Sickle Cell Anemia
Conditions
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.
Interventions
DRUGVoxelotor
daily voxelotor 1500mg oral medication
Sponsors
Pediatrix
University of California, San Francisco
Global Blood Therapeutics
Elizabeth Yang, MD, PhD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
single-arm, open-label, pilot study in which each subject compared to him/herself
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak oxygen consumption (VO2) | 8 weeks | Change in peak oxygen consumption (VO2) measured in CPET after voxelotor treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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: Reticulocyte Count | 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: Lactate Dehydrogenase (LDH) | 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: Point of Sickling (POS) | 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: P50 oxygen dissociation | 8 weeks | Measured before and after treatment with voxelotor. |
Other
| Measure | Time frame | Description |
|---|---|---|
| HRQOL: Patient's Global Impression of Change (PGIC) | 8 weeks | 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. 1. No change (or condition has got worse) 2. Almost the same, hardly any change at all 3. A little better, but not noticeable change at all 4. Somewhat better, but the change has not made any real difference 5. Moderately better, and a slight but noticeable change 6. Better, and a definite improvement that has made a real and worthwhile difference 7. A great deal better, and a considerable improvement that has made all the difference |
| HRQOL: Clinical Global Impression of Change (CGIC) | 8 weeks | 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: 1. = Very much improved 2. = Much improved 3. = Minimally improved 4. = No change 5. = Minimally worse 6. = Much worse 7. = Very much worse |
Countries
United States
Outcome results
None listed