Study of the Efficacy and Safety of NST-1024 Versus Placebo in Subjects With Hypertriglyceridemia

High Triglycerides Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled 28- Day Phase II Proof of Concept Study to Evaluate the Efficacy and Safety of NST-1024 400 mg BID Versus Placebo in Statin-Naïve or Statin-Stable Hypertriglyceridemic Subjects

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05889156
• Other study ID #: NST-1024-03
• Status: Recruiting
• Phase: Phase 2
• Start date: June 30, 2023
• Est. completion date: February 29, 2024

Study information

• Verified date: December 2023
• Source: NorthSea Therapeutics B.V.
• Contact: Brandy Dupee
• Phone: +31 (0) 35 760 65 05
• Email: brandy.dupee[@]northseatherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase IIa,multicentre proof of concept study consisting of 2 study periods to study Treatment with NST-1024 as an adjunct to diet to reduce triglyceride (TG) levels in subjects with TG levels of ≥500 mg/dL and ≤2000 mg/dL; determined by percentage change in TG from baseline after 28 days of treatment. The two periods consist of: 1. A 3-week screening period that includes a TG qualifying period, and 2. A 28-days, double-blind, randomized, parallel group, placebo-controlled treatment period. Subjects will return to the study site for a follow-up visit 2 weeks after the last dose. Approximately 50 subjects will be randomized at approximately 15-30 centres in USA.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: February 29, 2024
• Est. primary completion date: February 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria

1. Understanding of the study procedures, willing to adhere to the study schedules, and agreement to participate in the study by giving written informed consent prior to screening (Visit 1 Week -3]) assessments;

2. Men or women 18 to 79 years of age, inclusive;

3. On statin or non-statin lipid-altering therapy, such as ezetimibe, niacin >200 mg/day, bempedoic acid, fibrates, prescription omega-3 products, other consumer products containing omega-3 fatty acids, or other herbal products or dietary supplements with potential lipid and glucose-altering effects. Subjects must be stable for =28 days prior to the first TG baseline qualifying measurement (i.e., Visit 1 [Week -3]), and should remain stable thereafter for the duration of study participation;

4. Fasting TG levels =500 mg/dL and =2000 mg/dL (based on an average [arithmetic mean] of Visit 1 and Visit 2). Note: In cases in which a subject's average TG level from Visit 1 and Visit 2 falls outside the range for entry into the study, an additional visit (Visit 2a) can be arranged up to 7 days after Visit 2 for an additional measurement of fasting TG levels. If a third sample is collected, entry into the double-blind treatment period will be based on the average of the highest TG value from Visit 1 and 2 and the Visit 2a value. Neither one of the two values used for the arithmetic mean can be less than 400 mg/dL;

5. If using oral or injectable weight loss drug, subjects must maintain stable dose of all oral and injectable weight loss drugs (e.g., GLP-1 receptor agonists) for at least 3 months prior to study period.

6. Willingness to maintain stable diet and physical activity level throughout the study

7. If a smoker, no plans to change smoking habits during the study period.

8. Agree to use appropriate contraceptive methods based on biological sex and child-bearing potential as outlined in Section 12.5 of the protocol.

9. Agree to abstain from sperm or egg donation through 90 or 30 days, respectively, after administration of the last dose of IP. Exclusion criteria

1. Body mass index >50 kg/m2;

2. Participation in another clinical study involving an investigational agent within 30 days prior to screening or 5 ½ half-lives whichever is longer(Visit 1 [Week -3]);

3. Type 1 diabetes mellitus;

4. HbA1c > 9.5% at screening (Visit 1 [Week -3]);

5. History of stroke, myocardial infarction, life-threatening arrhythmia, or coronary revascularization within 6 months prior to screening;

6. History of chronic pancreatitis or acute pancreatitis in the last year. Subjects at risk of developing pancreatitis (e.g., known cholelithiasis, known alcohol abuse or multiple incidences of acute pancreatitis) per the PI's assessment are excluded. Subjects with a history of acute pancreatitis due to gallstones who have been treated with cholecystectomy are allowed.

7. History of symptomatic gallstone disease unless treated with cholecystectomy;

8. History of nephrotic range (>3 g/day) proteinuria;

9. Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2

10. QTcF interval of >450ms for males or >470 for females

11. A history of additional risk factors for torsades de pointes (TdP) (e.g., heart failure, hypokalaemia, family history of Long QT Syndrome)

12. The use of concomitant medications that prolong the QT/QTc interval (Table 1);

13. History or evidence of major and clinically significant hepatic, pulmonary, renal, hematologic, gastrointestinal (including clinically significant malabsorption), endocrine, immunologic, dermatologic, neurologic, psychiatric, oncologic, or allergic (including drug allergies, but excluding untreated or treated seasonal allergies at the time of dosing) disease that would interfere with the conduct of the study or interpretation of the data;

14. Known lipoprotein lipase impairment or deficiency (Fredrickson Type I), apolipoprotein C-II deficiency, or familial dysbetalipoproteinemia (Fredrickson Type III);

15. Requirement for peritoneal dialysis or haemodialysis for renal insufficiency;

16. History of malignancy, except subjects who have been disease-free for >5 years, or whose only malignancy has been treated basal or squamous cell skin carcinoma;

17. History of bariatric surgery less than 2 years prior to randomization. A history of bariatric surgery utilizing the gastric bypass technique (Roux-en-Y) or biliopancreatic diversion with duodenal switch is exclusionary;

18. Uncontrolled hypertension;

19. Known to be infected with human immunodeficiency virus (HIV);

20. Positive test for HIV antibody, hepatitis B surface antigen, hepatitis B Core Total or hepatitis C antibody at screening (Visit 1 [Week -3]), except for those who have been successfully treated for hepatitis C infection and have achieved sustained virologic response for =1 year and who have a negative reflex HCV RNA test;

21. Anticipation of major surgery during the screening or double-blind treatment periods of the study;

22. Treatment with chronic prescription pharmacotherapy for metabolic or CV disease management or risk factor modification (e.g., antihypertensive and antidiabetic medications) that has not been stable for =28 days prior to screening (Visit 1 [Week -3]);

23. Ongoing treatment with HIV-protease inhibitors, cyclophosphamide, or isotretinoin;

24. Treatment with tamoxifen, estrogens, or progestins that has not been stable for =28 days prior to screening (Visit 1 [Week -3]);

25. Routine or anticipated use of systemic corticosteroids at a dose >7.5mg daily prednisolone equivalent. Use of local injectable, inhaled, nasal administration, topical corticosteroids, or low dose glucocorticoids (=7.5 mg prednisolone equivalent) is permitted. Low dose oral glucocorticoids should have been used for = 3 months and stable for = 28 days prior to baseline;

26. Thyroid-stimulating hormone (TSH) > 2.0 x upper limit of normal (ULN), clinical evidence of hypothyroidism, or thyroid hormone therapy that has not been stable for =6 weeks prior to screening (Visit 1 [Week -3]);

27. Alanine aminotransferase or AST >2.5 x ULN, unless exercise-related;

28. Unexplained CK concentration >5 × ULN or CK elevation due to known muscle disease (e.g., polymyositis, mitochondrial dysfunction);

29. Other recent or current serious disease that may interfere with the conduct of the study (renal, ophthalmic, pulmonary, hepatic, biliary, gastrointestinal, mental disorder, infectious disease, or cancer);

30. Blood donation of =1 pint (0.5 L) within 30 days prior to screening (Visit 1 [Week -3]), or plasma donation within 7 days prior to screening (Visit 1 [Week -3]);

31. History of illicit drug use or alcohol abuse within 1 year of screening. Alcohol abuse is defined as >21 standard drinks per week in men and >14 standard drinks per week in women, on average;

32. Any condition or therapy, which, in the opinion of the investigator, might pose a risk to the subject or make participation in the study not in the subject's best interest;

33. Poor mental function or any other reason to expect subject difficulty in complying with the requirements of the study; or in the investigator's opinion, not able to comply with study procedures. Pregnancy or breastfeeding.

