Clinical trial NCT04581356: Voxelotor Sickle Cell Exercise Study
Official title: The Effect of Voxelotor on Exercise Capacity of Youths With Sickle Cell Anemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Sickle Cell Anemia
Lead sponsor: Pediatric Specialists of Virginia
Sponsor class: OTHER
Collaborators: name: Pediatrix
name: University of California, San Francisco
name: Global Blood Therapeutics
First posted: 2020-10-09
Enrollment: 14
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: single-arm, open-label, pilot study in which each subject compared to him/herself
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Peak oxygen consumption (VO2)
timeFrame: 8 weeks
Secondary outcomes:
measure: Change in Biochemical markers of red cell sickling: Hemoglobin
timeFrame: 8 weeks
measure: Change in Biochemical markers of red cell sickling: Reticulocyte Count
timeFrame: 8 weeks
measure: Change in Biochemical markers of red cell sickling: Bilirubin
timeFrame: 8 weeks
measure: Change in Biochemical markers of red cell sickling: Lactate Dehydrogenase (LDH)
timeFrame: 8 weeks
measure: Change in Biochemical markers of red cell sickling: Haptoglobin
timeFrame: 8 weeks
measure: Change in Biochemical markers of red cell sickling: % Fetal Hemoglobin expressing cells
timeFrame: 8 weeks
measure: Change in Biochemical markers of red cell sickling: P50 oxygen dissociation
timeFrame: 8 weeks
measure: Change in Biochemical markers of red cell sickling: Point of Sickling (POS)
timeFrame: 8 weeks
measure: Change in Biochemical markers of red cell sickling: Dense Cells
timeFrame: 8 weeks
Other outcomes:
measure: HRQOL: Patient's Global Impression of Change (PGIC)
timeFrame: 8 weeks
measure: HRQOL: Clinical Global Impression of Change (CGIC)
timeFrame: 8 weeks
Locations:
city: Fairfax
country: United States
facility: Pediatric Specialist of Virginia
state: Virginia
Study officials:
affiliation: Pediatric Specialists of Virginia
name: Elizabeth Yang, MD, PhD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Pediatric Specialists of Virginia
name: Vivian Phan, MS
role: STUDY_DIRECTOR
affiliation: Pediatric Specialists of Virginia
name: Kari Wheeler, BSN, RN
role: STUDY_DIRECTOR
References: