A Study of AZD8233 in Participants With Dyslipidemia

November 7, 2022 updated by: AstraZeneca

A Randomized, Parallel, Double-blind, Placebo-controlled, Dose-ranging, Phase 2b Study to Evaluate the Efficacy, Safety and Tolerability of AZD8233 Treatment in Participants With Dyslipidemia

AZD8233 is a PCSK9-targeted ASO for the reduction of circulating levels of LDL-C. This study aims to evaluate the dose-dependent reduction in LDL-C after SC administration of multiple doses of AZD8233 as well as the associated adverse effects profile. The data generated will be used to guide choice of doses, dosing regimens, and sample sizes, as well as safety and PD monitoring in the further clinical development program.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a randomized parallel, double-blind, placebo-controlled, dose-ranging Phase 2b study in approximately 108 participants with dyslipidemia. The primary objective of the study is to investigate the effect of AZD8233 on LDL-C across different dose levels. The study will be conducted at up to 25 sites in up to 4 countries.

The screening period starts up to 42 days before the randomization visit and ends on Day -1. Eligible participants will attend 7 visits during the treatment period and 7 additional visits during the safety follow up period. Eligible participants are randomized across four different treatment arms in a 1:1:1:1 ratio for a 12-week treatment period. The planned treatment arms are AZD8233 low dose, AZD8233 medium dose, AZD8233 high dose, and Placebo. Participants will be dosed SC on Days 1, 8, 29, and 57.

Study Type

Interventional

Enrollment (Actual)

119

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Aarhus N, Denmark, 8200
        • Research Site
      • Frederiksberg, Denmark, 2000
        • Research Site
      • Herlev, Denmark, 2730
        • Research Site
      • Roskilde, Denmark, 4000
        • Research Site
      • Viborg, Denmark, 8800
        • Research Site
      • Bratislava, Slovakia, 831 03
        • Research Site
      • Bratislava, Slovakia, 85101
        • Research Site
      • Rožňava, Slovakia, 048 01
        • Research Site
      • Trebišov, Slovakia, 7501
        • Research Site
    • California
      • Roseville, California, United States, 95661
        • Research Site
    • Florida
      • Inverness, Florida, United States, 34452
        • Research Site
      • Jacksonville, Florida, United States, 32216
        • Research Site
      • Pembroke Pines, Florida, United States, 33024
        • Research Site
    • Idaho
      • Meridian, Idaho, United States, 83646
        • Research Site
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • Research Site
    • New York
      • New Windsor, New York, United States, 12553
        • Research Site
    • North Carolina
      • Greensboro, North Carolina, United States, 27408
        • Research Site
    • North Dakota
      • Fargo, North Dakota, United States, 58104
        • Research Site
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  • Male or female.
  • Participant must be 18 to 75 years of age.
  • Body mass index between 19 and 40 kg/m2.
  • Participants who have a fasting LDL-C ≥ 70 mg/dL but < 190 mg/dL.
  • Have fasting triglycerides < 400 mg/dL.
  • Should be receiving moderate- or high-intensity statin therapy.
  • Should be on stable medication for ≥ 3 months prior to screening with no planned medication or dose change during study participation. The exception to this restriction is for fenofibrate; if the participant is receiving fenofibrate, the therapy must be stable for at least 6 weeks prior to randomization at a dose that is appropriate for the duration of the study in the judgement of the Investigator. Other fibrate therapy (and derivatives) are prohibited.

Key Exclusion Criteria:

  • Estimated glomerular filtration rate < 40 mL/min/1.73m2 CKD-EPI.
  • Any uncontrolled or serious disease, or any medical 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.
  • Poorly controlled type 2 diabetes mellitus, defined as HbA1c > 10% at Visit 1.
  • Acute ischaemic cardiovascular event in the last 12 months prior to randomization.
  • Heart failure with New York Heart Association (NYHA) Class III-IV.
  • High-risk of bleeding as judged by the Investigator.
  • Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal
  • Carcinoma in-situ, or Stage 1 prostate carcinoma) within the last 10 years.
  • LDL or plasma apheresis within 12 months prior to randomization.
  • Uncontrolled hypertension defined as average supine SBP > 160 mmHg or DBP > 90 mmHg at Visit 1 or Visit 3.
  • Heart rate after 10 minutes supine rest < 50 bpm or > 100 bpm.
  • Any laboratory values with the following deviations at Screening:

    • Positive result on screening for hepatitis B, hepatitis C or HIV.
    • ALT > 1.5 × ULN.
    • AST > 1.5 × ULN.
    • TBL > ULN.
    • ALP > 1.5 × ULN.
    • WBC < LLN.
    • Haemoglobin < 12 g/dL in men or < 11 g/dL in women.
    • Platelet count ≤ LLN.
    • aPTT > ULN and PT > ULN.
    • UACR > 11.3 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 as judged by the Investigator.
  • Mipomersen, or lomitapide within 12 months prior to randomization.
  • Previous administration of AZD8233/AZD6615.
  • Previous administration of PCSK9 inhibition treatment.
  • Participation in another clinical study with a study intervention administered in the last 3 months prior to randomization or 5 half-lives from last dose to first administration of study intervention, whichever is the longest.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo solution for subcutaneous injection.
Placebo solution
Experimental: AZD8233 high dose
AZD8233 high dose for subcutaneous injection.
PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.
Experimental: AZD8233 medium dose
AZD8233 medium dose for subcutaneous injection.
PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.
Experimental: AZD8233 low dose
AZD8233 low does for subcutaneous injection.
PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12.
Time Frame: Baseline to week 12
Change from baseline in low-density lipoprotein cholesterol (LDL-C) at week 12. Results are based on Mixed Model Repeated Measures (MMRM) analysis on the log-transformed change from baseline. Log-transformed change from baseline is calculated as the visit value in log minus the baseline value in log. The results from the model are then back transformed.
Baseline to week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relative Change From Baseline in PCSK9 Concentration in Plasma at Week 12.
Time Frame: Baseline to week 12
Relative change from baseline in PCSK9 concentration in plasma at week 12.
Baseline to week 12
Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol
Time Frame: Baseline to week 12
Percentage change from baseline in concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants cholesterol at week 12
Baseline to week 12
Plasma Concentration of AZD8233
Time Frame: Measurement at week 1, week 4, week 6, week 8, week 10, week 12, week 16, week 20, week 24 after first dose administration.
Plasma concentration of AZD8233 after first dose administration
Measurement at week 1, week 4, week 6, week 8, week 10, week 12, week 16, week 20, week 24 after first dose administration.
Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period
Time Frame: Measurement at week 0, week 1, week 4, week 8, week 12, week 16, week 20, week 24
ADA titre results for subjects with positive ADA during the treatment period and follow-up period.
Measurement at week 0, week 1, week 4, week 8, week 12, week 16, week 20, week 24
Percentage Change From Baseline in Levels of LDL-C in Plasma
Time Frame: Baseline to week 12
Percentage change from baseline in levels of LDL-C in plasma from baseline to week 12.
Baseline to week 12

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Subjects With an ECG Determined to be Abnormal and Clinically Significant
Time Frame: Baseline to Week 24
Number of subjects with an ECG determined to be abnormal and clinically significant at baseline and end of treatment.
Baseline to Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 28, 2020

Primary Completion (Actual)

July 20, 2021

Study Completion (Actual)

July 20, 2021

Study Registration Dates

First Submitted

October 28, 2020

First Submitted That Met QC Criteria

November 17, 2020

First Posted (Actual)

November 23, 2020

Study Record Updates

Last Update Posted (Actual)

November 18, 2022

Last Update Submitted That Met QC Criteria

November 7, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Other Study ID Numbers

  • D7990C00003

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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