Phase 2
N=411
A Study to Assess the Safety, Efficacy and Tolerability of AZD8233 Treatment in Participants With Hyperlipidaemia
Hyperlipidaemia
Bottom Line
View on ClinicalTrials.gov: NCT04964557 ↗Enrolled (actual)
411
Serious AEs
7.3%
Results posted
Dec 2023
Primary outcome: Primary: Percentage Change From Baseline on Serum LDL-C — -56.7; 5.6 percent change — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- AZD8233 (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- AstraZeneca
- Primary completion
- Jul 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage Change From Baseline on Serum LDL-C |
-56.7; 5.6 | <0.001 sig |
| PRIMARY Number of Subjects With Adverse Events (AEs) |
141; 127 | — |
| PRIMARY Vital Signs - Temperature |
36.434; 36.369; 36.344; 36.387; 36.360; 36.361 | — |
| PRIMARY Vital Sign - Weight |
86.642; 88.750; 85.493; 88.759 | — |
| PRIMARY Number of Participants With an ECG Determined to be Abnormal and Clinically Significant |
0; 0; 1; 1; 0; 0 | — |
| PRIMARY Vital Sign - Systolic Blood Pressure |
130.918; 131.325; 130.438; 131.198; 130.741; 133.152 | — |
| PRIMARY Vital Sign - Diastolic Blood Pressure |
78.937; 78.562; 78.318; 78.559; 78.408; 79.611 | — |
| PRIMARY Vital Sign - Pulse Rate |
68.93; 67.88; 70.63; 69.48; 68.52; 68.90 | — |
| PRIMARY Treatment Emergent Platelet Count Abnormalities |
9; 11; 26; 20; 0; 0 | — |
| SECONDARY Percentage Change From Baseline on Serum PCSK9 |
-77.5; -0.8 | <0.001 sig |
| SECONDARY Plasma Concentration of AZD8233 |
0.2648; 0.3927; 0.5749; 1.0441; 0.6975 | — |
| SECONDARY Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period |
6; 4; 15; 3; 16; 3 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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 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 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
- AST > 1.5 × ULN
- TBL > ULN
- ALP > 1.5 × ULN
- WBC ULN or Prothrombin Time > ULN
- UACR > 11 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
- QTcF > 470 ms; high degree atrioventricular (AV)-block grade II-III and sinus node dysfunction with significant sinus pause untreated with pacemaker; and cardiac tachyarrhythmias
- History of drug and/or alcohol abuse or a positive screen for drugs of abuse
- Use of warfarin, direct or indirect thrombin inhibitors or factor Xa inhibitors
- Mipomersen, or lomitapide within 12 months prior to randomisation
- Any fibrate therapy other than fenofibrate; if the participant is on fenofibrate therapy, the dose should be stable for at least 6 weeks prior to randomisation
- Previous administration of AZD8233/AZD6615) or inclisiran (LEQVIO ® Novartis)
- Use of evolocumab (REPATHA® Amgen) and alirocumab (PRALUENT® Regeneron) within 3 months of screening
Data sourced from ClinicalTrials.gov (NCT04964557). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.