Related Conditions & MeSH terms

• High Triglycerides
• Hypertriglyceridemia

Intervention

Drug:
• NST-1024
400 mg BID

Other:
• Placebo
matched placebo to active arm

Locations

Country	Name	City	State
United States	Lynn Institute of Denver	Aurora	Colorado
United States	Apex Mobile Clinical Research	Bellaire	Texas
United States	Cenexel HRI	Berlin	New Jersey
United States	University of Alabama - Heersink School of Medicine	Birmingham	Alabama
United States	Velocity Clinical Research - Cincinnati	Cincinnati	Ohio
United States	Velocity Clinical Research - Cleveland	Cleveland	Ohio
United States	Alliance for Multispecialty Research, LLC (AMR) - Daphne	Daphne	Alabama
United States	Velocity Clinical Research, New Smyrna Beach	Edgewater	Florida
United States	Deaconess Clinic - Indiana	Evansville	Indiana
United States	Hatboro Medical Associates/ CCT Research	Hatboro	Pennsylvania
United States	Clay Platte Family Medicine / CCT Research	Kansas City	Missouri
United States	Velocity Clinical Research, San Diego	La Mesa	California
United States	Clearwater Cardiovascular Consultants	Largo	Florida
United States	Lifeline Primary Care/ CCT Research	Lilburn	Georgia
United States	Velocity Clinical Research - Kearney	Lincoln	Nebraska
United States	University of Louisville - UoL Physicians Outpatient Center	Louisville	Kentucky
United States	Velocity Clinical Research - Boise	Meridian	Idaho
United States	Floridian Clinical Research	Miami Lakes	Florida
United States	Alliance for Multispecialty Research, LLC (AMR) - Newton	Newton	Kansas
United States	Velocity Clinical Research, North Hollywood	North Hollywood	California
United States	Mercado Medical Practice / CCT Research	Philadelphia	Pennsylvania
United States	Ogden Clinic, Mount View/CCT Research	Pleasant View	Utah
United States	Velocity Clinical Research - Salt Lake City	Salt Lake City	Utah
United States	Pinnacle Clinical Research - San Antonio	San Antonio	Texas
United States	Velocity Clinical Research - Costal Heart	Santa Ana	California
United States	Palmetto Clinical Reserach	Summerville	South Carolina
United States	Alliance for Multispecialty Research, LLC (AMR) - Phoenix	Tempe	Arizona
United States	Troy Internal Medicine	Troy	Michigan
United States	Velocity Clinical Research - Union	Union	South Carolina
United States	Velocity Clinical Research, Valparaiso	Valparaiso	Indiana
United States	Metabolic Research Institute, Inc.	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
NorthSea Therapeutics B.V.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the efficacy of NST-1024 by percentage change in TG	Evaluate the efficacy of NST-1024 400 mg BID by assessment of the percentage change in TG from baseline after 28 days of treatment	4 weeks
Secondary	Percent Change in Cholesterol Values	Percent changes in TC, HDL-C, LDL-C, calculated. non-HDL-C, and VLDL-C from baseline to Week 4	4 weeks
Secondary	Percent change in Apolipoprotein B and Apolipoprotein C3	Percent changes in ApoB and ApoC3 from baseline to Week 4.	4 weeks
Secondary	Percent Change in Lipoprotein a	Percent change in Lp(a) from baseline to Week 4.	4 weeks
Secondary	Percent Change in remnant-like particle cholesterol (RLP-C)	Percent Change in RLP-C from baseline to Week 4.	4 weeks
Secondary	Changes in fasting plasma glucose, fasting plasma insulin, and HbA1c	Changes in fasting plasma glucose (FPG), fasting plasma insulin (FPI) and HbA1c from baseline to Week 4	4 weeks
Secondary	Change in insulin resistance.	Change in insulin resistance, as assessed by the homeostasis model index insulin resistance, from baseline to Week 4	4 weeks
Secondary	Change in lipoprotein associated phospholipase A2	Percent change in lipoprotein associated phospholipase A2 from baseline to Week 4	4 weeks
Secondary	Change in hsCRP	Change in hsCRP from baseline to Week 4	4 weeks
Secondary	Safety Assessments	Incidence of Treatment-Emergent Adverse Events and abnormalities in clinical laboratory measurements (chemistry, haematology, and urinalysis), 12-lead ECGs, blood pressure, and physical examinations will be evaluated and monitored for any safety events through the study duration from screening through follow up.	~ 8 weeks