Etavopivat for Sickle Cell Disease

(Hibiscus 2 Trial)

Recruiting at 192 trial locations

Overseen By Novo Nordisk

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Must be taking: Antimalarial prophylaxis

Must not be taking: Voxelotor, Selectin antagonists, CYP3A4 inducers, Erythropoietin

Disqualifiers: More than 15 VOCs, Chronic transfusion, Hepatic dysfunction, Severe renal dysfunction, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

408 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new medicine, etavopivat, can reduce sickle cell pain crises and improve overall health in individuals with sickle cell disease. Participants will receive either etavopivat or a placebo to compare effects. The trial seeks individuals with sickle cell disease who have experienced 1 to 15 pain crises in the past year. As a Phase 3 trial, this represents the final step before FDA approval, offering a chance to contribute to a potential new treatment for sickle cell disease.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as voxelotor, selectin antagonists, and strong inducers of CYP3A4, at least 28 days before starting the study. If you are on these or similar medications, you may need to stop them before participating.

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

Research has shown that etavopivat has been tested in earlier studies with people who have sickle cell disease. In one study, 36 patients received different doses of etavopivat. The treatment was generally well-tolerated, with most participants not experiencing severe side effects. Some reported mild or moderate symptoms like headaches or nausea, but these were not considered serious.

In another study, etavopivat helped reduce the number of painful episodes known as vaso-occlusive crises, which are common in sickle cell disease. This suggests the treatment might be effective while remaining safe. However, since this drug is still under study, anyone considering joining a trial should consult their doctor about the possible risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for sickle cell disease, which often focus on pain management and blood transfusions, Etavopivat offers a novel approach by targeting red blood cell metabolism. Researchers are excited about Etavopivat because it works by enhancing the oxygen-carrying capacity of red blood cells, potentially reducing the frequency of sickle cell crises. This mechanism is different from traditional therapies and could offer improved quality of life for patients by addressing the root cause of the disease rather than just its symptoms.

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

Research shows that etavopivat, which participants in this trial may receive, may help people with sickle cell disease by reducing the number of painful episodes. In an earlier study, patients taking etavopivat had better hemoglobin levels, allowing their red blood cells to carry oxygen more effectively. This improvement can lead to fewer blockages in blood vessels, which often cause pain. Additionally, early trials have shown that patients tolerate etavopivat well. These findings suggest that etavopivat could significantly help manage sickle cell symptoms. ^{1 2 6 7 8}

Who Is on the Research Team?

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

This trial is for adults and adolescents with sickle cell disease. Participants should be experiencing vaso-occlusive crises, which are painful episodes due to blood vessel blockages. The study aims to include those who could benefit from reduced organ damage, improved exercise tolerance, and less fatigue.

Inclusion Criteria

Hb levels between ≥5.0 and ≤10.0 g/dL at screening

I am either male or female.

I am 12 years old or older.

Exclusion Criteria

I haven't had a blood transfusion in the last 60 days or my HbA1c is under 10%.

My liver tests are not within normal limits.

I haven't used erythropoietin or blood cell growth factors in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either etavopivat or placebo to evaluate the reduction in Vaso-occlusive crisis (VOC) events and other health outcomes

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Etavopivat

Trial Overview The trial is testing Etavopivat's effectiveness in reducing the frequency of pain crises and improving overall health in sickle cell patients compared to a placebo. Patients will be randomly assigned to receive either Etavopivat or a placebo over approximately two years.

How Is the Trial Designed?

Group I: Etavopivat Experimental Treatment 1 Intervention

Participants will be randomised to receive oral dose of Etavopivat.

Group II: Placebo Placebo Group 1 Intervention

Participants will be randomised to receive oral dose of placebo.

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

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]

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]

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]

Citations

1. 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 ...

2. 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)

3. clinicaltrials.eu clinicaltrials.eu/trial/study-on-how-well-etavopivat-works-for-adolescents-and-adults-with-sickle-cell-disease/

Study on How Well Etavopivat Works for Adolescents and ... The purpose of the study is to determine if etavopivat is more effective than a placebo in treating adolescents and adults with sickle cell disease.

4. guidelinecentral.com guidelinecentral.com/clinical-trial/?id=NCT06609226&v=tabular

A Research Study Looking at Long-term Treatment With ... An Open-label, Multi-centre, Rollover Study to Characterise Long-term Safety and Efficacy of Etavopivat in Adults, Adolescents and Children Who Have Sickle Cell ...

5. 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 ...

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 ...