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

Primary Purpose

High Triglycerides

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
NST-1024
Placebo
Sponsored by
NorthSea Therapeutics B.V.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for High Triglycerides

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 1Week -3]) assessments; Men or women 18 to 79 years of age, inclusive; Women may be enrolled if all 3 of the following criteria are met They are not pregnant, They are not breastfeeding, and They do not plan on becoming pregnant during the study. Women of childbearing potential must have a negative urine pregnancy test at screening (Visit 1 [Week -3]). Note: Women are not considered to be of childbearing potential if they meet 1 of the following criteria as documented by the investigator: They have had a complete hysterectomy or tubal ligation prior to signing the informed consent form or They are post-menopausal, defined as ≥1 year since their last menstrual period or have a follicle-stimulating hormone (FSH) level in menopausal range. Women of childbearing potential and men whose partners are of childbearing potential must agree to use a highly effective method of avoiding pregnancy from screening to the end of the study. o Highly effective methods of avoiding pregnancy are contraceptive methods used consistently and correctly and include: Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation. Oral Intravaginal Transdermal Progestogen-only hormonal contraception associated with inhibition of ovulation. Oral Injectable Implantable Intrauterine device (IUD) Intrauterine hormone-releasing system Bilateral tubal occlusion Vasectomised partner Sexual abstinence 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 -1]), and should remain stable thereafter for the duration of study participation; 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; 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. Willingness to maintain stable diet and physical activity level throughout the study If a smoker, no plans to change smoking habits during the study period. Exclusion Criteria: Body mass index >40 kg/m2; 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]); Type 1 diabetes mellitus; HbA1c > 8.5% at screening (Visit 1 [Week -3]); Note: Subjects with elevated A1c >7% and not previously diagnosed with type 2 diabetes mellitus at screening will be excluded from the study and should be referred to their primary care physician for further treatment. History of stroke, myocardial infarction, life-threatening arrhythmia, or coronary revascularization within 6 months prior to screening; History of Acute or chronic pancreatitis; History of symptomatic gallstone disease unless treated with cholecystectomy; History of nephrotic range (>3 g/day) proteinuria; Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 QTcF interval of >450ms. A history of additional risk factors for torsades de pointes (TdP) (e.g., heart failure, hypokalaemia, family history of Long QT Syndrome) The use of concomitant medications that prolong the QT/QTc interval (Table 1); 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; Known lipoprotein lipase impairment or deficiency (Fredrickson Type I), apolipoprotein C-II deficiency, or familial dysbetalipoproteinemia (Fredrickson Type III); Requirement for peritoneal dialysis or haemodialysis for renal insufficiency; 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; History of bariatric surgery; Uncontrolled hypertension; Known to be infected with human immunodeficiency virus (HIV); 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 or who have a negative reflex HCV RNA test; Anticipation of major surgery during the screening or double-blind treatment periods of the study; 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]); Ongoing treatment with HIV-protease inhibitors, cyclophosphamide, or isotretinoin; Treatment with tamoxifen, estrogens, or progestins that has not been stable for ≥28 days prior to screening (Visit 1 [Week -3]); Routine or anticipated use of all systemic corticosteroids. Use of local injectable, inhaled, nasal administration or topical corticosteroids is permitted; 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]); Alanine aminotransferase or AST >2.5 x ULN, unless exercise-related; Unexplained CK concentration >5 × ULN or CK elevation due to known muscle disease (e.g., polymyositis, mitochondrial dysfunction); 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); 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]); History of illicit drug use or alcohol abuse within 1 year of screening. Alcohol consumption is defined as >21 standard drinks per week in men and >14 standard drinks per week in women, on average; 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; 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Placebo Comparator

    Active Comparator

    Arm Label

    Matched Placebo

    NST-1024

    Arm Description

    NST-1024 400 mg BID

    Outcomes

    Primary Outcome Measures

    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

    Secondary Outcome Measures

    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
    Percent change in Apolipoprotein B and Apolipoprotein C3
    Percent changes in ApoB and ApoC3 from baseline to Week 4.
    Percent Change in Lipoprotein a
    Percent change in Lp(a) from baseline to Week 4.
    Percent Change in remnant-like particle cholesterol (RLP-C)
    Percent Change in RLP-C from baseline to Week 4.
    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
    Change in insulin resistance.
    Change in insulin resistance, as assessed by the homeostasis model index insulin resistance, from baseline to Week 4
    Change in lipoprotein associated phospholipase A2
    Percent change in lipoprotein associated phospholipase A2 from baseline to Week 4
    Change in hsCRP
    Change in hsCRP from baseline to Week 4
    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.

    Full Information

    First Posted
    March 16, 2023
    Last Updated
    May 25, 2023
    Sponsor
    NorthSea Therapeutics B.V.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05889156
    Brief Title
    Study of the Efficacy and Safety of NST-1024 Versus Placebo in Subjects With Hypertriglyceridemia
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    June 30, 2023 (Anticipated)
    Primary Completion Date
    February 29, 2024 (Anticipated)
    Study Completion Date
    February 29, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    NorthSea Therapeutics B.V.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief 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: A 3-week screening period that includes a TG qualifying period, and 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 15-20 centres in USA.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    High Triglycerides

