Etavopivat for Sickle Cell Disease

Overseen By Novo Nordisk

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Novo Nordisk A/S

Must not be taking: Moderate/strong enzyme inhibitors/inducers

Disqualifiers: Pregnancy, Hypersensitivity, Recent investigational drug, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 10 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the new medicine, etavopivat, interacts with other common medicines in the body. The main goal is to determine if etavopivat alters how these medicines are metabolized and utilized. Participants will take etavopivat along with several approved medicines, such as midazolam and metformin, over 34 to 64 days. This trial suits healthy individuals who can manage daily medication routines and adhere to specific dietary guidelines. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

Yes, you will need to stop taking most medications, including prescription and non-prescription drugs, 14 days before the study and throughout its duration, except for certain contraceptives, hormone replacement therapy, and occasional acetaminophen use.

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

Research has shown that etavopivat is generally safe for people with sickle cell disease. In earlier studies, most patients did not experience serious side effects. Specifically, patients taking 400 mg of etavopivat daily for 12 weeks did not report major problems, suggesting the treatment is safe for extended use. However, as this is a Phase 1 study, it is important to note that researchers are still collecting safety information. Participants in the current study will contribute to understanding how etavopivat interacts with other medicines, which is crucial for assessing its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Most treatments for sickle cell disease focus on managing symptoms or preventing complications, often through medications like hydroxyurea or blood transfusions. But etavopivat works differently; it targets hemoglobin polymerization, the root cause of sickle cell crisis, by improving red blood cell health and oxygen delivery. Researchers are excited about etavopivat because it has the potential to directly address the underlying issues of sickle cell disease rather than just treating symptoms. This could mean fewer pain episodes and a better quality of life for patients.

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

Research has shown that etavopivat, which participants in this trial may receive, may help treat sickle cell disease. Studies have found that it can reduce the number of painful episodes, known as vaso-occlusive crises, over time. Etavopivat also increases hemoglobin levels, which are important for carrying oxygen in the blood. In previous studies, patients taking etavopivat showed better results compared to those taking a placebo, with more significant improvements in hemoglobin levels. Overall, these findings suggest that etavopivat could be an effective option for managing sickle cell disease. ^{6 7 8 9 10}

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 study is for healthy individuals who may help researchers understand if a new medicine, etavopivat, affects how the body processes other common drugs. Participants should not have sickle cell disease or thalassemia but will contribute to research that could benefit those conditions.

Inclusion Criteria

Considered to be generally healthy based on medical history, physical examination, and results of vital signs, electrocardiogram, and clinical laboratory tests performed during the screening visit, as judged by the investigator

My weight is over 50 kg.

Body mass index (BMI) between 18.5 and 29.9 kilograms per square meter (kg/m^2) at screening

Exclusion Criteria

Known or suspected hypersensitivity to study interventions or related products

I am willing and able to follow all study rules, including diet and medication restrictions.

I can avoid taking certain strong medications and St. John's Wort for 28 days before and during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive etavopivat and substrate drugs to evaluate pharmacokinetics

10 days

Daily visits for drug administration

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 tests whether etavopivat changes how the body breaks down and uses five approved medicines: digoxin (heart medication), pitavastatin and rosuvastatin (cholesterol medications), metformin (diabetes medication), and midazolam (sedative). Participants take etavopivat with these drugs over 10 days.

How Is the Trial Designed?

Group I: Period 2: etavopivat+midazolam+rosuvastatin Experimental Treatment 3 Interventions

Participants will receive a daily dose of oral etavopivat, single dose of oral midazolam and rosuvastatin.

Group II: Period 2: etavopivat+midazolam Experimental Treatment 2 Interventions

Participants will receive a daily dose of oral etavopivat and single dose of oral midazolam.

Group III: Period 2: etavopivat+digoxin+pitavastatin+metformin Experimental Treatment 4 Interventions

Participants will receive a daily dose of oral etavopivat, single dose of oral digoxin, pitavastatin and metformin.

Group IV: Period 1: midazolam+rosuvastatin Experimental Treatment 2 Interventions

Participants will receive a single dose of oral midazolam and rosuvastatin.

