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Sickle Cell DiseasePhase 3HOPE Kids 2NCT04218084

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

A Phase 3 study testing Voxelotor in people with Sickle Cell Disease, run by Pfizer at 35 sites in 9 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study is a Phase 3, randomized, double-blind, placebo-controlled study of voxelotor in pediatric participants, aged ≥ 2 to < 15 years old, with Sickle Cell Disease. The primary objective is to evaluate the effect of voxelotor on the TCD (Transcranial Doppler Ultrasound) measurements in SCD participants in this… Read more about this study

Who is it for?
Ages 2 to 14 years
Conditions the study is for
Sickle Cell Disease
What is being tested?
Voxelotor
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
236 participants
Where
35 sitesin 9 countries
Study dates
11 Nov 2020to 6 Nov 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 14 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Male or female participants with Sickle Cell Anemia (SCA) HbSS, HbSβ0 thalassemia genotype
  • TCD time averaged maximum of the mean velocity (TAMMV) arterial cerebral blood flow ≥ 170 to < 200cm/sec during the Screening Period
  • Hb ≥ 5.5 and ≤ 10.5 g/dL during screening
  • For participants taking HU, the dose of HU (mg/kg) must be stable for at least 90 days prior to signing the informed consent form (ICF) and/or assent form, and with no anticipated need for dose adjustments (other than weight based) or for initiation of HU for non-chronic use during the study, in the opinion of the Investigator
  • Written informed parental/guardian consent and participant assent (where applicable) has been obtained per IRB/EC policy and requirements, consistent with ICH guidelines.

Who cannot join

  • Body weight < 10kg at the screening visit
  • Hospitalization for VOC or acute chest syndrome (ACS) within the 14 days prior to execution of informed consent/assent
  • More than 10 VOCs within the past 12 months that required hospitalization, emergency room, or clinic visit
  • Stroke resulting in focal neurological deficit; previous silent infarcts are permitted.
  • Known history or findings suggestive of significant cerebral vasculopathy
  • History of seizure disorder
  • Has been treated with erythropoietin or other hematopoietic growth factors within 28 days of signing informed consent/assent or if, in the opinion of the Investigator, there is an anticipated need for such agents during the study
  • RBC transfusion therapy (also termed chronic, prophylactic, or preventative transfusion) or has received an RBC transfusion or exchange transfusion for any reason within 90 days of signing the informed consent/assent

Trial locations and contacts

35 sites in 9 countries.

35 sites in 9 countries

United States13 sites

  • Children's Healthcare of Atlanta: Hughes Spalding

    Atlanta, Georgia, 30303

  • Boston Children's Hospital - Clinical Research Pharmacy

    Boston, Massachusetts, 02115

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

  • Medical University of South Carolina: Investigational Drug Services

    Charleston, South Carolina, 29425

  • Medical University of South Carolina: Shawn Jenkins Women's and Children's Hospital

    Charleston, South Carolina, 29425

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Texas Children's Hospital - Investigational Pharmacy

    Houston, Texas, 77030

  • Texas Children's Hospital- Wallace Tower

    Houston, Texas, 77030

  • Texas Children's Hospital

    Houston, Texas, 77030

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • University of Miami

    Miami, Florida, 33136

  • The Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

Nigeria5 sites

  • University of Nigeria Teaching Hospital

    Enugu, 460000

  • College of Medicine, University of Ibadan

    Ibadan, Oyo State, 200212

  • Barau Dikko Teaching/Kaduna State University

    Kaduna, 800212

  • Aminu Kano Teaching Hospital

    Kano, 700233

  • Lagos University Teaching Hospital

    Surulere, Lagos, 100254

Other trials in Nigeria

Egypt4 sites

  • Alexandria Clinical Research Center, Faculty of Medicine, Alexandria University

    Alexandria, 21131

  • Ain Shams University Hospital- Clinical Research Center (MASRI)

