ENHANCE-IT: Pharmacodynamic Effects of a Free-Fatty Acid Formulation of Omega-3 Pentaenoic Acid in Adults With Hypertriglyceridemia

• Sponsor: Matinas BioPharma Nanotechnologies, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04177680
• Collaborator: Matinas Biopharma, Inc (Industry), MB Clinical Research and Consulting LLC (Other)
• Enrollment: 100
• Locations: 8
• Arms: 2
• Actual Duration (Months): 7.5
• Patients Per Site: 12.5
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

Pharmacodynamic effects of MAT9001 compared to Vascepa in adults with hypertriglyceridemia

Condition or Disease	Intervention/Treatment	Phase
Hypertriglyceridemia	Drug: Omega 3 pentaenoic acid; Drug: icosapent ethyl	Phase 2

Detailed Description

An open-label, randomized, crossover study to assess the pharmacodynamic effects of MAT-9001, an omega-3 free fatty acid compared to Vascepa (icosapent ethyl) on triglycerides and other lipoprotein lipids in men and women with elevated triglycerides.

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pharmacodynamic Effects of a Free-fatty Acid Formulation of Omega-3 Pentaenoic Acid to ENHANCE Efficacy in Adults With Hypertriglyceridemia: The ENHANCE-IT Trial
• Actual Study Start Date: Jun 3, 2020
• Actual Primary Completion Date: Nov 27, 2020
• Actual Study Completion Date: Jan 18, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Omega-3 pentaenoic acid (MAT9001) 2g MAT9001 capsules twice daily with meals	Drug: Omega 3 pentaenoic acid; Encapsulated omega-3 pentaenoic acid; Other Names: MAT9001
Active Comparator: Icosapent ethyl (Vascepa) 2g Vascepa capsules twice daily with meals	Drug: icosapent ethyl; Encapsulated omega-3 acid ethyl esters; Other Names: Vascepa

Outcome Measures

Primary Outcome Measures

1. Percent Change in Plasma Triglycerides (Pharmacodynamic Population) [baseline to 28 days]

   Percent change in triglycerides from baseline to end of treatment in the pharmacodynamic population

Secondary Outcome Measures

1. Percent Change in Other Plasma Lipoprotein Lipids (Pharmacodynamic Population) [baseline to 28 days]

   Percent change in other lipoprotein lipids from baseline to end of treatment in the pharmacodynamic population

2. Percent Change in Lipoprotein Lipids (Per Protocol Population) [baseline to 28 days]

   Percent change from baseline in lipoprotein lipids in the per protocol population

3. Percent Changes in Apolipoproteins, PCSK9 and Hs-CRP (Pharmacodynamic Population) [baseline to 28 days]

   The percent change from baseline in Apolipoproteins, PCSK9 and hs-CRP in the PD Population

4. Percent Change From Baseline in Omega-3 Fatty Acid Concentrations (Pharmacodynamic Population) [Baseline to 28 days]

   The percent change from baseline in Omega-3 fatty acid concentrations in the Pharmacodynamic population

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female, ≥18 y of age

• Judged to be in generally good health

• Fasting triglycerides ≥150 mg/dL to ≤499 mg/dL during screening

• Body mass index of ≥20.0 kg/m2

• No clinically significant findings in a 12-lead ECG or physical examination

• Willing and able to undergo the scheduled study procedures

• Understands study procedures and signs forms documenting informed consent to participate in the study

Exclusion Criteria:

• Laboratory test result of clinical significance

• Uncontrolled hypertension

• Clinically significant gastrointestinal, endocrine, cardiovascular, renal, hepatic, pulmonary, pancreatic, neurologic, or biliary disorder

• History of human immunodeficiency virus, hepatitis B or hepatitis C infection

• Used any medication intended to alter the lipid profile within 4 weeks of the first qualification visit

• Active systemic infection

• A condition the Investigator believes would interfere subject ability to provide informed consent and/or comply with the study protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Matinas Investigational Site	Jacksonville	Florida	United States	32216
2	Matinas Investigational site	Jupiter	Florida	United States	33458
3	Matinas Investigational Site	Port Saint Lucie	Florida	United States	34952
4	Matinas Investigational Site	Addison	Illinois	United States	60101
5	Matinas Investigational Site	Chicago	Illinois	United States	60640
6	Matinas Investigational site	Indianapolis	Indiana	United States	46260
7	Matinas Investigational site	Louisville	Kentucky	United States	40213
8	Matinas Investigational site	Richmond	Virginia	United States	23294

Sponsors and Collaborators

• Matinas BioPharma Nanotechnologies, Inc.
• Matinas Biopharma, Inc
• MB Clinical Research and Consulting LLC

Investigators

• Study Director: Kevin Maki, MB Clinical Research and Consulting

Study Documents (Full-Text)

• Study Protocol - Nov 21, 2019
• Statistical Analysis Plan - Dec 7, 2020

More Information

Publications

None provided.

