What side effects are associated with this type of intervention?

Common treatments for Sickle Cell Anemia include hydroxyurea and L-glutamine. Hydroxyurea is generally well-tolerated but can cause side effects such as bone marrow suppression, leading to lower blood cell counts, and gastrointestinal issues. It is also contraindicated during pregnancy and breastfeeding. L-glutamine, another treatment, has minimal side effects, primarily mild gastrointestinal symptoms. Both treatments aim to reduce the frequency of vaso-occlusive crises and other complications associated with Sickle Cell Anemia.

What prior FDA approvals exist?

The FDA has approved several treatments for Sickle Cell Anemia, including hydroxyurea, which has long-term evidence for reducing acute painful episodes and other complications. Hydroxyurea works by increasing fetal hemoglobin levels, thus reducing the sickling of red blood cells. Another approved treatment is L-glutamine, which helps reduce oxidative stress in red blood cells. More recently, voxelotor, which increases hemoglobin's affinity for oxygen, and crizanlizumab, a monoclonal antibody that reduces the frequency of vaso-occlusive crises, have been approved. These treatments, while not prodrugs like GSK4172239D, represent the range of therapeutic strategies aimed at managing Sickle Cell Anemia.

What other types of research exist?

Promising novel alternatives to GSK4172239D for Sickle Cell Anemia patients include voxelotor, which increases hemoglobin's affinity for oxygen, and crizanlizumab, a monoclonal antibody that targets P-selectin to reduce vaso-occlusive crises. Both have shown efficacy in clinical trials and are approved for use in SCA.

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Prodrug

GSK4172239D for Sickle Cell Anemia

Phase 1

Recruiting

Research Sponsored by GlaxoSmithKline

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be between 18 and 65 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Summary

This trial is testing a new drug called GSK4172239D in people with sickle cell disease. The drug changes into an active form inside the body to help treat the condition. The study aims to see if the drug is safe and how it behaves in the body.

Who is the study for?

Adults aged 18-50 with Sickle Cell Disease (SCD), not on gamma-globin increasing meds, weighing over 50 kg, and able to consent. Men must practice abstinence or use contraception; women must be non-childbearing. Excludes those with certain blood counts, drug abuse history, significant heart disease, organ disorders affecting drug metabolism, abnormal blood pressure or kidney function, recent transfusions or certain medications.

What is being tested?

The trial is testing GSK4172239D's safety and how the body processes it compared to a placebo in people with SCD. It involves three phases: screening, treatment where participants are randomly given either the study drug or placebo in varying doses including under fed conditions for some after a break period.

What are the potential side effects?

Specific side effects aren't listed but generally could include reactions related to the body's processing of GSK4172239D versus placebo. Safety and tolerability will be closely monitored throughout the study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Trial Design

6Treatment groups

Experimental Treatment

Group I: Food effect cohortExperimental Treatment2 Interventions

One selected cohort will also receive an additional single dose of GSK4172239D (or matching placebo) under fed (high calorie and high fat) conditions.

Group II: Cohort 5Experimental Treatment2 Interventions

Participants in this arm will receive either single dose of GSK4172239D (Dose 5) or matching placebo.

Group III: Cohort 4Experimental Treatment2 Interventions

Participants in this arm will receive either single dose of GSK4172239D (Dose 4) or matching placebo.

Group IV: Cohort 3Experimental Treatment2 Interventions

Participants in this arm will receive either single dose of GSK4172239D (Dose 3) or matching placebo.

Group V: Cohort 2Experimental Treatment2 Interventions

Participants in this arm will receive either single dose of GSK4172239D (Dose 2) or matching placebo.

Group VI: Cohort 1Experimental Treatment2 Interventions

Participants in this arm will receive either single dose of GSK4172239D (Dose 1) or matching placebo.

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Sickle Cell Anemia include hydroxyurea, l-glutamine, and investigational therapies like GBT440 and GSK4172239D. Hydroxyurea increases fetal hemoglobin (Hb F) production, reducing the sickling of red blood cells (RBCs) and decreasing vaso-occlusive events. L-glutamine helps reduce oxidative stress in RBCs, thereby lowering the frequency of pain crises. GBT440 increases hemoglobin's oxygen affinity, preventing RBC sickling and prolonging RBC lifespan. GSK4172239D, a prodrug converted into GSK4106401, is being studied for its safety and efficacy in Sickle Cell Disease. These treatments are crucial as they target the underlying mechanisms of RBC sickling and vaso-occlusion, improving patient outcomes and quality of life.

A reanalysis of pain crises data from the pivotal l-glutamine in sickle cell disease trial.GBT440 increases haemoglobin oxygen affinity, reduces sickling and prolongs RBC half-life in a murine model of sickle cell disease.