Trial to Evaluate the Effect of ALN-PCSSC Treatment on Low Density Lipoprotein Cholesterol (LDL-C) (ORION-1)

• ClinicalTrials.gov Identifier: NCT02597127
• Recruitment Status: Completed
• First Posted: November 5, 2015
• Results First Posted: May 17, 2019
• Last Update Posted: May 17, 2019
• Sponsor: The Medicines Company
• Information provided by (Responsible Party): The Medicines Company

Study Description

Brief Summary:

This study is a Phase II, placebo-controlled, double-blind, randomized trial in 480 participants with atherosclerotic cardiovascular disease (ASCVD) or ASCVD-risk equivalents (for example, diabetes and familial hypercholesterolemia) and elevated LDL-C despite maximum tolerated dose of LDL-C lowering therapies to evaluate the efficacy, safety, and tolerability of ALN-PCSSC injection(s).

Condition or disease	Intervention/treatment	Phase
Atherosclerotic Cardiovascular Disease; Familial Hypercholesterolemia; Diabetes	Drug: ALN-PCSSC; Drug: Normal Saline	Phase 2

Detailed Description:

Participants will be screened and 480 eligible participants will be randomized: 60 participants per each of six ALN-PCSSC dose groups plus 120 participants total across the placebo groups (20 participants each to match each of the six drug dose groups). Treatment allocation will be stratified by country and by current use of statins or other lipid-modifying therapies. Each participant will receive either one or two injections on Day 1 or a single injection on Day 1 and on Day 90 of blinded ALN-PCSSC or placebo.

Formation of anti-drug antibodies (ADA) will be assessed on Day 1 (prior to and 4 hours after the injection) and on Days 30, 60, 90, 120, 150, 180 (Days 150 and 180 only in participants who receive a second dose of study drug), and 210 or until any ADA response becomes negative within the study duration.

The independent Data Monitoring Committee (DMC) will review safety data beginning after the first 40 participants receive the first injection of ALN-PCSSC or placebo and complete the Day 14 follow-up visit. Thereafter, the DMC will review safety data every 2 months until the end of the trial. A recommendation may be taken to stop or amend the study at any of these reviews.

On Day 1, all eligible participants will be randomized and receive the first subcutaneous (SC) administration of ALN-PCSSC or placebo. After the first study drug administration, the participant will be observed in the clinic for at least 4 hours post injection before being discharged. Participants will return at Day 14 and then at monthly intervals for 6 months. Participants randomized to receive a second dose of study drug will receive the second injection of ALN-PCSSC or placebo at the Day 90 visit.

Efficacy assessments will include the measurement of the effects of ALN-PCSSC on levels of LDL-C lipids and lipoproteins including total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, very low-density lipoprotein (VLDL), apolipoprotein A1 (Apo-AI), apolipoprotein B (Apo-B), lipoprotein (a) [Lp(a)], C-reactive protein (CRP), and proprotein convertase subtilisin/kexin type 9 (PCSK9).

End of study (EOS) evaluations will be conducted at the EOS visit (Day 210). The expected duration of the participants' involvement in the study will be approximately 374 days, which includes screening, study drug administration, the course of single or multiple injections, and the follow-up period to Day 360.

Participants completing the study to Day 210 will be given the opportunity to enroll in a separate long-term extension study. Any participants in whom LDL-C levels have not returned to >80% of baseline values will continue to be followed as part of this study until either this level has been reached or until a maximum of Day 360, at which point they will be given the opportunity to enroll in the long-term extension study. At each visit, LDL-C levels, adverse events, serious adverse events, concomitant medications, and safety laboratory assessments will be collected.

Objectives:

Primary:

To evaluate the effect of ALN-PCSSC treatment on LDL-C levels at Day 180.

Secondary:

To evaluate the effect of ALN-PCSSC on the following:

• LDL-C at Day 90
• LDL-C levels at other time points
• PCSK9 levels over time
• Other lipids, lipoproteins, apolipoproteins
• Proportion of participants achieving pre-specified global lipid guidelines
• Individual responsiveness to different doses
• Duration of lipid-lowering effect of different doses
• Safety and tolerability profile of ALN-PCSSC

Exploratory:

To collect/evaluate the effect of ALN-PCSSC on the following:

• Cardiovascular (CV) events such as CV death, non-fatal myocardial infarction, resuscitated cardiac arrest and non-fatal stroke (ischemic and hemorrhagic)
• Evaluation of ADA for the investigational product

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 501 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Placebo-controlled, Double-blind, Randomized Trial to Compare the Effect of Different Doses of ALN-PCSSC Given as Single or Multiple Subcutaneous Injections in Subjects With High Cardiovascular Risk and Elevated LDL-C
• Study Start Date: January 2016
• Actual Primary Completion Date: June 7, 2017
• Actual Study Completion Date: June 7, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: ALN-PCSSC 200 mg (bi-annual dosing); ALN-PCSSC 200 milligram (mg) SC administration once at Day 1	Drug: ALN-PCSSC; ALN-PCSSC is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis and is given as SC injections; Other Names: PCSK9 synthesis inhibitor; Inclisiran
Experimental: ALN-PCSSC 300 mg (bi-annual dosing); ALN-PCSSC 300 mg SC administration once at Day 1	Drug: ALN-PCSSC; ALN-PCSSC is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis and is given as SC injections; Other Names: PCSK9 synthesis inhibitor; Inclisiran
Experimental: ALN-PCSSC 500 mg (bi-annual dosing); ALN-PCSSC 500 mg SC administration once at Day 1	Drug: ALN-PCSSC; ALN-PCSSC is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis and is given as SC injections; Other Names: PCSK9 synthesis inhibitor; Inclisiran
Placebo Comparator: Normal Saline (bi-annual dosing); Saline SC administration once at Day 1	Drug: Normal Saline; Saline (sterile, normal, 0.9%) solution given as SC injections
Experimental: ALN-PCSSC 100 mg (quarterly dosing); ALN-PCSSC 100 mg SC administration twice at Day 1 and Day 90	Drug: ALN-PCSSC; ALN-PCSSC is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis and is given as SC injections; Other Names: PCSK9 synthesis inhibitor; Inclisiran
Experimental: ALN-PCSSC 200 mg (quarterly dosing); ALN-PCSSC 200 mg SC administration twice at Day 1 and Day 90	Drug: ALN-PCSSC; ALN-PCSSC is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis and is given as SC injections; Other Names: PCSK9 synthesis inhibitor; Inclisiran
Experimental: ALN-PCSSC 300 mg (quarterly dosing); ALN-PCSSC 300 mg SC administration twice at Day 1 and Day 90	Drug: ALN-PCSSC; ALN-PCSSC is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis and is given as SC injections; Other Names: PCSK9 synthesis inhibitor; Inclisiran
Placebo Comparator: Normal Saline (quarterly dosing); Saline SC administration twice at Day 1 and Day 90	Drug: Normal Saline; Saline (sterile, normal, 0.9%) solution given as SC injections

Outcome Measures

Primary Outcome Measures :

1. Percentage Change in LDL-C From Baseline to Day 180 [ Time Frame: Baseline to 180 days ]
   Percent Change in LDL-C (beta-quantification) from Baseline to Day 180 in MITT Population

Secondary Outcome Measures :

1. Percentage Change in LDL-C From Baseline to Day 90 [ Time Frame: Baseline to 90 days ]
   Percent Change in LDL-C (beta-quantification) from Baseline to Day 90 in MITT Population
2. Percent Change From Baseline In LDL-C Levels At Day 60, Day 120, and Day 210 [ Time Frame: Baseline, Day 60, Day 120, and Day 210 ]
   This outcome measure evaluated the effects of both single- and double-dose inclisiran on LDL-C levels in the mITT population from baseline to Day 60, Day 120, and Day 210.
3. Number of Participants With an LDL-C Greater Than 80% of the Baseline Value at Day 180 and Day 210 [ Time Frame: Baseline, Day 180, Day 210 ]
   This outcome measure evaluated the number of participants (single and double dose) in the mITT population with an LDL-C greater than 80% of the baseline value at Day 180 and Day 210.
4. Number of Participants With Individual Responsiveness as Measured By LDL-C Levels at Day 90 and Day 180 [ Time Frame: Day 90, Day 180 ]
   This outcome measure evaluated the individual responsiveness of participants to inclisiran (single and double dose) in the mITT population as defined by an LDL-C level of <25 mg/deciliter [dL] at Day 90 and Day 180.
5. Number of Participants With Greater Or Equal To 50% LDL-C Reduction From Baseline At Day 180 [ Time Frame: Baseline, Day 180 ]
   This outcome measure evaluated the number of participants (single and double dose) in the mITT population with an LDL-C reduction greater than 50% of the baseline value at Day 180.
6. Percentage Change in PCSK9 Levels From Baseline at Day 180 [ Time Frame: Baseline, Day 180 ]
   This outcome measure evaluated the percent change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline to Day 180 in participants (single and double dose) in the mITT population.
7. Percentage Change in Other Lipids and Apolipoproteins From Baseline to Day 180 [ Time Frame: Baseline, Day 180 ]
   This outcome measure evaluated the percent change from baseline to Day 180 in cholesterol (total, high-density lipoprotein [HDL], non-HDL) and apolipoproteins (B, A1) in participants (single and double dose) in the mITT population.
8. Number of Participants Who Attained Global Lipid Modification Targets for Level of Atherosclerotic Cardiovascular Disease Risk [ Time Frame: Baseline, Day 180 ]

   This outcome measure evaluated the proportion of participants (single and double dose) in the mITT population who attained a global lipid modification target by baseline cardiovascular risk group, looking specifically at LDL-C levels (mg/dL) in the category of cardiovascular disease (CVD).

