Voxelotor Sickle Cell Exercise Study

Phase 4

Completed

• Conditions: Sickle Cell Anemia
• Interventions: Drug: Voxelotor

• Registration Number: NCT04581356
• Lead Sponsor: Elizabeth Yang, MD, PhD

Brief Summary

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).

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 Timeline

• Study First Submitted: 2020-09-11
• Study Start: 2020-09-21
• Study First Submitted QC: 2020-10-02
• Study First Posted: 2020-10-09
• Primary Completion: 2021-10-25
• Study Completion: 2021-12-29
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-14
• Last Update Posted: 2022-06-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
voxelotor	Voxelotor	Voxelotor 1500mg daily orally

Primary Outcome Measures

Name	Time	Method
Peak oxygen consumption (VO2)	8 weeks	Change in peak oxygen consumption (VO2) measured in CPET after voxelotor treatment

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Pediatric Specialist of Virginia; 🇺🇸 Fairfax, Virginia, United States