Group V: Period 1: digoxin+pitavastatin+metformin Experimental Treatment 3 Interventions

Participants will receive a single dose of oral digoxin, pitavastatin and metformin.

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

Voxelotor, a first-in-class therapy for sickle cell disease (SCD), targets the root cause of the disease by preventing sickle hemoglobin polymerization, and has been shown to improve hemoglobin levels and reduce hemolysis in patients.

In a study of 27 patients treated for at least 8 weeks, both clinicians and patients reported significant improvements in health-related quality of life and disease symptoms, indicating voxelotor's positive impact on SCD outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient perception of voxelotor treatment benefit in sickle cell disease. Idowu, M., Haque, A., Williams, EM., et al.[2022]

A series of workshops and educational sessions were organized to empower sickle cell disease (SCD) patients in Europe, allowing them to influence research priorities and enhance their involvement in the scientific community.

These initiatives have improved patient experience and empowerment, benefiting not only patients and caregivers but also health professionals, highlighting the importance of patient-centered approaches in medical research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sickle cell disease: embedding patient participation into an international conference can transform the role of lived experience. Pellegrini, M., Chakravorty, S., Del Mar Manu Pereira, M., 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]

Patients with sickle cell disease (SCD) experience significant quality of life impairments due to the disease's complications, highlighting the need for effective disease-modifying therapies.

Recent initiatives, such as the ASH Research Collaborative SCD Clinical Trials Network and the Cure Sickle Cell Initiative, aim to improve clinical trial designs and patient-centered outcomes, emphasizing the importance of patient-reported outcomes in evaluating treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial considerations in sickle cell disease: patient-reported outcomes, data elements, and the stakeholder engagement framework. Badawy, SM.[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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/179/530725/Etavopivat-Reduces-Incidence-of-Vaso-Occlusive

Etavopivat Reduces Incidence of Vaso-Occlusive Crises in ... Conclusions: Compared with PBO, etavopivat reduced annualized VOC rate through Week 52, increased Hb levels at Week 24, and improved hemolysis ...

2. academic.oup.com academic.oup.com/jscd/article/2/Supplement_1/yoaf013.002/8156965

Hibiscus Trial Phase 2 Results through 52 Weeks | Journal of ... Etavopivat treatment in patients with sickle cell disease (SCD) resulted in a rapid and sustained increase of hemoglobin (Hb) levels and decreased markers of ...

3. 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)

4. healio.com healio.com/news/hematology-oncology/20241208/etavopivat-could-offer-great-benefit-in-sickle-cell-disease

Etavopivat could offer 'great benefit' in sickle cell disease Researchers also reported higher rates of hemoglobin response at week 24 with etavopivat 200 mg (46%) and 400 mg (33%) than placebo (13%).

5. sciencedirect.com sciencedirect.com/science/article/pii/S247395292400257X

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 ...

6. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper204962.html

Etavopivat Reduces Incidence of Vaso-Occlusive ... Treatment with etavopivat in patients with sickle cell disease (SCD) resulted in a rapid and sustained increase of hemoglobin (Hb) levels and decreased markers ...

7. ashpublications.org ashpublications.org/bloodadvances/article/8/16/4459/515784/Multicenter-phase-1-study-of-etavopivat-FT-4202

Multicenter, phase 1 study of etavopivat (FT-4202) treatment ... Clinically, this translated to 73.3% of patients with SCD treated with etavopivat having an Hb increase >1 g/dL at any time during treatment.

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

Multicenter, phase 1 study of etavopivat (FT-4202) ... In this, to our knowledge, the first study of etavopivat in SCD, 400 mg once daily for 12 weeks was well tolerated, resulting in rapid and ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06198712

NCT06198712 | A Study to Evaluate the Pharmacokinetics ... This study is being done to learn about etavopivat, a once a day medicine taken by mouth in adolescents with sickle cell disease.

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124029264

Etavopivat Reduces Incidence of Vaso-Occlusive Crises in ... Treatment with etavopivat in patients with sickle cell disease (SCD) resulted in a rapid and sustained increase of hemoglobin (Hb) levels and decreased markers ...