Clinical trial NCT04400487: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Sickle Cell Disease
Sickle Cell Anemia
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-05-22
Enrollment: 25
Sex: ALL
Minimum age (years): 12
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change From Baseline in Total Daily Physical Activity (Counts Per Minute) to Week 10-12
timeFrame: Baseline, Week 10-12
measure: Change From Baseline in Total Daily Physical Activity (Counts Per Minute) to Week 22-24
timeFrame: Baseline, Week 22-24
measure: Change From Baseline in Light Physical Activity to Week 10-12
timeFrame: Baseline, Week 10-12
measure: Change From Baseline in Light Physical Activity to Week 22-24
timeFrame: Baseline, Week 22-24
measure: Change From Baseline in Moderate Physical Activity to Week 10-12
timeFrame: Baseline, Week 10-12
measure: Change From Baseline in Moderate Physical Activity to Week 22-24
timeFrame: Baseline, Week 22-24
measure: Change From Baseline in Vigorous Physical Activity to Week 10-12
timeFrame: Baseline, Week 10-12
measure: Change From Baseline in Vigorous Physical Activity to Week 22-24
timeFrame: Baseline, Week 22-24
measure: Change From Baseline in Total Nocturnal Sleep Time to Week 10-12
timeFrame: Baseline, Week 10-12
measure: Change From Baseline in Total Nocturnal Sleep Time to Week 22-24
timeFrame: Baseline, Week 22-24
measure: Change From Baseline in Wake Time After Sleep Onset to Week 10-12
timeFrame: Baseline, Week 10-12
measure: Change From Baseline in Wake Time After Sleep Onset to Week 22-24
timeFrame: Baseline, Week 22-24
measure: Change From Baseline in Sleep Efficiency to Week 10-12
timeFrame: Baseline, Week 10-12
measure: Change From Baseline in Sleep Efficiency to Week 22-24
timeFrame: Baseline, Week 22-24
measure: Percentage of Participants With a More Than (>)1 Grams Per Deciliter (g/dL) Increase in Hemoglobin (Hb) at Week 12
timeFrame: Week 12
measure: Percentage of Participants With a >1 g/dL Increase in Hemoglobin (Hb) at Week 24
timeFrame: Week 24
measure: Change From Baseline in Mean Overnight Oxygen Saturation (SpO2 Percentage [%]) to Week 10-12
timeFrame: Baseline, Week 10-12
measure: Change From Baseline in Mean Overnight SpO2 % to Week 22-24
timeFrame: Baseline, Week 22-24
measure: Change From Baseline in Median Number of Overnight SpO2 Dips > 3% Per Hour to Week 10-12
timeFrame: Baseline, Week 10-12
measure: Change From Baseline in Median Number of Overnight SpO2 Dips > 3% Per Hour to Week 22-24
timeFrame: Baseline, Week 22-24
Secondary outcomes:
Other outcomes:
Locations:
city: Farmington
country: United States
facility: UConn Health
state: Connecticut
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Bronx
country: United States
facility: The Children's Hospital at Montefiore
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Durham
country: United States
facility: Duke Department of Pediatrics
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Richmond
country: United States
facility: VCU Health
state: Virginia
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: