- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT04197817
A Single Dose Escalation Study of PCSK9 Inhibitor (JS002) in Health Subjects
A Randomized, Double-blind, Placebo-controlled, Single-dose Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JS002 (Recombinant Humanized Anti-PCSK9 Monoclonal Antibody) Injection in Healthy Subjects.
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.
Přehled studie
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 1
Kontakty a umístění
Studijní místa
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Beijing
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Beijing, Beijing, Čína, 100020
- Fuwai Hospital Chinese Academy of Medical Sciences
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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.
- Drug abuse or alcohol dependence in the past 1 year.
- HIV infection, or HIV antibody positive at screening visit.
- Syphilis infection, or serotonin antibody (TPPA) positive at screening visit.
- Hepatitis B surface antigen (HBsAg) was positive at screening visit.
- Hepatitis C virus (HCV) antibody was positive at screening visit.
- 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).
- Allergy history to mammalian-derived biological agents, including monoclonal antibodies.
- Women during pregnancy and lactation.
- 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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Jiný
- Přidělení: Randomizované
- Intervenční model: Sekvenční přiřazení
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Aktivní komparátor: JS002
JS002, Subcutaneous or intravenous injection
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JS002, Subcutaneous or intravenous injection of a single dose of JS002, dose cohort according to ascending dose design
Ostatní jména:
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Komparátor placeba: Placebo,
Placebo,Subcutaneous or intravenous injection
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Placebo,Subcutaneous or intravenous injection of a single dose of placebo, dose cohort according to ascending dose design
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Časové okno |
|---|---|
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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.
Časové okno: Up to 84 days after dose administration
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Up to 84 days after dose administration
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Sekundární výstupní opatření
Měření výsledku |
Časové okno |
|---|---|
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Number of participants with anti-drug antibodies.
Časové okno: Up to 84 days after dose administration
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Up to 84 days after dose administration
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Serum concentrations of JS002 at different timepoint after the drug administration.
Časové okno: Up to 84 days after dose administration
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Up to 84 days after dose administration
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Change from baseline in LDL-C and other lipid parameters (TC, HDL-C, non-HDL-C, VLDL-C, ApoB, ApoA1, Lp(a) and TG).
Časové okno: Up to 84 days after dose administration
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Up to 84 days after dose administration
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Další výstupní opatření
Měření výsledku |
Časové okno |
|---|---|
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Changes over time of serum concentrations of JS002.
Časové okno: Up to 84 days after dose administration
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Up to 84 days after dose administration
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Changes over time of LDL-C.
Časové okno: Up to 84 days after dose administration
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Up to 84 days after dose administration
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Change over time of unbound/total serum PCSK9.
Časové okno: Up to 84 days after dose administration
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Up to 84 days after dose administration
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Spolupracovníci a vyšetřovatelé
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- JS002-001
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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