LIBerate-VI
Research type
Research Study
Full title
Randomized, Open Label, Phase 3 Study to Evaluate the Efficacy and Safety of Lerodalcibep (LIB003) compared to Inclisiran 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-VI)
IRAS ID
1004562
Contact name
Minal Kara
Contact email
Sponsor organisation
LIB Therapeutics, LLC
Eudract number
2021-002871-20
Clinicaltrials.gov Identifier
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-VI is a randomised, open label, Phase 3 study to learn if LIB003 (study drug) given by subcutaneous injection (injection under the skin) for 9 months, is effective and safe compared to inclisiran in reducing LDL-cholesterol level. Inclisiran (brand name Leqvio®) is a medication that is already approved for treatment of high LDL cholesterol.
Approximately 160 males and females aged ≥18 years who fulfill all of the inclusion and none of the exclusion criteria will be enrolled at up to 30 sites worldwide.
Patients will be randomized in a 1:1 ratio to LIB003 (80 patients) or inclisiran (80 patients) administered subcutaneous (under the skin) injection monthly. The study will consist of a Screening Period and a Treatment Period. The total study duration will be up to 11 months which includes up to 9 weeks in a Screening Period and approximately 9 months of study drug treatment.Lay Summary
"LIB Therapeutics, the Sponsor, would like to thank the participants in this clinical study for their time and effort. Study participation allows the researchers to see how well LIB003 works and how safe it is in treating people with cardiovascular disease (CVD), or at high risk for CVD.
Many things that can increase the risk of getting CVD. One of the main risks factors for CVD is a high level of low-density lipoprotein (LDL) cholesterol the “bad” cholesterol) in blood. High levels of LDL-C in blood can cause blood vessels to narrow and increase the risk of developing a blood clot. LDL-C is normally removed from the blood stream by special “ports” or “terminals” on the liver cells, called the LDL receptors. LDL-C binds to the LDL receptor and delivers its cholesterol to the liver where it is used to make many essential products for the body. If LDL-C is not cleared by the liver, it builds up in the blood stream, 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 blood levels of LDL-C. PCSK9 attaches to the LDL receptor and reduces or prevents the LDL receptor from clearing LDL-C from blood. Medicines were then developed which block PCSK9 and allow the LDL receptors to improve the clearance of LDL-C, these medicines are called PCSK9 inhibitors. LIB003 is a PCSK9 inhibitor.
This study’s purpose was to learn if the investigational medicine LIB003 was effective and safe compared to inclisiran, another drug acting on PCSK9 but in a different way in the liver cells, in reducing the LDL-C levels in participants with CVD, or at high risk for CVD. The study participants were on a stable diet and taking standard cholesterol-lowering medicines.
This study started in June 2022 and ended in March 2024 in the following countries: France, Germany, Norway, Spain and United Kingdom.
Patients in the study had to meet the following criteria:
Be over the age of 18.
Be diagnosed with CVD or at high risk of developing CVD.
Be on a stable diet and cholesterol-lowering medicines taken by mouth.
LIB003 (also named Lerodalcibep) 300 mg was given as a subcutaneous (SC, under the skin) injection in the abdomen, thigh or upper arm, every 4 weeks over a period of 270-days (9 months), with a total of 9 doses. It was compared to inclisiran (also named Leqvio®) 284mg, given as SC injections at Days 1 and 90 of the treatment period. Inclisiran is approved by the European Medicines Agency (EMA) for the treatment of high LDL cholesterol.
Participants were randomly assigned to either LIB003 or inclisiran for the 270-days treatment period. The participants had a 1 in 2 (or 50%) chance of receiving either LIB003 or inclisiran. Open-Label means that the participant, the research team, and the Sponsor knew which study medicine and dose the participant was treated with.
The duration of study participation was up to 11 months. Several procedures were done during the study visits, including blood and urine tests, electrocardiograms ( to see how the heart was working), and physical examinations.LIB003 significantly reduced the amount of LDL-C or bad cholesterol in participant’s blood. The reduction in LDL-C in participants receiving LIB003 was 51.5%, compared to aLDL-C reduction of 45.0% in participants receiving inclisiran, after 270 days of treatment.
That means that on average, LIB003 reduced the amount of LDL-C at the time participants entered the study by:more than half of its value after 270 days of treatment: for example, from 100 at baseline to 49 at Day 270.
more than 6% compared to the reduction in participants treated with inclisiran.
Overall LIB003 was well tolerated over the treatment period of the study. There were no serious adverse reactions in the study. The most common adverse reactions in the study considered to be related to the treatment by the Sponsor were “injection site reactions” (seen in 13.1% or about 13 out of 100 participants receiving LIB003), which could be redness (3.6%), itching (7.1%), or pain (1.2%) at the site of the SC injection. All other adverse reactions considered related to LIB003 were reported by 1.4% of the participants. Most adverse reactions were mild or moderate in severity and none were considered severe.
Participants receiving LIB003 for 270 days showed a significant reduction of LDL-C in blood, and a significant reduction compared to participants receiving inclisiran.However, 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 authorities make decisions on if LIB003 should be allowed to treat people with CVD or at high risk of developing CVD."
REC name
Wales REC 5
REC reference
22/WA/0055
Date of REC Opinion
8 Apr 2022
REC opinion
Further Information Favourable Opinion