Efficacy and SafetyPhase 3NCT04759534
Application of PCSK9 Inhibitors in Patients With Heterozygous Familial Hypercholesterolemia
A Phase 3 study testing protein convertase subtilisin/kexin type 9 inhibitor in people with Efficacy and Safety and Heterozygous Familial Hypercholesterolemia, run by Shenzhen People's Hospital at 1 site in China.
Trial summary
This study plans to enroll several patients with heterozygous familial hypercholesterolemia, randomly assigned to different dose groups, and randomly receiving subcutaneous injection of IBI306150 mg or placebo every two weeks: or subcutaneous injection of IBI306 450mg every four weeks (n=49) or placebo (n=25)… Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Efficacy and Safety, Heterozygous Familial Hypercholesterolemia, PCSK9
- What is being tested?
- protein convertase subtilisin/kexin type 9 inhibitor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 10 Sep 2020to 30 Nov 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Provide a signed and dated informed consent form.
- Men or women aged ≥18 and ≤80 at the time of screening.
- Body weight ≥ 40 kg at the time of screening.
- According to British Simon Broome (SBR) standards, HeFH is diagnosed or suspected:
- Diagnosis of HeFH: Total cholesterol> 7.5 mmol/L, or LDL-C concentration> 4.9 mmol/L, and at least one of the following two can be diagnosed: 1) The patient has tendon xanthoma, or his relatives (first-degree or At least one person at Level 2) has tendon xanthoma; 2) has evidence of LDL receptor, ApoB-100 or PCSK9 gene mutation; Suspected HeFH: Total cholesterol> 7.5 mmol/L, or LDL-C concentration> 4.9 mmol/L, and at least one of the following two is suspected HeFH: 1) Second-degree relatives before 50 years old or first-degree relatives 60 years old Previous history of myocardial infarction; 2) First-degree or second-degree adult relatives have a history of total cholesterol>7.5mmol/L or children, brothers, sisters have a history of total cholesterol>6.7mmol/L before the age of 16 or 16 years old.
- Maintain a low-fat diet and stably take the current lipid-lowering therapy (taking moderate-intensity or above statins, except for statin intolerance, with or without ezetimibe, niacin, and omega fatty acids) for at least 4 weeks. If you are taking fibrates, the fibrates are treated stably for at least 6 weeks.
- The fasting LDL cholesterol concentration of patients with a history of atherosclerotic cardiovascular disease at the time of screening was ≥1.8 mmol/L; the fasting LDL cholesterol concentration of patients without a history of atherosclerotic cardiovascular disease was ≥2.6 mmol/L.
- The subject indicated that they are willing and cooperate to complete all the steps in the study and the study intervention period.
Who cannot join
- Patients diagnosed as homozygous familial hypercholesterolemia.
- He had undergone dialysis or plasma exchange within 4 months before screening.
- Patients who have received liver transplant surgery in the past.
- Adjust the treatment plan or dose of statins, ezetimibe, niacin, and omega fatty acids within 4 weeks before the screening of subjects (these subjects can stabilize the current lipid-lowering drug dosage for 1 month, and then Re-filter).
- New York Heart Association (NYHA) grade III or IV heart failure, or recently detected left ventricular ejection fraction ≤ 30%.
- Poorly controlled severe arrhythmia, defined as recurrent and highly symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular rate or supraventricular tachycardia.
Show all 25Show fewer
- Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass grafting or stroke occurred within 3 months before enrollment.
- Plan to perform percutaneous coronary intervention, coronary artery bypass grafting or other heart surgery during the study period.
- Type 1 diabetes or poor blood sugar control (HbA1c>8.5%), or type 2 diabetes requiring multiple injections of insulin daily.
- There are uncontrolled clinical diseases that may affect blood lipids or lipoprotein levels (in patients with thyroid hormone replacement therapy, the thyroid hormone dose needs to be stable for at least 6 weeks before the screening visit). Poorly controlled hypothyroidism or hyperthyroidism is defined as TSH <the lower limit of normal, or> 1.5 times the upper limit of normal.
- Poorly controlled hypertension is defined as a sitting systolic blood pressure> 180 mmHg or diastolic blood pressure> 110 mmHg confirmed by repeated measurements.
- Moderate to severe renal insufficiency, defined as the estimated glomerular filtration rate <30 ml / min / 1.73 m2 during the screening period.
- Active liver disease or liver function impairment is defined as the screening period determined by local laboratory analysis, aspartate aminotransferase or alanine aminotransferase> 3 times the upper limit of normal (ULN).
- Creatine kinase (CK) ≥ 3 times of ULN during screening.
