Etavopivat for Sickle Cell Disease

(HIBISCUS KIDS Trial)

Recruiting at 23 trial locations

Overseen By Novo Nordisk

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Forma Therapeutics, Inc.

Must not be taking: Voxelotor, Erythropoietin, CYP3A4/5 inducers

Disqualifiers: Frequent VOCs, Recent hospitalization, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 96 weeks

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but if you are taking hydroxyurea, crizanlizumab, or L-glutamine, you can continue as long as your dose has been stable for a certain period. You cannot use voxelotor, erythropoietin, or strong inducers of certain liver enzymes close to the start of the study.

How is the drug Etavopivat different from other treatments for sickle cell disease?

Etavopivat is unique because it is an oral drug that activates an enzyme in red blood cells to increase their energy and improve their flexibility, which helps prevent the cells from sickling and blocking blood flow. This mechanism is different from other treatments that primarily focus on reducing pain or increasing hemoglobin levels. ^{1 2 3 4 5}

What is the purpose of this trial?

This study is being done to learn about etavopivat, a once a day medicine taken by mouth in adolescents with sickle cell disease. The main goals are to study safety and how long etavopivat stays in the bloodstream, while also studying if there are benefits from taking etavopivat. Eligible participants who enter the study will start a 96-week treatment period. At the end of the 96 weeks, participants will have an end of study visit that occurs 4 weeks later. The participants will receive etavopivat every day throughout the treatment period.

Research Team

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

This trial is for adolescents with Sickle Cell Disease who've been hospitalized for related complications in the last year. They must have a stable dose of hydroxyurea or crizanlizumab, if taking them, and meet specific health criteria like hemoglobin levels and proteinuria. Those on chronic transfusion therapy or with unstable conditions are excluded.

Inclusion Criteria

My hemoglobin level is between 5.5 and 10.5 g/dL.

I had a specific blood flow test result last year but am not on regular blood transfusions.

I have been on a stable dose of hydroxyurea for at least 12 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive etavopivat once daily for 96 weeks

96 weeks

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

End of study visit

Treatment Details

Interventions

• Etavopivat

Trial Overview The study tests etavopivat, an oral medication taken daily by patients with sickle cell disease over a period of 96 weeks. It aims to assess the drug's safety, how long it stays in the blood, and potential benefits.

Participant Groups

Group I: Etavopivat Experimental Treatment 1 Intervention

Participants will receive Etavopivat once daily (QD) orally.

Who Is Running the Clinical Trial?

Forma Therapeutics, Inc.

Lead Sponsor

Trials

13

Recruited

1,300+

Novo Nordisk A/S

Industry Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Findings from Research

Etavopivat, an investigational oral medication, activates erythrocyte pyruvate kinase, leading to decreased levels of 2,3-diphosphoglycerate (2,3-DPG) and increased hemoglobin-oxygen affinity, which may help reduce sickling of red blood cells in sickle cell disease (SCD).

In studies involving nonhuman primates and healthy human subjects, etavopivat significantly increased ATP production and hemoglobin-oxygen affinity, and it also showed effectiveness in reducing sickling in red blood cells from SCD patients, indicating its potential as a promising treatment for SCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etavopivat, a Pyruvate Kinase Activator in Red Blood Cells, for the Treatment of Sickle Cell Disease. Schroeder, P., Fulzele, K., Forsyth, S., et al.[2022]

Etavopivat, an oral medication being developed for sickle cell disease, was found to be safe in a phase 1 trial with 90 healthy adults, where most side effects were mild and did not lead to discontinuation of the study.

The drug effectively activated erythrocyte pyruvate kinase-R, leading to beneficial changes in hemoglobin-oxygen affinity, with pharmacodynamic effects lasting 48 to 72 hours, supporting its potential for once-daily dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Pharmacokinetics, and Pharmacodynamics of Etavopivat (FT-4202), an Allosteric Activator of Pyruvate Kinase-R, in Healthy Adults: A Randomized, Placebo-Controlled, Double-Blind, First-in-Human Phase 1 Trial. Forsyth, S., Schroeder, P., Geib, J., et al.[2022]

In a 1-year study involving 10 patients with sickle cell disease, mitapivat was well tolerated and led to a significant increase in hemoglobin levels (mean increase of 1.1 g/dL) and a reduction in vaso-occlusive events from a historical baseline.

The treatment also improved the ATP:2,3-DPG ratio and Hb-oxygen affinity, indicating a potential mechanism for its efficacy in reducing sickling of red blood cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year safety and efficacy of mitapivat in sickle cell disease: follow-up results of a phase 2, open-label study. van Dijk, MJ., Rab, MAE., van Oirschot, BA., et al.[2023]

A simulation model based on pharmacokinetic data from 109 patients was developed to recommend dosing for rivipansel in children aged 6-11 years with sickle cell disease, taking into account renal function and disease-specific factors.

The recommended dosing regimen of a 40-mg/kg loading dose followed by a 20-mg/kg maintenance dose every 12 hours is expected to achieve effective drug concentrations, and its efficacy will be validated in an ongoing phase III study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose Selection Based on Modeling and Simulation for Rivipansel in Pediatric Patients Aged 6 to 11 Years With Sickle Cell Disease. Tammara, BK., Harnisch, LO.[2019]

In a phase 3 trial involving 274 patients with sickle cell disease, voxelotor 1500 mg significantly improved hemoglobin levels over 72 weeks compared to placebo, demonstrating its efficacy as a treatment.

Voxelotor also led to notable reductions in hemolysis markers, indicating its potential to alleviate symptoms associated with hemolytic anemia in sickle cell disease, while serious adverse events were infrequent and unrelated to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voxelotor in adolescents and adults with sickle cell disease (HOPE): long-term follow-up results of an international, randomised, double-blind, placebo-controlled, phase 3 trial. Howard, J., Ataga, KI., Brown, RC., et al.[2021]

References

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

Etavopivat, a Pyruvate Kinase Activator in Red Blood Cells, for the Treatment of Sickle Cell Disease. [2022]

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

Safety, Pharmacokinetics, and Pharmacodynamics of Etavopivat (FT-4202), an Allosteric Activator of Pyruvate Kinase-R, in Healthy Adults: A Randomized, Placebo-Controlled, Double-Blind, First-in-Human Phase 1 Trial. [2022]

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

One-year safety and efficacy of mitapivat in sickle cell disease: follow-up results of a phase 2, open-label study. [2023]

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

Dose Selection Based on Modeling and Simulation for Rivipansel in Pediatric Patients Aged 6 to 11 Years With Sickle Cell Disease. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Voxelotor in adolescents and adults with sickle cell disease (HOPE): long-term follow-up results of an international, randomised, double-blind, placebo-controlled, phase 3 trial. [2021]