Olpasiran Trials of Cardiovascular Events And LipoproteiN(a) Reduction - DOSE Finding Study

A Double-blind, Randomized, Placebo-controlled Phase 2 Study to Evaluate Efficacy, Safety, and Tolerability of Olpasiran (AMG 890) in Subjects With Elevated Lipoprotein(a)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04270760

Enrollment

281

Registered

2020-02-17

Start date

2020-07-28

Completion date

2022-11-08

Last updated

2026-03-31

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

Conditions

Cardiovascular Disease

Keywords

Olpasiran, AMG 890, siRNA, lipoprotein (a) Lp(a), Cardiovascular, Cardiovascular disease, Atherosclerotic cardiovascular disease, Cholesterol, Apolipoprotein (B), Hyperlipidemia, Dyslipidemia

Brief summary

Evaluate the effect of olpasiran administered subcutaneously (SC) compared with placebo, on percent change from baseline in lipoprotein(a) (Lp\[a\]).

Interventions

DRUGOlpasiran

Dose 1 Dose 2 Dose 3 Dose 4

DRUGPlacebo

Dose 5

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

Inclusion criteria

* Age 18 to 80 years * Lipoprotein (a) \> 150 nmol/L * Evidence of atherosclerotic cardiovascular disease

Exclusion criteria

* Severe renal dysfunction * History or clinical evidence of hepatic dysfunction * Malignancy within the last 5 years * Currently receiving, or less than 3 months at Day 1 since receiving \> 200 mg/day Niacin

Design outcomes

Primary

Measure	Time frame	Description
Percentage Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 36	Baseline and Week 36	Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit.

Secondary

Measure	Time frame	Description
Percentage Change From Baseline in Lp(a) at Week 48	Baseline and Week 48	Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit.
Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48	Baseline; Week 36 and Week 48	Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit.
Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48	Baseline; Week 36 and Week 48	Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit.
Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Pre-dose and 1, 3, 6-12, and 24-72 hours post-dose on Day 1 and Week 24; Week 48	Pharmacokinetic blood draws were collected at one timepoint during the 6-12 and 24-72 hour flexible time windows and at Week 48. Lower limit of quantification (LLOQ) = 0.400 ng/mL. Values below the LLOQ were set to zero.

Countries

Australia, Canada, Denmark, Iceland, Japan, Netherlands, United States

Contacts

STUDY_DIRECTORMD

Amgen

Participant flow

Recruitment details

This study was conducted at 34 centers in Australia, Denmark, Iceland, the Netherlands, Canada, the United States, and Japan between 28 July 2020 and 08 November 2022.

Pre-assignment details

The Treatment Period was 48 weeks with investigational product (IP) administered subcutaneously (SC) every 12 weeks (Q12W) or 24 weeks (Q24W). After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants remained on standard of care per their local guidelines during the Treatment Period and Extended Safety Follow-up Period.

Participants by arm

Arm	Count
Group 1: Olpasiran 10 mg Q12W Participants were administered SC olpasiran 10 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks.	58
Group 2: Olpasiran 75 mg Q12W Participants were administered SC olpasiran 75 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks.	58
Group 3: Olpasiran 225 mg Q12W Participants were administered SC olpasiran 225 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks.	56
Group 4: Olpasiran 225 mg Q24W Participants were administered SC olpasiran 225 mg Q24W for 48 weeks with doses at Day 1 and Week 24. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks.	55
Group 5: Placebo Q12W Participants were administered SC placebo Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks.	54
Total	281

