Epeleuton for Sickle Cell Anemia

Recruiting at 26 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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

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

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.

What evidence supports the effectiveness of the drug Epeleuton for sickle cell anemia?

Epeleuton, a synthetic fatty acid, has shown potential in reducing inflammation and improving blood markers in other conditions like nonalcoholic fatty liver disease. Similar treatments, like DHA ethyl ester formulations, have been effective in reducing sickle cell crises and improving blood flow in sickle cell disease, suggesting Epeleuton might offer similar benefits. ^{1 2 3 4 5}

Is Epeleuton safe for use in humans?

In a study involving children with sickle cell disease, a treatment similar to Epeleuton was found to be safe and well tolerated at all tested doses. ^{2 3 5 6 7}

How does the drug Epeleuton differ from other treatments for sickle cell anemia?

Epeleuton is unique because it is a form of omega-3 fatty acid that may help reduce inflammation and improve blood flow in sickle cell anemia, potentially reducing pain and complications. Unlike some other treatments, it specifically targets the low levels of omega-3 fatty acids found in patients with sickle cell disease. ^{2 3 5 6 8}

Eligibility Criteria

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

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

I have had a stem cell transplant.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2022]

2. Scotland pubmed.ncbi.nlm.nih.gov

SC411 treatment can enhance survival in a mouse model of sickle cell disease. [2021]

3. Italy pubmed.ncbi.nlm.nih.gov

LC-MS/MS analysis of plasma polyunsaturated fatty acids in patients with homozygous sickle cell disease. [2022]

4. England 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. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Double-blind, randomized, multicenter phase 2 study of SC411 in children with sickle cell disease (SCOT trial). [2021]

6. Netherlands 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. [2019]

7. Ireland 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. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Patients with sickle cell disease have reduced blood antioxidant protection. [2022]