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

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

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03573882

Acronym

034OLE

Enrollment

179

Registered

2018-06-29

Start date

2018-06-06

Completion date

2024-11-12

Last updated

2025-11-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Sickle Cell Disease

Keywords

Open Label Extension

Brief summary

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

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).

Interventions

DRUGVoxelotor

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

12 Years to 65 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Annualized Incidence Rate (VOC Events Per Person Years) of On-Treatment Vaso-occlusive Crisis (VOCs)	From date of informed consent to last dose of study drug (maximum up to 296.7 weeks)	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.
Number of Participants With Non- SCD-Related TEAEs	From date of informed consent up to 28 days after last dose of study drug (maximum up to 300.7 weeks)	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.
Number of Participants With SCD-Related Treatment Emergent Serious Adverse Events (TESAEs)	From date of informed consent up to 28 days after last dose of study drug (maximum up to 300.7 weeks)	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.
Number of Participants With Non-SCD-Related TESAEs	From date of informed consent up to 28 days after last dose of study drug (maximum up to 300.7 weeks)	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.
Annualized Incidence Rate (Events Per Person Years) of SCD-Related Complications	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 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.
Number of Participants With Sickle Cell Disease (SCD)-Related Treatment Emergent Adverse Events (TEAEs)	From date of informed consent up to 28 days after last dose of study drug (maximum up to 300.7 weeks)	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.

Secondary

Measure	Time frame	Description
Percent Change From Baseline in Reticulocytes Percentage at Week 48	Baseline, 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.
Percent Change From Baseline in Absolute Reticulocytes at Week 48	Baseline, 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.
Percent Change From Baseline in Indirect Bilirubin at Week 48	Baseline, 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.
Change From Baseline in Hemoglobin Level at Week 48	Baseline, 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.

Countries

Canada, Egypt, France, Italy, Kenya, Lebanon, Netherlands, Oman, Turkey (Türkiye), United Kingdom, United States

Participant flow

Recruitment details

This was an open label extension (OLE) study which included eligible participants from study GBT440-031 (NCT03036813). All participants were administered voxelotor 1500 milligrams (mg) in this study. Results were stratified according to previous treatment in GBT440-031 (NCT03036813).

Pre-assignment details

A total of 179 participants were enrolled in the study. The study was terminated as emerging clinical data observed in studies other than the current study (GBT440-034) indicated that risk profile of voxelotor in people with sickle cell disease (SCD) exceeded benefits observed in previously generated global research and required further assessment.

Participants by arm

Arm	Count
Prior Treatment of Placebo in GBT440-031 (NCT03036813) Participants who received placebo in study GBT440-031 (NCT03036813) were administered voxelotor 1500 mg once daily in this study as long as they received clinical benefit and/or until the participant had access to voxelotor from an alternative source.	62
Prior Treatment of Voxelotor 900mg in GBT440-031(NCT03036813) Participants who received voxelotor 900 mg in study GBT440-031 (NCT03036813) were administered voxelotor 1500 mg once daily in this study as long as they received clinical benefit and/or until the participant had access to voxelotor from an alternative source.	58
Prior Treatment of Voxelotor 1500mg in GBT440-031(NCT03036813) Participants who received voxelotor 1500 mg in study GBT440-031 (NCT03036813) were administered voxelotor 1500 mg once daily in this study as long as they received clinical benefit and/or until the participant had access to voxelotor from an alternative source.	58
Total	178

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	7	5	6
Overall Study	Lost to Follow-up	2	5	3
Overall Study	Other	4	2	2
Overall Study	Participant is Noncompliant with Study Drug	1	2	1
Overall Study	Physician Decision	4	3	2
Overall Study	Pregnancy	1	2	0
Overall Study	Study Terminated by Sponsor	22	17	18
Overall Study	Withdrawal by Subject	6	11	7

Baseline characteristics

Characteristic	Prior Treatment of Placebo in GBT440-031 (NCT03036813)	Total	Prior Treatment of Voxelotor 1500mg in GBT440-031(NCT03036813)	Prior Treatment of Voxelotor 900mg in GBT440-031(NCT03036813)
Age, Continuous	28.5 Years STANDARD_DEVIATION 10.8	28.7 Years STANDARD_DEVIATION 11.84	29.0 Years STANDARD_DEVIATION 13	28.5 Years STANDARD_DEVIATION 11.9
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants	9 Participants	1 Participants	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	57 Participants	168 Participants	56 Participants	55 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	1 Participants	0 Participants
Race/Ethnicity, Customized African	14 Participants	34 Participants	12 Participants	8 Participants
Race/Ethnicity, Customized Arab	9 Participants	28 Participants	9 Participants	10 Participants
Race/Ethnicity, Customized Asian	0 Participants	1 Participants	1 Participants	0 Participants
Race/Ethnicity, Customized Black or African American	26 Participants	79 Participants	26 Participants	27 Participants
Race/Ethnicity, Customized Middle Eastern	5 Participants	9 Participants	2 Participants	2 Participants
Race/Ethnicity, Customized Multiple	2 Participants	10 Participants	4 Participants	4 Participants
Race/Ethnicity, Customized Other	2 Participants	4 Participants	0 Participants	2 Participants
Race/Ethnicity, Customized White	4 Participants	13 Participants	4 Participants	5 Participants
Sex: Female, Male Female	28 Participants	100 Participants	37 Participants	35 Participants
Sex: Female, Male Male	34 Participants	78 Participants	21 Participants	23 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	3 / 62	2 / 58	5 / 58
other Total, other adverse events	60 / 62	50 / 58	54 / 58
serious Total, serious adverse events	42 / 62	35 / 58	26 / 58

Outcome results

Primary

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)