Trial Outcomes & Findings for A Study of AZD8233 in Participants With Dyslipidemia (NCT NCT04641299)

Last Updated: 2022-11-18

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

119 participants

Primary outcome timeframe

Baseline to week 12

Results posted on

2022-11-18

Participant Flow

This study was conducted at 19 clinical research center in Denmark, Slovakia and the USA. First subject enrolled (First subject first visit/first consent signed date): 28 October 2020. Last subject last visit: 20 July 2021.

Participant milestones

Participant milestones
Measure	AZD8233 Low Dose AZD8233 low dose for subcutaneous injection.	AZD8233 Medium Dose AZD8233 medium dose for subcutaneous injection.	AZD8233 High Dose AZD8233 high dose for subcutaneous injection.	Placebo Placebo solution for subcutaneous injection.
Overall Study STARTED	30	30	29	30
Overall Study COMPLETED	28	29	27	30
Overall Study NOT COMPLETED	2	1	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	AZD8233 Low Dose AZD8233 low dose for subcutaneous injection.	AZD8233 Medium Dose AZD8233 medium dose for subcutaneous injection.	AZD8233 High Dose AZD8233 high dose for subcutaneous injection.
Overall Study Adverse Event	0	0	2
Overall Study Lost to Follow-up	0	1	0
Overall Study Withdrawal by Subject	1	0	0
Overall Study Reason not given	1	0	0

Baseline Characteristics

A Study of AZD8233 in Participants With Dyslipidemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AZD8233 High Dose n=29 Participants AZD8233 high dose for subcutaneous injection.	AZD8233 Medium Dose n=30 Participants AZD8233 medium dose for subcutaneous injection.	AZD8233 Low Dose n=30 Participants AZD8233 low dose for subcutaneous injection.	Placebo n=30 Participants Placebo solution for subcutaneous injection.	Total n=119 Participants Total of all reporting groups
Age, Continuous	60.4 Years STANDARD_DEVIATION 8.4 • n=93 Participants	60.6 Years STANDARD_DEVIATION 7.4 • n=4 Participants	61.8 Years STANDARD_DEVIATION 7.1 • n=27 Participants	63.9 Years STANDARD_DEVIATION 7.3 • n=483 Participants	61.7 Years STANDARD_DEVIATION 7.6 • n=36 Participants
Sex: Female, Male Female	11 Participants n=93 Participants	12 Participants n=4 Participants	16 Participants n=27 Participants	18 Participants n=483 Participants	57 Participants n=36 Participants
Sex: Female, Male Male	18 Participants n=93 Participants	18 Participants n=4 Participants	14 Participants n=27 Participants	12 Participants n=483 Participants	62 Participants n=36 Participants
Race/Ethnicity, Customized AMERICAN INDIAN OR ALASKA NATIVE	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race/Ethnicity, Customized ASIAN	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants
Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN	1 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants	3 Participants n=483 Participants	8 Participants n=36 Participants
Race/Ethnicity, Customized NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race/Ethnicity, Customized WHITE	28 Participants n=93 Participants	28 Participants n=4 Participants	27 Participants n=27 Participants	27 Participants n=483 Participants	110 Participants n=36 Participants

PRIMARY outcome

Timeframe: Baseline to week 12

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants Placebo solution for subcutaneous injection.	AZD8233 High Dose n=26 Participants AZD8233 high dose for subcutaneous injection.	AZD8233 Medium Dose n=28 Participants AZD8233 medium dose for subcutaneous injection.	AZD8233 Low Dose n=27 Participants AZD8233 low dose for subcutaneous injection.
Change in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12.	0.978 Ratio Interval 0.834 to 1.147	0.206 Ratio Interval 0.174 to 0.242	0.270 Ratio Interval 0.23 to 0.317	0.606 Ratio Interval 0.517 to 0.71

SECONDARY outcome

Timeframe: Baseline to week 12

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

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants Placebo solution for subcutaneous injection.	AZD8233 High Dose n=26 Participants AZD8233 high dose for subcutaneous injection.	AZD8233 Medium Dose n=28 Participants AZD8233 medium dose for subcutaneous injection.	AZD8233 Low Dose n=28 Participants AZD8233 low dose for subcutaneous injection.
Relative Change From Baseline in PCSK9 Concentration in Plasma at Week 12.	0.950 Ratio Interval 0.77 to 1.18	0.060 Ratio Interval 0.05 to 0.08	0.110 Ratio Interval 0.09 to 0.14	0.420 Ratio Interval 0.34 to 0.52

