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NCT04641299

A Study of AZD8233 in Participants With Dyslipidemia

Completed Phase 2 Results posted Last updated 18 November 2022
What this trial tests

Phase 2 trial testing AZD8233 in Dyslipidaemia in 119 participants. Completed in 20 July 2021.

Timeline
28 October 2020
Primary endpoint
20 July 2021
20 July 2021

Quick facts

Lead sponsorAstraZeneca
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment119
Start date28 October 2020
Primary completion20 July 2021
Estimated completion20 July 2021
Sites19 locations across Denmark, Slovakia, United States

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 75, any sex, with Dyslipidaemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12. Primary · 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.

GroupValue95% CI
Placebo0.9780.834 – 1.147
AZD8233 High Dose0.2060.174 – 0.242
AZD8233 Medium Dose0.2700.230 – 0.317
AZD8233 Low Dose0.6060.517 – 0.710
Relative Change From Baseline in PCSK9 Concentration in Plasma at Week 12. Secondary · Baseline to week 12

Relative change from baseline in PCSK9 concentration in plasma at week 12.

GroupValue95% CI
Placebo0.9500.770 – 1.180
AZD8233 High Dose0.0600.050 – 0.080
AZD8233 Medium Dose0.1100.090 – 0.140
AZD8233 Low Dose0.4200.340 – 0.520
Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol Secondary · 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

Triglycerides
GroupValue95% CI
Placebo2.69-8.19 – 13.56
AZD8233 High Dose-12.70-23.88 – -1.52
AZD8233 Medium Dose-12.95-23.77 – -2.12
AZD8233 Low Dose-7.70-18.44 – 3.05
Total cholesterol
GroupValue95% CI
Placebo-1.11-6.56 – 4.35
AZD8233 High Dose-47.58-53.37 – -41.78
AZD8233 Medium Dose-43.90-49.43 – -38.37
AZD8233 Low Dose-21.13-26.56 – -15.70
HDL-C
GroupValue95% CI
Placebo1.34-3.28 – 5.97
AZD8233 High Dose5.570.90 – 10.25
AZD8233 Medium Dose6.501.96 – 11.04
AZD8233 Low Dose3.37-1.12 – 7.86
Non-HDL-C
GroupValue95% CI
Placebo-0.65-7.81 – 6.51
AZD8233 High Dose-67.92-75.38 – -60.45
AZD8233 Medium Dose-61.25-68.38 – -54.11
AZD8233 Low Dose-29.57-36.58 – -22.56
VLDL-C
GroupValue95% CI
Placebo3.22-7.90 – 14.35
AZD8233 High Dose-11.13-22.59 – 0.33
AZD8233 Medium Dose-12.09-23.04 – -1.15
AZD8233 Low Dose-7.54-18.36 – 3.27
ApoB
GroupValue95% CI
Placebo-1.65-7.83 – 4.53
AZD8233 High Dose-67.07-73.46 – -60.68
AZD8233 Medium Dose-60.13-66.33 – -53.93
AZD8233 Low Dose-29.50-35.64 – -23.35
Lp(a)
GroupValue95% CI
Placebo31.22-2.88 – 65.33
AZD8233 High Dose-37.74-72.02 – -3.46
AZD8233 Medium Dose-36.64-70.69 – -2.59
AZD8233 Low Dose-6.02-40.62 – 28.58
Remnants cholesterol
GroupValue95% CI
Placebo6.38-20.28 – 33.05
AZD8233 High Dose-26.84-54.23 – 0.54
AZD8233 Medium Dose-16.54-42.97 – 9.88
AZD8233 Low Dose-13.50-39.57 – 12.56
Plasma Concentration of AZD8233 Secondary · 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

Week 1
GroupValue95% CI
AZD8233 High Dose1.201± 0.49
AZD8233 Medium Dose0.681± 0.24
AZD8233 Low Dose0.346± 0.59
Week 4
GroupValue95% CI
AZD8233 High Dose1.366± 0.71
AZD8233 Medium Dose0.699± 0.33
AZD8233 Low Dose0.238± 0.21
Week 6
GroupValue95% CI
AZD8233 High Dose1.917± 1.09
AZD8233 Medium Dose0.870± 0.34
AZD8233 Low Dose0.288± 0.21
Week 8
GroupValue95% CI
AZD8233 High Dose1.000± 0.68
AZD8233 Medium Dose0.628± 0.57
AZD8233 Low Dose0.152± 0.10
Week 10
GroupValue95% CI
AZD8233 High Dose1.562± 0.84
AZD8233 Medium Dose0.751± 0.29
AZD8233 Low Dose0.241± 0.15
Week 12
GroupValue95% CI
AZD8233 High Dose0.976± 0.75
AZD8233 Medium Dose0.476± 0.23
AZD8233 Low Dose0.134± 0.07
Week 16
GroupValue95% CI
AZD8233 High Dose0.507± 0.70
AZD8233 Medium Dose0.297± 0.53
AZD8233 Low Dose0.087± 0.09
Week 20
GroupValue95% CI
AZD8233 High Dose0.376± 0.68
AZD8233 Medium Dose0.153± 0.26
AZD8233 Low Dose0.053± 0.004
Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period Secondary · 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.

Baseline
GroupValue95% CI
Placebo100100 – 100
AZD8233 Medium Dose200200 – 200
AZD8233 Low Dose100100 – 100
Week 1
GroupValue95% CI
Placebo100100 – 100
AZD8233 Medium Dose200200 – 200
AZD8233 Low Dose10050 – 800
Week 4
GroupValue95% CI
Placebo100100 – 100
AZD8233 High Dose7550 – 100
AZD8233 Medium Dose200100 – 400
AZD8233 Low Dose150100 – 1600
Week 8
GroupValue95% CI
Placebo100100 – 100
AZD8233 High Dose7550 – 100
AZD8233 Medium Dose200100 – 400
AZD8233 Low Dose400200 – 3200
Week 12
GroupValue95% CI
Placebo5050 – 50
AZD8233 High Dose200200 – 200
AZD8233 Medium Dose200100 – 400
AZD8233 Low Dose200200 – 1600
Week 16
GroupValue95% CI
Placebo100100 – 100
AZD8233 High Dose300200 – 400
AZD8233 Medium Dose20050 – 400
AZD8233 Low Dose400100 – 1600
Week 20
GroupValue95% CI
Placebo100100 – 100
AZD8233 High Dose500200 – 800
AZD8233 Medium Dose200100 – 400
AZD8233 Low Dose400200 – 1600
Week 24
GroupValue95% CI
Placebo100100 – 100
AZD8233 High Dose20050 – 800
AZD8233 Medium Dose300100 – 400
AZD8233 Low Dose400200 – 800
Percentage Change From Baseline in Levels of LDL-C in Plasma Secondary · Baseline to week 12

Percentage change from baseline in levels of LDL-C in plasma from baseline to week 12.

GroupValue95% CI
Placebo-1.53-9.14 – 6.09
AZD8233 High Dose-76.50-84.37 – -68.63
AZD8233 Medium Dose-69.26-76.89 – -61.63
AZD8233 Low Dose-32.22-39.79 – -24.66
Number of Subjects With an ECG Determined to be Abnormal and Clinically Significant Secondary · Baseline to Week 24

Number of subjects with an ECG determined to be abnormal and clinically significant at baseline and end of treatment.

Baseline
GroupValue95% CI
Placebo0
AZD8233 High Dose0
AZD8233 Medium Dose0
AZD8233 Low Dose0
End of treatment
GroupValue95% CI
Placebo0
AZD8233 High Dose0
AZD8233 Medium Dose0
AZD8233 Low Dose0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from time of first IP dose throughout the treatment period of 12 weeks and including the follow-up period of 12 weeks - a total of 24 weeks. Serious AEs were recorded from the time of signature of informed consent.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

AZD8233 High Dose
Serious: 1/29 (3%)
Deaths: 0/29
AZD8233 Medium Dose
Serious: 2/30 (7%)
Deaths: 0/30
AZD8233 Low Dose
Serious: 1/30 (3%)
Deaths: 0/30
Placebo
Serious: 0/30 (0%)
Deaths: 0/30

Serious adverse events (7 terms)

ReactionSystemAZD8233 High DoseAZD8233 Medium DoseAZD8233 Low DosePlacebo
Covid-19 pneumoniaInfections and infestations
Staphylococcal infectionInfections and infestations
ConcussionInjury, poisoning and procedural complications
Atrial fibrillationCardiac disorders
Cardiac failure acuteCardiac disorders
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
Orthostatic hypotensionVascular disorders
Other adverse events (88 terms — click to expand)

ReactionSystemAZD8233 High DoseAZD8233 Medium DoseAZD8233 Low DosePlacebo
Abdominal painGastrointestinal disorders
HypertensionVascular disorders
Abdominal pain upperGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Injection site painGeneral disorders
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
Transaminases increasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
MigraineNervous system disorders
VertigoEar and labyrinth disorders
HaemorrhoidsGastrointestinal disorders
NauseaGastrointestinal disorders
ToothacheGastrointestinal disorders
AstheniaGeneral disorders
FatigueGeneral disorders
Feeling coldGeneral disorders
AnaemiaBlood and lymphatic system disorders
Injection site haematomaGeneral disorders
Injection site reactionGeneral disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
Asymptomatic covid-19Infections and infestations
Covid-19Infections and infestations
GastroenteritisInfections and infestations
Gastroenteritis viralInfections and infestations
LeukopeniaBlood and lymphatic system disorders
Herpes zosterInfections and infestations
Nasal vestibulitisInfections and infestations
NasopharyngitisInfections and infestations
OsteomyelitisInfections and infestations
SinusitisInfections and infestations
Tooth infectionInfections and infestations
Spontaneous haematomaBlood and lymphatic system disorders
Facial bones fractureInjury, poisoning and procedural complications
FallInjury, poisoning and procedural complications
Head injuryInjury, poisoning and procedural complications
Joint injuryInjury, poisoning and procedural complications
Post-traumatic neck syndromeInjury, poisoning and procedural complications

Most-reported serious reactions: Covid-19 pneumonia, Staphylococcal infection, Concussion, Atrial fibrillation, Cardiac failure acute, Acute respiratory failure, Orthostatic hypotension.

Data from ClinicalTrials.gov NCT04641299 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.
    Bao X, Liang Y, Chang H, Cai T, et al · · 2024 · cited 101× · PMID 38185721 · DOI 10.1038/s41392-023-01690-3
  2. RNA-based therapies in liver metabolic diseases.
    Fontanellas A, Berraondo P, Urigo F, Jericó D, et al · · 2025 · cited 9× · PMID 39988358 · DOI 10.1136/gutjnl-2023-331742
  3. Targeting PCSK9 and Beyond for the Management of Low-Density Lipoprotein Cholesterol.
    Mohamed F, Mansfield B, Raal FJ. · · 2023 · cited 9× · PMID 37568484 · DOI 10.3390/jcm12155082
  4. Strategy for Pre-Clinical Development of Active Targeting MicroRNA Oligonucleotide Therapeutics for Unmet Medical Needs.
    Thibonnier M, Ghosh S. · · 2023 · cited 7× · PMID 37108289 · DOI 10.3390/ijms24087126
  5. Advances in Oral Biomacromolecule Therapies for Metabolic Diseases.
    Jiao Q, Huang Y, He J, Xu Y. · · 2025 · cited 3× · PMID 40006605 · DOI 10.3390/pharmaceutics17020238
  6. Population pharmacokinetics of a novel PCSK9 antisense oligonucleotide.
    Clewe O, Rekić D, Quartino AL, Carlsson B, et al · · 2024 · cited 3× · PMID 38504437 · DOI 10.1111/bcp.16046
  7. Pleiotropic Effects of PCSK9 Inhibitors on Cardio-Cerebrovascular Diseases.
    Li Z, Zhu L, Xu Y, Zhang Y, et al · · 2024 · cited 2× · PMID 39767636 · DOI 10.3390/biomedicines12122729
  8. Development of a protocol complexity tool: a framework designed to stimulate discussion and simplify study design.
    Willigers BJA, Wiesiolek AE, Potter B, Pszczółkowska A, et al · · 2025 · PMID 40883682 · DOI 10.1186/s12874-025-02652-9

Verify or expand the search:

Other trials of AZD8233

Trials testing the same drug.

Other recruiting trials for Dyslipidaemia

Currently open trials in the same condition.

Other AstraZeneca trials

Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04641299.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing