A Single Dose Escalation Study of PCSK9 Inhibitor (JS002) in Health Subjects

NCT ID: NCT04197817

Last Updated: 2019-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

84 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-12-11

Study Completion Date

2018-08-14

Brief Summary

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JS002 is a recombinant humanized Anti- PCSK9 monoclonal antibody; This is a phase Ia, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of a single subcutaneous injection of JS002 in healthy subjects.

In this study, the dose ascending design includes five dose level cohorts (15 mg, 50 mg, 150 mg, 300 mg, and 450 mg) administered by subcutaneous injection, and three intravenous administration cohorts (15 mg, 150 mg, and 450 mg). Each cohort will enroll 8 to 12 subjects (distribution of study drug and placebo in a 3:1 ratio).

The duration of the study is 84-day per subjects.

Detailed Description

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Conditions

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Hypercholesterolemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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JS002

JS002, Subcutaneous or intravenous injection

Group Type ACTIVE_COMPARATOR

JS002

Intervention Type DRUG

JS002, Subcutaneous or intravenous injection of a single dose of JS002, dose cohort according to ascending dose design

Placebo,

Placebo,Subcutaneous or intravenous injection

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo,Subcutaneous or intravenous injection of a single dose of placebo, dose cohort according to ascending dose design

Interventions

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JS002

JS002, Subcutaneous or intravenous injection of a single dose of JS002, dose cohort according to ascending dose design

Intervention Type DRUG

Placebo

Placebo,Subcutaneous or intravenous injection of a single dose of placebo, dose cohort according to ascending dose design

Intervention Type DRUG

Other Intervention Names

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Recombinant humanized Anti- PCSK9 monoclonal antibody Placebo of Recombinant humanized Anti- PCSK9 monoclonal antibody

Eligibility Criteria

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Inclusion Criteria

1. Healthy men or women aged 18 to 45 years old at screening visit;
2. Have the ability to read and understand, volunteer to participate in the study, and signed written informed consent.
3. The body mass index (BMI) at screening visit was in the range of 18 to 30 kg/m2 (inclusive) and the body weight ≥ 50 kg.
4. The sitting blood pressure ≥90/60 mmHg and \<140/90 mmHg at screening visit.
5. Serum LDL-C level ≥ 70 mg/dL (1.8 mmol/L) and \< 190 mg/dL (4.9 mmol/L) at screening visit.
6. Serum Triglyceride (TG) level \< 250 mg/dL (2.8 mmol/L) at screening visit.
7. No fertility \[female: documented hysterectomy, bilateral oophorectomy, tubal ligation or other female permanent sterilization, or menopause (menopause for more than one year)\], or those with fertility are willing to take, during the entire study period, strict and effective contraceptive measures, in addition, female subjects with fertility should have a negative blood/urine pregnancy test at screening visit.

Exclusion Criteria

1. Subjects who meet any of the following criteria will be excluded from the study:
2. Evolocumab and/or Alirocumab, or other targeted drugs to PCSK9, has been used at any time.
3. Any therapeutic or research biological agents has been used during the first 6 months of baseline/random (Day 0).
4. Participated in any clinical study within 3 months prior to baseline/random (Day 0).
5. Any drug or health supplement that affects blood lipids or lipid metabolism during the first 30 days of baseline/random (Day 0), including but not limited to: Probucol, statins (e.g. Atorvastatin, Rosuvastatin, etc.), cholesterol absorption inhibitors (such as Ezetimibe), bile acid sequestrants (such as Cholestyramine), red yeast and hawthorn preparations, fibrates, high-purity fish oil preparations (or omega-fatty acids ≥ 1000 mg / day) and niacin preparation (nicotinic acid ≥ 50 mg), etc.
6. Start a new intense exercise or diet control within 30 days of random (Day 0) or major changes to previous diet and lifestyle (including exercise, smoking and drinking). The following conditions occur before the baseline/random (Day 0) 1 day (ie Day-1) need to be excluded:

* Creatine kinase (CK) ≥ 3 times the upper limit of normal (ULN) (Note: related to exercise), or
* Urinary cotinine is positive, or
* Positive alcohol saliva test.
7. Previous or concomitant diseases (such as nephrotic syndrome, liver disease, diabetes, hypothyroidism, etc.) or any clinically significant abnormalities found in physical examinations, laboratory tests, and electrocardiograms, which would make the subject unsuitable for this study.
8. The medical history or clinical evidence indicates that the subject had severe acute or chronic disease (including not limited to: heart, kidney, nerves, endocrine, blood, immunity, infection, metabolic disorders, etc.), and the disease has not been controlled, which may confuse the outcome of the study or put the subject at risk judged by the investigator, The following situations need to be excluded:

* had major surgery in the last 6 months, or
* has been hospitalized (e.g. infection) in the last 3 months, or
* donated blood or blood loss ≥500 mL in the past 3 months, or
* has used any prescription or over-the-counter drugs in the past 1 month.
9. Transplantation History of organs (such as heart, lung, liver, kidney, etc.) Malignant tumors history, except for cervical carcinoma in situ or surgically resected skin cancer (basal cells and squamous epithelial cells) for more than 5 years.
10. Drug abuse or alcohol dependence in the past 1 year.
11. HIV infection, or HIV antibody positive at screening visit.
12. Syphilis infection, or serotonin antibody (TPPA) positive at screening visit.
13. Hepatitis B surface antigen (HBsAg) was positive at screening visit.
14. Hepatitis C virus (HCV) antibody was positive at screening visit.
15. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 2 times the upper limit of normal (ULN); alkaline phosphatase and bilirubin ≥ 1.5 times the upper limit of normal (ULN).
16. Allergy history to mammalian-derived biological agents, including monoclonal antibodies.
17. Women during pregnancy and lactation.
18. Any other investigator believes that the subject is not suitable for the study, such as the subject has potential compliance issues, cannot complete all tests and assessments according to the protocol requirements.
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Shanghai Junshi Bioscience Co., Ltd.

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Fuwai Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Site Status

Countries

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China

Other Identifiers

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JS002-001

Identifier Type: -

Identifier Source: org_study_id