• Responsible Party: Matinas BioPharma Nanotechnologies, Inc.
• ClinicalTrials.gov Identifier: NCT04177680
• Other Study ID Numbers: MAT-002
• First Posted: Nov 26, 2019
• Last Update Posted: Mar 4, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hypertriglyceridemia; Eicosapentaenoic acid ethyl ester

Study Results

Participant Flow

Pre-assignment Detail	Crossover study - each patient received both treatments

Arm/Group Title	MAT9001 Then Vascepa	Vascepa Then MAT9001
Arm/Group Description	2g MAT9001 capsules twice daily with meals for 4 weeks; 4 week washout; 2 g Vascepa (icosapent ethyl) twice daily with meals for 4 weeks Crossover design - Patients in this arm received initial treatment with MAT9001, a washout period, and treatment with Vascepa	2g Vascepa (icosapent ethyl) twice daily with meals for 4 weeks; 4 week washout; MAT9001 2g twice daily with meals for 4 weeks Crossover design - Patients were randomized to receive initial treatment with Vascepa, a washout period, and treatment with MAT9001
Period Title: Overall Study
STARTED	49	51
COMPLETED	47	48
NOT COMPLETED	2	3

Baseline Characteristics

Arm/Group Title	Total Study Population
Arm/Group Description	All patients received both treatments
Overall Participants	100
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.3 (10.9)
Sex: Female, Male (Count of Participants)
Female	57 57%
Male	43 43%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 2%
White	97 97%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	100 100%
Body Mass Index (kg/m^2) (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	32.1 (6.6)
Lipid Drugs (Count of Participants)
Neither statin nor ezetimibe	53 53%
Statin only	46 46%
Both statin and ezetimibe	1 1%
Triglyceride stratification (Count of Participants)
< 2.26 mmol/L (< 200 mg/dL)	41 41%
>= 2.26 - 5.64 mmol/l (200-499 mg/dL)	59 59%

Outcome Measures

1. Primary Outcome

Title	Percent Change in Plasma Triglycerides (Pharmacodynamic Population)
Description	Percent change in triglycerides from baseline to end of treatment in the pharmacodynamic population
Time Frame	baseline to 28 days

Outcome Measure Data

Analysis Population Description

All patients with measurable results who received both drugs

Arm/Group Title	Omega-3 Pentaenoic Acid (MAT9001)	Icosapent Ethyl (Vascepa)
Arm/Group Description	2g MAT9001 capsules twice daily with meals Omega 3 pentaenoic acid: Encapsulated omega-3 pentaenoic acid	2g Vascepa capsules twice daily with meals icosapent ethyl: Encapsulated omega-3 acid ethyl esters
Measure Participants	94	94
Median (Inter-Quartile Range) [Percent Change from baseline]	-20.9	-18.3

2. Secondary Outcome

Title	Percent Change in Other Plasma Lipoprotein Lipids (Pharmacodynamic Population)
Description	Percent change in other lipoprotein lipids from baseline to end of treatment in the pharmacodynamic population
Time Frame	baseline to 28 days

Outcome Measure Data

Analysis Population Description

All patients with measurable results who received both drugs

Arm/Group Title	Omega-3 Pentaenoic Acid (MAT9001)	Icosapent Ethyl (Vascepa)
Arm/Group Description	2g MAT9001 capsules twice daily with meals Omega 3 pentaenoic acid: Encapsulated omega-3 pentaenoic acid	2g Vascepa capsules twice daily with meals icosapent ethyl: Encapsulated omega-3 acid ethyl esters
Measure Participants	94	94
Total Cholesterol	-5.6	-4.1
Low density lipoprotein (LDL)-Cholesterol	-4.8	-3.1
High density lipoprotein (HDL)-Cholesterol	-1.7	-1.1
Very low density lipoprotein (VLDL)-Cholesterol	-15.5	-13.3
non-HDL-Cholesterol	-7	-5.2

3. Secondary Outcome

Title	Percent Change in Lipoprotein Lipids (Per Protocol Population)
Description	Percent change from baseline in lipoprotein lipids in the per protocol population
Time Frame	baseline to 28 days

Outcome Measure Data

Analysis Population Description

All patients who had measurable values for both treatments and had at least 80% compliance with study medication

