Primary Objective: • To evaluate the effect of Olpasiran administered subcutaneous (SC) once every 12 weeks (Q12W) compared with placebo, on percent change from baseline in lipoprotein(a) (Lp[a]) after 36 weeks of treatment. Secondary Objectives: •…
ID
Source
Brief title
Condition
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Percent change in Lp(a) from baseline at week 36
Secondary outcome
• Percentage change from baseline in:
- Lp(a) at week 48
- LDL-C at week 36 and week 48
- ApoB at week 36 and week 48
• PK parameters for olpasiran including, but not limited to, maximum observed
concentration (Cmax), and the area under the concentration time curve (AUC)
Background summary
ASCVD is a condition that may restrict the amount of blood and oxygen reaching
your heart and other vital organs in your body due to a narrowing of your
arteries. There are many factors that contribute to ASCVD, but some remain
unknown. Known risk factors include smoking, high blood pressure, high
cholesterol, diabetes and more. Current treatments that focus on these risk
factors do not always work.
Lipoprotein(a) or Lp(a) is produced in the liver and found in the blood. Some
people have high Lp(a) in their blood, and this has been found to increase the
risk of developing ASCVD.
Olpasiran has been designed to lower Lp(a) in the blood by inhibiting its
production in the liver. Based on this, the investigational study drug is being
investigated in those with high Lp(a) and atherosclerotic cardiovascular
disease to see how effective it is.
There are currently no approved drug treatments to reduce the risk of
cardiovascular disease from specifically targeting high Lp(a).
For more information about the background of the study, please see protocol
section 2.2.
Study objective
Primary Objective:
• To evaluate the effect of Olpasiran administered subcutaneous (SC) once every
12 weeks (Q12W) compared with placebo, on percent change from baseline in
lipoprotein(a) (Lp[a]) after 36 weeks of treatment.
Secondary Objectives:
• To evaluate the effect of Olpasiran administered SC Q12W compared with
placebo, on percent change from baseline in:
- Lp(a) after 48 weeks of treatment
- Low-density lipoprotein cholesterol (LDL C) after 36 and 48 weeks of treatment
- Apolipoprotein(B) (ApoB) after 36 and 48 weeks of treatment
• To characterize the pharmacokinetic (PK) properties of Olpasiran
Safety:
• To evaluate the safety and tolerability of olpasiran administered SC compared
with placebo in subjects with elevated Lp(a)
Study design
This is a phase 2, double-blind, randomized, placebo-controlled, multicenter,
dose finding study to evaluate efficacy, safety, and tolerability of Olpasiran
on Lp(a) compared to placebo in subjects with atherosclerotic cardiovascular
disease and with elevated Lp(a).
Subjects will be randomized in a 1:1:1:1:1 ratio to 1 of the following 5
treatment groups (some olpasiran arms will include placebo to maintain blind):
• Group 1: 10 mg Q12W
• Group 2: 75 mg Q12W
• Group 3: 225 mg Q12W
• Group 4: 225 mg Q24W
• Group 5: Placebo Q12W
The randomization will be stratified by screening Lp(a) > 200 vs. > 200 nmol/L
and by region (Japan vs. Non-Japan).
The study treatment period is 48 weeks with doses at day 1, week 12, week 24,
and week 36. After week 48 there is an extended safety follow-up without
further dosing with investigational product for a minimum of 24 weeks.
Subjects will remain on standard of care (including stable lipid lowering
therapy) per their local guidelines during the treatment period and extended
safety follow-up period.
The overall study design is described by a study schema in protocol Section
1.2. The endpoints are defined in protocol Section 3.
Intervention
Subcutaneous administration of IP.
Study burden and risks
Please see E9 of the ABR form.
Minervum 7061
Breda 4817 ZK
NL
Minervum 7061
Breda 4817 ZK
NL
Listed location countries
Age
Inclusion criteria
-Subject has provided informed consent prior to initiation of any study
specific activities/procedures.
-Age 18 to 80 years
-Fasting Lp(a) > 150 nmol/L during screening by central laboratory
(approximately corresponds to > 60 mg/dL: note that molarity determines
eligibility)
-Atherosclerotic cardiovascular disease based on 1 of the following:
• History of coronary revascularization with percutaneous coronary
intervention (PCI) or coronary
artery bypass grafting (CABG)
• Diagnosis of coronary artery disease with or without prior myocardial
infarction
• Diagnosis of atherosclerotic cerebrovascular disease
• Diagnosis of peripheral arterial disease
-For subjects receiving lipid-altering therapy (not required to participate in
this study), lipid-altering therapy, including statin dose, must remain stable
per local guidelines for >= 4 weeks prior to and during screening
Exclusion criteria
Disease Related
-Severe renal dysfunction, defined as an estimated glomerular filtration rate
(eGFR) < 30 mL/min/1.73 m2 during screening
-History or clinical evidence of active liver disease or hepatic dysfunction,
defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >
3 x upper limit of normal (ULN), or total bilirubin (TBL) > 2 x ULN during
screening
-Inherited or other bleeding disorders
-Recent major cardiovascular event (myocardial infarction, unstable angina,
PCI, CABG, or stroke) within 6 months prior to day 1
-Planned cardiac surgery, PCI or carotid stenting, or planned major non-cardiac
surgery during the study period
Other Medical Conditions
-Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma,
breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last
5 years prior to day 1
-Moderate to severe heart failure (New York Heart Association (NYHA) Functional
Classification III or IV at day 1) or last known left ventricular ejection
fraction < 30%
-Uncontrolled cardiac arrhythmia defined as recurrent and highly symptomatic
ventricular tachycardia, atrial fibrillation with rapid ventricular response,
or supraventricular tachycardia that are not controlled by medications, in the
past 3 months prior to day 1
-Uncontrolled hypertension at day 1, defined as an average systolic blood
pressure of >= 160 mmHg or an average diastolic blood pressure of >= 100 mmHg at
rest
-Fasting triglycerides >= 400 mg/dL (4.5 mmol/L) during screening
-Type 1 diabetes or poorly controlled (HbA1c >= 8.5%) type 2 diabetes mellitus
as determined by central laboratory at screening
Refer to page 31 of the protocol for more information.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-003688-23-NL |
| ClinicalTrials.gov | NCT-nummernognietbekend.Hetnummervolgt. |
| CCMO | NL72368.000.20 |