Etavopivat for Sickle Cell Disease

(HIBISCUS KIDS Trial)

Recruiting at 22 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new daily pill called etavopivat for people with sickle cell disease (SCD), a condition where red blood cells can become misshaped and cause health problems. The study aims to determine if etavopivat is safe, how it behaves in the body, and if it can benefit those with SCD. Participants will take the medication daily for 96 weeks. This trial may suit adolescents with SCD who experience frequent painful episodes or have had hospital visits due to their condition in the past year. As a Phase 2 trial, it measures how well the treatment works in an initial, smaller group of people, offering participants a chance to contribute to important research.

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.

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

Research has shown that etavopivat is generally safe for people with sickle cell disease. In one study with 36 participants, researchers tested different doses of the treatment, both as single and multiple doses. The results indicated that most participants did not experience serious side effects. While some side effects occurred, they were uncommon and mostly mild. Another study found that etavopivat reduced the number of pain crises in patients, suggesting it could be a helpful treatment. Overall, the evidence so far indicates that etavopivat is safe for humans. ^{1 2 3 4 5}

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

Etavopivat is unique because it offers a new approach for treating sickle cell disease by increasing the flexibility and lifespan of red blood cells. Unlike standard treatments like hydroxyurea or blood transfusions, which primarily manage symptoms or temporarily increase healthy blood cells, Etavopivat works by enhancing the red blood cells' ability to carry oxygen more effectively. Researchers are excited about Etavopivat because it targets the root cause of the disease, potentially reducing the frequency and severity of painful episodes and improving overall quality of life for patients.

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

Research has shown that etavopivat, the treatment under study in this trial, can reduce the number of painful episodes in people with sickle cell disease. In one study, patients who took 400 mg of etavopivat daily for 12 weeks had higher hemoglobin levels and healthier red blood cells. These improvements are promising because they can lead to fewer pain crises. Another study found that etavopivat reduced these painful episodes over 52 weeks. This suggests that etavopivat might be an effective treatment for managing sickle cell disease. ^{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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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 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]

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 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]

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.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 ... This study investigates the efficacy and safety of etavopivat in treating adolescents and adults suffering from sickle cell disease.

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 ...