    Cairo, Abassia, 11566

  • Abu El Rich Hospital, Cairo University Hospital

    Cairo, 11562

  • Zagazig University Hospital

    Zagazig, Alsharkia

Other trials in Egypt

Italy4 sites

  • Azienda Ospedaliera Universitaria Meyer "A.O.U. Meyer" - SOC "Oncologia, Ematologia e TCSE"

    Florence, 50139

  • Azienda Ospedaliera Universitaria (A.O.U.) "Luigi Vanvitelli"

    Naples, 80138

  • Azienda Ospedaliera Universita' (AOU ) Padova

    Padova, 35128

  • Azienda Ospedaliera Universita' (AOU) Padova

    Padova, 35128

Other trials in Italy

Kenya4 sites

  • Kemri/Crdr,Siaya,Kemri Clinical Research Annex

    Kisumu, Siaya County, 40600

  • KEMRI CRDR Clinical Research Annex

    Nairobi, 00100

  • Strathmore University Medical Centre

    Nairobi, 00200

  • Gertrude's Children Hospital

    Nairobi, 100

Other trials in Kenya

Ghana2 sites

  • Department of Child Health, University of Ghana Medical School, College of Health Sciences, Korle-Bu

    Accra, Greater Accra Region, GA-221-1570

  • Komfo Anokye Teaching Hospital

    Kumasi, Ashanti Region, 00233

Other trials in Ghana

Oman1 site

  • Sultan َQaboos University Hospital

    Muscat

Other trials in Oman

Saudi Arabia1 site

  • King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard - Health

    Riyadh, 11481

Other trials in Saudi Arabia

United Kingdom1 site

  • Barts Health NHS Trust

    London, E1 1BB

Other trials in United Kingdom

About this study

Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Voxelotor (GBT440) in Pediatric Participants With Sickle Cell Disease (HOPE Kids 2)

This study is a Phase 3, randomized, double-blind, placebo-controlled study of voxelotor in pediatric participants, aged ≥ 2 to < 15 years old, with Sickle Cell Disease. The primary objective is to evaluate the effect of voxelotor on the TCD (Transcranial Doppler Ultrasound) measurements in SCD participants in this age range.

Read the detailed description

This study is a Phase 3, randomized, double-blind, placebo-controlled study of voxelotor in pediatric participants, aged ≥ 2 to < 15 years old, with Sickle Cell Disease. The study will be conducted at approximately 50 international clinical sites, and will enroll approximately 224 participants. Participants will be randomized in a 1:1 ratio to receive voxelotor or placebo. All participants younger than 12 years of age and randomized to voxelotor will receive a dose based on their body weight, to provide exposure corresponding to the adult dose of 1500 mg/day.

Being tested
Voxelotor, Placebo
Keywords
Sickle Cell Disease, Transcranial Doppler Ultrasound (TCD)
Medical subject headings
Anemia, Sickle Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VoxelotorDrug

    Participants are randomized 1:1 to receive voxelotor or placebo.

  • PlaceboDrug

    Matching placebo.

Study groups in NCT04218084
Study groupRoleWhat they receive
VoxelotorExperimentalVoxelotor 1500mg or equivalent daily as a tablet, dispersible tablet, or as powder for oral suspension.
Receives: Drug: Voxelotor
PlaceboPlacebo comparatorMatching placebo.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Time-Averaged Maximum of Mean Velocity (TAMMV) Arterial Cerebral Blood Flow at 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.

    Measured: Baseline (value at screening), Week 24

Secondary outcomes (10)

  1. Change From Baseline in TAMMV Arterial Cerebral Blood Flow at Week 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.

    Measured: Baseline (value at Screening), Weeks 48

  2. Time to Conversion to Abnormal TCD Flow

    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).

    Measured: Up to 96 weeks

  3. Time to Reversion to Normal TCD Flow

    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.