Baseline characteristics

Characteristic	Group 1: Olpasiran 10 mg Q12W	Group 2: Olpasiran 75 mg Q12W	Group 3: Olpasiran 225 mg Q12W	Group 4: Olpasiran 225 mg Q24W	Group 5: Placebo Q12W	Total
Age, Continuous	63.4 Years STANDARD_DEVIATION 9.5	61.3 Years STANDARD_DEVIATION 9.2	59.7 Years STANDARD_DEVIATION 10.1	61.8 Years STANDARD_DEVIATION 9.4	63.4 Years STANDARD_DEVIATION 8.9	61.9 Years STANDARD_DEVIATION 9.5
Age, Customized 18 - 64 years	31 Participants	35 Participants	37 Participants	31 Participants	29 Participants	163 Participants
Age, Customized 65 - 74 years	19 Participants	17 Participants	18 Participants	19 Participants	17 Participants	90 Participants
Age, Customized 75 - 84 years	8 Participants	6 Participants	1 Participants	5 Participants	8 Participants	28 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	0 Participants	0 Participants	2 Participants	2 Participants	6 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	56 Participants	58 Participants	56 Participants	53 Participants	52 Participants	275 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian	6 Participants	5 Participants	5 Participants	5 Participants	3 Participants	24 Participants
Race/Ethnicity, Customized Black or African American	0 Participants	1 Participants	2 Participants	1 Participants	2 Participants	6 Participants
Race/Ethnicity, Customized Other	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants	3 Participants
Race/Ethnicity, Customized White	52 Participants	52 Participants	47 Participants	49 Participants	48 Participants	248 Participants
Sex: Female, Male Female	12 Participants	23 Participants	15 Participants	22 Participants	18 Participants	90 Participants
Sex: Female, Male Male	46 Participants	35 Participants	41 Participants	33 Participants	36 Participants	191 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk
deaths Total, all-cause mortality	0 / 58	0 / 58	0 / 56	0 / 55	1 / 54	0 / 57	0 / 57	0 / 54	0 / 55	0 / 53
other Total, other adverse events	35 / 58	40 / 58	37 / 56	36 / 55	29 / 54	18 / 57	25 / 57	21 / 54	17 / 55	17 / 53
serious Total, serious adverse events	3 / 58	3 / 58	6 / 56	4 / 55	8 / 54	4 / 57	2 / 57	6 / 54	5 / 55	4 / 53

Outcome results

Primary

Percentage Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 36

Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit.

Time frame: Baseline and Week 36

Population: Participants in the FAS with data available at each time point. FAS: includes all randomized participants who received at least one dose of IP.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Group 1: Olpasiran 10 mg Q12W	Percentage Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 36	-66.91 Percentage Change in Lp(a)	Standard Error 1.78
Group 2: Olpasiran 75 mg Q12W	Percentage Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 36	-93.78 Percentage Change in Lp(a)	Standard Error 1.78
Group 3: Olpasiran 225 mg Q12W	Percentage Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 36	-97.53 Percentage Change in Lp(a)	Standard Error 1.82
Group 4: Olpasiran 225 mg Q24W	Percentage Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 36	-96.89 Percentage Change in Lp(a)	Standard Error 1.85
Group 5: Placebo Q12W	Percentage Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 36	3.60 Percentage Change in Lp(a)	Standard Error 1.89

Comparison: Group 1 versus (vs) Group 5p-value: <0.00195% CI: [-75.12, -65.9]Repeated measures linear effects model

Comparison: Group 2 vs Group 5p-value: <0.00195% CI: [-101.98, -92.77]Repeated measures linear effects model

Comparison: Group 3 vs Group 5p-value: <0.00195% CI: [-105.79, -96.47]Repeated measures linear effects model

Comparison: Group 4 vs Group 5p-value: <0.00195% CI: [-105.16, -95.82]Repeated measures linear effects model

Secondary

Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48

Pharmacokinetic blood draws were collected at one timepoint during the 6-12 and 24-72 hour flexible time windows and at Week 48. Lower limit of quantification (LLOQ) = 0.400 ng/mL. Values below the LLOQ were set to zero.

Time frame: Pre-dose and 1, 3, 6-12, and 24-72 hours post-dose on Day 1 and Week 24; Week 48

Population: Participants in the FAS with data available at each time point. FAS: includes all randomized participants who received at least one dose of IP.

Arm	Measure	Group	Value (MEAN)	Dispersion
Group 1: Olpasiran 10 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: 3 Hours Post-dose	16.3 ng/mL	Standard Deviation 9.2
Group 1: Olpasiran 10 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: Pre-dose	0.00 ng/mL	Standard Deviation 0
Group 1: Olpasiran 10 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: 6-12 Hours Post-dose	18.6 ng/mL	Standard Deviation 10.1
Group 1: Olpasiran 10 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: 24-72 Hours Post-dose	0.995 ng/mL	Standard Deviation 0.946
Group 1: Olpasiran 10 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: 6-12 Hours Post-dose	17.2 ng/mL	Standard Deviation 10.2
Group 1: Olpasiran 10 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 48	0.00 ng/mL	Standard Deviation 0
Group 1: Olpasiran 10 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: 24-72 Hours Post-dose	1.27 ng/mL	Standard Deviation 1.82
Group 1: Olpasiran 10 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: Pre-dose	0.00 ng/mL	Standard Deviation 0
Group 1: Olpasiran 10 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: 1 Hour Post-dose	12.4 ng/mL	Standard Deviation 7.23
Group 1: Olpasiran 10 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: 1 Hour Post-dose	12.3 ng/mL	Standard Deviation 6.9
Group 1: Olpasiran 10 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: 3 Hours Post-dose	18 ng/mL	Standard Deviation 9.85
Group 2: Olpasiran 75 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: 1 Hour Post-dose	67.1 ng/mL	Standard Deviation 47.4
Group 2: Olpasiran 75 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: 1 Hour Post-dose	73.6 ng/mL	Standard Deviation 43.6
Group 2: Olpasiran 75 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: Pre-dose	0.00 ng/mL	Standard Deviation 0
Group 2: Olpasiran 75 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: 6-12 Hours Post-dose	61.7 ng/mL	Standard Deviation 36
Group 2: Olpasiran 75 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: Pre-dose	0.0315 ng/mL	Standard Deviation 0.134
Group 2: Olpasiran 75 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: 24-72 Hours Post-dose	20.4 ng/mL	Standard Deviation 13.2
Group 2: Olpasiran 75 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: 3 Hours Post-dose	96.3 ng/mL	Standard Deviation 63.5
Group 2: Olpasiran 75 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: 24-72 Hours Post-dose	17.3 ng/mL	Standard Deviation 18.9
Group 2: Olpasiran 75 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: 6-12 Hours Post-dose	76.3 ng/mL	Standard Deviation 54.7
Group 2: Olpasiran 75 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 48	0.0599 ng/mL	Standard Deviation 0.168
Group 2: Olpasiran 75 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: 3 Hours Post-dose	80.3 ng/mL	Standard Deviation 43.2
Group 3: Olpasiran 225 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: 3 Hours Post-dose	291 ng/mL	Standard Deviation 273
Group 3: Olpasiran 225 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: Pre-dose	0.498 ng/mL	Standard Deviation 1.88
Group 3: Olpasiran 225 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: 1 Hour Post-dose	204 ng/mL	Standard Deviation 144
Group 3: Olpasiran 225 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 48	0.533 ng/mL	Standard Deviation 0.592
Group 3: Olpasiran 225 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: Pre-dose	0.00 ng/mL	Standard Deviation 0
Group 3: Olpasiran 225 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: 1 Hour Post-dose	220 ng/mL	Standard Deviation 218
Group 3: Olpasiran 225 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: 6-12 Hours Post-dose	420 ng/mL	Standard Deviation 432
Group 3: Olpasiran 225 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: 24-72 Hours Post-dose	63.2 ng/mL	Standard Deviation 59.7
Group 3: Olpasiran 225 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: 3 Hours Post-dose	278 ng/mL	Standard Deviation 193
Group 3: Olpasiran 225 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: 6-12 Hours Post-dose	271 ng/mL	Standard Deviation 229
Group 3: Olpasiran 225 mg Q12W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: 24-72 Hours Post-dose	99 ng/mL	Standard Deviation 59.1
Group 4: Olpasiran 225 mg Q24W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: 3 Hours Post-dose	332 ng/mL	Standard Deviation 255
Group 4: Olpasiran 225 mg Q24W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: 1 Hour Post-dose	275 ng/mL	Standard Deviation 450
Group 4: Olpasiran 225 mg Q24W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: 24-72 Hours Post-dose	96.3 ng/mL	Standard Deviation 50.3
Group 4: Olpasiran 225 mg Q24W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: Pre-dose	0.00 ng/mL	Standard Deviation 0
Group 4: Olpasiran 225 mg Q24W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: Pre-dose	0.0645 ng/mL	Standard Deviation 0.22
Group 4: Olpasiran 225 mg Q24W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: 6-12 Hours Post-dose	315 ng/mL	Standard Deviation 191
Group 4: Olpasiran 225 mg Q24W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 24: 1 Hour Post-dose	253 ng/mL	Standard Deviation 247
Group 4: Olpasiran 225 mg Q24W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: 6-12 Hours Post-dose	329 ng/mL	Standard Deviation 191
Group 4: Olpasiran 225 mg Q24W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Week 48	0.127 ng/mL	Standard Deviation 0.693
Group 4: Olpasiran 225 mg Q24W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: 24-72 Hours Post-dose	103 ng/mL	Standard Deviation 47.3
Group 4: Olpasiran 225 mg Q24W	Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48	Day 1: 3 Hours Post-dose	324 ng/mL	Standard Deviation 383

