dyslipidemia heterozygous familial hypercholesterolemia (HeFH) 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
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 and =18 years of age at Screening; o Females 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. o Females of childbearing potential must have a negative urine pregnancy test at Screening. 3. Have a history of HeFH as defined by at least 1 of the following: o Genotyping by a central laboratory; o Clinical assessment using the WHO Criteria/Dutch Lipid Clinical Network Criteria with a score of >8 points; and/or o Meet the Simon Broome Register Diagnostic Criteria for definite or possible Familial Hypercholesterolemia (FH). 4. Are on maximally tolerated lipid-modifying therapy, as an adjunct to diet, defined as follows: o A statin at a maximally tolerated stable dose; o Ezetimibe for at least 8 weeks with or without maximally tolerated statin prior to Screening; o Bempedoic acid for at least 8 weeks in combination with maximally tolerated statin prior to Screening; o 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; 5. Have a fasting serum LDL-C =70 mg/dL (=1.81 mmol/L) at Screening; 6. Have fasting TG =65 years) yes F.1.3.1 Number of subjects for this age range 113
Exclusion criteria
Exclusion criteria: 1. Have current or any previous history of New York Heart Association class III or IV heart failure (HF) or left ventricular ejection fraction 3 x upper limit of normal (ULN); or total bilirubin >2 x ULN at Screening; 7. Have glycosylated hemoglobin =10.0% (=0.100 hemoglobin fraction) or a fasting glucose =270 mg/dL (=15.0 mmol/L) at Screening; 8. Have thyroid-stimulating hormone >1.5 X ULN at Screening; 9. Have creatine kinase >3 x ULN at Screening; 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; 11. Have a known history of alcohol and/or drug abuse within 5 years prior to Randomization; 12. Have received treatment with other investigational products or devices within 30 days of Screening or 5 half-lives of the previous investigational product, whichever is longer; 13.Are taking gemfibrozil; 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. Other protocol-defined criteria apply.
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 fasting apolipoprotein B (ApoB), non-high-density lipoprotein cholesterol (non HDL C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG) at Days 84, 180, and 365; - To evaluate the effect of obicetrapib on fasting LDL-C levels at Days 180 and 365; - To evaluate the effect of obicetrapib on fasting lipoprotein (a) (Lp[a]) at Days 84 and 365; and - To evaluate the safety and tolerability profile of obicetrapib in a representative population of adult males and females with HeFH, assessed by adverse events (AEs), events of special interest (ESIs), vital signs (including blood pressure), electrocardiogram (ECG) measurements, and clinical laboratory values.;Primary end point(s): The percent change from Baseline to Day 84 in fasting 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 fasting LDL-C in the obicetrapib group compared to the placebo group; 2. Percent change from Baseline to Days 84, 180, and 365 in fasting ApoB in the obicetrapib group compared to the placebo group; 3. Percent change from Baseline to Days 84, 180, and 365 in fasting non-HDL-C in the obicetrapib group compared to the placebo group; 4. Percent change from Baseline to Days 84, 180, and 365 in fasting HDL-C in the obicetrapib group compared to the placebo group; 5. Percent change from Baseline to Days 84 and 365 in fasting Lp(a) 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. 8. Trough levels of obicetrapib from Baseline to Day 365 in the obicetrapib group. ;Timepoint(s) of evaluation of this end point: Baseline, Days 84, 180 and 365 | — |
Countries
Canada, Czechia, Czech Republic, Georgia, Netherlands, Norway, Poland, South Africa, Spain, United Kingdom, United States
Contacts
Public ContactClinical Operations
NewAmsterdam Pharma B.V.
Outcome results
None listed