A Study on Efficacy and Safety of HST101 in Chinese Patients with Hypercholesterolemia

NCT06568471 | Recruiting Phase 3 FDA Drug

• 1 other identifier: HST101-301
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 18

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.

Conditions

Hypercholesterolemia; Dyslipidemias; Primary Hypercholesterolemia; Heterozygous Familial Hypercholesterolemia; Hyperlipidemia; Mixed; Metabolic Disease; ASCVD

Keywords

PCSK9 inhibitor; Lerodalcibep; LDL-C

Outcome Measures

Primary Outcomes (2)

• LDL-C change compared to Placebo

  Percent change in LDL-C level from baseline (calculated by Friedewald formula) compared to Placebo

  12 weeks

• Mean LDL-C change at Weeks 10 and 12 compared to Placebo

  Percent change in mean LDL-C level from baseline (calculated by Friedewald formula) compared to placebo at Weeks 10 and 12

  12 weeks

Secondary Outcomes (5)

• LDL-C change over time

  12 weeks

• Free PCSK9 change

  12 weeks

• Other Lipid parameters change

  12 weeks

• Percentage of patients achieving LDL-C goals recommended by 2023 Chinese guideline

  12 weeks

• Incidence of treatment-emergent adverse events

  52 weeks

Other Outcomes (3)

• Long time free PCSK9 change

  52 weeks

• Long time LDL-C change

  52 weeks

• Percentage of patients achieving LDL-C goals recommended by 2023 Chinese guideline

  52 weeks

Study Arms (2)

HST101(Lerodalcibep)

EXPERIMENTAL

300 mg subcutaneously Q4W

Drug: Lerodalcibep

Placebo

PLACEBO COMPARATOR

subcutaneously Q4W

Drug: matching placebo

Interventions

Lerodalcibep DRUG

PCSK9 inhibitor

Also known as: HST101, LIB003

HST101(Lerodalcibep)

matching placebo DRUG

placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Hasten Biopharmaceutical Co., Ltd.: lead

Study Sites (18)

Beijing Anzhen Hospital of Capital Medical University

Beijing, Beijing Municipality, China

RECRUITING

Beijing Luhe Hospital, Capital Medical Univeristy

Beijing, Beijing Municipality, China

RECRUITING

Beijing Tsinghua Changgeng Hospital

Beijing, Beijing Municipality, China

RECRUITING

Fuwai Hospital, CAMS & PUMC

Beijing, Beijing Municipality, China

RECRUITING

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, China

RECRUITING

Shijiazhuang People's Hospital

Shijiazhuang, Hebei, China

RECRUITING

Daqingshi People's Hospital

Daqing, Heilingjiang, China

RECRUITING

The 2nd Xiangya Hospital of Central South University

Changsha, Hunan, China

RECRUITING

The Third Xiangya Hospital of Central South University

Changsha, Hunan, China

RECRUITING

Nanchang People's Hospital

Nanchang, Jiangxi, China

RECRUITING

Binzhou Medical University Hospital

Binzhou, Shandong, China

RECRUITING

Heze Municipal Hospital

Heze, Shandong, China

RECRUITING

Qilu Hospital of Shandong University

Jinan, Shandong, China

RECRUITING

Zibo Municipal Hospital

Zibo, Shandong, China

RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, China

RECRUITING

Tianjin People's Hospital

Tianjin, Tianjin Municipality, China

RECRUITING

The First Affiliated Hospital of Wenzhou Medical Univesity

Wenzhou, Zhejiang, China

RECRUITING

Peking University First Hospital

Beijing, 100034, China

NOT YET RECRUITING

MeSH Terms

Conditions

Hypercholesterolemia; Dyslipidemias; Hyperlipoproteinemia Type II; Metabolic Diseases

Condition Hierarchy (Ancestors)

Hyperlipidemias; Lipid Metabolism Disorders; Nutritional and Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias

Study Officials

• Yong Huo

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yong Huo

CONTACT

+86 13901333060; huoyong@263.net.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study consists of the preceding 12-week double-blind, placebo-controlled treatment period and the subsequent 40-week (incluing 36-week HST101 treatment and 4-week follow-up) open-label treatment period.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All participants will be in-parallel randomized in a 2:1 ratio to HST101 or Placebo

Study Record Dates

• First Submitted: August 21, 2024
• First Posted: August 23, 2024
• Study Start: November 16, 2024
• Primary Completion: February 1, 2026
• Study Completion: May 1, 2026
• Last Updated: February 6, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (18)