Study to Assess the Effect of Long-term Treatment With Voxelotor in Participants Who Have Completed Treatment in Study GBT440-031 (034OLE)

An Open Label Extension Study of Voxelotor (GBT440) Administered Orally to Participants With Sickle Cell Disease Who Have Participated in Voxelotor Clinical Trials

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

Study Overview

• Status: Terminated
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Voxelotor

Detailed Description

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
• Enrollment (Actual): 179
• Phase: Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital-University Health Network
• Egypt
  • Alexandria, Egypt
    • Alexandria Clinical Research Center, Faculty of Medicine, Alexandria University
  • Alexandria, Egypt
    • Alexandria Clinical Research Center, Faculty of Medicine
  • Alsharkia, Egypt
    • Zagazig University Hospital
  • Cairo, Egypt
    • Ain Shams University Hospital
  • Cairo, Egypt, 11541
    • Abu El Rich Hospital,Cairo University Hospital
  • Cairo, Egypt
    • The Egyptian Thalassemia Association ( E.T.A)
• France
  • Paris, France, 75015
    • Hôpital Européen Georges Pompidou - Medecine Interne
• Italy
  • Padova Veneto
    • Padua, Padova Veneto, Italy, 35128
      • Azienda Ospedaliera di Padova
• Kenya
  • Nairobi, Kenya
    • Gertrude's Children's Hospital
  • Nairobi, Kenya, 00101
    • KEMRI/CRDR - Kenya Medical Research Insititute - Center for respiratory Disease Research
  • Kisumu County
    • Siaya, Kisumu County, Kenya
      • Centres for Disease Control and Prevention
• Lebanon
  • Beirut, Lebanon
    • American University of Beirut
  • Tripoli, Lebanon
    • Nini Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academic Medical Center(AMC)
  • Rotterdam, Netherlands, 3015 CN
    • ErasmusMC
• Oman
  • Muscat, Oman, 123
    • Sultan Qaboos University Hospital
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01130
    • Adana Acibadem Hospital
  • Kayseri, Turkey (Türkiye), 38039
    • Erciyes Universitesi Tip Fakultesi
  • Mersin, Turkey (Türkiye), 33343
    • Mersin Universitesi Tip Fakultesi Saglik Arastirma ve Uygulama Hastanesi
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
  • London, United Kingdom, W12 0HS
    • Imperial College Healthcare NHS Trust, Hammersmith Hospital
  • London, United Kingdom, WC1E 6AG
    • McMillan Cancer Centre
  • Greater London
    • London, Greater London, United Kingdom, E1 1BB
      • Barts Health NHS Trust
    • London, Greater London, United Kingdom, E9 6SR
      • Homerton University Hospital NHS Foundation Trust
  • London
    • Great Maze Pond, London, United Kingdom, SE1 9RT
      • Guys and St. Thomas Hospital NHS Foundation Trust
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • Arkansas Primary Care Clinic, PA
  • California
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital Oakland
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33136
      • Jackson Memorial Hospital
    • Miami, Florida, United States, 33136
      • Jackson Memorial Hospital (Investigational Drug Services)
    • Miami, Florida, United States, 33136
      • University of Miami Hospital & Clinics/SCCC, Research Pharmacy (Investigational Drug Services)
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Children's Healthcare of Atlanta - Scottish Rite
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago Clinical Research Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois Hospital and Health Science System
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Indiana Hemophilia and Thrombosis Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Our Lady of the Lake Physician Group-Medical Oncology
    • Baton Rouge, Louisiana, United States, 70808
      • St. Jude Affiliate Clinic Baton Rouge
    • New Orleans, Louisiana, United States, 70112
      • University Medical Center New Orleans
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sickle Cell Infusion Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Brigham and Women's Hospital Research Pharmacy
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • New Jersey
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center - Herbert Irving Pavilion
    • The Bronx, New York, United States, 10461
      • Montefiore - Einstein Center for Cancer Care
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Hospitals
    • Chapel Hill, North Carolina, United States, 27599
      • Clinical and Translational Research Center (CTRC)
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Durham, North Carolina, United States, 27710
      • Investigational Drug Service, Duke University Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center (UPMC)
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina - Comprehensive Sickle Cell Clinic
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina: Investigational Drug Services Pharmacy
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Methodist Comprehensive Sickle Cell Clinic
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital - Investigational Pharmacy
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Clinical Research Services Unit- Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Voxelotor; Participants will receive voxelotor (GBT440) at the highest dose (either 900 mg or 1500 mg) deemed safe by the Data Safety Monitoring Board (DSMB).	Drug: Voxelotor; 300mg or 500mg Tablet, Oral, With or Without Food; Other Names: GBT440

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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 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.	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.	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.	From date of informed consent to last dose of study drug (maximum up to 296.7 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	Baseline, Week 48

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2018
• Primary Completion (Actual): November 12, 2024
• Study Completion (Actual): November 12, 2024

Study Registration Dates

• First Submitted: May 15, 2018
• First Submitted That Met QC Criteria: June 28, 2018
• First Posted (Actual): June 29, 2018

Study Record Updates

• Last Update Posted (Estimated): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 5, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Open Label Extension
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; voxelotor
• Other Study ID Numbers: GBT440-034; C5341022 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No