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

NCT04964557 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: D7990C000042020-005845-18
• Study Type: interventional
• Target: 411
• Locations: 8 countries
• Sites: 66

Brief Summary

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.

Conditions

Hyperlipidaemia

Keywords

AZD8233; Efficacy; PK; PD; Safety; Tolerability

Outcome Measures

Primary Outcomes (9)

• Percentage Change From Baseline on Serum LDL-C

  Percentage change in Low-density Lipoprotein Cholesterol (LDL-C) from baseline to Day 197.

  From baseline to Day 197

• Number of Subjects With Adverse Events (AEs)

  Please refer to the adverse event module for specifics.

  On-study includes adverse events with an onset date on or after the date of first dose of IP through study competition, planned visit date Day 281.

• Vital Signs - Temperature

  Mean and standard deviation of Temperature at each scheduled visit by treatment.

  Baseline, Days 15, 29, 57, 85, 113, 141, 169, 197, 225, and 281.

• Vital Sign - Weight

  Mean and standard deviation of Weight at each scheduled visit by treatment.

  Baseline and Day 281.

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

  Number of participants With an ECG Determined to be Abnormal and Clinically Significant at each scheduled visit by treatment

  Baseline, Days 85, 169, 225, and 281.

• Vital Sign - Systolic Blood Pressure

  Mean and standard deviation of Systolic Blood Pressure at each scheduled visit by treatment.

  Baseline, Days 15, 29, 57, 85, 113, 141, 169, 197, 225, and 281.

• Vital Sign - Diastolic Blood Pressure

  Mean and standard deviation of Diastolic Blood Pressure at each scheduled visit by treatment.

  Baseline, Days 15, 29, 57, 85, 113, 141, 169, 197, 225, and 281.

• Vital Sign - Pulse Rate

  Mean and standard deviation of Pulse rate at each scheduled visit by treatment.

  Baseline, Days 15, 29, 57, 85, 113, 141, 169, 197, 225, and 281.

• Treatment Emergent Platelet Count Abnormalities

  Treatment emergent platelet count abnormalities by pre-specified criteria by treatment.

  Treatment emergent includes results after the first dose of IP through study competition, planned visit date Day 281.

Secondary Outcomes (3)

• Percentage Change From Baseline on Serum PCSK9

  From baseline to Day 197

• Plasma Concentration of AZD8233

  Pre-dose of Day 29, Day 85, Day 141, Day 183, Day 197

• Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period

  Pre-dose of Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 281

Study Arms (2)

AZD8233

EXPERIMENTAL

AZD8233 for subcutaneous use

Drug: AZD8233

Placebo

PLACEBO COMPARATOR

Placebo solution for subcutaneous injection

Drug: Placebo

Interventions

AZD8233 DRUG

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

AZD8233

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:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (66)

Research Site

Huntsville, Alabama, 35801, United States

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Canoga Park, California, 91303, United States

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Lincoln, California, 95648, United States

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Inverness, Florida, 34452, United States

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Jacksonville, Florida, 32216, United States

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Pembroke Pines, Florida, 33024, United States

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Meridian, Idaho, 83646, United States

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Indianapolis, Indiana, 46260, United States

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New Windsor, New York, 12553, United States

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Greensboro, North Carolina, 27408, United States

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Fargo, North Dakota, 58104, United States

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Cincinnati, Ohio, 45219, United States

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Cincinnati, Ohio, 45246, United States

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Stow, Ohio, 44224, United States

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Mt. Pleasant, South Carolina, 29464, United States

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Suffolk, Virginia, 23435, United States

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Benešov, 256 01, Czechia

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Brandýs nad Labem, 250 01, Czechia

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Brno, 603 00, Czechia

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Jaroměř, 551 01, Czechia

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Liberec, 460 01, Czechia

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Louny, 440 01, Czechia

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Ostrava-Dubina, 700 30, Czechia

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Příbram, 261 01, Czechia

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Teplice, 415 01, Czechia

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Uherské Hradiště, 686 01, Czechia

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Aarhus N, 8200, Denmark

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Herlev, 2730, Denmark

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Herning, 7400, Denmark

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Hvidovre, 2650, Denmark

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København NV, 2400, Denmark

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Roskilde, 4000, Denmark

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Svendborg, 5700, Denmark

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Viborg, 8800, Denmark

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Balatonfüred, 8230, Hungary

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Békéscsaba, 5600, Hungary

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Debrecen, 4032, Hungary

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Orosháza, 5900, Hungary

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Amsterdam, 1105 AZ, Netherlands

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Doetinchem, 7009 BL, Netherlands

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Ede, 6716 RP, Netherlands

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Gouda, 2803 HH, Netherlands

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Harderwijk, 3844 DG, Netherlands

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Rotterdam, 3045 PM, Netherlands

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Bydgoszcz, 85-079, Poland

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Chrzanów, 32-500, Poland

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Krakow, 30-082, Poland

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Lodz, 91-002, Poland

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Puławy, 24-100, Poland

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Ruda Śląska, 41-710, Poland

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Tychy, 43-100, Poland

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Wierzchosławice, 33-122, Poland

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Bratislava, 831 03, Slovakia

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Brezno, 977 01, Slovakia

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Lučenec, 984 01, Slovakia

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Prešov, 080 01, Slovakia

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Rožňava, 048 01, Slovakia

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Svidník, 08901, Slovakia

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Trebišov, 7501, Slovakia

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A Coruña, 15006, Spain

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Ferrol, 15405, Spain

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L'Hospitalet de Llobregat, 08907, Spain

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Santiago de Compostela, 15706, Spain

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Seville, 41009, Spain

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Seville, 41014, Spain

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Zaragoza, 50009, Spain

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Related Links

• CSRsynopsis\_redacted
• CSP\_redacted
• SAP\_redacted

MeSH Terms

Conditions

Hyperlipidemias

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: AstraZeneca Clinical Study Information Center
• Organization: AstraZeneca

information.center@astrazeneca.com

+1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• 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: June 15, 2021
• First Posted: July 16, 2021
• Study Start: July 7, 2021
• Primary Completion: July 15, 2022
• Study Completion: July 15, 2022
• Last Updated: December 15, 2023
• Results First Posted: December 15, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

DK (8); ES (7); HU (4); PL (8); NL (6); US (16); CZ (10); SL (7)