Secondary

Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48

Time frame: Baseline; Week 36 and Week 48

Population: Participants in the FAS with data available at each time point. FAS: includes all randomized participants who received at least one dose of IP.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Group 1: Olpasiran 10 mg Q12W	Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48	Week 36	-11.496 Percentage Change in ApoB	Standard Error 2.886
Group 1: Olpasiran 10 mg Q12W	Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48	Week 48	-7.748 Percentage Change in ApoB	Standard Error 3.307
Group 2: Olpasiran 75 mg Q12W	Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48	Week 48	-4.768 Percentage Change in ApoB	Standard Error 3.305
Group 2: Olpasiran 75 mg Q12W	Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48	Week 36	-9.302 Percentage Change in ApoB	Standard Error 2.885
Group 3: Olpasiran 225 mg Q12W	Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48	Week 48	-7.218 Percentage Change in ApoB	Standard Error 3.393
Group 3: Olpasiran 225 mg Q12W	Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48	Week 36	-10.241 Percentage Change in ApoB	Standard Error 2.96
Group 4: Olpasiran 225 mg Q24W	Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48	Week 36	-11.378 Percentage Change in ApoB	Standard Error 3.012
Group 4: Olpasiran 225 mg Q24W	Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48	Week 48	-9.548 Percentage Change in ApoB	Standard Error 3.443
Group 5: Placebo Q12W	Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48	Week 36	7.394 Percentage Change in ApoB	Standard Error 3.066
Group 5: Placebo Q12W	Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48	Week 48	12.292 Percentage Change in ApoB	Standard Error 3.501

Comparison: Week 36: Group 1 vs Group 5p-value: <0.00195% CI: [-26.303, -11.477]Repeated measures linear effects model

Comparison: Week 36: Group 2 vs Group 5p-value: <0.00195% CI: [-24.107, -9.284]Repeated measures linear effects model

Comparison: Week 36: Group 3 vs Group 5p-value: <0.00195% CI: [-25.139, -10.131]Repeated measures linear effects model

Comparison: Week 36: Group 4 vs Group 5p-value: <0.00195% CI: [-26.303, -11.241]Repeated measures linear effects model

Comparison: Week 48: Group 1 vs Group 5p-value: <0.00195% CI: [-28.757, -11.323]Repeated measures linear effects model

Comparison: Week 48: Group 2 vs Group 5p-value: <0.00195% CI: [-25.774, -8.345]Repeated measures linear effects model

Comparison: Week 48: Group 3 vs Group 5p-value: <0.00195% CI: [-28.336, -10.682]Repeated measures linear effects model

Comparison: Week 48: Group 4 vs Group 5p-value: <0.00195% CI: [-30.7, -12.979]Repeated measures linear effects model