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants Placebo solution for subcutaneous injection.	AZD8233 High Dose n=26 Participants AZD8233 high dose for subcutaneous injection.	AZD8233 Medium Dose n=28 Participants AZD8233 medium dose for subcutaneous injection.	AZD8233 Low Dose n=28 Participants AZD8233 low dose for subcutaneous injection.
Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol Triglycerides	2.69 Percent Interval -8.19 to 13.56	-12.70 Percent Interval -23.88 to -1.52	-12.95 Percent Interval -23.77 to -2.12	-7.70 Percent Interval -18.44 to 3.05
Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol Total cholesterol	-1.11 Percent Interval -6.56 to 4.35	-47.58 Percent Interval -53.37 to -41.78	-43.90 Percent Interval -49.43 to -38.37	-21.13 Percent Interval -26.56 to -15.7
Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol HDL-C	1.34 Percent Interval -3.28 to 5.97	5.57 Percent Interval 0.9 to 10.25	6.50 Percent Interval 1.96 to 11.04	3.37 Percent Interval -1.12 to 7.86
Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol Non-HDL-C	-0.65 Percent Interval -7.81 to 6.51	-67.92 Percent Interval -75.38 to -60.45	-61.25 Percent Interval -68.38 to -54.11	-29.57 Percent Interval -36.58 to -22.56
Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol VLDL-C	3.22 Percent Interval -7.9 to 14.35	-11.13 Percent Interval -22.59 to 0.33	-12.09 Percent Interval -23.04 to -1.15	-7.54 Percent Interval -18.36 to 3.27
Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol ApoB	-1.65 Percent Interval -7.83 to 4.53	-67.07 Percent Interval -73.46 to -60.68	-60.13 Percent Interval -66.33 to -53.93	-29.50 Percent Interval -35.64 to -23.35
Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol Lp(a)	31.22 Percent Interval -2.88 to 65.33	-37.74 Percent Interval -72.02 to -3.46	-36.64 Percent Interval -70.69 to -2.59	-6.02 Percent Interval -40.62 to 28.58
Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol Remnants cholesterol	6.38 Percent Interval -20.28 to 33.05	-26.84 Percent Interval -54.23 to 0.54	-16.54 Percent Interval -42.97 to 9.88	-13.50 Percent Interval -39.57 to 12.56

SECONDARY outcome

Timeframe: Measurement at week 1, week 4, week 6, week 8, week 10, week 12, week 16, week 20, week 24 after first dose administration.

Population: No analysis made for placebo group.

Plasma concentration of AZD8233 after first dose administration

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Placebo solution for subcutaneous injection.	AZD8233 High Dose n=30 Participants AZD8233 high dose for subcutaneous injection.	AZD8233 Medium Dose n=30 Participants AZD8233 medium dose for subcutaneous injection.	AZD8233 Low Dose AZD8233 low dose for subcutaneous injection.
Plasma Concentration of AZD8233 Week 1	1.201 ug/L Standard Deviation 0.49	0.681 ug/L Standard Deviation 0.24	0.346 ug/L Standard Deviation 0.59	—
Plasma Concentration of AZD8233 Week 4	1.366 ug/L Standard Deviation 0.71	0.699 ug/L Standard Deviation 0.33	0.238 ug/L Standard Deviation 0.21	—
Plasma Concentration of AZD8233 Week 6	1.917 ug/L Standard Deviation 1.09	0.870 ug/L Standard Deviation 0.34	0.288 ug/L Standard Deviation 0.21	—
Plasma Concentration of AZD8233 Week 8	1.000 ug/L Standard Deviation 0.68	0.628 ug/L Standard Deviation 0.57	0.152 ug/L Standard Deviation 0.10	—
Plasma Concentration of AZD8233 Week 10	1.562 ug/L Standard Deviation 0.84	0.751 ug/L Standard Deviation 0.29	0.241 ug/L Standard Deviation 0.15	—
Plasma Concentration of AZD8233 Week 12	0.976 ug/L Standard Deviation 0.75	0.476 ug/L Standard Deviation 0.23	0.134 ug/L Standard Deviation 0.07	—
Plasma Concentration of AZD8233 Week 16	0.507 ug/L Standard Deviation 0.70	0.297 ug/L Standard Deviation 0.53	0.087 ug/L Standard Deviation 0.09	—
Plasma Concentration of AZD8233 Week 20	0.376 ug/L Standard Deviation 0.68	0.153 ug/L Standard Deviation 0.26	0.053 ug/L Standard Deviation 0.004	—
Plasma Concentration of AZD8233 Week 24	0.350 ug/L Standard Deviation 0.62	0.111 ug/L Standard Deviation 0.15	0.111 ug/L Standard Deviation 0.31	—

SECONDARY outcome

Timeframe: Measurement at week 0, week 1, week 4, week 8, week 12, week 16, week 20, week 24

Population: Number Analyzed per Row reflects the study participants with positive ADA results at each time point.

ADA titre results for subjects with positive ADA during the treatment period and follow-up period.

