Clinical trial NCT03400800: Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol
Official title: A Placebo-Controlled, Double-Blind, Randomized Trial to Evaluate the Effect of 300 mg of Inclisiran Sodium Given as Subcutaneous Injections in Subjects With Atherosclerotic Cardiovascular Disease (ASCVD) or ACSVD Risk-Equivalents and Elevated Low-Density Lipoprotein Cholesterol (LDL-C)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ASCVD
Risk Factor, Cardiovascular
Elevated Cholesterol
Keywords: Inclisiran sodium
ASCVD
LDL-C
Lead sponsor: The Medicines Company
Sponsor class: INDUSTRY
First posted: 2018-01-17
Enrollment: 1617
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase III, placebo-controlled, double-blind, randomized study in participants with ASCVD or ASCVD-Risk equivalents and elevated LDL-C despite maximum tolerated dose of LDL-C lowering therapies to evaluate the efficacy, safety, and tolerability of subcutaneous (SC) inclisiran injection(s). The study will be an international multicenter study (non-United States).


Eligibility criteria: Inclusion Criteria:

Participants may be included if they meet all of the following inclusion criteria prior to randomization:

1. Male or female participants ≥18 years of age.
2. History of ASCVD (coronary heart disease \[CHD\], cardiovascular disease \[CVD\], or peripheral arterial disease \[PAD\]).
3. Serum LDL-C ≥1.8 millimole (mmol)/liter (L) (≥70 mg/dL).
4. Fasting triglyceride \<4.52 mmol/L (\<400 mg/dL) at screening.
5. Calculated glomerular filtration rate \>30 mL/min by estimated glomerular filtration rate (eGFR) using standardized clinical methodology
6. Participants on statins should be receiving a maximally tolerated dose.
7. Participants not receiving statins must have documented evidence of intolerance to all doses of at least 2 different statins.
8. Subjects on lipid-lower therapies (such as a statin and/or ezetimibe) should be on a stable dose for ≥30 days before screening with no planned medication or dose change during study participation.
9. Subjects were 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:

Participants will be excluded from the study if any of the following exclusion criteria apply prior to randomization:

1. New York Heart Association (NYHA) class IV heart failure.
2. Uncontrolled cardiac arrhythmia.
3. Uncontrolled severe hypertension.
4. Active liver disease.
5. Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least 2 methods of highly effective contraception (failure rate less than 1% per year) (for example, combined oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, or 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. Males who are unwilling to use an acceptable method of birth control during the entire study period (such as condom with spermicide).
7. Treatment with other investigational products or devices within 30 days or 5 half-lives of the screening visit, whichever is longer.
8. Treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9.

