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

NCT04197817 | Completed Phase 1

• 1 other identifier: JS002-001
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events（SAE, drug-related (S)AE etc）based on physical examinations, vital signs, 12 lead ECGs , laboratory tests and injection site reactions.

  Up to 84 days after dose administration

Secondary Outcomes (3)

• Number of participants with anti-drug antibodies.

  Up to 84 days after dose administration

• Serum concentrations of JS002 at different timepoint after the drug administration.

  Up to 84 days after dose administration

• Change from baseline in LDL-C and other lipid parameters (TC, HDL-C, non-HDL-C, VLDL-C, ApoB, ApoA1, Lp(a) and TG).

  Up to 84 days after dose administration

Other Outcomes (3)

• Changes over time of serum concentrations of JS002.

  Up to 84 days after dose administration

• Changes over time of LDL-C.

  Up to 84 days after dose administration

• Change over time of unbound/total serum PCSK9.

  Up to 84 days after dose administration

Study Arms (2)

JS002

ACTIVE COMPARATOR

JS002, Subcutaneous or intravenous injection

Drug: JS002

Placebo,

PLACEBO COMPARATOR

Placebo,Subcutaneous or intravenous injection

Drug: Placebo

Interventions

JS002 DRUG

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

Also known as: Recombinant humanized Anti- PCSK9 monoclonal antibody

JS002

Placebo DRUG

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

Also known as: Placebo of Recombinant humanized Anti- PCSK9 monoclonal antibody

Placebo,

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy men or women aged 18 to 45 years old at screening visit;
• Have the ability to read and understand, volunteer to participate in the study, and signed written informed consent.
• 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.
• The sitting blood pressure ≥90/60 mmHg and \<140/90 mmHg at screening visit.
• Serum LDL-C level ≥ 70 mg/dL (1.8 mmol/L) and \< 190 mg/dL (4.9 mmol/L) at screening visit.
• Serum Triglyceride (TG) level \< 250 mg/dL (2.8 mmol/L) at screening visit.
• 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.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from the study:
• Evolocumab and/or Alirocumab, or other targeted drugs to PCSK9, has been used at any time.
• Any therapeutic or research biological agents has been used during the first 6 months of baseline/random (Day 0).
• Participated in any clinical study within 3 months prior to baseline/random (Day 0).
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Shanghai Junshi Bioscience Co., Ltd.: lead

Study Sites (1)

Fuwai Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100020, China

Location

MeSH Terms

Conditions

Hypercholesterolemia

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2019
• First Posted: December 13, 2019
• Study Start: December 11, 2017
• Primary Completion: August 14, 2018
• Study Completion: August 14, 2018
• Last Updated: December 13, 2019

Record last verified: 2019-12

Locations

CN (1)