Clinical trial NCT04365400: Assess Efficacy and Safety of Epeleuton in Patients With Hypertriglyceridemia and Type 2 Diabetes
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hypertriglyceridemia
Type 2 Diabetes
Lead sponsor: Afimmune
Sponsor class: INDUSTRY
First posted: 2020-04-28
Enrollment: 233
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change in Triglycerides From Baseline to Week 16
timeFrame: 16 weeks
measure: Change in HbA1c From Baseline to Week 26
timeFrame: 26 weeks
Secondary outcomes:
measure: % Change in Triglycerides From Baseline to Weeks 4, 8, 12, 20 and 26
timeFrame: 26 weeks
measure: Change in HbA1c From Baseline to Weeks 4, 8, 12, 16 and 20
timeFrame: 20 weeks
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: US Site 5
state: Arkansas
city: Cerritos
country: United States
facility: US Site 23
state: California
city: Huntington Park
country: United States
facility: US Site 18
state: California
city: Los Angeles
country: United States
facility: US Site 19
state: California
city: Panorama City
country: United States
facility: US Site 20
state: California
city: Santa Ana
country: United States
facility: US Site 21
state: California
city: Santa Ana
country: United States
facility: US Site 13
state: California
city: Adairsville
country: United States
facility: US Site 15
state: Georgia
city: Ames
country: United States
facility: US Site 35
state: Iowa
city: Albany
country: United States
facility: US Site 2
state: New York
city: Hickory
country: United States
facility: US Site 25
state: North Carolina
city: Morehead City
country: United States
facility: US Site 11
state: North Carolina
city: Raleigh
country: United States
facility: US Site 34
state: North Carolina
city: Rocky Mount
country: United States
facility: US Site 26
state: North Carolina
city: Salisbury
country: United States
facility: US Site 28
state: North Carolina
city: Statesville
country: United States
facility: US Site 32
state: North Carolina
city: Wilmington
country: United States
facility: US Site 27
state: North Carolina
city: Edmond
country: United States
facility: US Site 22
state: Oklahoma
city: Wyomissing
country: United States
facility: US Site 1
state: Pennsylvania
city: Yardley
country: United States
facility: US Site 3
state: Pennsylvania
city: Jackson
country: United States
facility: US Site 12
state: Tennessee
city: Dallas
country: United States
facility: US Site 7
state: Texas
city: Fort Worth
country: United States
facility: US Site 8
state: Texas
city: Fort Worth
country: United States
facility: US Site 14
state: Texas
city: Houston
country: United States
facility: US Site 24
state: Texas
city: Houston
country: United States
facility: US Site 30
state: Texas
city: Houston
country: United States
facility: US Site 6
state: Texas
city: Houston
country: United States
facility: US Site 33
state: Texas
city: Missouri City
country: United States
facility: US Site 29
state: Texas
city: North Richland Hills
country: United States
facility: US Site 31
state: Texas
city: Waco
country: United States
facility: US Site 10
state: Texas
city: Winchester
country: United States
facility: US Site 17
state: Virginia
city: Batumi
country: Georgia
facility: Georgia Site 1
city: Kutaisi
country: Georgia
facility: Georgia Site 2
city: Kutaisi
country: Georgia
facility: Georgia Site 3
city: Tbilisi
country: Georgia
facility: Georgia Site 4
city: Dresden
country: Germany
facility: Germany Site 7
city: Hamburg
country: Germany
facility: Germany Site 3
city: Heidelberg
country: Germany
facility: Germany Site 1
city: Lübeck
country: Germany
facility: Germany Site 5
city: Herzliya
country: Israel
facility: Israel Site 9
city: H̱olon
country: Israel
facility: Israel Site 1
city: Jerusalem
country: Israel
facility: Israel Site 5
city: Jerusalem
country: Israel
facility: Israel Site 6
city: Nahariya
country: Israel
facility: Israel Site 4
city: Sakhnīn
country: Israel
facility: Israel Site 8
city: Tel Aviv
country: Israel
facility: Israel Site 2
city: Tel Aviv
country: Israel
facility: Israel Site 3
city: Ogre
country: Latvia
facility: Latvia Site 4
city: Riga
country: Latvia
facility: Latvia Site 1
city: Riga
country: Latvia
facility: Latvia Site 2
city: Riga
country: Latvia
facility: Latvia Site 3
city: Lausanne
country: Switzerland
facility: Switzerland Site 3
city: Luzern
country: Switzerland
facility: Switzerland Site 4
city: Olten
country: Switzerland
facility: Switzerland Site 2
city: Saint Gallen
country: Switzerland
facility: Switzerland Site 1
Study officials:
affiliation: Afimmune
name: Markus Weissbach, MD
role: STUDY_DIRECTOR
References: