hardly any change at all; A little better, but not noticeable change at all; Somewhat better, but the change has not made any real difference; Moderately better, and a slight but noticeable change; Better, and a definite improvement that has made a real and worthwhile difference; A great deal better, and a considerable improvement that has made all the difference	8 weeks
HRQOL: Clinical Global Impression of Change (CGIC)	Health-related quality of life (HRQoL) as assessed by clinician-reported outcome via Clinical Global Impression of Change-Improvement (CGIC-I) scale at end of treatment study visit. The CGIC-I is a one-item questionnaire that requires the clinician to assess how much the patient's illness has improved or worsened relative to their baseline state at the beginning of the intervention on a 7-point scale: = Very much improved; = Much improved; = Minimally improved; = No change; = Minimally worse; = Much worse; = Very much worse	8 weeks

Collaborators and Investigators

• Sponsor: Elizabeth Yang, MD, PhD
• Collaborators: University of California, San Francisco; Global Blood Therapeutics; Pediatrix
• Investigators: Principal Investigator: Elizabeth Yang, MD, PhD., Pediatric Specialists Of Virginia; Study Director: Vivian Phan, MS, Pediatric Specialists Of Virginia; Study Director: Kari Wheeler, BSN, RN, Pediatric Specialists Of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2020
• Primary Completion (Actual): October 25, 2021
• Study Completion (Actual): December 29, 2021

Study Registration Dates

• First Submitted: September 11, 2020
• First Submitted That Met QC Criteria: October 2, 2020
• First Posted (Actual): October 9, 2020

Study Record Updates

• Last Update Posted (Actual): June 15, 2022
• Last Update Submitted That Met QC Criteria: June 14, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia; Anemia, Sickle Cell
• Other Study ID Numbers: ESR-C006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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