Study to Evaluate the Effect of GBT440 in Pediatrics with Sickle Cell
Research type
Research Study
Full title
A Phase 2a, Open-label, Single and Multiple Dose Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Treatment Effect of GBT440 in Pediatric Participants with Sickle Cell Disease
IRAS ID
251251
Contact name
Samah Babiker
Contact email
Sponsor organisation
Global Blood Therapeutics, Inc.
Eudract number
2016-004209-15
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
121,691, IND Number
Duration of Study in the UK
2 years, 7 months, 28 days
Research summary
Research Summary -
The main purpose of this study is to assess the effect of the study drug in pediatric participants with Sickle Cell Disease(SCD).The study drug is known as GBT440 (Voxelotor). This study consists of three parts, Part A, Part B and Part C. Only Part C will be conducted in UK sites.
Part C will assess the safety, tolerability and pharmacokinetics, as well as the hematological effects and the effect on Transcranial Doppler (TCD) flow velocity of GBT440 in pediatric participants with SCD who are 4 to 17 years of age.
Up to 50 pediatric participants will be enrolled into Part C in about 25 research centers in the United Kingdom, Lebanon and the United States.
We expect the duration of each patient’s participation to be approximately 399 days.Lay Summaryy of Results -
Clinical Study Results This summary reports the results of only one study. Researchers must look at the results of many types of studies to understand if a study medication works, how it works, and if it is safe to prescribe to patients. The results of this study might be different than the results of other studies that the researchers review.
Sponsor: Pfizer Inc. Medicine Studied: Oxbryta (voxelotor, also known as PF-06759497 or GBT440) Protocol Number: C5341020 (GBT440-007) Dates of Study: 21 July 2016 to 02 October 2023 Title of this Study: A Study to Evaluate the Effect of Voxelotor in Participants 6 Months to 17 Years of Age With Sickle Cell Disease (HOPE-KIDS) [A Phase 2a, Open-label, Single and Multiple Dose Study to Evaluate the Pharmacokinetics, Safety, Tolerability, and Treatment Effect of GBT440 in Pediatric Participants With Sickle Cell Disease] Date of this Report: 23 January 2025 If you or your child participated in this study, Pfizer, the Sponsor, would like to thank you for your participation.
This summary will describe the study results. If you have any questions about the study or the results, please contact the doctor or staff at your study site.
Why was this study done?
What is sickle cell disease?
Sickle cell disease (SCD) is a disorder wherein red blood cells are shaped like a crescent moon (sickle cells) and break down faster than normal (hemolysis). Compared to round (normal) red blood cells, sickle cells become rigid and sticky, which can slow or block blood flow. The blood of people with SCD is less able to carry oxygen around the body. SCD is a common inherited blood disorder, which means it is passed down from parents to their children. SCD can cause anemia (a shortage of hemoglobin), severe tiredness and attacks of pain, and frequent infections. Hemoglobin is a protein in the red blood cells that carries oxygen throughout the body. Almost half of the people with SCD are infants, children, and teenagers as SCD and its symptoms often start in the first year of life.
What is voxelotor?
Voxelotor (also known as Oxbryta®, PF-06759497, or GBT440) is a medicine given as a capsule, tablet, or suspension that is swallowed. Suspension is a liquid with solid particles of the medicine (not completely dissolved in the liquid). Researchers think that voxelotor may help treat SCD. Voxelotor is designed to prevent the formation of sickle cells, which reduces hemolysis of red blood cells and therefore increases the hemoglobin levels.
What was the purpose of this study?
This study had 4 parts:
- Part A: the main goal was to find out how voxelotor was absorbed, changed (metabolized), and removed from the body.
- Part B: the main goal was to find out whether voxelotor could help increase the hemoglobin levels in the blood.
- Part C: the main goal was to find out whether voxelotor could improve the blood flow in the brain.
- Part D: the main goal was to find out whether voxelotor could safely treat infants and children with SCD.
Additionally, in Parts C and D, researchers wanted to learn whether voxelotor could increase the hemoglobin levels in the blood.
Researchers wanted to know:
- How did voxelotor act in the body among participants 6 years to 17 years of age (Part A)?
- Did voxelotor increase the hemoglobin levels in the blood among participants 6 months to 17 years of age (Parts B, C, and D)?
- Did voxelotor improve the blood flow in the brain among participants 4 years to 17 years of age (Part C)?
- Did participants 6 months to less than 4 years of age tolerate voxelotor during the study (Part D)?
What happened during the study?
How was the study done?
Researchers checked each participant’s health to make sure they could join the study. They also asked each participant to complete and sign consent.
In Part A:
Researchers tested voxelotor in 2 groups of participants to find out the amount of voxelotor in the blood:
- Group 1: participants who were 12 years to 17 years old.
- Group 2: participants who were 6 years to 11 years old.
Participants took a single (1) dose of voxelotor as a capsule on Day 1 of the study. Then, participants returned to the study site up to 5 times for their health checks.
In Part B:
Researchers tested voxelotor in participants who were 12 years to 17 years old to learn whether voxelotor could increase hemoglobin levels.
Participants took voxelotor as capsules or tablets once daily for 24 weeks. After their first dose on Day 1, participants returned to the study site up to 10 times for their health checks.
In Part C:
Researchers tested voxelotor in participants who were 4 years to 11 years old and had normal or slightly increased (conditional) brain blood flow. This was done to learn whether voxelotor could improve the blood flow in the brain. Changes in the brain blood flow can happen in children with SCD and may contribute to strokes.
Participants took voxelotor as a dispersible tablet or suspension once daily for 48 weeks. Dispersible tablet means the tablet can be easily dissolved in water. After their first dose on Day 1, participants returned to the study site up to 10 times for their health checks.
In Part D:
Researchers tested voxelotor in participants who were 6 months to less than 4 years old to learn whether participants can tolerate voxelotor.
Participants took voxelotor as a dispersible tablet or suspension once daily for 48 weeks. After their first dose on Day 1, participants returned to the study site up to 10 times for their health checks.
Parts A to D:
Each part of the study was “open-label.” This means the participants (or their parents or caregivers) and researchers knew participants took voxelotor during the study.
At each visit in Parts A to D, researchers took samples of blood from participants during the study. Researchers also checked the participants’ health during the study and asked them (or their parents or caregivers) how they were feeling.
Where did this study take place?
The Sponsor ran this study at 29 locations in Lebanon, the United Kingdom, and the United States.
When did this study take place?
It began on 21 July 2016 and ended on 02 October 2023.
Who participated in this study?
The study included participants who have SCD and were 6 months to 17 years old.
- A total of 147 participants participated across 4 parts of the study:
76 boys and 71 girls.
- All participants were between the ages of 6 months and 17 years old.
Of the 147 participants in the study:
- 116 participants (79%) finished the study.
- 31 participants (21%) did not finish the study, with the most common reason being that they left before the study was over by their parent's or caregiver’s choice.
How long did the study last?
Study participants were in Part A for about 6 weeks and in Part B for about 7 months. Parts A and B of the study took about 2 years to complete. Study participants were in Part C for about 13 months. Part C of the study took about 4 years to complete. Study participants were in Part D for about 13 months. Part D of the study took about 3 years to complete.
When Parts A and B of the study ended in January 2019, Part C in October 2022, and Part D in October 2023, the Sponsor began reviewing the information collected. The Sponsor then created reports of the results.
This is a summary of all those reports.
What were the results of the study?
How did voxelotor act in the body among participants 6 years to 17 years of age (Part A)?
To answer this question, researchers measured the amount of voxelotor in the blood of participants in Part A of the study. Researchers then compared the amount of voxelotor in the blood of participants in Group 1 to those in Group 2.
Researchers found that, after 1 dose of voxelotor, participants in Group 2 had a higher total amount of voxelotor in the blood over time compared to those in Group 1. The highest amount of voxelotor in the blood was also higher in Group 2 participants than those in Group 1.
