GBT021601 for Sickle Cell Disease

Recruiting at 61 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

429 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing an oral medication called osivelotor to see if it can safely help people with sickle cell disease feel better. It will also study how the medication works in the body.

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.

What data supports the effectiveness of the drug GBT021601 for treating sickle cell disease?

The research highlights the importance of fetal hemoglobin (HbF) in reducing the severity of sickle cell anemia, and genetic factors that increase HbF levels are associated with milder disease symptoms. While GBT021601 is not directly mentioned, treatments that boost HbF levels, like hydroxyurea, have shown benefits in managing sickle cell disease. ^{1 2 3 4 5}

How does the drug GBT021601 differ from other treatments for sickle cell disease?

GBT021601 is unique because it increases the affinity of hemoglobin S for oxygen, which helps prevent the sickling of red blood cells and reduces hemolysis (breakdown of red blood cells). Unlike some other treatments, it is taken orally and may allow for once-daily dosing, potentially offering a more convenient option for patients. ^{6 7 8 9 10}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Germany 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. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Genomic polymorphisms in sickle cell disease: implications for clinical diversity and treatment. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Fetal hemoglobin in sickle cell anemia: molecular characterization of the unusually high fetal hemoglobin phenotype in African Americans. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Genetic modifiers of sickle cell disease. [2011]

5. United States pubmed.ncbi.nlm.nih.gov

Survival among children and adults with sickle cell disease in Belgium: Benefit from hydroxyurea treatment. [2022]

6. England pubmed.ncbi.nlm.nih.gov

GBT021601 improves red blood cell health and the pathophysiology of sickle cell disease in a murine model. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Advances in the Treatment of Sickle Cell Disease. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of a Novel Lentiviral Vector Driving Lineage-Specific BCL11A Knockdown for Sickle Cell Gene Therapy. [2020]

9. United States 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. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

GBT440 reverses sickling of sickled red blood cells under hypoxic conditions in vitro. [2023]