Study to Evaluate the Efficacy, Safety and Tolerability of AZD8233 Treatment in Participants With Dyslipidemia

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 - A Phase 2b Study of AZD8233 in Participants With Dyslipidemia

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2020-000767-23-SK

Enrollment

108

Registered

2020-09-14

Start date

2020-11-12

Completion date

Unknown

Last updated

2021-08-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Dyslipidemia, especially: evaluation of low-density lipoprotein cholesterol reduction at steady state at different doses of AZD8233 in order to select a therapeutic dose. MedDRA version: 20.0 Level: PT Classification code 10058108 Term: Dyslipidaemia System Organ Class: 10027433 - Metabolism and nutrition disorders

Interventions

Product Name: AZD8233 solution for injection Product Code: N/A Pharmaceutical Form: Solution for injection INN or Proposed INN: N/A CAS Number: N/A Current Sponsor code: AZD8233 sodium Concentration u

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Participant must be 18 to 75 years of age, inclusive, at the time of signing the informed consent. Type of Participant and Disease Characteristics: Participants who have a fasting LDL-C = 70 mg/dL (1.8 mmol/L) but =65 years) yes F.1.3.1 Number of subjects for this age range 108

Exclusion criteria

Exclusion criteria: Medical Conditions Estimated glomerular filtration rate 10% (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. - 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 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. - Recipient of any major organ transplant, eg, lung, liver, heart, bone marrow, renal. - LDL or plasma apheresis within 12 months prior to randomization. - Uncontrolled hypertension defined as sitting SBP > 160 mmHg or DBP > 90 mmHg (visit 1 or 3). - Heart rate after 10 minutes supine rest 100 bpm (visit 1 or 3). - 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. -QTcF > 470 ms; high degree atrioventricular-block grade II-III and sinus node dysfunction with significant sinus pause untreated with pacemaker; and cardiac tachyarrhythmias. - Mipomersen, or lomitapide within 12 months prior to randomization. - Previous administration of AZD8233/AZD6615 or other PCSK9 inhibition treatment (approved or investigational). - Received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days of last follow-up to first administration of the study intervention of this study or 5 half-lives from last dose to first administration of study intervention, whichever is the longest. - Optional Genetic Sampling Optional Genetic Sampling should be in line with following exclusion criteria: Previous allogeneic bone marrow transplant ; Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection.

Design outcomes

Primary

Measure	Time frame
Main Objective: To investigate the effect of AZD8233 on level of dyslipidemia related biomarker (LDL-C) across different dose levels (absolute change from baseline in log transformed LDL-C in plasma).;Secondary Objective: To assess the effect of different doses of AZD8233 on PCSK9 versus placebo (absolute change from baseline in log-transformed PCSK9 in plasma) To assess the effect of different doses of AZD8233 on LDL-C versus placebo (percentage change from baseline in levels of LDL-C in plasma) To assess the effect of AZD8233 on other lipid parameters versus placebo (levels of other lipid parameters, including:TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants cholesterol) To evaluate the PK of AZD8233 (plasma parameters: population PK parameters to be reported in a separate report) To evaluate the immunogenicity of AZD8233 (development of ADA and titer (if participants are ADA positive) during treatment and follow-up) To assess the safety and tolerability of AZD8233 (safety and tolerability will be evaluated in terms of AEs, vital signs, ECG, and clinical laboratory evaluations including platelet count);Primary end point(s): Primary objective: to assess the effect of different doses of AZD8233 on LDL-C versus placebo (absolute change from baseline in log transformed LDL-C in plasma).;Timepoint(s) of evaluation of this end point: D1; D8; D22; D29; D43; D57; D71 (treatment period); D85, D99, D113, D127, D141, D155; D169 (safety follow-up period)	—