Did voxelotor increase the hemoglobin levels in the blood among participants 6 months to 17 years of age (Parts B, C, and D)?
To answer this question, researchers checked the hemoglobin levels in the blood of participants in Parts B, C, and D of the study. Researchers then compared the hemoglobin levels of participants before and after treatment with voxelotor.
Study results showed that:
- In Part B, the participants’ hemoglobin levels increased after 2 weeks of taking voxelotor. This improvement continued through 24 weeks of taking voxelotor.
- In Part C, half (50%) of the participants had increased hemoglobin levels after 2 weeks of taking voxelotor. This increase in hemoglobin levels continued through 48 weeks of taking voxelotor.
- In Part D, 45% of participants 2 years to less than 4 years old had increased hemoglobin levels after 48 weeks of taking voxelotor.
The number of participants 6 months to less than 2 years old who had increased hemoglobin levels after 48 weeks of taking voxelotor was similar to the number of participants 2 years to less than 4 years old. However, the results of participants 6 months to less than 2 years old should be taken with caution because there were not enough participants to reach a clear conclusion.
Did voxelotor improve the blood flow in the brain among participants 4 years to 11 years of age (Part C)?
To answer this question, researchers used a tool called transcranial doppler (TCD) to measure the blood flow in the brain. The TCD uses sound waves to measure the speed and direction of the brain's blood flow.
Study results showed that:
- No participants with normal brain blood flow developed an abnormal brain blood flow after 48 weeks of taking voxelotor.
- Additionally, a total of 5 participants with slightly increased (conditional) brain blood flow returned to a normal brain blood flow after 48 weeks of taking voxelotor.
Did participants 6 months to less than 4 years of age tolerate voxelotor during the study (Part D)?
To answer this question, researchers checked the safety information collected for participants during Part D of the study.
Study results showed that:
- The safety profile of voxelotor was acceptable in participants 6 months to less than 4 years of age.
- Participants in Part D of the study were able to tolerate voxelotor for up to 48 weeks.
- No new safety issues were found during the study.
What medical problems did participants have during the study?
The researchers recorded any medical problems the participants had during the study. Participants could have had medical problems for reasons not related to the study (for example, caused by an underlying disease or by chance). Or, medical problems could also have been caused by a study treatment or by another medicine the participant was taking. Sometimes the cause of a medical problem is unknown. By comparing medical problems across many treatment groups in many studies, doctors try to understand what effects a study medication might have on a participant.
In Part A:
- Nine (9) out of 13 participants (69%) had at least 1 medical problem not related to SCD. The most common medical problems not related to SCD – those reported by 2 participants – were feeling sick and pain in limbs.
- Two (2) out of 13 participants (15%) had at least 1 medical problem related to SCD. The most common medical problem related to SCD was sudden pain crisis.
- No participants left the study because of medical problems.In Part B:
- A total of 35 out of 40 participants (88%) had at least 1 medical problem not related to SCD. The most common medical problems not related to SCD – those reported by more than 10 participants – were headache, pain in limbs, and feeling sick. One (1) out of 40 participants (3%) left the study because of medical problems not related to SCD.
- Twenty-one (21) out of 40 participants (53%) had at least 1 medical problem related to SCD. The most common medical problem related to SCD was sudden pain crisis.
In Part C:
- A total of 58 out of 62 participants (94%) had at least 1 medical problem not related to SCD. The most common medical problems not related to SCD – those reported by more than 15 participants – were fever and vomiting. Five (5) out of 62 participant (8%) left the study because of medical problems not related to SCD.
- Thirty (30) out of 62 participants (48%) had at least 1 medical problem related to SCD. The most common medical problem related to SCD was sudden pain crisis. Two (2) out of 62 participants (3%) left the study because of medical problems related to SCD.In Part D:
- A total of 29 out of 32 participants (91%) had at least 1 medical problem not related to SCD. The most common medical problems not related to SCD – those reported by more than 5 participants – were anemia, infection of nose and throat, vomiting, and pain in limbs. One (1) out of 32 participant (3%) left the study because of medical problems not related to SCD.
- Twenty (20) out of 32 participants (63%) had at least 1 medical problem related to SCD. The most common medical problem related to SCD was sudden pain crisis.
Did study participants have any serious medical problems?
A medical problem is considered “serious” when it is life-threatening, needs hospital care, or causes lasting problems.
In Part A:
- No participant had serious medical problems not related to SCD.
- One (1) out of 13 participants (8%) had a serious medical problem related to SCD, which was reported as sudden pain crisis.
In Part B:
- Five (5) out of 40 participants (13%) had at least 1 serious medical problem not related to SCD. All serious medical problems not related to SCD happened in 1 participant each.
- Fifteen (15) out 40 participants (38%) had at least 1 serious medical problem related to SCD. The most common serious medical problem related to SCD was sudden pain crisis.In Part C:
- A total of 15 out of 62 participants (24%) had at least 1 serious medical problem not related to SCD. The most common medical problem not related to SCD – those reported by more than 5 participants – was fever.
- Twenty-six (26) out of 62 participants (42%) had at least 1 serious medical problem related to SCD. The most common medical problem related to SCD was sudden pain crisis.
In Part D:
- A total of 18 out of 32 participants (56%) had at least 1 serious medical problem not related to SCD. The most common medical problem not related to SCD – those reported by more than 5 participants – was anemia.
- Twelve (12) out of 32 participants (38%) had serious medical problems related to SCD. The most common medical problem related to SCD was sudden pain crisis.
In Parts A to D:
No participants died due to serious medical problems in any part of the study.
Where can I learn more about this study?
If you and your child have questions about the results of your study, please speak with the doctor or staff at your study site. For more details on your study protocol, please visit: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3t%2Fwww.pfizer.com%252Fresearch%252Fresearch_clinical_trials%252Ftrial_results%2FNBTI%2FRhO8AQ%2FAQ%2F37d32a7d-a6b5-4fac-b7c4-75b9b5bd9214%2F1%2FVrStgOi2F0&data=05%7C02%7Champstead.rec%40hra.nhs.uk%7Ce83c4731369c40a1434808dd65f82b85%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638778838744892420%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=b62qW3EIN89jmyuzPXwKIqnnN32bToqQVwbuj1OiWvk%3D&reserved=0
Use the protocol number C5341020 (GBT440-007) The full scientific report of this study is available online at:
https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fwww.clinicaltrials.gov%252F%2FNBTI%2FRhO8AQ%2FAQ%2F37d32a7d-a6b5-4fac-b7c4-75b9b5bd9214%2F2%2FIfAnvb1KKx&data=05%7C02%7Champstead.rec%40hra.nhs.uk%7Ce83c4731369c40a1434808dd65f82b85%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638778838744915312%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=wB2Pt2%2BwLE4L%2BswMfsm2w%2FGBFLoAnUv0wCClWNORNZI%3D&reserved=0
Use the study identifier NCT02850406
https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fwww.clinicaltrialsregister.eu%252F%2FNBTI%2FRhO8AQ%2FAQ%2F37d32a7d-a6b5-4fac-b7c4-75b9b5bd9214%2F3%2Fk7Xz1hTAZV&data=05%7C02%7Champstead.rec%40hra.nhs.uk%7Ce83c4731369c40a1434808dd65f82b85%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638778838744928680%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=ooYZcYy2RY71hZxuM1IWdyF2PseE%2FLRVw0%2BcDlSML5Y%3D&reserved=0
Use the study identifier 2016-004209-15
Please remember that researchers look at the results of many studies to find out which medicines can work and are safe for patients.
Again, if you and your child participated in this study, thank you for volunteering. We do research to try to find the best ways to help patients, and you helped us to do that!REC name
London - Hampstead Research Ethics Committee
REC reference
18/LO/1922
Date of REC Opinion
8 Jan 2019
REC opinion
Further Information Favourable Opinion