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Allocation
    Randomized
    Enrollment
    50 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Matched Placebo
    Arm Type
    Placebo Comparator
    Arm Title
    NST-1024
    Arm Type
    Active Comparator
    Arm Description
    NST-1024 400 mg BID
    Intervention Type
    Drug
    Intervention Name(s)
    NST-1024
    Intervention Description
    400 mg BID
    Intervention Type
    Other
    Intervention Name(s)
    Placebo
    Intervention Description
    matched placebo to active arm
    Primary Outcome Measure Information:
    Title
    Evaluate the efficacy of NST-1024 by percentage change in TG
    Description
    Evaluate the efficacy of NST-1024 400 mg BID by assessment of the percentage change in TG from baseline after 28 days of treatment
    Time Frame
    4 weeks
    Secondary Outcome Measure Information:
    Title
    Percent Change in Cholesterol Values
    Description
    Percent changes in TC, HDL-C, LDL-C, calculated. non-HDL-C, and VLDL-C from baseline to Week 4
    Time Frame
    4 weeks
    Title
    Percent change in Apolipoprotein B and Apolipoprotein C3
    Description
    Percent changes in ApoB and ApoC3 from baseline to Week 4.
    Time Frame
    4 weeks
    Title
    Percent Change in Lipoprotein a
    Description
    Percent change in Lp(a) from baseline to Week 4.
    Time Frame
    4 weeks
    Title
    Percent Change in remnant-like particle cholesterol (RLP-C)
    Description
    Percent Change in RLP-C from baseline to Week 4.
    Time Frame
    4 weeks
    Title
    Changes in fasting plasma glucose, fasting plasma insulin, and HbA1c
    Description
    Changes in fasting plasma glucose (FPG), fasting plasma insulin (FPI) and HbA1c from baseline to Week 4
    Time Frame
    4 weeks
    Title
    Change in insulin resistance.
    Description
    Change in insulin resistance, as assessed by the homeostasis model index insulin resistance, from baseline to Week 4
    Time Frame
    4 weeks
    Title
    Change in lipoprotein associated phospholipase A2
    Description
    Percent change in lipoprotein associated phospholipase A2 from baseline to Week 4
    Time Frame
    4 weeks
    Title
    Change in hsCRP
    Description
    Change in hsCRP from baseline to Week 4
    Time Frame
    4 weeks
    Title
    Safety Assessments
    Description
    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.
    Time Frame
    ~ 8 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    79 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 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 1Week -3]) assessments; Men or women 18 to 79 years of age, inclusive; Women may be enrolled if all 3 of the following criteria are met They are not pregnant, They are not breastfeeding, and They do not plan on becoming pregnant during the study. Women of childbearing potential must have a negative urine pregnancy test at screening (Visit 1 [Week -3]). Note: Women are not considered to be of childbearing potential if they meet 1 of the following criteria as documented by the investigator: They have had a complete hysterectomy or tubal ligation prior to signing the informed consent form or They are post-menopausal, defined as ≥1 year since their last menstrual period or have a follicle-stimulating hormone (FSH) level in menopausal range. Women of childbearing potential and men whose partners are of childbearing potential must agree to use a highly effective method of avoiding pregnancy from screening to the end of the study. o Highly effective methods of avoiding pregnancy are contraceptive methods used consistently and correctly and include: Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation. Oral Intravaginal Transdermal Progestogen-only hormonal contraception associated with inhibition of ovulation. Oral Injectable Implantable Intrauterine device (IUD) Intrauterine hormone-releasing system Bilateral tubal occlusion Vasectomised partner Sexual abstinence 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 -1]), and should remain stable thereafter for the duration of study participation; 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; 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. Willingness to maintain stable diet and physical activity level throughout the study If a smoker, no plans to change smoking habits during the study period. Exclusion Criteria: Body mass index >40 kg/m2; 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]); Type 1 diabetes mellitus; HbA1c > 8.5% at screening (Visit 1 [Week -3]); Note: Subjects with elevated A1c >7% and not previously diagnosed with type 2 diabetes mellitus at screening will be excluded from the study and should be referred to their primary care physician for further treatment. History of stroke, myocardial infarction, life-threatening arrhythmia, or coronary revascularization within 6 months prior to screening; History of Acute or chronic pancreatitis; History of symptomatic gallstone disease unless treated with cholecystectomy; History of nephrotic range (>3 g/day) proteinuria; Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 QTcF interval of >450ms. A history of additional risk factors for torsades de pointes (TdP) (e.g., heart failure, hypokalaemia, family history of Long QT Syndrome) The use of concomitant medications that prolong the QT/QTc interval (Table 1); 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; Known lipoprotein lipase impairment or deficiency (Fredrickson Type I), apolipoprotein C-II deficiency, or familial dysbetalipoproteinemia (Fredrickson Type III); Requirement for peritoneal dialysis or haemodialysis for renal insufficiency; 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; History of bariatric surgery; Uncontrolled hypertension; Known to be infected with human immunodeficiency virus (HIV); 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 or who have a negative reflex HCV RNA test; Anticipation of major surgery during the screening or double-blind treatment periods of the study; 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]); Ongoing treatment with HIV-protease inhibitors, cyclophosphamide, or isotretinoin; Treatment with tamoxifen, estrogens, or progestins that has not been stable for ≥28 days prior to screening (Visit 1 [Week -3]); Routine or anticipated use of all systemic corticosteroids. Use of local injectable, inhaled, nasal administration or topical corticosteroids is permitted; 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]); Alanine aminotransferase or AST >2.5 x ULN, unless exercise-related; Unexplained CK concentration >5 × ULN or CK elevation due to known muscle disease (e.g., polymyositis, mitochondrial dysfunction); 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); 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]); History of illicit drug use or alcohol abuse within 1 year of screening. Alcohol consumption is defined as >21 standard drinks per week in men and >14 standard drinks per week in women, on average; 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; 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.

    12. IPD Sharing Statement

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

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