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A Study of AZD8233 in Participants With Dyslipidemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04641299
Recruitment Status : Completed
First Posted : November 23, 2020
Last Update Posted : August 12, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE October 28, 2020
First Posted Date  ICMJE November 23, 2020
Last Update Posted Date August 12, 2021
Actual Study Start Date  ICMJE October 28, 2020
Actual Primary Completion Date July 20, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 17, 2020)
Percentage change from baseline in geometric mean of LDL-C concentration in plasma at week 12. [ Time Frame: Measurement at week 12 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2020)
  • Percentage change from baseline in geometric mean of PCSK9 concentration in plasma at weeks 1, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24. [ Time Frame: Measurement at screening, week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
  • Percentage change from baseline in concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants cholesterol [ Time Frame: Measurement at screening, week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
  • 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 ]
  • 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 ]
  • Percentage change from baseline in levels of LDL-C in plasma [ Time Frame: Measurement at screening, week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: November 17, 2020)
  • Number of subjects with adverse events (AEs) [ Time Frame: Measurement at week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
  • Vital sign: Systolic blood pressure (SBP) [ Time Frame: Measurement at week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
  • Vital sign: Diastolic blood pressure (DBP) [ Time Frame: Measurement at week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
  • Vital sign: Pulse rate [ Time Frame: Measurement at week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
  • Vital sign: Oral body temperature [ Time Frame: Measurement at week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
  • Number of subjects with an ECG determined to be abnormal and clinically significant [ Time Frame: Measurement at week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
  • Number of subjects with clinically significant changes in haematology and or clinical chemistry parameters [ Time Frame: Measurement at week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Study of AZD8233 in Participants With Dyslipidemia
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Dyslipidaemia
Intervention  ICMJE
  • Drug: AZD8233
    PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.
  • Drug: Placebo
    Placebo solution
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo solution for subcutaneous injection.
    Intervention: Drug: Placebo
  • Experimental: AZD8233 high dose
    AZD8233 high dose for subcutaneous injection.
    Intervention: Drug: AZD8233
  • Experimental: AZD8233 medium dose
    AZD8233 medium dose for subcutaneous injection.
    Intervention: Drug: AZD8233
  • Experimental: AZD8233 low dose
    AZD8233 low does for subcutaneous injection.
    Intervention: Drug: AZD8233
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 23, 2021)
119
Original Estimated Enrollment  ICMJE
 (submitted: November 17, 2020)
108
Actual Study Completion Date  ICMJE July 20, 2021
Actual Primary Completion Date July 20, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark,   Slovakia,   United States
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT04641299
Other Study ID Numbers  ICMJE D7990C00003
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP