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

February 4, 2025 updated by: Hasten Biopharmaceutical Co., Ltd.

A Randomized, Double-blind, Placebo-controlled Phase 3 Clinical Study to Evaluate the Efficacy and Safety of HST101 in Chinese Patients with Hypercholesterolemia

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

210

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Beijing, China, 100034
        • Not yet recruiting
        • Peking University First Hospital
        • Contact:
    • Beijing
      • Beijing, Beijing, China
        • Recruiting
        • Fuwai Hospital, CAMS & PUMC
        • Contact:
      • Beijing, Beijing, China
        • Recruiting
        • Beijing Anzhen Hospital of Capital Medical University
        • Contact:
      • Beijing, Beijing, China
        • Recruiting
        • Beijing Luhe Hospital, Capital Medical Univeristy
        • Contact:
      • Beijing, Beijing, China
        • Recruiting
        • Beijing Tsinghua Changgeng Hospital
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China
        • Recruiting
        • Guangdong Provincial People's Hospital
        • Contact:
    • Hebei
      • Shijiazhuang, Hebei, China
        • Recruiting
        • Shijiazhuang People's Hospital
        • Contact:
    • Heilingjiang
      • Daqing, Heilingjiang, China
        • Recruiting
        • Daqingshi People's Hospital
        • Contact:
    • Hunan
      • Changsha, Hunan, China
        • Recruiting
        • The Third Xiangya Hospital of Central South University
        • Contact:
      • Changsha, Hunan, China
        • Recruiting
        • The 2nd Xiangya Hospital of Central South University
        • Contact:
    • Jiangxi
      • Nanchang, Jiangxi, China
        • Recruiting
        • Nanchang People's Hospital
        • Contact:
    • Shandong
      • Binzhou, Shandong, China
        • Recruiting
        • Binzhou Medical University Hospital
        • Contact:
      • Heze, Shandong, China
        • Recruiting
        • Heze Municipal Hospital
        • Contact:
      • Jinan, Shandong, China
        • Recruiting
        • Qilu Hospital of Shandong University
        • Contact:
      • Zibo, Shandong, China
        • Recruiting
        • Zibo Municipal Hospital
        • Contact:
    • Sichuan
      • Chengdu, Sichuan, China
        • Recruiting
        • West China Hospital of Sichuan University
        • Contact:
    • Tianjin
      • Tianjin, Tianjin, China
        • Recruiting
        • Tianjin People's Hospital
        • Contact:
    • Zhejiang
      • Wenzhou, Zhejiang, China
        • Recruiting
        • The First Affiliated Hospital of Wenzhou Medical Univesity
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HST101(Lerodalcibep)
300 mg subcutaneously Q4W
Drug: Lerodalcibep
PCSK9 inhibitor
Other Names:
  • LIB003
  • HST101
Placebo Comparator: Placebo
subcutaneously Q4W
Drug: matching placebo
placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
LDL-C change compared to Placebo
Time Frame: 12 weeks
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
Time Frame: 12 weeks
Percent change in mean LDL-C level from baseline (calculated by Friedewald formula) compared to placebo at Weeks 10 and 12
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
LDL-C change over time
Time Frame: 12 weeks
Absolute and percent change in LDL-C level from baseline at Weeks 4, 8, 10, and 12
12 weeks
Free PCSK9 change
Time Frame: 12 weeks
Absolute and Percent change in serum free PCSK9 level from baseline at Weeks 4,8 and 12
12 weeks
Other Lipid parameters change
Time Frame: 12 weeks
Absolute and Percent change in TC, TG, HDL-C, non-HDL-C, VLDL-C, Apo B and Lp(a) from baseline at Weeks 4,8 and 12
12 weeks
Percentage of patients achieving LDL-C goals recommended by 2023 Chinese guideline
Time Frame: 12 weeks
To assess the effect of HST101 on the percentage of patients achieving LDL-C<2.6 mmol/L (high-risk for ASCVD patients), LDL-C<1.8 mmol/L and >50% reduction from baseline (very-high risk for ASCVD patients), LDL-C<1.4 mmol/L and >50% reduction from baseline (ultra-high risk for ASCVD patients)
12 weeks
Incidence of treatment-emergent adverse events
Time Frame: 52 weeks
Evaluation of adverse events, clinical lab tests, 12-lead ECG, vital signs, injection site reactions (ISRs)
52 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Long time free PCSK9 change
Time Frame: 52 weeks
Absolute and percent change in serum free PCSK9 levels from baseline at Weeks 16,20,24,36,48 and 52
52 weeks
Long time LDL-C change
Time Frame: 52 weeks
Absolute and percent change in LDL-C level from baseline at Weeks 16,20,22,24,36,48,50 and 52
52 weeks
Percentage of patients achieving LDL-C goals recommended by 2023 Chinese guideline
Time Frame: 52 weeks
To assess the effect of HST101 on the percentage of patients achieving LDL-C<2.6 mmol/L (high-risk for ASCVD patients), LDL-C<1.8 mmol/L and >50% reduction from baseline (very-high risk for ASCVD patients), LDL-C<1.4 mmol/L and >50% reduction from baseline (ultra-high risk for ASCVD patients) at Weeks 16, 20, 24, 36, 48 and 52
52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hasten Biopharmaceutical Co., Ltd.

Investigators

  • Principal Investigator: Yong Huo, Peking University First Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 16, 2024

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

May 1, 2026

Study Registration Dates

First Submitted

August 21, 2024

First Submitted That Met QC Criteria

August 21, 2024

First Posted (Actual)

August 23, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 4, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HST101-301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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