Cardiovascular Disease
Conditions
Brief summary
This is a first-in-human, randomized, double-blind, placebo-controlled, single ascending dose study in subjects with elevated plasma Lipoprotein(a) \[Lp(a)\]. AMG 890 will be evaluated in approximately 80 subjects to assess safety, tolerability, pharmacokinetics and pharmacodynamic effects.
Interventions
DRUGAMG 890
Ascending Single Doses of AMG 890
DRUGPlacebo
Calculated volume to match experimental drug.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
The subjects and the investigative site staff, except for the unblinded pharmacist, will be blinded to treatment assignment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Men and women with ages between 18 and 70 years old, inclusive. * Protocol-defined elevated plasma Lp(a) level. * Body mass index (BMI) greater than or equal to 18 and less than or equal to 40 kg/m2, at screening. * Women must be of non-reproductive potential. * Other Inclusion criteria may apply
Exclusion criteria
* Currently receiving treatment in another investigational device or drug study. * Women who are lactating/breastfeeding or who plan to breastfeed while on study or through 90 days after receiving the last dose of investigational product (for subjects who withdraw prior to end of study). * History or evidence of a clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion. * History or clinical evidence of bleeding diathesis or any coagulation disorder. * History or clinical evidence of peripheral neuropathy. * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | From first dose of trial until the end of trial; median (min, max) duration was 8.54 (0.23, 23.92) months | An adverse event was defined as any untoward medical occurrence in a clinical trial participant. A TEAE was defined as any event with onset after the administration of the first dose of investigational product and up to and including the end of treatment date, or end of trial for participants who discontinued the trial during the treatment period. Clinically significant changes in vital signs, electrocardiograms (ECGs), and safety laboratory analytes were included as TEAEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentration (Cmax) of Olpasiran | Cohorts 1-5:pre-dose, Days 1-4, 7, 15, 29, 57, 85 post-dose; Cohorts 6-7:pre-dose, Days 1, 2, 4, 7, 15 post-dose; Cohort 8:pre-dose, Days 1, 2, 4, 7, 15, 29, 57, 85, 113 post-dose; Cohort 9:pre-dose, Days 1, 2, 4, 7, 15, 29, 57, 85, 113, 155 post-dose | Blood samples were collected for measurement of serum concentrations of Olpasiran. |
| Time to Reach Cmax (Tmax) of Olpasiran | Cohorts 1-5:pre-dose, Days 1-4, 7, 15, 29, 57, 85 post-dose; Cohorts 6-7:pre-dose, Days 1, 2, 4, 7, 15 post-dose; Cohort 8:pre-dose, Days 1, 2, 4, 7, 15, 29, 57, 85, 113 post-dose; Cohort 9:pre-dose, Days 1, 2, 4, 7, 15, 29, 57, 85, 113, 155 post-dose | Blood samples were collected for measurement of serum concentrations of Olpasiran. |
| Area Under the Concentration-time Curve (AUC) From Time Zero to the Last Quantifiable Timepoint (AUC0-last) of Olpasiran | Cohorts 1-5:pre-dose, Days 1-4, 7, 15, 29, 57, 85 post-dose; Cohorts 6-7:pre-dose, Days 1, 2, 4, 7, 15 post-dose; Cohort 8:pre-dose, Days 1, 2, 4, 7, 15, 29, 57, 85, 113 post-dose; Cohort 9:pre-dose, Days 1, 2, 4, 7, 15, 29, 57, 85, 113, 155 post-dose | Blood samples were collected for measurement of serum concentrations of Olpasiran. |
| Change From Baseline in Plasma Lp(a) Levels | Cohorts 1-2:Baseline,Days 2,4,7,15,18,22,29,43,57,71,85,113;3-5:Baseline,Days 2,4,7,15,18,22,29,43,57,71,85,113,155,183,225;6-7:Baseline,Days 2,4,7,15,29,43,57,85,113,155,183,225;8-9:Baseline,Days 2,4,7,15,29,43,57,85,113,155,183,225,253,281,309,337,365 | Change from baseline for plasma Lp(a) by cohort and at scheduled time points were presented. |
| Percent Change From Baseline in Plasma Lp(a) Levels | Cohorts 1-2:Baseline,Days 2,4,7,15,18,22,29,43,57,71,85,113;3-5:Baseline,Days 2,4,7,15,18,22,29,43,57,71,85,113,155,183,225;6-7:Baseline,Days 2,4,7,15,29,43,57,85,113,155,183,225;8-9:Baseline,Days 2,4,7,15,29,43,57,85,113,155,183,225,253,281,309,337,365 | Percent change from baseline for plasma Lp(a) by cohort and at scheduled time points during the treatment period were presented. |
Countries
Australia, United States
Contacts
STUDY_DIRECTORMD
Amgen
Participant flow
Recruitment details
Participants were enrolled at 8 research centers in the United States (US) and Australia between July 2018 and April 2023.
Pre-assignment details
Participants were randomized in a 3:1 ratio to receive either Olpasiran or a volume-matched placebo via subcutaneous (SC) injection, across 9 single ascending dose cohorts.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 52.8 years STANDARD_DEVIATION 8.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 63 Participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 11 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 | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 9 | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 5 / 10 | 7 / 10 | 3 / 6 | 3 / 6 | 5 / 6 | 1 / 6 | 0 / 6 | 6 / 9 | 3 / 9 | 4 / 5 | 4 / 6 |
| serious Total, serious adverse events | 0 / 10 | 1 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 9 | 0 / 5 | 0 / 6 |
Outcome results
None listed