Phase 2
N=119
A Study of AZD8233 in Participants With Dyslipidemia
Dyslipidaemia
Bottom Line
View on ClinicalTrials.gov: NCT04641299 ↗Enrolled (actual)
119
Serious AEs
3.4%
Results posted
Nov 2022
Primary outcome: Primary: Change in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12. — 0.978; 0.206; 0.270; 0.606 Ratio
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 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12. |
0.978; 0.206; 0.270; 0.606 | — |
| SECONDARY Relative Change From Baseline in PCSK9 Concentration in Plasma at Week 12. |
0.950; 0.060; 0.110; 0.420 | — |
| SECONDARY Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol |
2.69; -12.70; -12.95; -7.70; -1.11; -47.58 | — |
| SECONDARY Plasma Concentration of AZD8233 |
1.201; 0.681; 0.346; 1.366; 0.699; 0.238 | — |
| SECONDARY Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period |
100; 200; 100; 100; 200; 100 | — |
| SECONDARY Percentage Change From Baseline in Levels of LDL-C in Plasma |
-1.53; -76.50; -69.26; -32.22 | — |
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.
Eligibility Criteria
Key Inclusion Criteria
- 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 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 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.
- TBL > ULN.
- ALP > 1.5 × ULN.
- WBC ULN and PT > ULN.
- UACR > 11.3 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 as judged by the Investigator.
- Mipomersen, or lomitapide within 12 months prior to randomization.
- Previous administration of AZD8233/AZD6615.
- Previous administration of PCSK9 inhibition treatment.
- Participation in another clinical study with a study intervention administered in the last 3 months prior to randomization or 5 half-lives from last dose to first administration of study intervention, whichever is the longest.
Data sourced from ClinicalTrials.gov (NCT04641299). 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.