Clinical trial NCT06568471: A Study on Efficacy and Safety of HST101 in Chinese Patients with Hypercholesterolemia
Official title: A Randomized, Double-blind, Placebo-controlled Phase 3 Clinical Study to Evaluate the Efficacy and Safety of HST101 in Chinese Patients with Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hypercholesterolemia
Dyslipidemias
Primary Hypercholesterolemia
Heterozygous Familial Hypercholesterolemia
Hyperlipidemia; Mixed
Metabolic Disease
ASCVD
Keywords: PCSK9 inhibitor
Lerodalcibep
LDL-C
Lead sponsor: Hasten Biopharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-08-23
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All participants will be in-parallel randomized in a 2:1 ratio to HST101 or Placebo
Primary purpose: TREATMENT

Brief summary: This randomized study is to assess LDL-C reductions at Week 12 with monthly (Q4W \[≤31 days\]) dosing of HST101 (lerodalcibep) 300 mg administered subcutaneously (SC) compared to placebo in patients with atherosclerotic cardiovascular disease (ASCVD) or very-high/high risk for ASCVD including Heterozygous familial hypercholesterolemia (HeFH) on a stable diet and oral LDL-C lowering drug therapy, followed by 36-week open-label treatment with subsequent 4-week follow-up for total 52-week long-term safety and efficacy evaluation.

Detailed description: This is a multi-center, randomized, double-blind, placebo-controlled Phase 3 study. Participants who fulfill the inclusion and exclusion criteria will be enrolled at up to 35 study sites in mainland China.

All eligible participants will be randomized in a 2:1 ratio to HST101 or placebo dosed subcutaneously (Q4W \[≤31 days\]) in the initial 12-week randomized double-blind treatment period. After 12-week treatment, all the participants will enter to the 36-week open-label treatment period where those who are on HST101 will continue to receive HST101 in the same dosing regimen as dosed in the randomized period, and those who are on placebo will be switched to HST101 300 mg (Q4W \[≤31 days\]) administered subcutaneously.

The total study duration will be up to 55 weeks which includes a up to 3-week Screening Period, 12-week randomized, double-blind, placebo-controlled treatment period, 36-week open-label treatment period, followed by a 4-week follow-up period.

Eligibility criteria: Inclusion Criteria:

* Provision of written and signed informed consent form prior to any study-specific procedure;
* Male or female participants ≥18 years of age at the screening visit;
* Body weight ≥ 40 kg and body mass index (BMI) ≥18 and ≤35 kg/m2;
* On a stable diet and lipid-lowering oral drugs (such as statins, ezetimibe or Hybutimibe, omega-3 compounds, fenofibrate, nicotinic acid, etc.) for at least 4 weeks prior to the first drug administration
* LDL-C≥1.8 mmol/L (70 mg/dL) and TG≤4.52 mmol/L (400 mg/dL) at screening for ASCVD patients or those at very (ultra)-high risk for ASCVD, including patients with HeFH; LDL-C ≥ 2.6 mmol/L (100 mg/dL) and TG ≤ 4.52 mmol/L (400 mg/dL) at screening for patients at high-risk for ASCVD including patients with HeFH;
* Patients on a PCSK9 mAb at a dose of 75 mg, 140 mg, or 150 mg Q2W must undergo a washout period of ≥6 weeks after the last dose; for those on 300 mg or 420 mg Q4W, the washout period is ≥10 weeks following last dose;
* Female of childbearing potential must have a negative pregnancy test at the last screening visit and consent to use highly effective contraceptives during the trial and 3 months after the last dose of investigational drug.

Exclusion Criteria:

* Documented history of homozygous familial hypercholesterolemia (HoFH);
* Estimated glomerular filtration rate (eGFR)\<30 mL/min/1.73m2;
* Active liver disease or hepatic dysfunction, history of liver transplant, and/or ALT or AST \>2.5 × ULN at screening;
* Poorly controlled thyroid disorder including hypothyroidism or hyperthyroidism;
* Poorly controlled Type 1 or Type 2 diabetes mellitus defined as fasting blood glucose ≥11.0 mmol/L (200 mg/dL) and glycosylated hemoglobin (HbA1c) ≥ 9%;
* Serious arrhythmia, MI, unstable angina pectoris, PCI, CABG, implantable cardioverter defibrillator, aortic valve surgery or stroke within 3 months prior to the first dose;
* Planned cardiac surgery or revascularization during the study period;
* New York Heart Association (NYHA) Class III-IV heart failure;
* Pregnant or lactating women;
* Poorly controlled hypertension (SBP≥160 mmHg or DBP≥100 mmHg in a sitting position)
* Unexplained creatine kinase (CK) \> 5 x ULN (retested once is needed if suspected to be related to excessive exercise or abnormal activity);
* LDL apheresis or plasma exchange within 2 months prior to the first dose;
* HIV, Treponema pallidum, or HCV antibody test positive, or HBV-DNA \>ULN at screening;
* History of prescription drug abuse, illicit drug use or alcohol abuse within 6 months prior to screening;
* History of any major drug allergy, including allergy to protein biologics;
* Participate another clinical trial within 30 days or less than 5 half-lifes (drug) before screening, whichever is longer

Primary outcomes:
measure: LDL-C change compared to Placebo
timeFrame: 12 weeks
measure: Mean LDL-C change at Weeks 10 and 12 compared to Placebo
timeFrame: 12 weeks
Secondary outcomes:
measure: LDL-C change over time
timeFrame: 12 weeks
measure: Free PCSK9 change
timeFrame: 12 weeks
measure: Other Lipid parameters change
timeFrame: 12 weeks
measure: Percentage of patients achieving LDL-C goals recommended by 2023 Chinese guideline
timeFrame: 12 weeks
measure: Incidence of treatment-emergent adverse events
timeFrame: 52 weeks
Other outcomes:
measure: Long time free PCSK9 change
timeFrame: 52 weeks
measure: Long time LDL-C change
timeFrame: 52 weeks
measure: Percentage of patients achieving LDL-C goals recommended by 2023 Chinese guideline
timeFrame: 52 weeks
Locations:
city: Beijing
country: China
facility: Beijing Anzhen Hospital of Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Luhe Hospital, Capital Medical Univeristy
state: Beijing
city: Beijing
country: China
facility: Beijing Tsinghua Changgeng Hospital
state: Beijing
city: Beijing
country: China
facility: Fuwai Hospital, CAMS & PUMC
state: Beijing
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Shijiazhuang
country: China
facility: Shijiazhuang People's Hospital
state: Hebei
city: Daqing
country: China
facility: Daqingshi People's Hospital
state: Heilingjiang
city: Changsha
country: China
facility: The 2nd Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Nanchang
country: China
facility: Nanchang People's Hospital
state: Jiangxi
city: Binzhou
country: China
facility: Binzhou Medical University Hospital
state: Shandong
city: Heze
country: China
facility: Heze Municipal Hospital
state: Shandong
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Zibo
country: China
facility: Zibo Municipal Hospital
state: Shandong
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin People's Hospital
state: Tianjin
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical Univesity
state: Zhejiang
city: Beijing
country: China
facility: Peking University First Hospital
Study officials:
affiliation: Peking University First Hospital
name: Yong Huo
role: PRINCIPAL_INVESTIGATOR
References: