* LIBerate-HR:
Research type
Research Study
Full title
Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Long-Term Efficacy and Safety of LIB003 in Patients with Cardiovascular Disease, or at High Risk for Cardiovascular Disease, on Stable Lipid-Lowering Therapy Requiring Additional Low-Density Lipoprotein Cholesterol Reduction (LIBerate-HR)
IRAS ID
293829
Contact name
Devaki Nair
Contact email
Sponsor organisation
LIB Therapeutics, LLC
Eudract number
2020-004393-22
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 5 months, 27 days
Research summary
Research Summary
Atherosclerotic cardiovascular(CV) disease (ASCVD) is the main cause of morbidity and mortality in industrialised countries and despite progress in treatment, is projected to cause >22 million deaths over the next 15 years. Lowdensity lipoprotein cholesterol (LDL-C) has been identified as 1 of the major, and easily modifiable, risk factors for atherosclerosis. The introduction of statin therapy has transformed the treatment of CVD and is now widely used to reduce LDL-C in patients with existing ASCVD and those at increased CV risk. However, there remains an unmet
medical need for additional LDL-C reduction in some patients including those unable to tolerate statins or effective doses of statins and those with higher LDL-C levels.LIBerate-HR is a randomised, double-blind, placebo-controlled, Phase 3 study to evaluate the long-term safety and effect of LIB003 in patients with cardiovascular disease, or at high risk for cardiovascular disease, on stable lipid-lowering therapy requiring additional low-density lipoprotein cholesterol reduction. Patients unable to tolerate approved doses of a statin may take lower than approved doses and less frequently than daily as long as the dose and dosing frequency are consistent. Patients with documented intolerance and unable to tolerate any statin may also participate. Approximately 900 males and females aged ≥18 years who fulfill all of the inclusion and none of the exclusion criteria will be enrolled at up to 90 sites worldwide.
Patients will be randomized in a 2:1 ratio to LIB003 (600 patients) or placebo (300 patients) administered SC Q4W (≤31 days). The study will consist of a Screening Period and a Treatment Period. The total study duration will be up to 63 weeks which includes up to an 11-week Screening Period (which may include up to an 8-week washout) and 52 weeks of study drug treatment.
Summary of Results
LIB Therapeutics, LLC, the Sponsor, would like to thank the participants in this clin-ical study for their time and effort. Study participation allows LIB Therapeutics, LLC, and the doctors, nurses, and study staff responsible for the study, to examine how well LIB003 works and how safe it is in treating people with cardiovascular disease (CVD) or at high risk to develop CVD. CVD involves different conditions affecting the heart or blood vessels.
GENERAL INFORMATION ABOUT THE STUDY/WHY WAS THIS STUDY DONE?
There are lots of things that can increase the risk of getting CVD. These are called "risk factors". One of the main risks factors for CVD is having high levels of low-density lipoprotein (LDL) cholesterol (LDL-C, the “bad” cholesterol) in blood. High levels of LDL-C in blood can cause the blood vessels to narrow and increase the risk of developing a blood clot. LDL-C is normally removed from the blood stream by special “port” or “terminal” on the liver cells, called the LDL receptors. LDL-C usually binds to the LDL receptor and delivers its cholesterol to the liver cells where it is used to make many essential products needed by the body. If LDL-C is not cleared fairly quickly by the liver, it builds up in the blood stream and breaks down, and the cholesterol sticks to the walls of arteries leading to heart disease.
About 20 years ago, it was discovered that high levels of the protein PCSK9 were associated with high levels of LDL-C in blood. This is because the protein PCSK9 attaches to the LDL receptor and reduces or prevents the LDL receptor from clearing LDL-C from blood. Medicines were subsequently developed which blocked PCSK9 and allowed the LDL receptors to improve their ability to clear LDL-C, these medi-cines are called PCSK9 inhibitors. The first of these medicines was approved for general use in late 2015. LIB003 is a PCSK9 inhibitor.
