Study to Assess the Effect of Long-term Treatment With Voxelotor in Participants Who Have Completed Treatment in Study GBT440-031

Phase 3TerminatedNCT03573882

Pfizer179 enrolled

Overview

Open Label Extension Study of Voxelotor Clinical Trial Participants with Sickle Cell Disease Who Participated in Voxelotor Clinical Trials

This open label extension (OLE), multi-center study will be conducted at approximately 100 clinical sites globally and will be available to eligible participants from study GBT440-031. The study will enroll participants from GBT440-031 (approximately 435) under any of the following conditions: * Participant has completed 72 weeks of treatment regardless of dose selection for GBT440-031 * Dose selection has occurred for GBT440-031 and participant is on non-selected dose on GBT440-031 * GBT440-031 study interim data analysis and/or study modifications have occurred * GBT440-031 study has completed The objective of this open-label extension (OLE) study is to assess the long-term safety and treatment effect of voxelotor in participants who have completed treatment in study GBT440-031, using the following parameters: 1. Safety based upon AEs, clinical laboratory tests, physical examinations (PE) and other clinical measures. 2. Frequency of sickle cell disease (SCD)-related complications. 3. Hemolytic anemia as measured by hematological laboratory parameters (e.g. hemoglobin, reticulocytes and unconjugated bilirubin). All participants will receive daily voxelotor treatment. Participants may receive study drug as long they continue to receive clinical benefit which outweighs risk as determined by the Investigator and/or until the participant has access to voxelotor from an alternative source (i.e., commercialization or through a managed access program).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

179

Conditions

Sickle Cell Disease

Interventions

VoxelotorDRUG

300mg or 500mg Tablet, Oral, With or Without Food

Eligibility

Sex: ALLMin age: 12 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female study participants with SCD who participated and received study treatment in Study GBT440-031. Note: Participants in GBT440-031 who discontinued study drug due to an AE, but who remained on study may be eligible for treatment in this study provided the AE does not pose a risk for treatment with voxelotor. * Females of child-bearing potential are required to have a negative urine pregnancy test prior to dosing on Day 1. * 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. * Participant has provided written informed consent or assent (the ICF must be reviewed and signed by each participant; in the case of pediatric participants, both the consent of the participant's legal representative or legal guardian, and the participant's assent must be obtained). Exclusion Criteria: * Female who is breast-feeding or pregnant. * Participant withdrew consent from Study GBT440-031. * Participant was lost to follow-up from Study GBT440-031. * Participant requiring chronic dialysis. * Any medical, psychological, safety, or behavioral conditions, which, in the opinion of the Investigator, may confound safety interpretation, interfere with compliance, or preclude informed consent.

Locations (60)

Outcomes

Primary Outcomes

Number of Participants With Sickle Cell Disease (SCD)-Related Treatment Emergent Adverse Events (TEAEs)

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs were defined as AEs with onset on or after the date of informed consent until 28 days after last dose of study drug. SCD-related TEAEs included preferred terms (PTs) of sickle cell anaemia with crisis, acute chest syndrome (ACS), pneumonia, priapism, and osteonecrosis. The number of participants with any SCD-related TEAEs was reported in this outcome measure.

Time frame: From date of informed consent up to 28 days after last dose of study drug (maximum up to 300.7 weeks)

Number of Participants With Non- SCD-Related TEAEs

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs were defined as AEs with onset on or after the date of informed consent until 28 days after last dose of study drug. Non-SCD-related TEAEs included all the PTs of TEAEs other than SCD- related TEAEs. The number of participants with any non-SCD-related TEAEs was reported in this outcome measure.

Time frame: From date of informed consent up to 28 days after last dose of study drug (maximum up to 300.7 weeks)

Number of Participants With SCD-Related Treatment Emergent Serious Adverse Events (TESAEs)

An SAE is an AE at any dose, in view of investigator resulted in any of following outcomes: death; life-threatening AE; inpatient hospitalization/prolongation of existing hospitalization; persistent/significant incapacity or disability; a congenital anomaly/birth defect and important medical events (IME) that may not result in death, be immediately life threatening; or require hospitalization may be considered serious when based upon medical judgement, they may jeopardize study participant and may require medical or surgical intervention to prevent one of outcomes listed in definition. TESAEs were defined as SAEs with onset on or after the date of informed consent until 28 days after last dose of study drug. Number of participants with SCD-Related TESAEs was reported in this outcome measure.

