Trial to Assess the Effect of Long Term Dosing of Inclisiran in Subjects With High CV Risk and Elevated LDL-C

• Register: ClinicalTrials.gov
• Last refreshed on: 20 March 2023
• Main ID: NCT03814187
• Date of registration: 17/01/2019
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Trial to Assess the Effect of Long Term Dosing of Inclisiran in Subjects With High CV Risk and Elevated LDL-C ORION-8
• Scientific title: An Open-label Extension Trial of the Phase III Lipid-lowering Trials to Assess the Effect of Long Term Dosing of Inclisiran Given as Subcutaneous Injections in Subjects With High Cardiovascular Risk and Elevated LDL-C
• Date of first enrolment: April 16, 2019
• Target sample size: 3275
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03814187
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Canada, Czechia, Denmark, Germany, Hungary, Netherlands, Poland, South Africa, Spain, Sweden, Ukraine, United Kingdom, United States

Contacts

• Name: Scott Wright, MD
• Affiliation: Mayo Clinic

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Completion on a previously qualifying inclisiran Phase II trial MDCO-PCS-16-01
(ORION-3), or Phase III lipid lowering ORION feeder study [MDCO-PCS-17-03 (ORION-9),
MDCO-PCS-17-4 (ORION-10), or MDCO-PCS-17-08 (ORION-11)] meaning the subject received
the last dose of study drug and completed the final study visit per applicable
protocol.

2. On current lipid-lowering therapies (such as a statin and/or ezetimibe) from previous
study with no planned medication or dose change during study participation.

3. Willing and able to give informed consent before initiation of any study-related
procedures and willing to comply with all required study procedures.

Exclusion Criteria:

1. Any uncontrolled or serious disease, or any medical or surgical condition, that may
either interfere with participation in the clinical study, and/or put the subject at
significant risk [according to investigator's (or delegate's) judgment] if he/she
participates in the clinical study.

2. An underlying known disease, or surgical, physical, or medical condition that, in the
opinion of the investigator (or delegate) might interfere with interpretation of the
clinical study results.

3. Severe concomitant noncardiovascular disease that carries the risk of reducing life
expectancy to less than 3 years,

4. Active liver disease defined as any known current infectious, neoplastic, or metabolic
pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate
aminotransferase (AST), elevation >3x the upper limit of normal (ULN), or total
bilirubin (TBIL) elevation >2x ULN at the last recorded visit in the feeder study
prior to study entry visit.

5. Females who are pregnant or nursing, or who are of childbearing potential and
unwilling to use at least one method of acceptable effective contraception (eg, oral
contraceptives, barrier methods, approved contraceptive implant, long-term injectable
contraception, intrauterine device) for the entire duration of the study. Exemptions
from this criterion:

1. Women >2 years postmenopausal (defined as 1 year or longer since last menstrual
period) and more than 55 years of age.

2. Postmenopausal women (as defined above) and less than 55 years of age with a
negative pregnancy test within 24 hours of randomization.

3. Women who are surgically sterilized at least 3 months prior to enrollment.

6. Planned use of other investigational medicinal products other than inclisiran or
devices during the course of the study.

7. Any condition that according to the investigator could interfere with the conduct of
the study, such as but not limited to:

1. Subjects who are unable to communicate or to cooperate with the investigator

2. Unable to understand the protocol requirements, instructions and study-related
restrictions, the nature, scope, and possible consequences of the study
(including subjects whose cooperation is doubtful due to drug abuse or alcohol
dependency)

3. Unlikely to comply with the protocol requirements, instructions, and
study-related restrictions (eg, uncooperative attitude, inability to return for
follow-up visits, and improbability of completing the study)

4. Have any medical or surgical condition, which in the opinion of the investigator
would put the subject at increased risk from participating in the study

5. Persons directly involved in the conduct of the study.

The above information is not intended to contain all considerations relevant to a
participant's potential participation in a clinical trial.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Elevated Cholesterol

Heterozygous Familial Hypercholesterolemia

ASCVD

Homozygous Familial Hypercholesterolemia

Intervention(s)

Drug: Inclisiran Sodium

Primary Outcome(s)

Incidence of Adverse Events and Serious Adverse Events [Time Frame: Baseline, Day 1080]

Percentage of subjects achieving prespecified LDL-C targets. [Time Frame: Day 1080]

Secondary Outcome(s)

Absolute and percentage change in other lipids and lipoprotein from baseline. [Time Frame: Baseline, Day 1080]

Absolute and percentage change in LDL-C from baseline. [Time Frame: Baseline, Day 1080]

Secondary ID(s)

2017-003092-55

CKJX839A12306B

MDCO-PCS-17-05

Source(s) of Monetary Support

Please refer to primary and secondary sponsors