Measure

Time frame

Main Objective: To investigate the effect of AZD8233 on level of dyslipidemia related biomarker (LDL-C) across different dose levels (absolute change from baseline in log transformed LDL-C in plasma).;Secondary Objective: To assess the effect of different doses of AZD8233 on PCSK9 versus placebo (absolute change from baseline in log-transformed PCSK9 in plasma) To assess the effect of different doses of AZD8233 on LDL-C versus placebo (percentage change from baseline in levels of LDL-C in plasma) To assess the effect of AZD8233 on other lipid parameters versus placebo (levels of other lipid parameters, including:TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants cholesterol) To evaluate the PK of AZD8233 (plasma parameters: population PK parameters to be reported in a separate report) To evaluate the immunogenicity of AZD8233 (development of ADA and titer (if participants are ADA positive) during treatment and follow-up) To assess the safety and tolerability of AZD8233 (safety and tolerability will be evaluated in terms of AEs, vital signs, ECG, and clinical laboratory evaluations including platelet count);Primary end point(s): Primary objective: to assess the effect of different doses of AZD8233 on LDL-C versus placebo (absolute change from baseline in log transformed LDL-C in plasma).;Timepoint(s) of evaluation of this end point: D1; D8; D22; D29; D43; D57; D71 (treatment period); D85, D99, D113, D127, D141, D155; D169 (safety follow-up period)

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Secondary

Measure	Time frame
Secondary end point(s): To assess the effect of different doses of AZD8233 on PCSK9 versus placebo (absolute change from baseline in log-transformed PCSK9 in plasma) To assess the effect of different doses of AZD8233 on LDL-C versus placebo (percentage change from baseline in levels of LDL-C in plasma) To assess the effect of AZD8233 on other lipid parameters versus placebo (levels of other lipid parameters, including:TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants cholesterol) To evaluate the PK of AZD8233 (plasma parameters: population PK parameters to be reported in a separate report) To evaluate the immunogenicity of AZD8233 (development of ADA and titer (if participants are ADA positive) during treatment and follow-up) To assess the safety and tolerability of AZD8233 (safety and tolerability will be evaluated in terms of AEs, vital signs, ECG, and clinical laboratory evaluations including platelet count);Timepoint(s) of evaluation of this end point: Absolute change from baseline in log-transformed PCSK9 in plasma; Percentage change from baseline in levels of LDL-C in plasma; Levels of other lipid parameters, including:TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants cholesterol): D1; D8; D22; D29; D43; D57; D71; D85, D99; D113; D127; D141; D155; D169. Plasma PK parameters: D8; D29; D43; D57; D71; D85; D113; D141; D169. Development of ADA and titer (if participants are ADA positive):D1; D8; D29; D57; D85; D99; D113; D127; D141; D155; D169. Safety and tolerability: AEs, vital signs, ECG, and clinical laboratory evaluations including platelet count): D-42 to D-8 (screening visit#1); D1; D8; D22; D29; D43; D57; D71; D85; D99; D113; D127; D141; D155; D169.	—

Measure

Time frame

Secondary end point(s): To assess the effect of different doses of AZD8233 on PCSK9 versus placebo (absolute change from baseline in log-transformed PCSK9 in plasma) To assess the effect of different doses of AZD8233 on LDL-C versus placebo (percentage change from baseline in levels of LDL-C in plasma) To assess the effect of AZD8233 on other lipid parameters versus placebo (levels of other lipid parameters, including:TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants cholesterol) To evaluate the PK of AZD8233 (plasma parameters: population PK parameters to be reported in a separate report) To evaluate the immunogenicity of AZD8233 (development of ADA and titer (if participants are ADA positive) during treatment and follow-up) To assess the safety and tolerability of AZD8233 (safety and tolerability will be evaluated in terms of AEs, vital signs, ECG, and clinical laboratory evaluations including platelet count);Timepoint(s) of evaluation of this end point: Absolute change from baseline in log-transformed PCSK9 in plasma; Percentage change from baseline in levels of LDL-C in plasma; Levels of other lipid parameters, including:TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants cholesterol): D1; D8; D22; D29; D43; D57; D71; D85, D99; D113; D127; D141; D155; D169. Plasma PK parameters: D8; D29; D43; D57; D71; D85; D113; D141; D169. Development of ADA and titer (if participants are ADA positive):D1; D8; D29; D57; D85; D99; D113; D127; D141; D155; D169. Safety and tolerability: AEs, vital signs, ECG, and clinical laboratory evaluations including platelet count): D-42 to D-8 (screening visit#1); D1; D8; D22; D29; D43; D57; D71; D85; D99; D113; D127; D141; D155; D169.

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Countries

Denmark, Slovakia, United States

Contacts

Public ContactAstraZeneca Information Center

AstraZeneca AB

information.center@astrazeneca.com+1 302 885 1180

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026