GBT021601 for Sickle Cell Disease

Not currently recruiting at 75 trial locations

Overseen By Pfizer Pfizer CT.gov Call Center

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Pfizer

Must be taking: Hydroxyurea, L-glutamine

Disqualifiers: Pregnancy, Breastfeeding, Frequent VOCs, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called GBT021601 for people with sickle cell disease (SCD). It will assess the treatment's safety and effectiveness by comparing it to a placebo (a pill with no active medicine) and different doses of the treatment. Suitable candidates for this trial have stable sickle cell disease, are not experiencing frequent crisis events, and are not regularly receiving blood transfusions. Participants should not have been hospitalized for a sickle cell crisis in the past two weeks. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering a chance to contribute to important advancements in SCD treatment.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but if you are on hydroxyurea or L-glutamine, your dose must be stable for at least 90 days before joining the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that GBT021601 is generally well-tolerated by people with sickle cell disease. Studies have found that patients taking a 100 mg dose experienced improvements in red blood cell health. The treatment also increased hemoglobin levels, which is beneficial because hemoglobin helps carry oxygen in the blood.

Regarding safety, reports indicate that the treatment did not cause major side effects. Safety data from previous patients suggest the treatment is manageable, with changes in lab results and vital signs closely monitored over several years.

Overall, the evidence so far suggests GBT021601 is safe for use in sickle cell patients, but ongoing studies will continue to evaluate its safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell disease?

GBT021601 is unique because it targets sickle cell disease at a molecular level, potentially offering new hope for patients. Unlike standard treatments like hydroxyurea and blood transfusions, which mainly address symptoms, GBT021601 aims to prevent the sickling of red blood cells by stabilizing hemoglobin. This approach could lead to fewer pain crises and complications associated with the disease. Researchers are particularly excited about the possibility of more effective and longer-lasting management of sickle cell disease with this innovative mechanism.

What evidence suggests that this trial's treatments could be effective for sickle cell disease?

Research shows that GBT021601, also known as osivelotor, is designed to prevent sickle hemoglobin (HbS) from clumping. These clumps cause red blood cells in sickle cell disease to change shape, leading to health issues. Studies have found that GBT021601 can improve red blood cell health and even normalize hemoglobin levels in animal studies. Early results suggest this treatment might be more effective than some current options because it works at lower doses. This could simplify treatment for patients by reducing the number of pills needed. Participants in this trial will receive different doses of GBT021601 or a placebo to assess its efficacy and safety over 48 weeks. ^{1 2 5 6 7}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for individuals aged 12-65 with Sickle Cell Disease (SCD) who have had 2 to 10 pain episodes related to the disease in the past year. They must not be pregnant or breastfeeding, and should not need regular blood transfusions or have received one within the last 90 days.

Inclusion Criteria

Participants with stable Hb value as judged by the Investigator

Part B:

I am between 12 and 65 years old and have sickle cell disease.

Exclusion Criteria

I am currently pregnant or breastfeeding.

I have had more than 10 pain crises in the last year.

I regularly get or have had a red blood cell transfusion in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Evaluation of safety, tolerability, and efficacy of osivelotor in adult participants to determine an optimal dose

12 weeks

Treatment Part B

Efficacy and safety assessment of osivelotor versus placebo in adult and adolescent participants

48 weeks

Treatment Part C

Evaluation of pharmacokinetics and safety of single and multiple doses of osivelotor in pediatric participants

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GBT021601

Trial Overview The study is testing GBT021601's safety and effectiveness in treating SCD. It will look at how the body processes the drug and its impact on health outcomes for both adults and children with stable hemoglobin levels.

How Is the Trial Designed?

Group I: Part C Experimental Treatment 1 Intervention

100 mg dose in cohort C1, dose level for cohorts C2 to C4 to be determined based on emerging data

Group II: Part A Active Control 1 Intervention

Initially, participants will be randomized 1:1 to 100 mg and 150 mg daily. Upon review of the 150 mg safety data from at least 6 participants, there will be 1:1:1 randomization: 100 mg, 150 mg, and up to 200 mg. Participants will then receive maintenance once daily doses through Week 12.

Group III: Part B Placebo Group 1 Intervention

Following the selection of the optimal safe and effective dose from Part A of the study, Part B of the study will assess the efficacy and safety of 48 weeks of the optimal dose, compared to placebo

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Global Blood Therapeutics

Lead Sponsor

Trials

36

Recruited

3,200+

Published Research Related to This Trial

A CRISPR-Cas9 gene correction strategy demonstrated up to 60% correction of the sickle cell disease-causing mutation in patient-derived hematopoietic stem cells, showing promising efficacy for potential treatment.

Preclinical studies in mice showed that the corrected cells engrafted successfully without signs of abnormal blood cell formation or tumor development, indicating a favorable safety profile for this gene therapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of β-globin gene correction in human hematopoietic stem cells as a potential durable treatment for sickle cell disease. Lattanzi, A., Camarena, J., Lahiri, P., et al.[2022]

Research has identified various genetic factors, including SNPs and haplotypes, that influence the clinical outcomes of sickle cell disease (SCD), affecting risks for complications like stroke and pulmonary hypertension.

Advancements in genetic analysis, particularly through genome-wide association studies, highlight the role of the TGF-β superfamily and oxidative stress in SCD, paving the way for future treatments tailored to individual genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomic polymorphisms in sickle cell disease: implications for clinical diversity and treatment. Fertrin, KY., Costa, FF.[2013]

The BCH-BB694 lentiviral vector effectively reactivates fetal hemoglobin production while reducing harmful adult sickle hemoglobin in sickle cell disease, showing a 3- to 5-fold increase in fetal hemoglobin levels in transduced cells.

Preclinical studies indicate that BCH-BB694 is non-toxic and can be produced at a clinically relevant scale, supporting its potential for safe and effective use in human trials for treating sickle cell disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of a Novel Lentiviral Vector Driving Lineage-Specific BCL11A Knockdown for Sickle Cell Gene Therapy. Brendel, C., Negre, O., Rothe, M., et al.[2020]

In a study of 250 children with sickle cell anemia, specific noncoding SNPs in the BCL11A and HMIP-2 loci were found to be significantly associated with higher fetal hemoglobin (HbF) levels, which can reduce the severity of the disease.

Carriers of HbF-boosting alleles showed milder clinical outcomes, including lower rates of transfusions and acute chest syndrome, suggesting that increasing HbF levels may improve patient health in sickle cell anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional polymorphisms of BCL11A and HBS1L-MYB genes affect both fetal hemoglobin level and clinical outcomes in a cohort of children with sickle cell anemia. Sales, RR., Belisário, AR., Faria, G., et al.[2021]

Sickle cell disease (SCD) affects around 100,000 Americans and millions globally, with current treatments including red blood cell transfusions and hydroxyurea, while hematopoietic stem cell transplants offer a potential cure but face significant barriers.

L-glutamine has been FDA-approved for patients aged 5 and older to help prevent acute pain episodes by reducing red blood cell oxidant injury, showcasing a novel therapeutic approach in the management of SCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the Treatment of Sickle Cell Disease. Kapoor, S., Little, JA., Pecker, LH.[2019]

In a study of 20 African American patients with sickle cell anemia (SCA) and high fetal hemoglobin (HbF) levels (mean 17.2%), significant associations were found between elevated HbF and specific genetic variants in the BCL11A and HMIP loci.

Four SNPs identified in a 14.1 kb DNA fragment between the (A)γ-(HBG1) and δ-globin genes showed higher frequencies in patients with high HbF, suggesting these genetic variations may influence HbF levels by altering transcription factor binding sites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fetal hemoglobin in sickle cell anemia: molecular characterization of the unusually high fetal hemoglobin phenotype in African Americans. Akinsheye, I., Solovieff, N., Ngo, D., et al.[2022]

Citations

1. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/274/501848/Preliminary-Results-from-a-Multicenter-Phase-2-3

Preliminary Results from a Multicenter Phase 2/3 Study of ... GBT021601 has the potential for higher Hb occupancies at lower doses than voxelotor and could potentially reduce treatment burden and improve ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2531137924003845

Hematology, Transfusion and Cell Therapy Osivelotor (previously GBT021601) is a next-generation sickle hemoglobin (HbS) polymerization inhibitor in development for sickle cell disease (SCD).

3. pfizerclinicaltrials.com pfizerclinicaltrials.com/sites/default/files/2024-09/2022-06-09_GBT_EHA%202022%20601.pdf

Safety, Tolerability, and Results From Phase 1 Studies of GBT021601: A Next-Generation HbS ... , partial pressure of oxygen; RBC, red blood cell; SCD, sickle cell disease.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36960712/

GBT021601 improves red blood cell health and the ... In summary, GBT021601 improves RBC health and normalizes haemoglobin in SS mice, suggesting that it may be useful for the treatment of SCD.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05632354

A Study of GBT021601 in Participants With Sickle Cell ... An open-label extension study to evaluate the long-term safety and efficacy of GBT021601 administered to participants with Sickle Cell Disease.

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121050333

GBT021601, a Next Generation HbS Polymerization ... GBT021601, a Next Generation HbS Polymerization Inhibitor: Results of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Adults Living with Sickle ...

7. journals.lww.com journals.lww.com/hemasphere/fulltext/2022/06003/s268__safety,_tolerability,_and.169.aspx

S268: SAFETY, TOLERABILITY, AND... : HemaSphere In patients with SCD, the GBT021601 100 mg maintenance dose led to a mean Hb occupancy >30%, increased Hb, reduced markers of hemolysis, and improved RBC health ...