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

Primary outcomes:
measure: Percentage Change in LDL-C From Baseline to Day 510
timeFrame: Baseline, Day 510
measure: Time-adjusted Percent Change in LDL-C Levels From Baseline After Day 90 and up to Day 540
timeFrame: Baseline, Day 90 to Day 540
Secondary outcomes:
measure: Absolute Change In LDL-C From Baseline To Day 510
timeFrame: Baseline, Day 510
measure: Time-adjusted Absolute Change in LDL-C From Baseline After Day 90 and up to Day 540
timeFrame: Baseline, Day 90 to Day 540
measure: Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 510
timeFrame: Baseline, Day 510
measure: Percentage Change in Total Cholesterol From Baseline to Day 510
timeFrame: Baseline, Day 510
measure: Percentage Change in Apolipoprotein B (ApoB) From Baseline to Day 510
timeFrame: Baseline, Day 510
measure: Percentage Change in Non-HDL-C From Baseline to Day 510
timeFrame: Baseline, Day 510
Other outcomes:
Locations:
city: Chomutov
country: Czechia
facility: Research Site 11420-002
city: Uherské Hradiště
country: Czechia
facility: Research Site 11420-003
city: Berlin
country: Germany
facility: Research Site 11049-006
city: Bochum
country: Germany
facility: Research Site 11049-002
city: Frankfurt
country: Germany
facility: Research Site 11049-003
city: Heidelberg
country: Germany
facility: Research Site 11049-007
city: Leipzig
country: Germany
facility: Research Site 11049-001
city: Budapest
country: Hungary
facility: Research Site 11036-001
city: Debrecen
country: Hungary
facility: Research Site 11036-004
city: Hatvan
country: Hungary
facility: Research Site 11036-002
city: Zalaegerszeg
country: Hungary
facility: Research Site 11036-003
city: Bydgoszcz
country: Poland
facility: Research Site 11048-018
state: Kujawsko-pomorskie
city: Brzozów
country: Poland
facility: Research Site 11048-016
state: Podkarpackie
city: Ruda Śląska
country: Poland
facility: Research Site 11048-019
state: Slaskie
city: Bydgoszcz
country: Poland
facility: Research Site 11048-011
city: Gdańsk
country: Poland
facility: Research Site 11048-004
city: Gdańsk
country: Poland
facility: Research Site 11048-017
city: Gdynia
country: Poland
facility: Research Site 11048-005
city: Katowice
country: Poland
facility: Research Site 11048-007
city: Katowice
country: Poland
facility: Research Site 11048-012
city: Kraków
country: Poland
facility: Research Site 11048-014
city: Kraków
country: Poland
facility: Research Site 11048-003
city: Lublin
country: Poland
facility: Research Site 11048-008
city: Poznań
country: Poland
facility: Research Site 11048-001
city: Rzeszów
country: Poland
facility: Research Site 11048-013
city: Tarnów
country: Poland
facility: Research Site 11048-015
city: Warsaw
country: Poland
facility: Research Site 11048-009
city: Warszawice
country: Poland
facility: Research Site 11048-006
city: Wrocław
country: Poland
facility: Research Site 11048-002
city: Wrocław
country: Poland
facility: Research Site 11048-010
city: Bloemfontein
country: South Africa
facility: Research Site 11027-003
state: Free State
city: Johannesburg
country: South Africa
facility: Research Site 11027-005
state: Gauteng
city: Cape Town
country: South Africa
facility: Research Site 11027-001
state: Western Cape
city: Cape Town
country: South Africa
facility: Research Site 11027-013
state: Western Cape
city: Kuilsrivier
country: South Africa
facility: Research Site 11027-007
state: Western Cape
city: Somerset West
country: South Africa
facility: Research Site 11027-004
state: Western Cape
city: Pretoria
country: South Africa
facility: Research Site 11027-006
city: Welkom
country: South Africa
facility: Research Site 11027-011
city: Cherkasy
country: Ukraine
facility: Research Site - 11380-005
city: Kharkiv
country: Ukraine
facility: Research Site - 11380-008
city: Kiev
country: Ukraine
facility: Research Site - 11380-004
city: Kiev
country: Ukraine
facility: Research Site - 11380-009
city: Kyiv
country: Ukraine
facility: Research Site - 11380-001
city: Kyiv
country: Ukraine
facility: Research Site - 11380-002
city: Kyiv
country: Ukraine
facility: Research Site - 11380-003
city: Lviv
country: Ukraine
facility: Research Site - 11380-007
city: Uzhhorod
country: Ukraine
facility: Research Site - 11380-006
city: Edgbaston
country: United Kingdom
facility: Research Site - 11044-006
state: Birmingham
city: Sale
country: United Kingdom
facility: Research Site - 11044-022
state: Cheshire
city: Sale
country: United Kingdom
facility: Research Site - 11044-023
state: Cheshire
city: Timperley
country: United Kingdom
facility: Research Site - 11044-021
state: Cheshire
city: Liskeard
country: United Kingdom
facility: Research Site - 11044-012
state: Cornwall
city: Exeter
country: United Kingdom
facility: Research Site - 11044-009
state: Devon
city: Plymouth
country: United Kingdom
facility: Research Site - 11044-019
state: Devon
city: Chorley
country: United Kingdom
facility: Research Site - 11044-014
state: Lancashire
city: Waterloo
country: United Kingdom
facility: Research Site - 11044-004
state: Liverpool
city: Davyhulme
country: United Kingdom
facility: Research Site - 11044-027
state: Manchester
city: Bollington
country: United Kingdom
facility: Research Site - 11044-028
city: Bury
country: United Kingdom
facility: Research Site - 11044-026
city: Cardiff
country: United Kingdom
facility: Research Site - 11044-007
city: Cheadle Hulme
country: United Kingdom
facility: Research Site - 11044-024
city: Derby
country: United Kingdom
facility: Research Site - 11044-010
city: Glasgow
country: United Kingdom
facility: Research Site - 11044-001
city: Hexham
country: United Kingdom
facility: Research Site - 11044-008
city: Macclesfield
country: United Kingdom
facility: Research Site - 11044-020
city: Manchester
country: United Kingdom
facility: Research Site - 11044-025
city: Manchester
country: United Kingdom
facility: Research Site - 11044-005
city: Manchester
country: United Kingdom
facility: Research Site - 11044-029
city: Reading
country: United Kingdom
facility: Research Site - 11044-003
city: Stockton
country: United Kingdom
facility: Research Site - 11044-002
Study officials:
affiliation: Imperial College of London
name: Ray Kausik, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, Bisch JA, Richardson T, Jaros M, Wijngaard PLJ, Kastelein JJP; ORION-10 and ORION-11 Investigators. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020 Apr 16;382(16):1507-1519. doi: 10.1056/NEJMoa1912387. Epub 2020 Mar 18.