Time frame: From date of informed consent up to 28 days after last dose of study drug (maximum up to 300.7 weeks)

Data from ClinicalTrials.gov

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Arkansas Primary Care Clinic, PA

Little Rock, Arkansas, United States

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Jackson Memorial Hospital (Investigational Drug Services)

Miami, Florida, United States

Jackson Memorial Hospital

Miami, Florida, United States

University of Miami Hospital & Clinics/SCCC, Research Pharmacy (Investigational Drug Services)

Miami, Florida, United States

University of Miami

Miami, Florida, United States

Children's Healthcare of Atlanta - Scottish Rite

Atlanta, Georgia, United States

University of Illinois at Chicago Clinical Research Center

Chicago, Illinois, United States

University of Illinois Hospital and Health Science System

Chicago, Illinois, United States

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, United States

...and 50 more locations

Number of Participants With Non-SCD-Related TESAEs

An SAE is an AE at any dose, in view of investigator resulted in any of following outcomes: death; life-threatening AE; inpatient hospitalization/prolongation of existing hospitalization; persistent/significant incapacity or disability; a congenital anomaly/birth defect and IME that may not result in death, be immediately life threatening; or require hospitalization may be considered serious when based upon medical judgement, they may jeopardize study participant and may require medical or surgical intervention to prevent one of outcomes listed in definition. TESAEs were defined as SAEs with onset on or after the date of informed consent until 28 days after last dose of study drug. Number of participants with non-SCD related TESAEs was reported in this outcome measure.

Time frame: From date of informed consent up to 28 days after last dose of study drug (maximum up to 300.7 weeks)

Annualized Incidence Rate (Events Per Person Years) of SCD-Related Complications

Annualized incidence rate was defined as total number of events (i.e. complications observed for all participants) divided by total person years. Total person-years= sum of participant summary period in years where summary period=date of informed consent until the earlier of 28 days after last dose of study drug or end of study date. SCD related complications included acute chest syndrome, cerebrovascular accident, hepatic sequestration, ocular icterus, osteonecrosis, pneumonia, priapism, pulmonary hypertension, retinopathy, sickle cell anaemia with crisis, skin ulcer and splenic sequestration. The 95% CI was based on exact Poisson confidence limits. Incidence rate of all SCD related complications is reported in this outcome measure.

Time frame: From date of informed consent up to earlier of 28 days after last dose of study drug or end of study date (maximum up to 300.7 weeks)

Annualized Incidence Rate (VOC Events Per Person Years) of On-Treatment Vaso-occlusive Crisis (VOCs)

Annualized incidence rate was defined as total number of VOC events divided by total person years. Total person-years= sum of participant summary period in years where summary period=date of informed consent to last dose of study drug. VOC during the treatment period was defined as composite of acute painful crisis or acute chest syndrome (ACS) and included the following: moderate to severe pain lasting at least 2 hours; no explanation other than VOC; required oral or parenteral opioids, ketorolac, or other analgesics prescribed or directed by a healthcare professional. The 95% CI was based on exact Poisson confidence limits.

Time frame: From date of informed consent to last dose of study drug (maximum up to 296.7 weeks)

Secondary Outcomes

Change From Baseline in Hemoglobin Level at Week 48

Change from baseline in hemoglobin at Week 48 was reported in this outcome measure. Baseline value was defined as the last available value (including Week 72, end of treatment \[EOT\], or end of study \[EOS\] visits in the parent study GBT440-031 \[NCT03036813\]) collected on or prior to first dose in GBT440-034.

Time frame: Baseline, Week 48

Percent Change From Baseline in Reticulocytes Percentage at Week 48

Percent change from baseline in reticulocytes percentage at Week 48 was reported in this outcome measure. Baseline value was defined as the last available value (including Week 72, EOT, or EOS visits in the parent study GBT440-031 \[NCT03036813\]) collected on or prior to first dose in GBT440-034.

Time frame: Baseline, Week 48

Percent Change From Baseline in Absolute Reticulocytes at Week 48

Percent change from baseline in absolute reticulocytes at Week 48 was reported in this outcome measure. Baseline value was defined as the last available value (including Week 72, EOT, or EOS visits in the parent study GBT440-031 \[NCT03036813\]) collected on or prior to first dose in GBT440-034.

Time frame: Baseline, Week 48

Percent Change From Baseline in Indirect Bilirubin at Week 48

Percent change from baseline in indirect bilirubin at Week 48 was reported in this outcome measure. Baseline value was defined as the last available value (including Week 72, EOT, or EOS visits in the parent study GBT440-031 \[NCT03036813\]) collected on or prior to first dose in GBT440-034.

Time frame: Baseline, Week 48