Actigraphy Improvement With Voxelotor (ActIVe) Study (ActIVe)

• ClinicalTrials.gov Identifier: NCT04400487
• Recruitment Status: Completed
• First Posted: May 22, 2020
• Last Update Posted: December 19, 2022
• Sponsor: Global Blood Therapeutics
• Information provided by (Responsible Party): Global Blood Therapeutics

Tracking Information

• First Submitted Date: March 25, 2020
• First Posted Date: May 22, 2020
• Last Update Posted Date: December 19, 2022
• Actual Study Start Date: October 23, 2020
• Actual Primary Completion Date: September 18, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 21, 2020)

• Change in total daily physical activity [ Time Frame: Baseline, Week 10-12, Week 22-24 ]
  Change in total daily physical activity (expressed in counts per minute)
• Change in total nocturnal sleep time [ Time Frame: Baseline, Week 10-12, Week 22-24 ]
  Change in total nocturnal sleep time (TST)
• Change in wake time after sleep onset [ Time Frame: Baseline, Week 10-12, Week 22-24 ]
  Change in wake time after sleep onset (WASO)
• Change in sleep efficiency [ Time Frame: Baseline, Week 10-12, Week 22-24 ]
  Change in sleep efficiency (SE) measured as total sleep time/time in bed
• Change in mean nocturnal hemoglobin oxygen saturation percentage [ Time Frame: Baseline, Week 10-12, Week 22-24 ]
  Change in mean overnight SpO2 percentage as measured by pulse oximetry SpO2 percent
• Proportion of participants with a >1 g/dL increase in Hb [ Time Frame: Baseline, Week 10-12, Week 22-24 ]
  Proportion of participants with a >1 g/dL increase in Hb
• Change in median number of overnight SpO2 dips > 3% per hour [ Time Frame: Baseline, Week 10-12, Week 22-24 ]
  Change in median number of overnight SpO2 dips > 3% per hour as measured by pulse oximetry SpO2 percent

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Actigraphy Improvement With Voxelotor (ActIVe) Study
• Official Title: A Phase 4, Multicenter, Open-label Study to Evaluate the Treatment Effect of Voxelotor on Physical Activity in Adolescents and Adults With Sickle Cell Disease
• Brief Summary: This is a study to evaluate the effect of voxelotor on daily physical activity and sleep quality, as measured by a wrist-worn device in participants with sickle cell disease (SCD) and chronic moderate anemia.

Detailed Description

All participants will receive Voxelotor as treatment. There will be approximately 13 sites in the US.

Participant safety and tolerability will be monitored during the study using standard measures, including physical examinations, vital signs (including temperature, blood pressure, pulse rate, respiratory rate and peripheral oxygen saturation [SpO2]), clinical laboratory tests, and adverse event (AE) monitoring.

Screening Period (up to 4 weeks in duration): During this period, participants will sign the informed consent form (ICF), after which they will complete the screening assessments as detailed in the Schedule of Assessments (SOA).

Run-in Period (2 weeks in duration): During this period, participants will enter a 2-week run-in period (Day -14 to Day -1) during which baseline actigraphy measures of physical activity and sleep quality, overnight pulse oximetry assessments of oxygen saturation, and Patient-Reported Outcome (PRO) assessments will be collected before initiating treatment with voxelotor.

Treatment Period (24 weeks in duration): After completion of the 14-day Run-in Period, participants will enter the open label treatment period and receive voxelotor 1500 mg once daily for 24 weeks. Repeat actigraphy assessments of physical activity and sleep quality, and overnight pulse oximetry will be performed during the treatment period (Weeks 10 to 12 and Weeks 22 to 24). PRO and Clinical Global Impression (CGI) assessments will be completed at scheduled study visits. The open-label treatment period is considered the continuous 24 weeks of voxelotor treatment from date of first dose (Day 1).

Follow-up Period (4 weeks in duration): Immediately following the 24-week treatment period, participants will enter a 4-week Follow-up Period.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Sickle Cell Disease
• Sickle Cell Anemia

Intervention

Drug: Voxelotor

500 mg Tablet, Oral, With or Without Food

Other Names:

• GBT440
• Oxbryta

Study Arms

Experimental: Voxelotor

Participants will receive voxelotor at 1500 mg

Intervention: Drug: Voxelotor

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 7, 2022): 25
• Original Estimated Enrollment (submitted: May 21, 2020): 50
• Actual Study Completion Date: September 18, 2022
• Actual Primary Completion Date: September 18, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male or female participants with SCA (sickle hemoglobin with two sickle cell genes [HbSS] or sickle hemoglobin (S) and one beta thalassemia gene [HbS β0] thal genotype)
2. Between 12 to 55 years of age (inclusive)
3. Screening Hb level ≤8.0 g/dL
4. Treatment with hydroxyurea (HU) therapy on study is permitted if the participant has been on a stable dose for at least 90 days before enrollment with no dose modifications planned or anticipated by the Investigator
5. Treatment with glutamine is permitted
6. Treatment with erythropoiesis-stimulating agents (ESAs) is permitted if the participant has been on a stable dose for at least 12 weeks before enrollment with no dose modifications planned or anticipated by the Investigator
7. Female participants of child-bearing potential must use highly effective methods of contraception to 30 days after the last dose of study drug. Male participants must use barrier methods of contraception to 30 days after the last dose of study drug
8. Females of child-bearing potential are required to have a negative pregnancy test before the administration of study drug
9. Written informed consent and/or parental/guardian consent and participant assent per Institutional Review Board (IRB) policy and requirements, consistent with ICH guidelines

Exclusion Criteria:

1. Red blood cell (RBC transfusion within 3 months before initiation of study drug
2. Planned initiation of regularly scheduled RBC transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) during the study
3. Hospitalization for vaso-occlusive crisis (VOC) or acute chest syndrome (ACS) within 30 days prior to informed consent/assent.
4. More than 10 VOCs requiring hospitalization, emergency department or clinic visit within the past 12 months
5. Planned elective surgery within the next 6 months
6. Physical inactivity attributable to clinically significant musculoskeletal, cardiovascular, or respiratory comorbidities
7. Anemia due to bone marrow failure (eg, myelodysplasia)
8. Absolute reticulocyte count (ARC) < 100 x10^9/L
9. Screening alanine aminotransferase (ALT) > 4× upper limit of normal (ULN)
10. Severe renal dysfunction (estimated glomerular filtration rate [GFR] < 30 mL/min/1.73 m2 by Schwartz formula) or is on chronic dialysis
11. Known active hepatitis A, B or C or known to be human immunodeficiency virus (HIV)-positive.
12. Females who are breast-feeding or pregnant
13. Major surgery within 8 weeks before enrollment. Participants must have completely recovered from any previous surgery before enrollment
14. History of hematopoietic stem cell transplant or gene therapy
15. Received an investigational drug within 30 days or 5-half-lives, whichever is longer, prior to consent, or is currently participating in another trial of an investigational or marketed drug (or medical device)
16. Use of concomitant medications (eg, crizanlizumab) that confound the ability to interpret data from the study
17. Medical, psychological, or behavioral condition that, in the opinion of the Investigator, would confound or interfere with evaluation of safety and/or efficacy of the study drug, prevent compliance with the study protocol; preclude informed consent; or, render the participant unable/unlikely to comply with the study procedures
18. Use of herbal medications (e.g., St. John's Wort), sensitive cytochrome P450 (CYP) 3A4 substrates with a narrow therapeutic index, strong CYP3A4 inhibitors, fluconazole, or moderate or strong CYP3A4 inducers
19. Symptomatic coronavirus disease of 2019 (COVID-19) infection

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 55 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04400487
• Other Study ID Numbers: GBT440-039
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Global Blood Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Global Blood Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Global Blood Therapeutics
• Verification Date: December 2022