Assess Efficacy and Safety of Epeleuton in Patients With Hypertriglyceridemia and Type 2 Diabetes

Type 2 Diabetes Clinical Trial

— TRIAGE  

Official 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04365400
• Other study ID #: DS102A-07-CV1
• Secondary ID: 2020-000065-16
• Status: Terminated
• Phase: Phase 2
• Start date: October 13, 2020
• Est. completion date: May 3, 2022

Study information

• Verified date: June 2023
• Source: Afimmune
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To assess the efficacy and safety of orally administered Epeleuton capsules versus placebo, in the treatment of adult patients with hypertriglyceridemia and type 2 diabetes

Description:

This was a randomised, double-blind, Placebo-controlled, 3-arm, multi-centre Phase IIb study consisting of 26 weeks of active treatment and a 2-week post-treatment follow-up period in adult patients with hypertriglyceridemia and concomitant type 2 diabetes.

The screening period consisted of up to 6-weeks lead-in during which all patients were to undergo diet and lifestyle stabilisation, washout of disallowed medications and optimisation of statins.

After screening, patients were randomised (1:1:1) at the baseline visit into the following 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 500 mg 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 500 mg capsules orally administered twice a day, i.e., eight capsules daily for 26 weeks.

The observation period was 32-34 weeks (lead-in: 4-6 weeks, treatment duration: 26 weeks, follow-up period: 2 weeks). During the study, 10 visits to the clinic were scheduled: two screening visits (Visit 1 and Visit 2), one visit at the start of the comparative treatment period (baseline/Visit 3), six visits in the comparative treatment period (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) and one final safety follow-up visit (Visit 10/Week 28).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 233
• Est. completion date: May 3, 2022
• Est. primary completion date: May 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients diagnosed with type 2 diabetes mellitus at least 90 days prior to the first screening visit.

2. Patients with a HbA1C (glycosylated haemoglobin) between 7.0 - 10.0% (53-86 mmol/mol) (both inclusive)

3. Patients with a fasting triglyceride level =200 mg/dL (2.26 mmol/L) and <750mg/dL (8.46 mmol/L) at both screening visits.

Note: If the triglyceride level is outside the required range at the second screening visit, an additional measurement can be obtained 1 week later, to confirm eligibility.

Note: If a large difference in triglyceride level (>15%) is observed between screening 1 and screening 2, an additional measurement may be requested or patient may be deemed not eligible.

4. Patients who have been educated regarding diet and exercise at or before visit 1 (screening 1) and are willing to maintain and not alter a stable diet and activity routine throughout the study.

5. Patients who have been on a stable statin therapy at doses that are likely to achieve optimal LDL cholesterol and who are willing to continue this treatment throughout the study.

Note: Stable statin therapy may consist of a statin with or without ezetimibe.

6. Patients with an LDL cholesterol level <130mg/dL (3.34 mmol/L) at both screening visits.

7. Patients who have a body mass index (BMI) = 25kg/m2 and <50kg/m2.

8. Patients who have been on a stable daily dose of metformin (at least 1500mg or maximum tolerated dose for metformin monotherapy as documented in the subject medical record) and/or a sulfonylurea and/or a dipeptidyl peptidase-4 (DPP-4) inhibitor and/or a sodium-glucose transport protein 2 inhibitor (SGLT2i) and/or a GLP1-RA and/or basal insulin for at least 90 days prior to the day of first screening visit.

Note: Dose of GLP1-RA must be stable for 6 months prior to baseline with no weight change >2kg for 3 months prior to baseline.

Note: Dose of basal insulin must be stable for 4 months prior to baseline. All types of basal insulin are permitted, including insulin glargine, insulin degludec, insulin detemir, NPH insulin and pre-mixed insulin.

9. Female patients and male patients with female partners of childbearing potential must use highly effective contraceptive methods or have a sterilised partner for the duration of the study. Highly effective contraceptive methods are defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include hormonal contraception, intrauterine device or sexual abstinence.

Note: A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

Note: Hormonal contraceptives must be on a stable dose for at least one month before baseline.

Note: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient.

10. Patients whose pre-study or screening clinical laboratory findings do not interfere with their participation in the study, in the opinion of the Investigator, and do not violate any inclusion or exclusion criteria

11. Male or female patients aged 18 years and older on the day of signing the informed consent form (ICF).

12. Patients who are able to communicate well with the Investigator, to understand and comply with the requirements of the study, and understand and sign the written informed consent prior to initiation of any study specific activities or procedures.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Hypertriglyceridemia
• Type 2 Diabetes

Intervention

Drug:
• DS102
DS102 Epeleuton capsules
• Placebo
Placebo capsules

Locations

Country	Name	City	State
Georgia	Georgia Site 1	Batumi
Georgia	Georgia Site 2	Kutaisi
Georgia	Georgia Site 3	Kutaisi
Georgia	Georgia Site 4	Tbilisi
Germany	Germany Site 7	Dresden
Germany	Germany Site 3	Hamburg
Germany	Germany Site 1	Heidelberg
Germany	Germany Site 5	Lübeck
Israel	Israel Site 1	H_olon
Israel	Israel Site 9	Herzliya
Israel	Israel Site 5	Jerusalem
Israel	Israel Site 6	Jerusalem
Israel	Israel Site 4	Nahariya
Israel	Israel Site 8	Sakhnin
Israel	Israel Site 2	Tel Aviv
Israel	Israel Site 3	Tel Aviv
Latvia	Latvia Site 4	Ogre
Latvia	Latvia Site 1	Riga
Latvia	Latvia Site 2	Riga
Latvia	Latvia Site 3	Riga
Switzerland	Switzerland Site 3	Lausanne
Switzerland	Switzerland Site 4	Luzern
Switzerland	Switzerland Site 2	Olten
Switzerland	Switzerland Site 1	Saint Gallen
United States	US Site 15	Adairsville	Georgia
United States	US Site 2	Albany	New York
United States	US Site 35	Ames	Iowa
United States	US Site 23	Cerritos	California
United States	US Site 7	Dallas	Texas
United States	US Site 22	Edmond	Oklahoma
United States	US Site 14	Fort Worth	Texas
United States	US Site 8	Fort Worth	Texas
United States	US Site 25	Hickory	North Carolina
United States	US Site 24	Houston	Texas
United States	US Site 30	Houston	Texas
United States	US Site 33	Houston	Texas
United States	US Site 6	Houston	Texas
United States	US Site 18	Huntington Park	California
United States	US Site 12	Jackson	Tennessee
United States	US Site 5	Little Rock	Arkansas
United States	US Site 19	Los Angeles	California
United States	US Site 29	Missouri City	Texas
United States	US Site 11	Morehead City	North Carolina
United States	US Site 31	North Richland Hills	Texas
United States	US Site 20	Panorama City	California
United States	US Site 34	Raleigh	North Carolina
United States	US Site 26	Rocky Mount	North Carolina
United States	US Site 28	Salisbury	North Carolina
United States	US Site 13	Santa Ana	California
United States	US Site 21	Santa Ana	California
United States	US Site 32	Statesville	North Carolina
United States	US Site 10	Waco	Texas
United States	US Site 27	Wilmington	North Carolina
United States	US Site 17	Winchester	Virginia
United States	US Site 1	Wyomissing	Pennsylvania
United States	US Site 3	Yardley	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Afimmune

Countries where clinical trial is conducted

United States,  Georgia,  Germany,  Israel,  Latvia,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change in Triglycerides From Baseline to Week 16	Analysis of changes and percentage changes of triglycerides was performed using a Wilcoxon rank sum test with the Hodges Lehmann median and 95% confidence intervals estimates. For analysis of triglycerides, baseline was defined as the mean of the Baseline (Visit 3) and Screening 2/Week -1 (Visit 2) measurements.	16 weeks
Primary	Change in HbA1c From Baseline to Week 26	Changes from baseline of HbA1c at each visit were analysed using mixed model analysis of covariance (ANCOVA) with baseline value as a covariate.	26 weeks
Secondary	% Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26	Percent change in triglycerides from baseline to weeks 4, 8, 12, 20 and 26	26 weeks
Secondary	Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20	Change in HbA1c (glycosylated haemoglobin) from baseline to weeks 4, 8, 12, 16 and 20	20 weeks