- As judged by the investigator, there is a known active infection or major blood, kidney, metabolic, gastrointestinal, or endocrine dysfunction.
- Once diagnosed with deep vein thrombosis or pulmonary embolism.
- Except for those who have been sterilized or menopausal, female subjects with potential for pregnancy, if they are unwilling to inform their sexual partners that they will participate in the clinical study, and take effective measures during the use of the study drug and within 15 weeks after the last dose of the study drug Contraceptive measures. Male subjects are unwilling to inform their female sexual partners that they participate in the clinical study.
- Subjects who are pregnant or breastfeeding, or plan to become pregnant or breastfeeding during the period of study medication or within 15 weeks after the last dose of study medication.
- Suffered from malignant tumors in the past 5 years (except for non-melanoma skin cancer, cervical carcinoma in situ, ductal carcinoma in situ of the breast or stage 1 prostate cancer).
- The subject has received PCSK9 inhibitor treatment or participated in other studies that inhibit PCSK9.
- Known allergy to study drug and its ingredients.
- Those who are judged by the investigator to be unsuitable to participate in the study (for example, alcohol or other drug abuse, inability or unwillingness to comply with the agreement, or mental illness).
- Currently participating in another medical device or drug research, or the previous medical device or drug clinical research has ended, or receiving other research drugs for less than 30 days.
- In any other circumstances, the investigator or sponsor believes that it may impair the subject's ability or safety to give written informed consent and/or comply with all necessary research procedures.
- Human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), hepatitis C (HCV) antibodies, HIV or syphilis antibodies were positive at the time of screening.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase III Clinical Study to Evaluate the Efficacy and Safety of PCSK9 Inhibitors in the Prevention of Chinese Heterozygous Familial Hypercholesterolemia
This study plans to enroll several patients with heterozygous familial hypercholesterolemia, randomly assigned to different dose groups, and randomly receiving subcutaneous injection of IBI306150 mg or placebo every two weeks: or subcutaneous injection of IBI306 450mg every four weeks (n=49) or placebo (n=25) treatment, treatment lasted for 12 weeks. During randomization, the LDL-C level (<4.8mmol/L or ≥4.8mmol/L) observed during the screening period visit (VI), and whether ezetimibe was used for stratification. After 12 weeks, each group entered the 12-week open-period treatment, in which subjects in the IBI306 group continued to receive IBI306 treatment, and subjects in the placebo group stopped using placebo and received IBI306 treatment. The exploratory endpoint is the population pharmacokinetic characteristics of IBI306 in Chinese heterozygous familial hypercholesterolemia population.
Read the detailed description
This study plans to enroll 148 patients with heterozygous familial hypercholesterolemia, and maintain a low-fat diet and stably take the current anterior-lowering therapy for at least 4 weeks. Randomly enter different dose groups at 1:1. 2: 1 randomized to receive subcutaneous injection of IBI306150 mg (n=49) or placebo (n=25) every two weeks: or subcutaneous injection of IBI306 450mg (n=49) or placebo (n=25) every four weeks , The treatment lasted 12 weeks. During randomization, the LDL-C level (<4.8mmol/L or ≥4.8mmol/L) observed during the screening period visit (VI), and whether ezetimibe was used for stratification. After 12 weeks, each group entered the 12-week open-period treatment, in which subjects in the IBI306 group continued to receive IBI306 treatment, and subjects in the placebo group stopped using placebo and received IBI306 treatment. The primary endpoint was the percentage change in LDL-C levels from baseline at 12 weeks. The secondary endpoints were the changes in blood lipid levels from baseline at 12 and 24 weeks, drug safety, and immunogenicity. The exploratory endpoint is the population pharmacokinetic characteristics of IBI306 in Chinese heterozygous familial hypercholesterolemia population. If necessary, the dose of IBI306 will be adjusted according to the results of the ongoing multi-dose climbing study. After the open period, the subjects will undergo an 8-week safety visit.
