A Study to Assess the Safety, Efficacy and Tolerability of AZD8233 Treatment in Participants With Hyperlipidaemia

NCT ID: NCT04964557

Last Updated: 2023-12-15

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

411 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-07

Study Completion Date

2022-07-15

Brief Summary

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AZD8233 is a PCSK9-targeted ASO for the reduction of circulating levels of LDL-C. This study aims to evaluate safety, efficacy and tolerability of AZD8233.

Detailed Description

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This is a randomized parallel, double-blind, placebo-controlled Phase 2b study in approximately 376 participants with hyperlipidaemia. The primary objective of the study is to assess the safety and tolerability of AZD8233 as compared with placebo, and the effect of AZD8233 versus placebo on relative change in LDL-C. The study will be conducted at up to 100 sites in up to 8 countries.

The screening period starts up to 28 days before the randomization visit and ends on Day -1. Eligible participants will attend 1 enrollment visit and 15 visits during the treatment period and 2 additional visits during the safety follow up period.

Conditions

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Hyperlipidaemia

Keywords

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AZD8233 Efficacy PK PD Safety Tolerability

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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AZD8233

AZD8233 for subcutaneous use

Group Type EXPERIMENTAL

AZD8233

Intervention Type DRUG

PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.

Placebo

Placebo solution for subcutaneous injection

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo solution

Interventions

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AZD8233

PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.

Intervention Type DRUG

Placebo

Placebo solution

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Participant must be 18 to 75 years of age, inclusive, at the time of signing the informed consent
* Participants who have a fasting LDL-C ≥ 70 mg/dL (1.8 mmol/L) but \< 190 mg/dL (4.9 mmol/L) at screening
* Participants who have fasting triglycerides \< 400 mg/dL (\< 4.52 mmol/L) at screening
* Participants are receiving a stable dose (≥ 3 months) of maximally tolerated statin and/or ezetimibe therapy
* Male or female of non-childbearing potential
* Signed and dated written informed consent prior to any mandatory study specific procedures, sampling, and analyses

Exclusion Criteria

* eGFR \< 40 mL/min/1.73m2 using the CKD-EPI
* History or presence of gastrointestinal, hepatic or renal disease or any other conditions known to interfere with absorption, distribution, metabolism or excretion of drugs
* Any uncontrolled or serious disease, or any medical (eg,. known major active infection or major haematological, renal, metabolic, gastrointestinal or endocrine dysfunction) or surgical condition that, in the opinion of the investigator, may either interfere with participation in the clinical study and/or put the participant at significant risk (according to the investigator's judgment) if he/she participates in the clinical study
* Poorly controlled T2DM, defined as HbA1c \> 10%
* Acute ischaemic cardiovascular events including stroke within 30 days, or heart failure with New York Heart Association (NYHA) Class III to IV
* Blood dyscrasias with increased risk of bleeding including idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura or symptoms of increased risk of bleeding (frequent bleeding gums or nose bleeds)
* High-risk of bleeding diathesis or anti-platelet therapy other than low dose aspirin (≤100mg/day).
* Malignancy within the last 10 years
* Recipient of any major organ transplant
* LDL or plasma apheresis within 12 months prior to randomisation
* Uncontrolled hypertension defined as average supine SBP \> 160 mmHg or DBP \> 90 mmHg
* Heart rate after 10 minutes supine rest \< 50 or \> 100 bpm
* Any laboratory values with the following deviations at the Screening Visit; test may be repeated at the discretion of the investigator if abnormal:

* Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV)
* ALT \> 1.5 × ULN
* AST \> 1.5 × ULN
* TBL \> ULN
* ALP \> 1.5 × ULN
* WBC \< lower limit of normal (LLN).
* Haemoglobin \< 12 g/dL in males or \< 11 g/dL in females
* Platelet count ≤ LLN
* aPTT \> ULN or Prothrombin Time \> ULN
* UACR \> 11 mg/mmol (100 mg/g)
* UPCR \> 300 mg/g
* Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG
* QTcF \> 470 ms; high degree atrioventricular (AV)-block grade II-III and sinus node dysfunction with significant sinus pause untreated with pacemaker; and cardiac tachyarrhythmias
* History of drug and/or alcohol abuse or a positive screen for drugs of abuse
* Use of warfarin, direct or indirect thrombin inhibitors or factor Xa inhibitors
* Mipomersen, or lomitapide within 12 months prior to randomisation
* Any fibrate therapy other than fenofibrate; if the participant is on fenofibrate therapy, the dose should be stable for at least 6 weeks prior to randomisation
* Previous administration of AZD8233/AZD6615) or inclisiran (LEQVIO ® Novartis)
* Use of evolocumab (REPATHA® Amgen) and alirocumab (PRALUENT® Regeneron) within 3 months of screening
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Huntsville, Alabama, United States

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Canoga Park, California, United States

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Lincoln, California, United States

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Inverness, Florida, United States

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Jacksonville, Florida, United States

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Pembroke Pines, Florida, United States

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Meridian, Idaho, United States

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Indianapolis, Indiana, United States

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New Windsor, New York, United States

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Greensboro, North Carolina, United States

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Fargo, North Dakota, United States

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Cincinnati, Ohio, United States

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Cincinnati, Ohio, United States

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Stow, Ohio, United States

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Mt. Pleasant, South Carolina, United States

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Suffolk, Virginia, United States

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Benešov, , Czechia

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Brandýs nad Labem, , Czechia

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Brno, , Czechia

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Jaroměř, , Czechia

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Liberec, , Czechia

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Louny, , Czechia

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Ostrava-Dubina, , Czechia

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Příbram, , Czechia

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Teplice, , Czechia

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Uherské Hradiště, , Czechia

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Aarhus N, , Denmark

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Herlev, , Denmark

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Herning, , Denmark

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Hvidovre, , Denmark

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København NV, , Denmark

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Roskilde, , Denmark

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Svendborg, , Denmark

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Viborg, , Denmark

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Balatonfüred, , Hungary

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Békéscsaba, , Hungary

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Debrecen, , Hungary

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Orosháza, , Hungary

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Amsterdam, , Netherlands

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Doetinchem, , Netherlands

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Ede, , Netherlands

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Gouda, , Netherlands

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Harderwijk, , Netherlands

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Rotterdam, , Netherlands

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Bydgoszcz, , Poland

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Chrzanów, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Puławy, , Poland

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Ruda Śląska, , Poland

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Tychy, , Poland

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Wierzchosławice, , Poland

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Bratislava, , Slovakia

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Brezno, , Slovakia

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Lučenec, , Slovakia

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Prešov, , Slovakia

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Rožňava, , Slovakia

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Svidník, , Slovakia

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Trebišov, , Slovakia

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A Coruña, , Spain

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Ferrol, , Spain

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L'Hospitalet de Llobregat, , Spain

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Santiago de Compostela, , Spain

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Seville, , Spain

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Seville, , Spain

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Zaragoza, , Spain

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Countries

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United States Czechia Denmark Hungary Netherlands Poland Slovakia Spain

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2020-005845-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D7990C00004

Identifier Type: -

Identifier Source: org_study_id