Trial · NCT04218084

Study to Evaluate the Effect of GBT440 on TCD in Pediatrics With Sickle Cell Disease

NCT04218084, Phase 3, Terminated, Pfizer; results first posted 2025-06-13

3 sourcestrials-2026-11-12-0.5.0

Cite this record

ConductScience Library. Study to Evaluate the Effect of GBT440 on TCD in Pediatrics With Sickle Cell Disease. Trials, record NCT04218084. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04218084

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Study to Evaluate the Effect of GBT440 on TCD in Pediatrics With Sickle Cell Disease
NCT number: NCT04218084
Status: Terminated
Phases: Phase 3
Enrollment: 236 participants, actual
Lead sponsor: Pfizer
Conditions: Sickle Cell Disease
Interventions: Voxelotor, Placebo
First posted: 2020-01-06
Last updated: 2026-03-10
Other registries' IDs: eudract:2017-000903-26
Results first posted: 2025-06-13

Source ClinicalTrials.gov

Registered outcomes11

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Change From Baseline in Time-Averaged Maximum of Mean Velocity (TAMMV) Arterial Cerebral Blood Flow at Week 24	Baseline (value at screening), Week 24	TAMMV is an ultrasound measurement used in transcranial Doppler (TCD) to assess blood flow in cerebral arteries. TCD flow velocities were categorized as follows: (i) Normal: \< 170 centimeter per second (cm/sec); (ii) Conditional: 170 to \< 200 cm/sec - the eligible participant population for this study; (iii) Abnormal: \>= 200 cm/sec.
Secondary	Change From Baseline in TAMMV Arterial Cerebral Blood Flow at Week 48	Baseline (value at Screening), Weeks 48	TAMMV is an ultrasound measurement used in TCD to assess blood flow in cerebral arteries. TCD flow velocities were categorized as follows: (i) Normal: \< 170 cm/sec; (ii) Conditional: 170 to \< 200 cm/sec - the eligible participant population for this study; (iii) Abnormal: \>= 200 cm/sec.
Secondary	Time to Conversion to Abnormal TCD Flow	Up to 96 weeks	Time to conversion was the number of weeks from the date of randomization to the date of first determined TCD assessment when an abnormal TCD flow velocity (\>= 200 cm/sec) was determined. TCD flow velocities were categorized as follows: (i) Normal: \< 170 cm/sec; (ii) Conditional: 170 to \< 200 cm/sec - the eligible participant population for this study; (iii) Abnormal: \>= 200 cm/sec. The stratified Log Rank Test was stratified by stratification factors: baseline HU use (yes; no), age group (2 to \<= 8 years; \>8 to \<15 years), and baseline TAMMV value (170 cm/sec to \< 185 cm/sec; 185 cm/sec to \< 200 cm/sec).
Secondary	Time to Reversion to Normal TCD Flow	Up to 96 weeks	TCD was used to assess cerebral artery blood flow velocity in children with sickle cell disease (SCD). Time to first normal TCD flow was the number of weeks from randomization to the date of first determined normal TCD flow. Normal is \< 170 cm/sec.
Secondary	Percentage of Participants With TAMMV Reduced by >=15 cm/Sec From Baseline at Weeks 24, 48 and 96	At Weeks 24, 48 and 96	In this outcome measure, percentage of participants whose TAMMV reduced by \>=15 cm/sec from Baseline at Weeks 24, 48 and 96 is reported. TAMMV is an ultrasound measurement used in TCD to assess blood flow in cerebral arteries. TCD flow velocities are categorized as follows: (i) Normal: \< 170 cm/sec; (ii) Conditional: 170 to \< 200 cm/sec - the eligible participant population for this study; (iii) Abnormal: \>= 200 cm/sec.
Secondary	Change From Baseline in Hemoglobin (Hb) at Weeks 24, 48 and 96	Baseline (value at Screening), Weeks 24, 48 and 96	Change from baseline in hemoglobin at weeks 24, 48 and 96 were reported in this outcome measure.
Secondary	Percent Change From Baseline in Unconjugated Bilirubin at Weeks 24, 48 and 96	Baseline (value at Screening), Weeks 24, 48 and 96	Percent change from baseline in unconjugated bilirubin at weeks 24, 48 and 96 was reported in this outcome measure.
Secondary	Percent Change From Baseline in Reticulocyte at Weeks 24, 48 and 96	Baseline (value at Screening), Weeks 24, 48 and 96	Percent change from baseline in reticulocyte at weeks 24, 48 and 96 was reported in this outcome measure.
Secondary	Percent Change From Baseline in Absolute Reticulocyte at Weeks 24, 48 and 96	Baseline (value at Screening), Weeks 24, 48 and 96	Percent change from baseline in absolute reticulocyte at weeks 24, 48 and 96 was reported in this outcome measure.
Secondary	Percent Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 24, 48 and 96	Baseline (value at Screening), Weeks 24, 48 and 96	Percent change from baseline in LDH at weeks 24, 48 and 96 was reported in this outcome measure.

1 to 10 of 11Source ClinicalTrials.gov

See all 11 registered outcomes

Outcomes11

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Change From Baseline in Time-Averaged Maximum of Mean Velocity (TAMMV) Arterial Cerebral Blood Flow at Week 24	Baseline (value at screening), Week 24	ITT analysis population included all randomized participants. Here, Overall Number of Participants Analyzed'' signifies number of participants evaluable for this outcome measure.	cm/sec	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline in TAMMV Arterial Cerebral Blood Flow at Week 48	Baseline (value at Screening), Weeks 48	ITT analysis population included all randomized participants. Here, Overall Number of Participants Analyzed'' signifies number of participants evaluable for this outcome measure.	cm/sec	LEAST_SQUARES_MEAN
SECONDARY	Time to Conversion to Abnormal TCD Flow	Up to 96 weeks	ITT analysis population included all randomized participants. Participants in the analysis included all randomized participants (Intent-to Treat) population. Participants with an event after postbaseline HU initiation or without event are censored at the earliest date of last non-missing TAMMV assessment prior to start of HU or end of study date.	Weeks	MEDIAN
SECONDARY	Time to Reversion to Normal TCD Flow	Up to 96 weeks	ITT analysis population included all randomized participants. Here, Overall Number of Participants Analyzed'' signifies number of participants evaluable for this outcome measure.	Weeks	MEDIAN
SECONDARY	Percentage of Participants With TAMMV Reduced by >=15 cm/Sec From Baseline at Weeks 24, 48 and 96	At Weeks 24, 48 and 96	ITT analysis population=all randomized participants and at each timepoint ITT= total number of all randomized participants used in the analysis. Participants with any of the following scenarios were counted as non-responders:(i) TCD missing at assessment timepoint (including due to abnormal TCD discontinuation) (ii) post-randomization HU use prior to assessment timepoint for subjects with no HU use at baseline.For any missing values, data was imputed using last TAMMV value prior to transfusion.	Percentage of participants	NUMBER
SECONDARY	Change From Baseline in Hemoglobin (Hb) at Weeks 24, 48 and 96	Baseline (value at Screening), Weeks 24, 48 and 96	ITT analysis population included all randomized participants. Here, Overall Number of Participants Analyzed'' = number of participants evaluable for this outcome. All participants reported under Overall Number of Participants Analyzed'' contributed data to table but may not have evaluable data for every row. Number Analyzed = participants evaluable for each row.	Grams per deciliter (g/dL)	LEAST_SQUARES_MEAN
SECONDARY	Percent Change From Baseline in Unconjugated Bilirubin at Weeks 24, 48 and 96	Baseline (value at Screening), Weeks 24, 48 and 96	ITT analysis population included all randomized participants. Here, Overall Number of Participants Analyzed'' = number of participants evaluable for this outcome. All participants reported under Overall Number of Participants Analyzed'' contributed data to table but may not have evaluable data for every row. Number Analyzed = participants evaluable for each row.	Percentage change	LEAST_SQUARES_MEAN
SECONDARY	Percent Change From Baseline in Reticulocyte at Weeks 24, 48 and 96	Baseline (value at Screening), Weeks 24, 48 and 96	ITT analysis population included all randomized participants. Here, Overall Number of Participants Analyzed'' = number of participants evaluable for this outcome. All participants reported under this contributed data to table but may not have evaluable data for every row. 'Number Analyzed'=participants evaluable for each row.	Percent change	LEAST_SQUARES_MEAN
SECONDARY	Percent Change From Baseline in Absolute Reticulocyte at Weeks 24, 48 and 96	Baseline (value at Screening), Weeks 24, 48 and 96	ITT analysis population included all randomized participants. Here, Overall Number of Participants Analyzed'' = number of participants evaluable for this outcome. All participants reported under this contributed data to table but may not have evaluable data for every row. 'Number Analyzed'= participants evaluable for each row.	Percent change	LEAST_SQUARES_MEAN
SECONDARY	Percent Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 24, 48 and 96	Baseline (value at Screening), Weeks 24, 48 and 96	ITT analysis population included all randomized participants. Here, Overall Number of Participants Analyzed'' = number of participants evaluable for this outcome. All participants reported under this contributed data to table but may not have evaluable data for every row. 'Number Analyzed'= participants evaluable for each row.	Percent change	LEAST_SQUARES_MEAN

