Etavopivat for Sickle Cell Disease

Overseen By Erin Buckley, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Novo Nordisk A/S

Disqualifiers: Chronic transfusion, Severe renal dysfunction, Hepatic dysfunction, Cardiac or pulmonary disease, Chemotherapy, 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: 2

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests etavopivat, a treatment for sickle cell disease (SCD), to assess its effects on blood flow in the brain and muscles. People with SCD often face blood flow issues, leading to pain and other complications. The trial is open to individuals with specific types of SCD who have stable hemoglobin levels and are not experiencing severe symptoms or complications. Participants should not have had recent serious medical events, such as a vaso-occlusive crisis or the need for blood transfusions. Those managing SCD but still facing challenges might find this trial suitable. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial allows participants to continue taking hydroxyurea (a medication for sickle cell disease) if the dose has been stable for at least 3 months. The protocol does not specify about other medications, so it's best to discuss with the trial team.

Is there any evidence suggesting that etavopivat is likely to be safe for humans?

Research has shown that etavopivat has been tested in people with sickle cell disease. In one study with 36 participants, researchers administered different doses of etavopivat to observe reactions. The results indicated that the medicine was generally well-tolerated, as most participants did not experience major issues.

Some participants did experience side effects, but these were not serious, suggesting that etavopivat might be safe, particularly for those with sickle cell disease. However, more research is needed to fully understand its safety.

The current trial phase focuses on learning more about how the treatment affects the body. This phase helps researchers gather additional information about safety and side effects. ^{1 2 3 4 5}

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

Etavopivat is unique because it targets the root cause of sickle cell disease by increasing the oxygen affinity of hemoglobin, aiming to prevent the sickling of red blood cells. Unlike current treatments that primarily focus on managing symptoms or complications, such as hydroxyurea or blood transfusions, Etavopivat works directly to improve red blood cell function and lifespan. Researchers are excited about this treatment because it offers a new mechanism of action that could lead to more effective and lasting relief for patients with sickle cell disease.

What evidence suggests that etavopivat might be an effective treatment for sickle cell disease?

Research shows that etavopivat, the investigational treatment in this trial, may help treat sickle cell disease. Studies have found that it reduces the number of painful episodes caused by blocked blood flow, known as vaso-occlusive crises. In one study, patients taking etavopivat experienced fewer of these crises over a year. Another study found that etavopivat improved hemoglobin levels and the health of red blood cells. These findings suggest that etavopivat may help manage symptoms of sickle cell disease. ^{1 2 6 7 8}

Who Is on the Research Team?

Clinical Transparency dept. 2834

Principal Investigator

Novo Nordisk A/S

Amy Tang, MD

Principal Investigator

Children's Healthcare of Atlanta

Are You a Good Fit for This Trial?

This trial is for children aged 12-21 with Sickle Cell Disease, specifically those with hemoglobin SS or S/beta0 thalassemia and a hemoglobin level ≤ 9.0 g/dL. Stable hydroxyurea therapy is okay, but not if they've had recent severe complications like organ dysfunction, transfusions, surgery on stomach/small intestine, or unstable heart conditions.

Inclusion Criteria

I have sickle cell disease with either HbSS or HbS/β0 thalassemia.

Hemoglobin (Hb) ≤ 9.0 g/dL at baseline

I have been on a stable dose of hydroxyurea for 3 months without blood-related side effects.

Exclusion Criteria

I need regular blood transfusions to manage my condition.

Vaso-occlusive crisis (VOC) within 14 days prior to signing the informed consent form

Acute chest syndrome (ACS) within 14 days prior to signing the informed consent form

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Treatment

Participants receive etavopivat to evaluate its effect on cerebral and muscle hemodynamics

24 weeks

Safety Follow-up

Safety follow-up visit to monitor participants after the last dose of study drug

4 weeks

1 visit (in-person)

End of Study (EOS)

End of study visit to complete all final assessments

8 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Etavopivat

Trial Overview The study tests Etavopivat's effects on brain and muscle blood flow in young patients with Sickle Cell Disease. It's an open-label trial where all participants receive the drug to see how it influences their cerebral hemodynamics.

How Is the Trial Designed?

Group I: Etavopivat Experimental Treatment 1 Intervention

Single-arm, open-label

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead 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

Forma Therapeutics, Inc.

Lead Sponsor

Trials

13

Recruited

1,300+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06612268

NCT06612268 | A Study to Evaluate How Well Etavopivat ... This study is conducted to confirm whether etavopivat works well at reducing the number of Vaso-occlusive crisis VOCs (sickle cell pain crises)

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38640200/

Multicenter, phase 1 study of etavopivat (FT-4202) ... The first study of etavopivat in SCD, 400 mg once daily for 12 weeks was well tolerated, resulting in rapid and sustained increases in Hb, improved red blood ...

3. novonordisk-trials.com novonordisk-trials.com/trials-conditions/all-trials-v2/NN7535-7807.html

A Study to Evaluate How Well Etavopivat Works in People ... This study is conducted to confirm whether etavopivat works well at reducing the number of Vaso-occlusive crisis VOCs (sickle cell pain crises)

4. delta.larvol.com delta.larvol.com/Products/?ProductId=b6463a25-e529-406f-8996-f56e78abdd64

etavopivat (NN7535) / Novo Nordisk Etavopivat Reduces Incidence of Vaso-Occlusive Crises in Patients with Sickle Cell Disease: HIBISCUS Trial Phase 2 Results through 52 Weeks (ASH 2024) - P2 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05725902

Study of the Effect of Etavopivat on Cerebral Hemodynamic ... This study is a pilot, open-label, single-arm study to evaluate the effect of etavopivat on cerebral hemodynamics, as measured by frequency domain near-infrared ...

6. novonordisk-trials.com novonordisk-trials.com/trials-conditions/all-trials-v2/NN7535-7822.html

A Research Study Looking at Long-term Treatment With ... Etavopivat is a new medicine under development for treating blood disorders like sickle cell disease and thalassaemia.

7. euclinicaltrials.eu euclinicaltrials.eu/ctis-public/view/2024-510805-27-00?lang=en

Clinical Trials in the European Union - EMA A research study looking at long-term treatment with etavopivat in people with sickle cell disease or thalassaemia. EUCT number:2024-510805-27-00.

8. sigma.larvol.com sigma.larvol.com/product.php?e1=800423&tab=newstrac

etavopivat (NN7535) News etavopivat (NN7535) / Novo Nordisk Etavopivat Reduces Incidence of Vaso-Occlusive Crises in Patients with Sickle Cell Disease: HIBISCUS Trial Phase 2 Results ...