Epeleuton for Sickle Cell Anemia

Not currently recruiting at 28 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Afimmune

Must be taking: Hydroxyurea

Disqualifiers: Blood transfusions, Pregnancy, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test how a new treatment called Epeleuton works for people with sickle cell disease (SCD). Researchers seek to understand how the body processes the treatment, its effects on the disease, and its safety. The trial seeks adults with SCD who have experienced between 2 and 15 painful episodes, known as vaso-occlusive crises, in the past year. Participants must not be receiving regular blood transfusions or have recently undergone a stem cell transplant.

As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on hydroxyurea, you must have been on a stable dose for at least 3 months before joining the study and should not change the dose during the study.

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

Research has shown that Epeleuton has been studied for safety in humans. In studies with special mice that mimic sickle cell disease, Epeleuton, a type of fatty acid, protected the lungs and liver from damage. This suggests it might also have protective effects in humans.

Although specific human data on Epeleuton remain limited, the current trial is in Phase 2. This phase typically indicates that the treatment has shown some safety in earlier studies, and researchers are now examining its effectiveness and side effects.

Epeleuton has also received a patent for treating sickle cell disease, indicating its potential for future use. It's important to remember that while these findings are encouraging, more human studies are needed to fully understand its safety. ^{1 2 3 4 5}

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

Epeleuton is unique because it offers a new approach to treating sickle cell anemia by using a derivative of eicosapentaenoic acid, an omega-3 fatty acid. Unlike standard treatments like hydroxyurea, which primarily work by increasing fetal hemoglobin levels, Epeleuton might reduce inflammation and oxidative stress, potentially leading to fewer sickle cell crises and complications. Researchers are excited about Epeleuton because its anti-inflammatory properties could provide a complementary benefit to existing therapies, possibly enhancing overall patient outcomes.

What evidence suggests that Epeleuton might be an effective treatment for sickle cell anemia?

Research suggests that Epeleuton, a synthetic omega-3 fatty acid, might help treat sickle cell disease (SCD). In studies with mice that have a form of SCD similar to humans, Epeleuton lessened lung and liver damage caused by the disease. Another study found that Epeleuton reduced stress from low oxygen levels, a common issue in SCD. While these findings are encouraging, they are based on animal studies, so research with humans is needed to confirm its effectiveness. This trial will investigate the effects of Epeleuton in human participants with SCD, as early research shows promise in improving SCD symptoms by protecting organs and reducing stress. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

Adults aged 18+ with sickle cell disease (HbSS or HbSβ0-thalassemia) can join. They must have had 2-10 vaso-occlusive crises in the past year and, if on hydroxyurea, be on a stable dose for at least 3 months. Participants need to use effective contraception and cannot have had recent blood transfusions or stem cell transplants.

Inclusion Criteria

I have sickle cell disease with either HbSS or HbSβ0-thalassemia.

I am using or willing to use effective birth control during the study.

I've had 2-10 pain crises due to sickle cell in the last year.

Exclusion Criteria

Patients who are pregnant, planning pregnancy, breastfeeding and/or are unwilling to use adequate contraception during the trial

Patients with inadequate venous access as determined by the Investigator

I regularly get blood transfusions or had one in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive Epeleuton capsules for pharmacokinetics, pharmacodynamics, and safety assessment

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Epeleuton

Trial Overview The trial is testing Epeleuton capsules to understand how they're processed by the body (pharmacokinetics), their effects (pharmacodynamics), and safety in adults with sickle cell disease.

How Is the Trial Designed?

Group I: Epeleuton 4g/day Experimental Treatment 1 Intervention

Epeleuton is already approved in United States, European Union for the following indications:

Approved in United States as Epeleuton for:

• Sickle Cell Disease (under investigation)

Approved in European Union as Epeleuton for:

• Sickle Cell Disease (under investigation)

Who Is Running the Clinical Trial?

Afimmune

Lead Sponsor

Trials

5

Recruited

420+

Published Research Related to This Trial

In the SCOT trial involving 67 children with sickle cell disease, treatment with the novel DHA formulation SC411 significantly increased blood cell membrane levels of DHA and eicosapentaenoic acid, indicating enhanced bioavailability of DHA.

SC411 treatment led to a reduction in sickle cell crises, analgesic use, and school absences due to pain, with all doses being safe and well tolerated, although the reduction in crisis rate did not reach statistical significance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, randomized, multicenter phase 2 study of SC411 in children with sickle cell disease (SCOT trial). Daak, AA., Dampier, CD., Fuh, B., et al.[2021]

In patients with steady state sickle cell disease (SCD), levels of omega-6 fatty acids (arachidonic acid and dihomo-gamma-linolenic acid) were significantly higher, while omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) were significantly lower compared to healthy controls, indicating an imbalance in fatty acid profiles.

The study found elevated serum levels of prostaglandin E2 (PGE2) and increased ratios of AA/EPA and AA/DHA in SCD patients, suggesting a proinflammatory state that may contribute to the complications associated with sickle cell disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LC-MS/MS analysis of plasma polyunsaturated fatty acids in patients with homozygous sickle cell disease. Aslan, M., Celmeli, G., Özcan, F., et al.[2022]

Arachidonic acid (AA) and its derivative 15-L-(s)-hydroperoxyeicosatetraenoic acid (15-L-(s)-HPETE) were tested on MCF-7 human breast cancer cells, showing a dose-dependent and time-dependent cytotoxic effect.

15-L-(s)-HPETE was found to be more effective than AA in inducing cell death in MCF-7 cells, highlighting its potential as a more potent agent in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxicity of arachidonic acid and of its lipoxygenase metabolite 15-hydroperoxyeicosatetraenoic acid on human breast cancer MCF-7 cells in culture. Najid, A., Beneytout, JL., Tixier, M.[2019]

A novel lipid emulsion containing gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA) showed a dose-dependent ability to inhibit the growth of human pancreatic cancer cell lines in vitro, with effective concentrations identified for two different cell lines.

However, in a mouse model with pancreatic tumors, the treatment did not demonstrate any significant antitumor effects, indicating that further improvements in how these fatty acids are delivered are needed for them to be effective as anticancer agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of 1-(gamma)linolenyl-3-eicosapentaenoyl propane diol on the growth of human pancreatic carcinoma in vitro and in vivo. Ravichandran, D., Cooper, A., Johnson, CD.[2019]

Homozygous sickle cell (HbSS) patients have significantly lower levels of omega-3 fatty acids (EPA and DHA) in their blood cells compared to healthy individuals, which is not due to dietary intake but may be linked to reduced antioxidant status.

The study found that HbSS patients exhibited lower concentrations of key antioxidants like alpha-tocopherol and reduced activity of antioxidant enzymes, suggesting that oxidative stress may contribute to the decreased levels of EPA and DHA in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients with sickle cell disease have reduced blood antioxidant protection. Ren, H., Ghebremeskel, K., Okpala, I., et al.[2022]

In a study using a transgenic mouse model of sickle cell disease, treatment with SC411, a novel DHA formulation, significantly increased levels of beneficial omega-3 fatty acids and reduced harmful arachidonic acid, leading to improved blood flow and reduced red blood cell sickling.

SC411 treatment also alleviated neuroinflammation and improved cognitive function in the mice, suggesting potential for enhancing survival and providing new therapeutic options for managing ischemic injuries associated with sickle cell disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SC411 treatment can enhance survival in a mouse model of sickle cell disease. Wu, CYC., Lopez-Toledano, MA., Daak, AA., et al.[2021]

A new method using high-performance liquid chromatography has been developed to accurately measure 5-hydroperoxyeicosatetraenoic acid (5-HPETE) in cells, achieving a detection limit of about 100 picograms.

For the first time, 5-HPETE was successfully quantified in intact RBL-2H3 cells, showing that these cells produced approximately 480 picograms of 5-HPETE when stimulated, highlighting the method's sensitivity and applicability in cellular studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of 5-hydroperoxyeicosatetraenoic acid produced in rat basophilic leukemia cell line RBL-2H3 by high-performance liquid chromatography with chemiluminescence detection. Chiba, N., Imai, H., Nakagawa, Y.[2019]

In a study involving 96 adults with nonalcoholic fatty liver disease, epeleuton did not improve liver enzymes or stiffness but significantly reduced triglycerides, HbA1c, and markers of cardiovascular risk, suggesting potential benefits for metabolic health.

Epeleuton was well tolerated with a safety profile similar to placebo, indicating it may be a safe option for addressing hypertriglyceridemia and hyperglycemia in patients with nonalcoholic fatty liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Epeleuton, a Novel Synthetic Second-Generation n-3 Fatty Acid, on Non-Alcoholic Fatty Liver Disease, Triglycerides, Glycemic Control, and Cardiometabolic and Inflammatory Markers. Climax, J., Newsome, PN., Hamza, M., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38105727/

Epeleuton, a novel synthetic ω-3 fatty acid, reduces hypoxia Epeleuton, a novel synthetic ω-3 fatty acid, reduces hypoxia/ reperfusion stress in a mouse model of sickle cell disease. Haematologica. 2024 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9429060/

P1483: EPELEUTON, A NOVEL SYNTHETIC SECOND ... In humanized SCD mice, we previously showed that polyunsaturated fatty acid supplementation protects against acute sickle cell-related lung and liver damages ...

3. afimmune.com afimmune.com/2024/09/19/epeleuton-sickle-cell-disease-receives-key-us-patent-grant/

Epeleuton for Sickle Cell Disease receives key US patent ... The broad claims protect the use of Epeleuton for the treatment of Sickle Cell Disease (SCD) and other red blood disorders. These claims will be valid until ...

4. epeleuton-scdtrial.com epeleuton-scdtrial.com/about-study/

About this Study - Epeleuton Sickle Cell Study To assess how Epeleuton targets various aspects of Sickle Cell Disease (SCD) To continue to review how well Epeleuton is tolerated.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05861453

Study Details | NCT05861453 | Pharmacokinetics, ... The trial will consist of a 28-day screening period, 16 weeks of active treatment and a 30-day post-treatment follow-up period. Official Title. An Open-label ...

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/455855

Pharmacokinetics, Pharmacodynamics and Safety of ... To assess the pharmacokinetics, pharmacodynamics and safety of Epeleuton capsules in adult SCD patients who are aged ≥18 years.

7. withpower.com withpower.com/trial/phase-2-anemia-sickle-cell-8-2023-4bc42

Epeleuton for Sickle Cell Anemia This Phase 2 medical study run by Afimmune is evaluating whether Epeleuton will have tolerable side effects & efficacy for patients with Sickle Cell Disease ...