    Measured: Up to 96 weeks

  4. Percentage of Participants With TAMMV Reduced by >=15 cm/Sec From Baseline 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.

    Measured: At Weeks 24, 48 and 96

  5. Change From Baseline in Hemoglobin (Hb) at Weeks 24, 48 and 96

    Change from baseline in hemoglobin at weeks 24, 48 and 96 were reported in this outcome measure.

    Measured: Baseline (value at Screening), Weeks 24, 48 and 96

  6. Percent Change From Baseline in Unconjugated Bilirubin at Weeks 24, 48 and 96

    Percent change from baseline in unconjugated bilirubin at weeks 24, 48 and 96 was reported in this outcome measure.

    Measured: Baseline (value at Screening), Weeks 24, 48 and 96

  7. Percent Change From Baseline in Reticulocyte at Weeks 24, 48 and 96

    Percent change from baseline in reticulocyte at weeks 24, 48 and 96 was reported in this outcome measure.

    Measured: Baseline (value at Screening), Weeks 24, 48 and 96

  8. Percent Change From Baseline in Absolute Reticulocyte at Weeks 24, 48 and 96

    Percent change from baseline in absolute reticulocyte at weeks 24, 48 and 96 was reported in this outcome measure.

    Measured: Baseline (value at Screening), Weeks 24, 48 and 96

  9. Percent Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 24, 48 and 96

    Percent change from baseline in LDH at weeks 24, 48 and 96 was reported in this outcome measure.

    Measured: Baseline (value at Screening), Weeks 24, 48 and 96

  10. Annualized Incidence Rate of Vaso-Occlusive Crises (VOCs)

    VOC was defined as a composite of acute painful crisis and/or acute chest syndrome (ACS). Annualized incidence rate was defined as total number of events per total person-years on treatment. Total person-years was the sum of participants treatment period in years, which included the time from randomization date to the earliest of (last dose date, post-randomization HU initiation for participants with no HU at baseline, end of study, or study termination). The 95% CI of rate displayed the exact Poisson confidence limits.

    Measured: From randomization to the last dose date, post-randomization HU initiation with no HU at baseline, end of study or study termination, whichever occurred earlier (maximum up to 110 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jan 2020
  2. Study start11 Nov 2020
  3. Primary completion18 Jan 2024
  4. Study completion6 Nov 2024

Why it stopped: Emerging clinical data evaluated by Pfizer and shared with regulatory authorities indicates that the risk profile of voxelotor in people with SCD exceeds the benefits observed in previously generated global research and requires further assessment.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
236 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04218084
Sponsor's protocol ID
GBT440-032
Other IDs
2017-000903-26, C5341021, 2017
Acronym
HOPE Kids 2
Status last verified
Mar 2026
First submitted
20 Dec 2019
Last updated
10 Mar 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.
Expanded access
Available

Publications

  • Bello-Manga H, Abdullahi SU, Hassab H, Brown B, Nduba V, Githanga J, Akinsete AM, El-Beshlawy A, Hanna D, Segbefia C, Okpala I, Tantawy A, Ogutu B, Tubman VN, Paintsil V, Wali Y, Essa M, Telfer P, Dixon S, Hickman A, Doss JF, Davis MW, Rupon J, Kirkham FJ, Brown RC; HOPE Kids 2 Investigators. HOPE Kids 2: Phase 3, Randomized Trial of Voxelotor in Children With SCD and Conditional Cerebral Blood Flow Velocities. Am J Hematol. 2026 Aug 28. doi: 10.1002/ajh.70457. Online ahead of print.

    PubMed 42665434

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Voxelotor in people with Sickle Cell Disease, run by Pfizer at 35 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in United States, Nigeria, Egypt, Italy, Kenya and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Time-Averaged Maximum of Mean Velocity (TAMMV) Arterial Cerebral Blood Flow at Week 24 (time frame: Baseline (value at screening), Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04218084, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2026.

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