1 to 10 of 11Source ClinicalTrials.gov

See all 11 outcomes

Results by group46

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Category	Value	Spread	Units
Change From Baseline in Time-Averaged Maximum of Mean Velocity (TAMMV) Arterial Cerebral Blood Flow at Week 24	Voxelotor		-12.06	95% Confidence Interval -15.82 to -8.31	cm/sec
Change From Baseline in Time-Averaged Maximum of Mean Velocity (TAMMV) Arterial Cerebral Blood Flow at Week 24	Placebo		-4.29	95% Confidence Interval -8.17 to -0.40	cm/sec
Change From Baseline in TAMMV Arterial Cerebral Blood Flow at Week 48	Voxelotor		-10.33	95% Confidence Interval -14.14 to -6.52	cm/sec
Change From Baseline in TAMMV Arterial Cerebral Blood Flow at Week 48	Placebo		-3.86	95% Confidence Interval -7.77 to 0.05	cm/sec
Time to Conversion to Abnormal TCD Flow	Voxelotor		NA	95% Confidence Interval NA to NA	Weeks
Time to Conversion to Abnormal TCD Flow	Placebo		NA	95% Confidence Interval NA to NA	Weeks
Time to Reversion to Normal TCD Flow	Voxelotor		9.3	Full Range 7 to 73	Weeks
Time to Reversion to Normal TCD Flow	Placebo		17.0	Full Range 8 to 96	Weeks
Percentage of Participants With TAMMV Reduced by >=15 cm/Sec From Baseline at Weeks 24, 48 and 96	Voxelotor	Week 24	38.3		Percentage of participants
Percentage of Participants With TAMMV Reduced by >=15 cm/Sec From Baseline at Weeks 24, 48 and 96	Placebo	Week 24	25.9		Percentage of participants

1 to 10 of 46Source ClinicalTrials.gov

See all 46 results by group

Participant flow6

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Voxelotor	120
Overall Study	STARTED	Placebo	116
Overall Study	COMPLETED	Voxelotor	37
Overall Study	COMPLETED	Placebo	40
Overall Study	NOT COMPLETED	Voxelotor	83
Overall Study	NOT COMPLETED	Placebo	76

Source ClinicalTrials.gov

Adverse events354

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk
other	Sickle cell anaemia with crisis	Blood and lymphatic system disorders	Voxelotor	45	120
other	Sickle cell anaemia with crisis	Blood and lymphatic system disorders	Placebo	33	116
other	Anaemia	Blood and lymphatic system disorders	Voxelotor	4	120
other	Anaemia	Blood and lymphatic system disorders	Placebo	6	116
other	Lymphadenopathy	Blood and lymphatic system disorders	Voxelotor	2	120
other	Lymphadenopathy	Blood and lymphatic system disorders	Placebo	2	116
other	Thrombocytosis	Blood and lymphatic system disorders	Voxelotor	2	120
other	Thrombocytosis	Blood and lymphatic system disorders	Placebo	2	116
other	Leukocytosis	Blood and lymphatic system disorders	Voxelotor	1	120
other	Leukocytosis	Blood and lymphatic system disorders	Placebo	1	116

1 to 10 of 354Source ClinicalTrials.gov

See all 354 adverse events

Adverse event totals6

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Voxelotor	8	120
Total, all-cause mortality	Placebo	2	116
Total, other adverse events	Voxelotor	81	120
Total, other adverse events	Placebo	83	116
Total, serious adverse events	Voxelotor	63	120
Total, serious adverse events	Placebo	43	116

Source ClinicalTrials.gov

Papers1

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as
42665434	DERIVED

Source PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons2

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

Comparison	Source
Voxelotor vs Placebo: deaths from any cause	Trial comparisons
Voxelotor vs Placebo: serious adverse events	Trial comparisons

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

For software

Read this trial from software.

The record and each of its lists are JSON, twenty rows a page. No key.

GET https://conductscience.org/api/trials/v1/NCT04218084

GET https://conductscience.org/api/trials/v1/NCT04218084/results?page=2

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