Outcome measures

Outcome measures
Measure	Placebo n=1 Participants Placebo solution for subcutaneous injection.	AZD8233 High Dose n=3 Participants AZD8233 high dose for subcutaneous injection.	AZD8233 Medium Dose n=5 Participants AZD8233 medium dose for subcutaneous injection.	AZD8233 Low Dose n=4 Participants AZD8233 low dose for subcutaneous injection.
Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period Baseline	100 ADA titre Interval 100.0 to 100.0	—	200 ADA titre Interval 200.0 to 200.0	100 ADA titre Interval 100.0 to 100.0
Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period Week 1	100 ADA titre Interval 100.0 to 100.0	—	200 ADA titre Interval 200.0 to 200.0	100 ADA titre Interval 50.0 to 800.0
Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period Week 4	100 ADA titre Interval 100.0 to 100.0	75 ADA titre Interval 50.0 to 100.0	200 ADA titre Interval 100.0 to 400.0	150 ADA titre Interval 100.0 to 1600.0
Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period Week 8	100 ADA titre Interval 100.0 to 100.0	75 ADA titre Interval 50.0 to 100.0	200 ADA titre Interval 100.0 to 400.0	400 ADA titre Interval 200.0 to 3200.0
Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period Week 12	50 ADA titre Interval 50.0 to 50.0	200 ADA titre Interval 200.0 to 200.0	200 ADA titre Interval 100.0 to 400.0	200 ADA titre Interval 200.0 to 1600.0
Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period Week 16	100 ADA titre Interval 100.0 to 100.0	300 ADA titre Interval 200.0 to 400.0	200 ADA titre Interval 50.0 to 400.0	400 ADA titre Interval 100.0 to 1600.0
Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period Week 20	100 ADA titre Interval 100.0 to 100.0	500 ADA titre Interval 200.0 to 800.0	200 ADA titre Interval 100.0 to 400.0	400 ADA titre Interval 200.0 to 1600.0
Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period Week 24	100 ADA titre Interval 100.0 to 100.0	200 ADA titre Interval 50.0 to 800.0	300 ADA titre Interval 100.0 to 400.0	400 ADA titre Interval 200.0 to 800.0

SECONDARY outcome

Timeframe: Baseline to week 12

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

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants Placebo solution for subcutaneous injection.	AZD8233 High Dose n=26 Participants AZD8233 high dose for subcutaneous injection.	AZD8233 Medium Dose n=28 Participants AZD8233 medium dose for subcutaneous injection.	AZD8233 Low Dose n=27 Participants AZD8233 low dose for subcutaneous injection.
Percentage Change From Baseline in Levels of LDL-C in Plasma	-1.53 Percent Interval -9.14 to 6.09	-76.50 Percent Interval -84.37 to -68.63	-69.26 Percent Interval -76.89 to -61.63	-32.22 Percent Interval -39.79 to -24.66

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 24

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

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Placebo solution for subcutaneous injection.	AZD8233 High Dose n=29 Participants AZD8233 high dose for subcutaneous injection.	AZD8233 Medium Dose n=30 Participants AZD8233 medium dose for subcutaneous injection.	AZD8233 Low Dose n=30 Participants AZD8233 low dose for subcutaneous injection.
Number of Subjects With an ECG Determined to be Abnormal and Clinically Significant Baseline	0 Number of subjects	0 Number of subjects	0 Number of subjects	0 Number of subjects
Number of Subjects With an ECG Determined to be Abnormal and Clinically Significant End of treatment	0 Number of subjects	0 Number of subjects	0 Number of subjects	0 Number of subjects

Adverse Events

AZD8233 High Dose

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

AZD8233 Medium Dose

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

AZD8233 Low Dose

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	AZD8233 High Dose n=29 participants at risk AZD8233 high dose for subcutaneous injection.	AZD8233 Medium Dose n=30 participants at risk AZD8233 medium dose for subcutaneous injection.	AZD8233 Low Dose n=30 participants at risk AZD8233 low dose for subcutaneous injection.	Placebo n=30 participants at risk Placebo solution for subcutaneous injection.
Infections and infestations Covid-19 pneumonia	0.00% 0/29 • 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.	3.3% 1/30 • Number of events 1 • 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.	0.00% 0/30 • 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.	0.00% 0/30 • 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.
Infections and infestations Staphylococcal infection	0.00% 0/29 • 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.	3.3% 1/30 • Number of events 1 • 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.	0.00% 0/30 • 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.	0.00% 0/30 • 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.
Injury, poisoning and procedural complications Concussion	3.4% 1/29 • Number of events 1 • 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.	0.00% 0/30 • 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.	0.00% 0/30 • 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.	0.00% 0/30 • 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.
Cardiac disorders Atrial fibrillation	0.00% 0/29 • 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.	3.3% 1/30 • Number of events 1 • 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.	0.00% 0/30 • 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.	0.00% 0/30 • 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.
Cardiac disorders Cardiac failure acute	0.00% 0/29 • 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.	0.00% 0/30 • 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.	3.3% 1/30 • Number of events 1 • 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.	0.00% 0/30 • 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.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/29 • 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.	3.3% 1/30 • Number of events 1 • 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.	0.00% 0/30 • 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.	0.00% 0/30 • 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.
Vascular disorders Orthostatic hypotension	0.00% 0/29 • 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.	3.3% 1/30 • Number of events 1 • 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.	0.00% 0/30 • 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.	0.00% 0/30 • 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.

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60