Secondary

Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48

Time frame: Baseline; Week 36 and Week 48

Population: Participants in the FAS with data available at each time point. FAS: includes all randomized participants who received at least one dose of IP.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Group 1: Olpasiran 10 mg Q12W	Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48	Week 48	-14.743 Percentage Change in LDL-C	Standard Error 4.419
Group 1: Olpasiran 10 mg Q12W	Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48	Week 36	-17.425 Percentage Change in LDL-C	Standard Error 4.258
Group 2: Olpasiran 75 mg Q12W	Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48	Week 36	-16.284 Percentage Change in LDL-C	Standard Error 4.259
Group 2: Olpasiran 75 mg Q12W	Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48	Week 48	-11.481 Percentage Change in LDL-C	Standard Error 4.418
Group 3: Olpasiran 225 mg Q12W	Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48	Week 48	-17.308 Percentage Change in LDL-C	Standard Error 4.532
Group 3: Olpasiran 225 mg Q12W	Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48	Week 36	-16.733 Percentage Change in LDL-C	Standard Error 4.389
Group 4: Olpasiran 225 mg Q24W	Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48	Week 36	-18.462 Percentage Change in LDL-C	Standard Error 4.428
Group 4: Olpasiran 225 mg Q24W	Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48	Week 48	-16.908 Percentage Change in LDL-C	Standard Error 4.608
Group 5: Placebo Q12W	Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48	Week 36	6.234 Percentage Change in LDL-C	Standard Error 4.52
Group 5: Placebo Q12W	Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48	Week 48	10.113 Percentage Change in LDL-C	Standard Error 4.688

Comparison: Week 36: Group 1 vs Group 5p-value: <0.00195% CI: [-35.176, -12.143]Repeated measures linear effects model

Comparison: Week 36: Group 2 vs Group 5p-value: <0.00195% CI: [-34.036, -11]Repeated measures linear effects model

Comparison: Week 36: Group 3 vs Group 5p-value: <0.00195% CI: [-34.656, -11.278]Repeated measures linear effects model

Comparison: Week 36: Group 4 vs Group 5p-value: <0.00195% CI: [-36.399, -12.993]Repeated measures linear effects model

Comparison: Week 48: Group 1 vs Group 5p-value: <0.00195% CI: [-36.853, -12.859]Repeated measures linear effects model

Comparison: Week 48: Group 2 vs Group 5p-value: <0.00195% CI: [-33.59, -9.598]Repeated measures linear effects model

Comparison: Week 48: Group 3 vs Group 5p-value: <0.00195% CI: [-39.565, -15.277]Repeated measures linear effects model

Comparison: Week 48: Group 4 vs Group 5p-value: <0.00195% CI: [-39.24, -14.801]Repeated measures linear effects model

Secondary

Percentage Change From Baseline in Lp(a) at Week 48

Time frame: Baseline and Week 48

Population: Participants in the FAS with data available at each time point. FAS: includes all randomized participants who received at least one dose of IP.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Group 1: Olpasiran 10 mg Q12W	Percentage Change From Baseline in Lp(a) at Week 48	-64.89 Percentage Change in Lp(a)	Standard Error 2.17
Group 2: Olpasiran 75 mg Q12W	Percentage Change From Baseline in Lp(a) at Week 48	-92.54 Percentage Change in Lp(a)	Standard Error 2.17
Group 3: Olpasiran 225 mg Q12W	Percentage Change From Baseline in Lp(a) at Week 48	-97.29 Percentage Change in Lp(a)	Standard Error 2.22
Group 4: Olpasiran 225 mg Q24W	Percentage Change From Baseline in Lp(a) at Week 48	-82.36 Percentage Change in Lp(a)	Standard Error 2.25
Group 5: Placebo Q12W	Percentage Change From Baseline in Lp(a) at Week 48	3.59 Percentage Change in Lp(a)	Standard Error 2.3

Comparison: Group 1 vs Group 5p-value: <0.00195% CI: [-74.27, -62.67]Repeated measures linear effects model

Comparison: Group 2 vs Group 5p-value: <0.00195% CI: [-101.92, -90.33]Repeated measures linear effects model

Comparison: Group 3 vs Group 5p-value: <0.00195% CI: [-106.74, -95.02]Repeated measures linear effects model

Comparison: Group 4 vs Group 5p-value: <0.00195% CI: [-91.83, -80.06]Repeated measures linear effects model

Source: ClinicalTrials.gov · Data processed: Apr 1, 2026

Olpasiran Trials of Cardiovascular Events And LipoproteiN(a) Reduction - DOSE Finding Study

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Contacts

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Baseline characteristics

Adverse events

Outcome results

Percentage Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 36

Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48

Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48

Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48

Percentage Change From Baseline in Lp(a) at Week 48