- Being tested
- protein convertase subtilisin/kexin type 9 inhibitor
- Keywords
- PCSK9 inhibitor, heterozygous familial hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
protein convertase subtilisin/kexin type 9 inhibitorBiological
IBI306 is a kind of protein convertase subtilisin/kexin type 9 inhibitor.Received abdominal subcutaneous injection of IBI306 150 mg Q2W or 300 mg Q4W
| Study group | Role | What they receive |
|---|---|---|
| Treatment group 1 | Experimental | Received abdominal subcutaneous injection of IBI306 150 mg Q2W Receives: Biological: protein convertase subtilisin/kexin type 9 inhibitor |
| Treatment group 2 | Experimental | Received abdominal subcutaneous injection of IBI306 150 mg Q4W Receives: Biological: protein convertase subtilisin/kexin type 9 inhibitor |
| Placebo Group 1 | Placebo comparator | Received a subcutaneous injection of placebo Q2W in the abdomen Receives: Biological: protein convertase subtilisin/kexin type 9 inhibitor |
| Placebo Group 2 | Placebo comparator | Received a subcutaneous injection of placebo Q4W in the abdomen Receives: Biological: protein convertase subtilisin/kexin type 9 inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
LDL-C
Percentage decrease in LDL-C from baseline
Measured: 12 weeks after baseline
LDL-C
Percentage decrease in LDL-C from baseline
Measured: 24 weeks after baseline
non HDL-C
Percentage decrease in non HDL-C from baseline
Measured: 12 weeks after baseline
non HDL-C
Percentage decrease in non HDL-C from baseline
Measured: 24 weeks after baseline
ApoB
Percentage decrease in ApoB from baseline
Measured: 12 weeks after baseline
ApoB
Percentage decrease in ApoB from baseline
Measured: 24 weeks after baseline
Secondary outcomes (2)
safty
From the first administration to the last visit, the incidence of adverse events;
Measured: 12 weeks after baseline
safty
From the first administration to the last visit, the incidence of adverse events;
Measured: 24 weeks after baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2021
- Study start10 Sep 2020
- Primary completion30 Oct 2021 (estimated)
- Study completion30 Nov 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Efficacy and SafetyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shenzhen People's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Innovent Biopharmaceutical Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- dong shaohong, doctor, Study chair, Shenzhen People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04759534
- Sponsor's protocol ID
- LQY-PCSK9-heterozygous
- Status last verified
- Aug 2021
- First submitted
- 10 Feb 2021
- Last updated
- 25 Aug 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Clinical Study to Evaluate the Efficacy and Safety of PCSK9 Inhibitors in the Prevention of Chinese Heterozygous Familial Hypercholesterolemia
- ClinicalTrials.gov ID
- NCT04759534
- Acronym / sponsor ID
- LQY-PCSK9-heterozygous
- Keywords
- PCSK9 inhibitor, heterozygous familial hypercholesterolemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Shenzhen People's HospitalUniversity, hospital or other
- Collaborators
- Innovent Biopharmaceutical Co., Ltd.
- Study start
- 10 Sep 2020 (actual)
- Primary completion
- 30 Oct 2021 (estimated)
- Study completion
- 30 Nov 2021 (estimated)
- First posted
- 18 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study plans to enroll several patients with heterozygous familial hypercholesterolemia, randomly assigned to different dose groups, and randomly receiving subcutaneous injection of IBI306150 mg or placebo every two weeks: or subcutaneous injection of IBI306 450mg every four weeks (n=49) or placebo (n=25) treatment, treatment lasted for 12 weeks. During randomization, the LDL-C level (<4.8mmol/L or ≥4.8mmol/L) observed during the screening period visit (VI), and whether ezetimibe was used for stratification. After 12 weeks, each group entered the 12-week open-period treatment, in which subjects in the IBI306 group continued to receive IBI306 treatment, and subjects in the placebo group stopped using placebo and received IBI306 treatment. The exploratory endpoint is the population pharmacokinetic characteristics of IBI306 in Chinese heterozygous familial hypercholesterolemia population.
Detailed description
This study plans to enroll 148 patients with heterozygous familial hypercholesterolemia, and maintain a low-fat diet and stably take the current anterior-lowering therapy for at least 4 weeks. Randomly enter different dose groups at 1:1. 2: 1 randomized to receive subcutaneous injection of IBI306150 mg (n=49) or placebo (n=25) every two weeks: or subcutaneous injection of IBI306 450mg (n=49) or placebo (n=25) every four weeks , The treatment lasted 12 weeks. During randomization, the LDL-C level (<4.8mmol/L or ≥4.8mmol/L) observed during the screening period visit (VI), and whether ezetimibe was used for stratification. After 12 weeks, each group entered the 12-week open-period treatment, in which subjects in the IBI306 group continued to receive IBI306 treatment, and subjects in the placebo group stopped using placebo and received IBI306 treatment. The primary endpoint was the percentage change in LDL-C levels from baseline at 12 weeks. The secondary endpoints were the changes in blood lipid levels from baseline at 12 and 24 weeks, drug safety, and immunogenicity. The exploratory endpoint is the population pharmacokinetic characteristics of IBI306 in Chinese heterozygous familial hypercholesterolemia population. If necessary, the dose of IBI306 will be adjusted according to the results of the ongoing multi-dose climbing study. After the open period, the subjects will undergo an 8-week safety visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment group 1 | Experimental | Biological: protein convertase subtilisin/kexin type 9 inhibitorReceived abdominal subcutaneous injection of IBI306 150 mg Q2W |
| Treatment group 2 | Experimental | Biological: protein convertase subtilisin/kexin type 9 inhibitorReceived abdominal subcutaneous injection of IBI306 150 mg Q4W |
| Placebo Group 1 | Placebo comparator | Biological: protein convertase subtilisin/kexin type 9 inhibitorReceived a subcutaneous injection of placebo Q2W in the abdomen |
| Placebo Group 2 | Placebo comparator | Biological: protein convertase subtilisin/kexin type 9 inhibitorReceived a subcutaneous injection of placebo Q4W in the abdomen |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Provide a signed and dated informed consent form.
