Etavopivat for Sickle Cell Disease

(GLADIOLUS Trial)

No longer recruiting at 36 trial locations

Overseen By Novo Nordisk

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Forma Therapeutics, Inc.

Disqualifiers: Hepatic dysfunction, HIV, Hepatitis B/C, 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: 12 weeks

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 or thalassemia, conditions affecting red blood cells. The researchers aim to determine if etavopivat can reduce the need for red blood cell transfusions and increase hemoglobin levels. The trial includes different groups: those with sickle cell disease requiring regular transfusions and those with thalassemia, regardless of their transfusion needs. Ideal candidates are individuals who have been receiving regular transfusions for sickle cell disease or thalassemia, or those with thalassemia and low hemoglobin levels. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that etavopivat, a treatment in development for blood disorders such as sickle cell disease and thalassemia, appears safe. Early human tests revealed no major safety concerns. One study reported no significant safety issues in lab tests.

Other research found that patients generally tolerated etavopivat well. These findings suggest it could be a safe option for individuals with sickle cell disease and thalassemia. Although more research is needed to confirm these results, the current evidence is encouraging for those considering participation in a clinical trial for this treatment. ^{1 2 3 4 5}

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

Researchers are excited about Etavopivat for sickle cell disease because it works differently from existing treatments, like hydroxyurea or chronic red blood cell transfusions. Etavopivat is designed to enhance red blood cell function by increasing their flexibility and lifespan, which could reduce complications associated with sickle cell disease. This innovative approach may offer a more targeted way to manage the disease, potentially improving quality of life for patients who rely on regular transfusions. Additionally, this treatment is being explored for its benefits in thalassemia patients, both with and without chronic transfusions, showcasing its versatility and broader potential impact.

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

Research shows that etavopivat may help treat sickle cell disease by reducing painful events from blocked blood flow and increasing hemoglobin levels. In this trial, participants with sickle cell disease on chronic red blood cell transfusions will receive 400 mg of etavopivat daily. One study found that patients who took 400 mg daily for 12 weeks had improved red blood cell function and higher hemoglobin levels. For thalassemia, etavopivat is being studied in separate arms to determine if it can enhance the health and lifespan of red blood cells, both for those on chronic transfusions and those not on transfusions. Although research is ongoing, early results suggest it might reduce the need for blood transfusions in people with these conditions. ^{2 6 7 8 9}

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 individuals with thalassemia or sickle cell disease who consent to participate and agree to use contraception if applicable. It's not for those who are pregnant, breastfeeding, have significant liver issues (high ALT or bilirubin levels), HIV, active hepatitis B/C, severe kidney dysfunction, recent malignancies requiring intense treatment unless considered cured of certain cancers, or unstable heart/lung conditions.

Inclusion Criteria

I have been receiving monthly blood transfusions for at least 2 years to prevent or treat a stroke.

I am using or willing to use birth control methods if I can have children.

I regularly receive blood transfusions to prevent or because of a previous stroke.

Exclusion Criteria

I have an active hepatitis B or C infection.

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

I am HIV positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive etavopivat to evaluate safety and clinical activity, with a focus on reducing red blood cell transfusions and increasing hemoglobin levels

12 weeks

Extended Treatment

Continued evaluation of etavopivat's effects on liver iron concentration, hemoglobin levels, and serum ferritin levels

48 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 Etavopivat tablets in a Phase 2 trial to see if they're safe and effective for patients with thalassemia or sickle cell disease. The goal is to reduce the need for red blood cell transfusions and increase hemoglobin levels in participants.

How Is the Trial Designed?

Group I: Etavopivat 400 mg daily - Thalassemia with transfusions Experimental Treatment 1 Intervention

Patients with thalassemia on chronic red blood cell transfusions

Group II: Etavopivat 400 mg daily - Thalassemia Experimental Treatment 1 Intervention

Patients with thalassemia not on chronic red blood cell transfusions

Group III: Etavopivat 400 mg daily - SCD with transfusions Experimental Treatment 1 Intervention

Patients with sickle cell disease on chronic red blood cell transfusions

Who Is Running the Clinical Trial?

Forma Therapeutics, Inc.

Lead Sponsor

Trials

13

Recruited

1,300+

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

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 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 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]

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]

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35019238/

A Randomized, Placebo-Controlled, Double-Blind, First-in- ... This study also allowed for the selection of dose levels, projected to have an acceptable safety profile and provide therapeutic benefit, for ...

7. 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.

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

etavopivat (NN7535) News There were no adverse in vitro safety findings. FT-4202 offers a therapeutic opportunity to modify the course of SCD. |||||||||| ...

9. clinicaltrials.eu clinicaltrials.eu/trial/long-term-safety-study-of-etavopivat-for-adults-adolescents-and-children-with-sickle-cell-disease-or-thalassemia/

Long-term safety study of oral etavopivat tablets in children ... This study assesses the long-term safety and effectiveness of Etavopivat, a tablet-form medication, in treating individuals with blood ...