Arm/Group Title	Omega-3 Pentaenoic Acid (MAT9001)	Icosapent Ethyl (Vascepa)
Arm/Group Description	2g MAT9001 capsules twice daily with meals Omega 3 pentaenoic acid: Encapsulated omega-3 pentaenoic acid	2g Vascepa capsules twice daily with meals icosapent ethyl: Encapsulated omega-3 acid ethyl esters
Measure Participants	82	82
Triglycerides	-20	-15.1
Total Cholesterol	-5.7	-3.5
LDL-Cholesterol	-4.8	-2.8
HDL-Cholesterol	-2.4	-1.3
VLDL-Cholesterol	-15	-10.9
Non-HDL-Cholesterol	-6.9	-4.4

4. Secondary Outcome

Title	Percent Changes in Apolipoproteins, PCSK9 and Hs-CRP (Pharmacodynamic Population)
Description	The percent change from baseline in Apolipoproteins, PCSK9 and hs-CRP in the PD Population
Time Frame	baseline to 28 days

Outcome Measure Data

Analysis Population Description

All patients with measurable values who received both therapies

Arm/Group Title	Omega-3 Pentaenoic Acid (MAT9001)	Icosapent Ethyl (Vascepa)
Arm/Group Description	2g MAT9001 capsules twice daily with meals Omega 3 pentaenoic acid: Encapsulated omega-3 pentaenoic acid	2g Vascepa capsules twice daily with meals icosapent ethyl: Encapsulated omega-3 acid ethyl esters
Measure Participants	94	94
Apolipoprotein (Apo) A1	-4	-3.1
Apo B	-3.5	-2.5
Apo C3	-12.4	-11.1
Proprotein convertase subtilisin/kexin type 9 (PCSK9)	-6.6	-7.3
High-sensitivity C-reactive protein (hs-CRP)	-5.8	8.5

5. Secondary Outcome

Title	Percent Change From Baseline in Omega-3 Fatty Acid Concentrations (Pharmacodynamic Population)
Description	The percent change from baseline in Omega-3 fatty acid concentrations in the Pharmacodynamic population
Time Frame	Baseline to 28 days

Outcome Measure Data

Analysis Population Description

Pharmacodynamic population - all patients with measurable values who received both drugs

Arm/Group Title	Omega-3 Pentaenoic Acid (MAT9001)	Icosapent Ethyl (Vascepa)
Arm/Group Description	2g MAT9001 capsules twice daily with meals Omega 3 pentaenoic acid: Encapsulated omega-3 pentaenoic acid	2g Vascepa capsules twice daily with meals icosapent ethyl: Encapsulated omega-3 acid ethyl esters
Measure Participants	94	94
Eicosapentaenoic acid (EPA)	848	692
Docosahexaenoic acid (DHA)	1.7	-3.3
Docosapentaenoic acid (DPA)	177	140
EPA + DHA + DPA	205	165

Adverse Events

Time Frame	Adverse events were collected over Treatment period 1 and Treatment period 2
Adverse Event Reporting Description	Adverse events were noted at each study visit while under treatment
Arm/Group Title	Omega-3 Pentaenoic Acid (MAT9001)		Icosapent Ethyl (Vascepa)
Arm/Group Description	2g MAT9001 capsules twice daily with meals Omega 3 pentaenoic acid: Encapsulated omega-3 pentaenoic acid		2g Vascepa capsules twice daily with meals icosapent ethyl: Encapsulated omega-3 acid ethyl esters
All Cause Mortality
	Omega-3 Pentaenoic Acid (MAT9001)		Icosapent Ethyl (Vascepa)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/97 (0%)		0/100 (0%)
Serious Adverse Events
	Omega-3 Pentaenoic Acid (MAT9001)		Icosapent Ethyl (Vascepa)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/97 (0%)		0/100 (0%)
Other (Not Including Serious) Adverse Events
	Omega-3 Pentaenoic Acid (MAT9001)		Icosapent Ethyl (Vascepa)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/97 (44.3%)		28/100 (28%)
Eye disorders
cataract	0/97 (0%)		2/100 (2%)
Gastrointestinal disorders
Abdominal distension	1/97 (1%)		2/100 (2%)
Constipation	0/97 (0%)		3/100 (3%)
Diarrhea	10/97 (10.3%)		4/100 (4%)
Dyspepsia	2/97 (2.1%)		0/100 (0%)
Eructation	6/97 (6.2%)		0/100 (0%)
Flatulence	2/97 (2.1%)		1/100 (1%)
Nausea	11/97 (11.3%)		0/100 (0%)
Infections and infestations
Urinary Tract infection	2/97 (2.1%)		0/100 (0%)
Injury, poisoning and procedural complications
Muscle strain	2/97 (2.1%)		0/100 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/97 (3.1%)		4/100 (4%)
Nervous system disorders
Dizziness	2/97 (2.1%)		0/100 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.