TRIglyceride And Glucose control with Epeleuton in Metabolic Syndrome
Research type
Research Study
Full title
A Randomised, Double-Blind, Placebo-Controlled, Dose Finding Phase IIb Study to Assess the Efficacy and Safety of Orally Administered Epeleuton in Patients with Hypertriglyceridemia and Type 2 Diabetes.
IRAS ID
298537
Contact name
Ronnie Beboso
Contact email
Sponsor organisation
Afimmune Ltd.
Eudract number
2020-000065-16
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 0 months, 17 days
Research summary
Summary of Research
This study is investigating the triglyceride lowering, antihyperglycemic, and anti-inflammatory effects of Epeleuton as surrogate markers of its potential to improve diabetic control and cardiovascular outcomes.This is a randomised, double-blind, placebo-controlled, dose finding phase IIb study to assess the efficacy and safety of orally administered Epeleuton in adult patients with hypertriglyceridemia and type 2 diabetes.
At the screening visit, after giving informed consent, patients will be assessed using the screening examinations. A second screening visit will be used to confirm some of the inclusion criteria.
It is planned that 240 evaluable patients, 160 patients in active treatment group and 80 patients in the control placebo treatment group will be randomized to either of the following parallel treatment groups:
Treatment Group A: 4 x Placebo 500mg capsules orally administered twice a Day (8 capsules daily) for 26 weeks.
Treatment Group B: 2 x DS102 500mg capsule & 2 x Placebo 500mg capsule orally administered twice a Day (8 capsules daily) for 26 weeks.
Treatment Group C: 4 x DS102 500mg capsules orally administered twice a Day (8 capsules daily) for 26 weeks.
This is an outpatient study consisting of a screening period of up to 6 weeks, a 26-week treatment period and a 2-week follow up period as follows:
Ten outpatient visits to the clinic are scheduled, two screening visits, one at the start of the comparative treatment period and six in the comparative treatment period. A final safety follow-up visit, will be conducted two weeks after the
last visit in the treatment period. A phone call visit will also be conducted two weeks after the treatment period begins.All patients will complete the study at the week 28 visit.
Summary of Results
: A Randomised, Double-Blind, Placebo-Controlled, Dose Finding Phase IIb Study to Assess the Efficacy and Safety of Orally Administered Epeleuton in Patients with Hypertriglyceridemia and Type 2 Diabetes.Name of Sponsor: Afimmune Ltd.
Aim of the study:
To compare how effective and well-tolerated a drug called Epeleuton was when compared to placebo (no active ingredient) in patients with hypertriglyceridemia (high levels of triglycerides in the blood) and type 2 diabetes (high blood sugar).The active ingredient in Epeleuton is a fatty acid (15-Hydroxy-Eicosapentaenoic Acid Ethyl Ester [15-HEPE EE]) which is naturally found in the body in varying amounts.
Epeleuton was chosen to be developed as a treatment for patients with hypertriglyceridemia and type 2 diabetes because it had previously been shown in patients to reduce triglyceride levels, high blood sugar levels and inflammation.
Who took part in the study, where and when:
A total of 756 male and female patients with hypertriglyceridemia and type 2 diabetes, aged 18 years and older, were screened to take part in the study. Of these, 233 met the criteria required to be included and received a study treatment.Patients were from 62 investigational sites in Germany, Switzerland, Latvia, Israel, US, UK and Georgia. The first patient study visit was on 13th October 2020 and the last patient visit was on 3rd May 2022.
What happened during the study:
The study consisted of a screening period (up to 6 weeks), a treatment period (26 weeks) and a follow up period (2 weeks).Screening period (Visits 1 and 2)
Before starting in the study, patients who volunteered to participate were required to sign and date an Informed Consent Form (ICF). The purpose of the ICF was to explain the study and how it may affect participants so that they could decide if taking part was right for them. In addition, patients were asked to give their health history, medical and surgical history, and personal information, and tell study staff if they were taking any over the counter or prescription medicines, vitamins or herbs. They were also assigned a patient identifier number which was unique to each patient for the trial.During the screening period, the study doctor reviewed the study requirements and did tests to assess suitability for the study. These included physical examination, vital signs (blood pressure, temperature, heart rate), height, weight, BMI and waist circumference; blood withdrawal for routine laboratory tests; pregnancy test (blood - females capable of having children); assessment of, and consultation on, diet, weight management and physical activity; counselling on contraception methods. In addition, the screening period allowed for a washout period to eliminate the effects of previous treatment before receiving any study drug.
Treatment Period (Visits 3 to 9)
The treatment period began with the baseline visit (Visit 3). A telephone call visit was conducted two weeks after the baseline visit, followed by monthly clinic visits: Visit 4/ Week 4, Visit 5/ Week 8, Visit 6/Week 12, Visit 7/Week 16, Visit 8/Week 20 and Visit 9/Week 26 or Early Termination.During the baseline visit, participants were assigned to one of the following three treatment groups:
• Treatment Group A (placebo): four placebo capsules orally administered twice a day, i.e. eight capsules daily for 26 weeks.
• Treatment Group B (Epeleuton 2g): two Epeleuton 500mg capsules and two placebo capsules orally administered twice a day, i.e. eight capsules daily for 26 weeks.
• Treatment Group C (Epeleuton 4g): four Epeleuton 500mg capsules orally administered twice a day, i.e. eight capsules daily for 26 weeks.The capsules were taken with food or within 30 minutes after a meal.
The study drug received was assigned by chance, like the flip of a coin; participants had a 1:1:1 chance of receiving either 4g Epeleuton daily, 2g Epeleuton daily, or placebo daily.
At the baseline visit participants received access to an e-diary, or a paper diary, to document taking of the study drug. In addition, they were given a log to record blood glucose (blood sugar) levels up to four times per day, before meals and before bed from Visit 3 until at least Visit 4, as well as a form for recording any hypoglycemic episodes (when blood sugars fall too low). Other procedures included ECG; blood withdrawal (routine laboratory tests and sampling for analysis of 15-HEPE EE and biomarkers*; urine sampling (routine laboratory testing); pregnancy test (blood – females capable of having children); assessment of, and consultation on, diet, weight management and physical activity; counselling on contraception methods.
At other visits in the treatment period the procedures carried out included the recording of any medication changes, side effects or health problems; review of the hypoglycemic episode form; routine blood withdrawals for laboratory tests; physical examination, including vital signs, weight, BMI and waist circumference a check to see if the log for recording daily blood glucose levels had been completed (for those patients that at their doctor’s discretion continued self- monitoring after Visit 4).
*Biomarkers are chemicals found in blood that are related to a disease or organ. There are many biomarkers in use today such as measures of cholesterol or blood sugar. There are biomarkers found in blood that indicate how effectively different medications are used by the body.Follow Up (Visit 10)
Participants were asked to return to the clinic 14 days after Visit 9/ Week 26 or Early Termination for follow up assessments (physical examination, routine blood tests, review of hypoglycemic episode form, any medication changes and any health problems experienced).Study results and conclusions:
The study was terminated early on 3rd May 2022 following the results of an interim analysis of the data. This was recommended by an Independent Data Monitoring Committee (IDMC) because Epeleuton did not show a meaningful effect at either the 2g or 4g dose in the treatment of hypertriglyceridemia and type 2 diabetes.
Epeleuton at both doses was well tolerated and safe. Side effects were mostly mild to moderate, transient and self-resolving.REC name
London - Brent Research Ethics Committee
REC reference
21/LO/0341
Date of REC Opinion
26 May 2021
REC opinion
Further Information Favourable Opinion