Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol

Risk Factor, Cardiovascular Clinical Trial

— ORION-11  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03400800
• Other study ID #: MDCO-PCS-17-08
• Status: Completed
• Phase: Phase 3
• Start date: November 1, 2017
• Est. completion date: August 27, 2019

Study information

• Verified date: August 2020
• Source: The Medicines Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1617
• Est. completion date: August 27, 2019
• Est. primary completion date: July 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• ASCVD
• Elevated Cholesterol
• Hypercholesterolemia
• Risk Factor, Cardiovascular

Intervention

Drug:
• Inclisiran Sodium
Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
• Placebo
Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).

Locations

Country	Name	City	State
Czechia	Research Site 11420-002	Chomutov
Czechia	Research Site 11420-003	Uherské Hradište
Germany	Research Site 11049-006	Berlin
Germany	Research Site 11049-002	Bochum
Germany	Research Site 11049-003	Frankfurt
Germany	Research Site 11049-007	Heidelberg
Germany	Research Site 11049-001	Leipzig
Hungary	Research Site 11036-001	Budapest
Hungary	Research Site 11036-004	Debrecen
Hungary	Research Site 11036-002	Hatvan
Hungary	Research Site 11036-003	Zalaegerszeg
Poland	Research Site 11048-016	Brzozów	Podkarpackie
Poland	Research Site 11048-011	Bydgoszcz
Poland	Research Site 11048-018	Bydgoszcz	Kujawsko-pomorskie
Poland	Research Site 11048-004	Gdansk
Poland	Research Site 11048-017	Gdansk
Poland	Research Site 11048-005	Gdynia
Poland	Research Site 11048-007	Katowice
Poland	Research Site 11048-012	Katowice
Poland	Research Site 11048-003	Kraków
Poland	Research Site 11048-014	Kraków
Poland	Research Site 11048-008	Lublin
Poland	Research Site 11048-001	Poznan
Poland	Research Site 11048-019	Ruda Slaska	Slaskie
Poland	Research Site 11048-013	Rzeszów
Poland	Research Site 11048-015	Tarnów
Poland	Research Site 11048-009	Warsaw
Poland	Research Site 11048-006	Warszawice
Poland	Research Site 11048-002	Wroclaw
Poland	Research Site 11048-010	Wroclaw
South Africa	Research Site 11027-003	Bloemfontein	Free State
South Africa	Research Site 11027-001	Cape Town	Western Cape
South Africa	Research Site 11027-013	Cape Town	Western Cape
South Africa	Research Site 11027-005	Johannesburg	Gauteng
South Africa	Research Site 11027-007	Kuilsrivier	Western Cape
South Africa	Research Site 11027-006	Pretoria
South Africa	Research Site 11027-004	Somerset West	Western Cape
South Africa	Research Site 11027-011	Welkom
Ukraine	Research Site - 11380-005	Cherkasy
Ukraine	Research Site - 11380-008	Kharkiv
Ukraine	Research Site - 11380-004	Kiev
Ukraine	Research Site - 11380-009	Kiev
Ukraine	Research Site - 11380-001	Kyiv
Ukraine	Research Site - 11380-002	Kyiv
Ukraine	Research Site - 11380-003	Kyiv
Ukraine	Research Site - 11380-007	Lviv
Ukraine	Research Site - 11380-006	Uzhhorod
United Kingdom	Research Site - 11044-028	Bollington
United Kingdom	Research Site - 11044-026	Bury
United Kingdom	Research Site - 11044-007	Cardiff
United Kingdom	Research Site - 11044-024	Cheadle Hulme
United Kingdom	Research Site - 11044-014	Chorley	Lancashire
United Kingdom	Research Site - 11044-027	Davyhulme	Manchester
United Kingdom	Research Site - 11044-010	Derby
United Kingdom	Research Site - 11044-006	Edgbaston	Birmingham
United Kingdom	Research Site - 11044-009	Exeter	Devon
United Kingdom	Research Site - 11044-001	Glasgow
United Kingdom	Research Site - 11044-008	Hexham
United Kingdom	Research Site - 11044-012	Liskeard	Cornwall
United Kingdom	Research Site - 11044-020	Macclesfield
United Kingdom	Research Site - 11044-005	Manchester
United Kingdom	Research Site - 11044-025	Manchester
United Kingdom	Research Site - 11044-029	Manchester
United Kingdom	Research Site - 11044-019	Plymouth	Devon
United Kingdom	Research Site - 11044-003	Reading
United Kingdom	Research Site - 11044-022	Sale	Cheshire
United Kingdom	Research Site - 11044-023	Sale	Cheshire
United Kingdom	Research Site - 11044-002	Stockton
United Kingdom	Research Site - 11044-021	Timperley	Cheshire
United Kingdom	Research Site - 11044-004	Waterloo	Liverpool

Sponsors (1)

Lead Sponsor	Collaborator
The Medicines Company

Countries where clinical trial is conducted

Czechia,  Germany,  Hungary,  Poland,  South Africa,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage Change in LDL-C From Baseline to Day 510		Baseline, Day 510
Primary	Time-adjusted Percent Change in LDL-C Levels From Baseline After Day 90 and up to Day 540		Baseline, Day 90 to Day 540
Secondary	Absolute Change In LDL-C From Baseline To Day 510		Baseline, Day 510
Secondary	Time-adjusted Absolute Change in LDL-C From Baseline After Day 90 and up to Day 540		Baseline, Day 90 to Day 540
Secondary	Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 510		Baseline, Day 510
Secondary	Percentage Change in Total Cholesterol From Baseline to Day 510		Baseline, Day 510
Secondary	Percentage Change in Apolipoprotein B (ApoB) From Baseline to Day 510		Baseline, Day 510
Secondary	Percentage Change in Non-HDL-C From Baseline to Day 510		Baseline, Day 510