YN001-004 potilailla, joilla on sepelvaltimon ateroskleroosi Australiassa
Vaiheen Ⅱa kliininen tutkimus YN001:n tehon ja turvallisuuden arvioimiseksi potilailla, joilla on sepelvaltimon ateroskleroosi Australiassa
This study is to evaluate the efficacy and safety of intravenously administered YN001 in patients with coronary atherosclerosis in Australia. This study will be conducted in eligible participants with a diagnosis of coronary atherosclerosis, and at least 1 coronary artery is blocked determined by coronary computed tomography angiography (CCTA)
Tutkimuksen yleiskatsaus
Tila
Tila
Ehdot
Ehdot
Interventio / Hoito
Interventio / Hoito
Yksityiskohtainen kuvaus
This is a multicenter, randomized, open label, parallel-group, proof of concept study. It is designed to determine if the study drug, called YN001, administered in addition to evolocumab can effectively reduce the total amount of plaque formed in the coronary artery as measured by CCTA from baseline to week 13.
A total of 24 patients with coronary atherosclerosis are expected to be enrolled and will be randomly assigned in a 1:1 ratio to 1 of 2 YN001 treatment arms (12 patients per arm) with 2 different dose levels for 12 weeks.
The study will be comprised of a maximum 41-day screening period (Day -42-Day -2), a baseline period (Day-1), a treatment and observation period (W1D1- W13D7), and a safety follow-up period (14 days post last dose).
Opintotyyppi
Opintotyyppi
Ilmoittautuminen (Todellinen)
Ilmoittautuminen
Vaihe
Vaihe
- Vaihe 2
Yhteystiedot ja paikat
Opiskelupaikat
-
-
-
Tugun, Australia
- John Flynn Private Hospital
-
-
Australian Capital Territory
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Canberra, Australian Capital Territory, Australia
- Canberra Hospital
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-
New South Wales
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Albury, New South Wales, Australia, 1125
- Albury Wodonga Private Hospital
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-
Queensland
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Birtinya, Queensland, Australia, 4575
- Sunshine Coast University Private Hospital
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-
Victoria
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Melbourne, Victoria, Australia, 3025
- Altona Clinical Research
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Melbourne, Victoria, Australia, 3199
- Peninsula Heart Centre
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-
Osallistumiskriteerit
Kelpoisuusvaatimukset
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
Inclusion Criteria:
- Fully understand the purposes, features, and methods of the study, and sign the ICF before performing any assessment.
- Male or female Australia patients between 18 and 75 years.
- Patients diagnosed with coronary atherosclerosis, and at least 1 vessel with diameter stenosis determined by coronary computed tomography angiography (CTA).
- Female patients must be non-pregnant and non-lactating, and females of childbearing potential (including a female partner of a male patient) must agree to use 1 effective contraception method from the screening period to 3 months after receiving their last dose of the study drug. In addition, male patients must be willing to refrain from sperm donation during this time.
- Willing and able to comply with the requirements of protocol to the best of the patient's and investigator's knowledge.
Exclusion Criteria:
- Prior treatment with other investigational drug(s) within 30 days or 5 half-lives, whichever is longer, prior to randomization.
- Previously received YN001.
- Any type of vaccination within 4 weeks prior to randomization.
- Contraindication for coronary CTA (e.g., known history of anaphylactic contrast reactions).
- Multi-vessel severe disease.
- Recent acute ST-segment elevation myocardial infarction (STEMI) occurred within 2 weeks prior to randomization.
- Relapse and highly symptomatic arrhythmia uncontrolled by drugs within the past 3 months, such as ventricular tachycardia, atrial fibrillation with rapid ventricular rate and paroxysmal supraventricular tachycardia.
- Prior treatment with CABG, heart transplantation, SAVR/TAVR, etc., or CABG, heart transplantation, SAVR/TAVR, etc., is required or planned during the study.
- PCI performed within 4 weeks prior to randomization or PCI is required or planned during study treatment.
- New York Heart Association (NYHA) class III or IV, or last known left ventricular ejection fraction (LVEF) <40%.
- Recent clinically evident stroke occurred within 6 months prior to randomization (except for TIA).
- Presenting with history of myopathy/myalgia, or susceptible to myopathy/rhabdomyolysis.
- Known inflammatory bowel disease, ulcers, gastrointestinal or rectal bleeding within 6 months prior to randomization.
- Evidence of major diseases that not recovered within 2 weeks prior to randomization, or major surgery is expected during the study.
- Presenting with history of malignancy (except in patients who have been disease-free >5 years; or whose only malignancy has been basal or squamous cell skin carcinoma).
- Presence of any type of autoimmune disease.
- Allergy to multiple food or drugs or known sensitivity to any components to be administered during dosing
- Life expectancy is less than 1 year.
- Systolic blood pressure of ≥150 mmHg at final screening despite antihypertensive therapy.
- Known familial hypercholesterolemia
- Triglycerides≥400 mg/dl (4.5 mmol/l) at final screening.
- Active liver disease or hepatic dysfunction defined by any of ALT, AST, or total bilirubin > 2 times upper limit of normal (ULN) at final screening.
- Presence of renal insufficiency.
- Untreated or inadequately treated hypothyroidism defined by thyroid stimulating hormone (TSH) > 1.5 times ULN at final screening.
- Poorly controlled (defined by HbA1c > 9%) type 2 diabetes mellitus.
- A positive hepatitis B surface antigen (HBsAg), or positive antibody against hepatitis C virus (anti-HCV) or human immunodeficiency virus (anti-HIV), or positive treponema pallidum antibody (TP-Ab).
- Current smoker who has smoked an average of≥5 cigarettes (or equivalent) per day over the preceding year.
- Presence of any other diseases or conditions (apart from those outlined above) that, in the opinion of the investigator, would make it unsuitable for the patient to participate in this study.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Yksittäinen
Aseiden lukumäärä
Aseet ja interventiot
Osallistujaryhmä / ArmOsallistujaryhmä / Arm |
Interventio / HoitoInterventio / Hoito |
|---|---|
|
Kokeellinen: Dose 1 treatment arm
Dose 1 YN001 will be administrated intravenously weekly. |
Dose 1 YN001 will be administered on Day 1 of each week from Week 1 to Week 13, 13 times in total. Evolocumab 140 mg will be administered subcutaneously every 2 weeks.
Muut nimet:
|
|
Kokeellinen: Dose 2 treatment arm
Dose 2 YN001 will be administrated intravenously weekly. |
Evolocumab 140 mg will be administered subcutaneously every 2 weeks.
Muut nimet:
Dose 2 YN001 will be administered on Day 1 of each week from Week 1 to Week 13, 13 times in total. |
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Changes in coronary plaque characteristics (volume and composition)
Aikaikkuna: From baseline to Week 13
|
Evaluating YN001 on top of evolocumab therapy in changing coronary plaque volume assessed by coronary computed tomography angiography (CCTA). |
From baseline to Week 13
|
Toissijaiset tulostoimenpiteet
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Change in mean of mean carotid IMT
Aikaikkuna: From baseline to Week 13
|
Evaluating YN001 on top of evolocumab therapy in changing carotid intima-media thickness (IMT) assessed by carotid ultrasound. |
From baseline to Week 13
|
|
Change in mean of mean carotid IMT
Aikaikkuna: From baseline to Week 5
|
Evaluating YN001 on top of evolocumab therapy in changing carotid intima-media thickness (IMT) assessed by carotid ultrasound. |
From baseline to Week 5
|
|
Change in mean of mean carotid IMT
Aikaikkuna: From baseline to Week 9
|
Evaluating YN001 on top of evolocumab therapy in changing carotid intima-media thickness (IMT) assessed by carotid ultrasound. |
From baseline to Week 9
|
|
Change in mean peri-coronary Fat attenuation index (FAI)
Aikaikkuna: From baseline to Week 13
|
Evaluating YN001 on top of evolocumab therapy in changing inflammation using the peri-coronary FAI value measured by quantitative CTA analysis. |
From baseline to Week 13
|
|
The safety profile of YN001
Aikaikkuna: From baseline to Week 15
|
Incidence of Adverse events (AEs)/Serious adverse events (SAEs) |
From baseline to Week 15
|
|
Plasma concentration of total and free drug
Aikaikkuna: From Week 1 to Week 13
|
Plasma concentration of total and free drug at pre-dose (0 h) and at the end of infusion |
From Week 1 to Week 13
|
|
Population pharmacokinetics (PK)
Aikaikkuna: From Week 1 to Week 13
|
Plasma PK parameter (AUC) and patient covariates of interest will be evaluated graphically and in the population PK model. |
From Week 1 to Week 13
|
Muut tulostoimenpiteet
Muut tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Immunogenicity(ADA) analysis
Aikaikkuna: From Week 1 to Week 13
|
The proportion of patients who develop anti-drug antibodies (ADA) following drug administration. |
From Week 1 to Week 13
|
|
Immunogenicity (APA)analysis
Aikaikkuna: From screening to Week 13
|
The proportion of patients with pre-exsiting anti-PEG antibodies (APA), treatment emergent APA or treatment boosted APA following drug administration. |
From screening to Week 13
|
|
Exploratory dose-response analysis of plaque volume
Aikaikkuna: From Week 1 to Week 13
|
Exploratory dose-response analysis will be performed by comparing the difference of coronary plaque volume changing between 2 different dose levels |
From Week 1 to Week 13
|
|
Exploratory dose-response analysis of AEs
Aikaikkuna: From Week 1 to Week 13
|
Exploratory dose-response analysis will be performed by comparing the difference of incidence of AEs between 2 different dose levels |
From Week 1 to Week 13
|
Yhteistyökumppanit ja tutkijat
Sponsori
Sponsori
Tutkijat
Tutkijat
- Opintojohtaja: Teresa Chen, PhD, Beijing Inno Medicine Co., Ltd.
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Opiskelun aloitus
Ensisijainen valmistuminen (Todellinen)
Ensisijainen valmistuminen
Opintojen valmistuminen (Todellinen)
Opintojen valmistuminen
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Ensimmäinen Lähetetty
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin päivitys julkaistu
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
Muut tutkimustunnusnumerot
Muut tutkimustunnusnumerot
- YN001-004
Lääke- ja laitetiedot, tutkimusasiakirjat
Tutkii yhdysvaltalaista FDA sääntelemää lääkevalmistetta
Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta
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