The purpose of this study was to learn if the investigational medicine LIB003 was effective and safe compared to placebo in reducing the LDL-C levels when added to the standard cholesterol-lowering medicines, that participants were already tak-ing. The placebo looked like LIB003 but did not contain any medication (active in-gredient). Researchers use a placebo to see if a study medicine works better or is safer than not taking anything at all. “Investigational” means that LIB003 was not approved by any authorities when the study started. We use the term “study medi-cine” in this document to refer to both LIB003 and placebo.WHEN AND WHERE WAS THE STUDY DONE?
When was it performed?
This study started in December 2020 and ended in November 2023.
Where did the study take place?
The study took place in the following countries: United States, Canada, Israel, Unit-ed Kingdom, Turkey, Germany, South Africa, Norway, India, Spain, New ZealandWHO TOOK PART IN THIS STUDY?
Patients in the study had to meet the following criteria:
• Be over the age of 18.
• Be diagnosed with CVD or at high risk to develop CVD.
• Be on stable diet and cholesterol-lowering medicines taken by mouth (orally).
WHICH MEDICINES WERE STUDIED?
LIB003 (also named Lerodalcibep) 300 mg and placebo were given as subcutane-ous (SC) injection in the abdomen, thigh or upper arm, every 4 weeks during a treatment period of 52 weeks (a total of 13 doses).
HOW WAS THE STUDY DONE?
After up to 11 weeks of screening period, where participants underwent tests to see if they could receive the study medicine, participants were assigned by chance (randomly) to either LIB003 or placebo during the 52-week treatment period. Partici-pants had a 2 in 3 (or 66.7%) chance of receiving LIB003 and a 1 in 3 (or 33.3%) chance of receiving placebo. Double-blind means that neither the participant nor the research team or the Sponsor knew which study medicine the participant re-ceived until the end of the study. This was done to ensure there was no bias in any decisions made during the study.
The duration of study participation was up to 63 weeks (about 1 year and 3 months). Several procedures were done during the study visits, including blood and urine tests, electrocardiograms (tests to see how the heart was working), and physical ex-aminations. WHAT WERE THE MAIN RESULTS OF THE STUDY?LIB003 significantly reduced the amount of LDL-C or had cholesterol in partici-pant’s blood. The reduction in LDL-C in participants receiving LIB003 was 50% compared to LDL-C in participants receiving placebo after 52 weeks of treatment; and 55% as an average of weeks 50 and 52 of treatment.
That means that, on average, LIB003 reduced the amount of LDL-C at the time par-ticipants entered the study by:
• Half of its value after 52 weeks of treatment: for example, from 100 at base-line to 50 at week 52.
• A bit more than half of its baseline value as an average of 50 and 52 weeks of treatment: for example, from 100 to 45.WHERE THERE ANY UNWANTED EFFECTS?
Adverse reactions are unwanted events that the study doctor thinks are related to the study medicine. Adverse reactions can be “mild” in severity and pass without treatment, or “serious” requiring medical care, be long-lasting or permanent, and even life-threatening.
The most common adverse reactions in the study and the only ones considered to be related to treatment by the Sponsor were “injection site reactions” (seen in 6.4% or about 6 out of 100 participants receiving LIB003), which could be redness (3.3%), bruising (1.6%) or itching (1.3%) at the site of the SC injection. The majority of the adverse reactions were mild or moderate in severity and temporary, with very few participants needing to stop the study medicine.
The results of participant’s physical examinations, blood results and electrocardio-grams showed no significant differences between participants receiving LIB003 and those receiving placebo.
HOW HAS THE STUDY HELPED PATIENTS AND RESEARCHERS?
Participants receiving LIB003 for 52 weeks showed a significant reduction in the amount of LDL-C in blood compared to participants receiving placebo in this study.
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 country authori-ties make decisions on if LIB003 should be allowed to treat people with CVD or at high risk for CVD.
ARE THERE ANY PLANS FOR FUTURE STUDIES?
Participants who completed the study had the option to enter a long-term extension study to continue receiving LIB003 (or start receiving it if they had been assigned to placebo in this study) for additional 72 weeks (approximately one year and 5 months).
There are no additional studies of LIB003 in patients with CVD or at high risk for CVD planned at present.REC name
South Central - Oxford A Research Ethics Committee
REC reference
22/SC/0343
Date of REC Opinion
23 Jul 2021
REC opinion
Further Information Favourable Opinion