Etavopivat for Sickle Cell Disease

(HIBISCUS Trial)

Not currently recruiting at 263 trial locations

Overseen By Novo Nordisk

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Forma Therapeutics, Inc.

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

Disqualifiers: HIV, Hepatitis B/C, Renal dysfunction, others

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

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called etavopivat for individuals with sickle cell disease, a condition where red blood cells become misshapen and can block blood flow, causing pain. The goal is to determine if etavopivat can improve hemoglobin levels (the protein in red blood cells that carries oxygen) and reduce the number of painful blockages. Participants will be divided into groups to receive either a low dose, a high dose of etavopivat, or a placebo. Suitable candidates have been diagnosed with sickle cell disease and have experienced at least two painful episodes in the past year. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that if you are taking hydroxyurea, crizanlizumab, or L-glutamine, you must be on a stable dose for a certain period before starting the study. You cannot use voxelotor, certain experimental drugs, or erythropoietin within 28 days before starting the study. The protocol does not specify other medications, so check with the study team for more details.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. If you are on voxelotor, erythropoietin, or certain experimental drugs, you must stop them at least 28 days before starting the study. If you are taking hydroxyurea, crizanlizumab, or L-glutamine, you must be on a stable dose for a specific period before the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that etavopivat holds promise for people with sickle cell disease. In a previous study with 36 patients, researchers tested different doses of etavopivat and closely monitored any side effects. The treatment was generally well-tolerated, with no severe or unexpected problems reported.

The most common side effects so far have been mild, such as headaches or nausea. These findings suggest that etavopivat is relatively safe, but ongoing studies continue to monitor its safety closely. While the treatment is not yet approved by the FDA, the absence of severe side effects in earlier studies is a positive sign. ^{1 2 3 4 5}

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

Most treatments for sickle cell disease focus on managing symptoms and preventing complications, often using medications like hydroxyurea or blood transfusions. But etavopivat stands out because it targets the root cause of the condition by improving red blood cell health. This drug works by increasing the oxygen-carrying capacity of red blood cells, which could reduce the frequency of painful episodes and other complications. Researchers are excited about etavopivat because it offers a novel mechanism of action that could lead to better long-term outcomes for patients living with sickle cell disease.

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

Previous studies have shown that etavopivat helps people with sickle cell disease by increasing hemoglobin levels and reducing painful events called vaso-occlusive crises. Research indicates that taking etavopivat daily can quickly and steadily raise hemoglobin, which is crucial for carrying oxygen in the blood. Specifically, one study found that etavopivat reduced the number of these painful crises over a year. This trial will evaluate different dosages of etavopivat, including low and high doses, as well as a placebo, to further assess its potential as a promising option for managing 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

Are You a Good Fit for This Trial?

This trial is for adults and adolescents with sickle cell disease who have had at least 2 pain crises in the past year. They must be on a stable dose of certain medications, not pregnant or breastfeeding, without severe liver, kidney, heart or blood vessel problems. Participants need to use effective contraception.

Inclusion Criteria

I have been on a stable dose of hydroxyurea for at least 90 days.

I have had at least 2 pain crises due to sickle cell in the last year.

Provision of consent

Exclusion Criteria

I have severe kidney problems or am on long-term dialysis.

My liver tests show high levels of ALT and bilirubin.

I have an active hepatitis B or C infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive either etavopivat or placebo to evaluate efficacy on hemoglobin and vaso-occlusive crises

52 weeks

Regular visits as per study protocol

Open-label Extension

Participants may enter an open-label extension period to continue receiving etavopivat

112 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 study tests low and high doses of Etavopivat tablets against placebo tablets to see if they can increase hemoglobin levels and reduce pain crises caused by blocked blood vessels in patients with sickle cell disease.

How Is the Trial Designed?

Group I: Open label etavopivat Experimental Treatment 1 Intervention

Open label etavopivat

Group II: Double blind placebo Experimental Treatment 1 Intervention

Double blind placebo

Group III: Double blind etavopivat Low Dose Experimental Treatment 2 Interventions

Double blind etavopivat Low Dose

Group IV: Double blind etavopivat High Dose Experimental Treatment 2 Interventions

Double blind etavopivat High Dose

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 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]

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]

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 ...