BROOKLYN
Research type
Research Study
Full title
Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies (BROOKLYN): A Placebo-Controlled, Double-Blind, Randomized, Phase 3 Study to Evaluate the Effect of 10 mg Obicetrapib in Participants With a History of HeFH and LDL-C ≥70 mg/dL Who are Not Adequately Controlled by Their Lipid-Modifying Therapies
IRAS ID
1006592
Contact name
Marc Ditmarsch
Contact email
Sponsor organisation
NewAmsterdam Pharma B.V.
Eudract number
2021-005064-22
Clinicaltrials.gov Identifier
Research summary
Despite advances in treatment, Cardiovascular (CV) disease (CVD) is the leading cause of death globally, resulting in over 17 million deaths annually. Elevated Low Density Lipoprotein Cholesterol (LDL-C, the so called “bad cholesterol”) in blood is a major risk factor for the development of CVD. Lowering LDL-C has been shown to reduce the risk of death or heart attack and other major CV problems (cardiovascular events). Approximately 100 million people worldwide are treated with lipid-lowering therapies, mostly statins (a group of medicines), to reduce LDL-C and the associated risk of heart attack events.
The purpose of this study is to compare the effects of a study medicine, obicetrapib, versus a placebo (looks like the study medicine, but does not contain an active ingredient) to find out if obicetrapib is helpful for treating heterozygous familial hypercholesterolemia (HeFH) and reducing your LDL-C. HeFH is a genetic condition that increases the levels of LDL-C in blood.
This study is multicentral, approximately 70 study centers across several countries and approximately 300 participants with a history of HeFH who are not adequately controlled by their lipid-modifying therapy at are expected to.
Patients will be random assigned in a 2:1 ratio to:
• Obicetrapib group (200 patients): One 10mg Obicetrapib tablet once-daily; or
• Placebo group (100 patients): One placebo tablet once-daily.
Starting on Day 1, each participant will self-administer their assigned study drug once daily until Day 365. During the Treatment Period, participants will return to the study site for efficacy and safety assessments. An End of Study (EOS) Visit will be conducted approximately 35 days after the participant’s last dose of study drug, during which vital signs; limited serum chemistry, hematology, and coagulation parameters; pharmacokinetics; concomitant medications; and Adverse Events will be assessed.LAY SUMMARY OF STUDY RESULTS:
Obicetrapib 10mg, taken by mouth once a day, lowered the amount of LDL-C, a harmful cholesterol, measured in the participant’s blood significantly more compared to those individuals who were taking an identical placebo tablet that contained no active ingredients.
The average decrease of LDL-C in the blood, from study start to Day 84 of study medicine treatment, was about 36.4% in participants who received obicetrapib, as compared to 0.06% in the participants who received placebo. After one year of treatment with study medicine (at Day 365), the decrease of LDL-C in patients who received obicetrapib was maintained and comparable to the reductions seen at Day 84. The average decrease of LDL-C from study start to Day 365 in patients who received obicetrapib was about 33.3%, as compared to an average increase of 4 % for the group who received placebo.
Overall, obicetrapib taken by mouth at a dose of 10mg once a day was safe and well tolerated. Adverse events are unwanted effects reported by study participants or observed by the doctors looking after study participants. Once an adverse event is noted, the study doctor will make an assessment as to whether the event is likely to be caused by the investigational medicine or not, taking into account several factors relevant to both the study participant and what is already known about the investigational medicine’s characteristics from previous clinical studies. An adverse reaction is defined as an adverse event assessed to be possibly related to the study drug. The intensity or severity of an adverse event or of an adverse drug reaction (ADR) is graded as either “mild” (pass without needing treatment), “moderate” or “severe” (requiring medical care, be long-lasting or permanent, and even life threatening). 4.3% of the participants in the obicetrapib group and 6.8% in the placebo group experienced study medicine related adverse events. The most common adverse drug reactions among the participants who received obicetrapib were: • myalgia (muscle pain) (seen in 1.3% of participants) • diarrhea (seen in 0.9% of participants) The vast majority of adverse drug reactions were either mild or moderate in intensity, with very few participants needing to stop the study medicine because of the event. Overall, approximately 6.0% of participants experienced a Treatment Emergent (experienced during the study drug treatment period) Serious Adverse Events: 5.6% of participants in the obicetrapib group compared to 6.8% participants in the placebo group. Serious Adverse Events are defined as adverse events which result in any of the following outcomes: death, a life-threatening event, requires hospitalization or leads to prolongation of an existing hospitalization, a persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly or birth defect or an important medical event. All of the observed TE Serious Adverse Events for the BROOKLYN Study were considered moderate or severe by intensity and assessed as not related to the study drug. The results from the participants’ physical examinations, ECGs and other tests showed no significant differences between participants receiving obicetrapib or placebo.
The study showed that a group of participants who received obicetrapib for 84 days had significantly lower LDL-C in the blood compared to a group of participants who received a placebo, and that obicetrapib was safe and well tolerated. Nevertheless, this summary only shows the results from this study, which may be different to the results from other studies. The information from this study may help the Sponsor and authorities to decide whether obicetrapib should be studied further and to see if it can be used to treat high levels of LDL-C in people with HeFH."REC name
London - South East Research Ethics Committee
REC reference
22/LO/0824
Date of REC Opinion
17 Feb 2023
REC opinion
Further Information Favourable Opinion