A Study of AZD8233 in Participants With Dyslipidemia

NCT04641299 | Completed Phase 2 Results FDA Drug

• 1 other identifier: D7990C00003
• Study Type: interventional
• Target: 119
• Locations: 3 countries
• Sites: 19

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.

Conditions

Dyslipidaemia

Keywords

Dose Range Finding; AZD8233; Efficacy; PK; PD; Immunogenicity; Safety; Tolerability

Outcome Measures

Primary Outcomes (1)

• Change in Low-density Lipoprotein Cholesterol (LDL-C) at 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 Outcomes (5)

• 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

  Baseline to week 12

• Plasma Concentration of AZD8233

  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

  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

  Baseline to week 12

Other Outcomes (1)

• Number of Subjects With an ECG Determined to be Abnormal and Clinically Significant

  Baseline to Week 24

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo solution for subcutaneous injection.

Drug: Placebo

AZD8233 high dose

EXPERIMENTAL

AZD8233 high dose for subcutaneous injection.

Drug: AZD8233

AZD8233 medium dose

EXPERIMENTAL

AZD8233 medium dose for subcutaneous injection.

Drug: AZD8233

AZD8233 low dose

EXPERIMENTAL

AZD8233 low does for subcutaneous injection.

Drug: AZD8233

Interventions

AZD8233 DRUG

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

AZD8233 high dose; AZD8233 low dose; AZD8233 medium dose

Placebo DRUG

Placebo solution

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (19)

Research Site

Roseville, California, 95661, United States

Location

Research Site

Inverness, Florida, 34452, United States

Location

Research Site

Jacksonville, Florida, 32216, United States

Location

Research Site

Pembroke Pines, Florida, 33024, United States

Location

Research Site

Meridian, Idaho, 83646, United States

Location

Research Site

Indianapolis, Indiana, 46260, United States

Location

Research Site

New Windsor, New York, 12553, United States

Location

Research Site

Greensboro, North Carolina, 27408, United States

Location

Research Site

Fargo, North Dakota, 58104, United States

Location

Research Site

Cincinnati, Ohio, 45219, United States

Location

Research Site

Aarhus N, 8200, Denmark

Location

Research Site

Frederiksberg, 2000, Denmark

Location

Research Site

Herlev, 2730, Denmark

Location

Research Site

Roskilde, 4000, Denmark

Location

Research Site

Viborg, 8800, Denmark

Location

Research Site

Bratislava, 831 03, Slovakia

Location

Research Site

Bratislava, 85101, Slovakia

Location

Research Site

Rožňava, 048 01, Slovakia

Location

Research Site

Trebišov, 7501, Slovakia

Location

Related Publications (1)

• Clewe O, Rekic D, Quartino AL, Carlsson B, Higashimori M, Wernevik L, Hofherr A, Ryden-Bergsten T, Nilsson C, Knochel J. Population pharmacokinetics of a novel PCSK9 antisense oligonucleotide. Br J Clin Pharmacol. 2024 Jun;90(6):1503-1513. doi: 10.1111/bcp.16046. Epub 2024 Mar 19.

  PMID: 38504437 DERIVED

Related Links

• Redacted Protocol
• redacted Statistical Analysis Plan
• Redacted Clinical Study Report Synopsis

MeSH Terms

Conditions

Dyslipidemias

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2020
• First Posted: November 23, 2020
• Study Start: October 28, 2020
• Primary Completion: July 20, 2021
• Study Completion: July 20, 2021
• Last Updated: November 18, 2022
• Results First Posted: November 18, 2022

Record last verified: 2022-10

Locations

US (10); SL (4); DK (5)