- Men or women aged ≥18 and ≤80 at the time of screening.
- Body weight ≥ 40 kg at the time of screening.
- According to British Simon Broome (SBR) standards, HeFH is diagnosed or suspected:
- Diagnosis of HeFH: Total cholesterol> 7.5 mmol/L, or LDL-C concentration> 4.9 mmol/L, and at least one of the following two can be diagnosed: 1) The patient has tendon xanthoma, or his relatives (first-degree or At least one person at Level 2) has tendon xanthoma; 2) has evidence of LDL receptor, ApoB-100 or PCSK9 gene mutation; Suspected HeFH: Total cholesterol> 7.5 mmol/L, or LDL-C concentration> 4.9 mmol/L, and at least one of the following two is suspected HeFH: 1) Second-degree relatives before 50 years old or first-degree relatives 60 years old Previous history of myocardial infarction; 2) First-degree or second-degree adult relatives have a history of total cholesterol>7.5mmol/L or children, brothers, sisters have a history of total cholesterol>6.7mmol/L before the age of 16 or 16 years old.
Key exclusion criteria (25 listed)
- Patients diagnosed as homozygous familial hypercholesterolemia.
- He had undergone dialysis or plasma exchange within 4 months before screening.
- Patients who have received liver transplant surgery in the past.
- Adjust the treatment plan or dose of statins, ezetimibe, niacin, and omega fatty acids within 4 weeks before the screening of subjects (these subjects can stabilize the current lipid-lowering drug dosage for 1 month, and then Re-filter).
- New York Heart Association (NYHA) grade III or IV heart failure, or recently detected left ventricular ejection fraction ≤ 30%.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| protein convertase subtilisin/kexin type 9 inhibitorIBI306 is a kind of protein convertase subtilisin/kexin type 9 inhibitor.Received abdominal subcutaneous injection of IBI306 150 mg Q2W or 300 mg Q4W | Biological | Placebo Group 1, Placebo Group 2, Treatment group 1, Treatment group 2 |
Primary outcome
LDL-C
Time frame: 12 weeks after baseline
Percentage decrease in LDL-C from baseline
LDL-C
Time frame: 24 weeks after baseline
Percentage decrease in LDL-C from baseline
non HDL-C
Time frame: 12 weeks after baseline
Percentage decrease in non HDL-C from baseline
non HDL-C
Time frame: 24 weeks after baseline
Percentage decrease in non HDL-C from baseline
ApoB
Time frame: 12 weeks after baseline
Percentage decrease in ApoB from baseline
ApoB
Time frame: 24 weeks after baseline
Percentage decrease in ApoB from baseline
2 secondary outcomes
safty
Time frame: 12 weeks after baseline
safty
Time frame: 24 weeks after baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2021.
- Individual participant dataSharing planned: No
Related trials for Efficacy and Safety
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Recruiting
Endo-SPONGE for Treatment of Anastomotic or Hartmann's Stump Leakages in Lower Pelvic Area
Anastomotic Leaks, Hartmanns Stump Leakage
Active, not recruiting
Shockwave™ vs Surgical Endarterectomy for Calcified Severe Common Femoral Artery Stenosis: Comparison of Efficacy, Safety and Long-Term Outcomes
Common Femoral Artery Stenosis, Calcification; Heart
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
Active, not recruiting
A Phase 4 Clinical Study to Investigate the Effectiveness and Safety of Skin Resurfacing
Skin Resurfacing
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
dong shaohong, doctor study chair
Shenzhen People's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing protein convertase subtilisin/kexin type 9 inhibitor in people with Efficacy and Safety and Heterozygous Familial Hypercholesterolemia, run by Shenzhen People's Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
LDL-C (time frame: 12 weeks after baseline). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2021.