dyslipidemia heterozygous familial hypercholesterolemia (HeFH) atherosclerotic cardiovascular disease (ASCVD) MedDRA version: 20.1 Level: LLT Classification code 10020049 Term: High cholesterol System Organ Class: 100000004848 MedDRA version: 20.0 Level: LLT Classification code 10057079 Term: Heterozygous familial hypercholesterolemia System Organ Class: 100000004850 MedDRA version: 26.0 Level: LLT Classification code 10051615 Term: Atherosclerotic cardiovascular disease System Organ Class: 1
Conditions
Sponsors
NewAmsterdam Pharma B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Are willing and able to give written informed consent before initiation of any study-related procedures and willing to comply with all required study procedures; 2.Are male or female =18 years of age at Screening (Visit 1); oFemales 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; oFemales of childbearing potential must have a negative urine pregnancy test at Screening (Visit 1); 3.Have underlying HeFH and/or a history of ASCVD 4.Are on maximally tolerated lipid-modifying therapy as an adjunct to a lipid-lowering diet and other lifestyle modifications defined as follows: -A statin at a maximally tolerated stable dose; -Ezetimibe for at least 8 weeks with or without maximally tolerated statin prior to Screening (Visit 1); -Bempedoic acid for at least 8 weeks in combination with a maximally tolerated statin prior to Screening (Visit 1); and/or -A proprotein convertase subtilisin/kexin type 9 (PCSK9)-targeted therapy alone or in combination with other lipid-modifying therapy for at least 4 stable doses prior to Screening (Visit 1) Note: At least 70% of the participants enrolled into this study must be taking HISs. HISs include the following: -Atorvastatin 40 and 80 mg; and -Rosuvastatin 20 and 40 mg 5.Have a fasting serum LDL-C as follows: o Have a fasting serum LDL-C =55 mg/dL (=1.4 mmol/L) to 3 and 60 years; - High sensitivity C-reactive protein (hsCRP) >=2.0 mg/L (>=19.0 nmol/L) at Screening (Visit 1) or within 6 months prior to Screening (Visit 1) -Fasting TG >150 mg/dL (>1.7 mmol/L); -Fasting Lp(a) >30 mg/dL (>70 nmol/L); and/or -Fasting HDL-C =65 years) yes F.1.3.1 Number of subjects for this age range 520
Exclusion criteria
Exclusion criteria: 1.Have current or any previous history of New York Heart Association class III or IV HF or left ventricular ejection fraction 3 x upper limit of normal (ULN); or total bilirubin >2 x ULN at Screening; 7.Have HbA1c =10% (=0.100 hemoglobin fraction) or a fasting glucose =270 mg/dL (=15.0 mmol/L) at Screening (Visit 1); 8.Have thyroid-stimulating hormone >1.5 x ULN at Screening (Visit 1); 9.Have creatine kinase >3 x ULN at Screening (Visit 1); 10.Have a history of a malignancy that required surgery (excluding local and wide local excision), radiation therapy, and/or systemic therapy during the 3 years prior to Randomization (Visit 2); 11.Have a known history of alcohol and/or drug abuse within 5 years prior to Randomization (Visit 2); 12.Have received treatment with other investigational products or devices within 30 days of Screening (Visit 1) or 5 half lives of the previous investigational product, whichever is longer; 13.Are taking gemfibrozil or have taken gemfibrozil within 30 days of Screening (Visit 1); 14.Have planned use of other investigational products or devices during the course of the study; 15.Have participated in any clinical study evaluating obicetrapib; 16.Have a known allergy or hypersensitivity to the study drug, placebo, or any of the excipients in the study drug or placebo; or 17.Have any participant condition that, according to the Investigator, could interfere with the conduct of the study, such as, but not limited to, the following: o Are unable to communicate or to cooperate with the Investigator; o Are unable to understand the protocol requirements, instructions and study-related restrictions, and the nature, scope, and possible consequences of the study (including participants whose cooperation is doubtful due to drug abuse or alcohol dependency); o Are unlikely to comply with the protocol requirements, instructions, and study-related restrictions (eg, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study); o Have any medical or surgical condition which, in the opinion of the Investigator, would put the participant at increased risk from participating in the study; or o Are directly involved in the conduct of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of obicetrapib on LDL-C levels at Day 84.;Secondary Objective: -to evaluate the effect of obicetrapib on LDL-C levels at Days 180 and 365 -to evaluate the effect of obicetrapib on ApoB, non-high-density lipoprotein cholesterol (non-HDL-C), HDL-C, total cholesterol (TC), and triglycerides (TG) at Days 84, 180, and 365 -to evaluate the effect of obicetrapib on lipoprotein (a) (Lp[a]) and apolipoprotein A1 (ApoA1) at Day 84 -to evaluate the safety and tolerability profile of obicetrapib in a broadly representative population of adult males and females of all ages, including elderly and very elderly participants, assessed by AEs, events of special interest (ESIs), vital signs (including blood pressure), ECG measurements, and clinical laboratory values ;Primary end point(s): the percent change from Baseline to Day 84 in LDL-C in the obicetrapib group compared to the placebo group ;Timepoint(s) of evaluation of this end point: Baseline, Day 84 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Percent change from Baseline to Days 180 and 365 in LDL-C in the obicetrapib group compared to the placebo group 2.Percent change from Baseline to Days 84, 180 and 365 in ApoB in the obicetrapib group compared to the placebo group; 3.Percent change from Baseline to Day 84, 180 and 365 in non-HDL-C in the obicetrapib group compared to the placebo group; 4.Percent change from Baseline to Days 84, 180, and 365 in HDL-C in the obicetrapib group compared to the placebo group; 5.Percent change from Baseline to Day 84 in Lp(a) and ApoA1 in the obicetrapib group compared to the placebo group; 6.Percent change from Baseline to Days 84, 180, and 365 in fasting TC in the obicetrapib group compared to the placebo group; and 7.Percent change from Baseline to Days 84, 180, and 365 in fasting TG in the obicetrapib group compared to the placebo group. ;Timepoint(s) of evaluation of this end point: 1) Baseline, 180, 365 2,3,4,6,7) Baseline, Day 84, 180, 365 5) Baseline, Day 84 | — |
Countries
China, Czechia, Czech Republic, Denmark, Georgia, Japan, Netherlands, Poland, United States
Contacts
Public ContactClinical Operations
NewAmsterdam Pharma B.V.
Outcome results
None listed