   CVD was defined as a participant who had at least 1 of the following: prior myocardial infarction, prior percutaneous coronary intervention, prior coronary artery bypass graft, prior stroke, prior transient ischemic attack, peripheral artery disease.

9. Percentage Change in Other Lipids and Inflammatory Markers From Baseline to Day 180 [ Time Frame: Baseline, Day 180 ]
   This outcome measure evaluated the percent change from baseline to Day 180 in triglycerides, very-low-density lipoprotein (VLDL) cholesterol, lipoprotein(a), and high sensitivity C-reactive protein (hsCRP) in participants (single and double dose) in the mITT population.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female participants ≥18 years of age.
2. History of ASCVD or ASCVD-risk equivalents (symptomatic atherosclerosis, Type 2 diabetes, familial hypercholesterolemia, including participants whose 10-year risk of a CV event assessed by Framingham Risk Score (Framingham Risk Score >20%) or equivalent has a target LDL-C of <100 mg/deciliter [dL]).
3. Serum LDL-C ≥1.8 millimole (mmol)/liter (L) (≥70 mg/dL) for ASCVD participants or ≥2.6 mmol/L (≥100 mg/dL) for ASCVD-risk equivalent participants at screening.
4. Fasting triglyceride <4.52 mmol/L (<400 mg/dL) at screening.
5. Calculated glomerular filtration rate 30 mL/min or higher by estimated glomerular filtration rate (eGFR) using standardized local clinical methodology.
6. Participants on statins should be receiving a maximally tolerated dose (investigator's discretion).
7. Participants on lipid-lower therapies (such as 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.
8. 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 participant at significant risk (according to investigator's [or delegate] 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. New York Heart Association (NYHA) class II, III, or IV heart failure or last known left ventricular ejection fraction <30%.
4. Cardiac arrhythmia within 3 months prior to randomization that is not controlled by medication or via ablation.
5. Any history of hemorrhagic stroke.
6. Major adverse cardiac event within 6 months prior to randomization.
7. Uncontrolled severe hypertension: systolic blood pressure >180 millimeters of mercury (mmHg) or diastolic blood pressure >110 mmHg prior to randomization despite anti-hypertensive therapy.
8. Poorly controlled Type 2 diabetes, such as, glycated hemoglobin A1c (HbA1c)>10.0% prior to randomization.
9. Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation >2x the upper limit of normal (ULN), or total bilirubin elevation >1.5x ULN at screening confirmed by a repeat measurement at least 1 week apart.
10. Serious comorbid disease in which the life expectancy of the participant is shorter than the duration of the trial (for example, acute systemic infection, cancer, or other serious illnesses). This includes all cancers with the exception of treated basal-cell carcinoma occurring >5 years before screening.
11. Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least two methods of contraception (oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, intrauterine device or tubal litigation) for the entire duration of the study. Women who are >2 years postmenopausal defined as ≥1 year since last menstrual period and if less than 55 years old with a negative pregnancy test within 24 hours of randomization or surgically sterile are exempt from this exclusion.
12. Males who are unwilling to use an acceptable method of birth control during the entire study period (such as, condom with spermicide).
13. Known history of alcohol and/or drug abuse within the last 5 years.
14. Treatment with other investigational medicinal products or devices within 30 days or five half˗lives, whichever is longer.
15. Use of other investigational medicinal products or devices during the course of the study.

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

    • Inappropriate for this study, including participants who are unable to communicate or to cooperate with the investigator.
    • Unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study (including participants whose cooperation is doubtful due to drug abuse or alcohol dependency).
    • Unlikely to comply with the protocol requirements, instructions, and study-related restrictions (for example, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study).
    • Have any medical or surgical condition, which in the opinion of the investigator would put the participants at increased risk from participating in the study.
    • Involved with, or a relative of, someone directly involved in the conduct of the study.
    • Any known cognitive impairment (for example, Alzheimer's disease)
17. Previous or current treatment (within 90 days of screening) with monoclonal antibodies directed at PCSK9.

Contacts and Locations

Locations

United States, Florida

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States, 32216

United States, Indiana

Midwest Institute For Clinical Research

Indianapolis, Indiana, United States, 46260

United States, New York

Mount Sinai Icahn School of Medicine

New York, New York, United States, 10029

United States, Ohio

Metabolic And Atherosclerosis Research Center

Cincinnati, Ohio, United States, 45227

Sterling Research Group

Cincinnati, Ohio, United States, 45246

United States, Tennessee

Wellmont CVA Heart Institute

Greeneville, Tennessee, United States, 37745

United States, Texas

Amarillo Heart Clinical Research Institute, Inc.

Amarillo, Texas, United States, 79106

United States, Virginia

National Clinical Research, Inc.

Richmond, Virginia, United States, 23294

Canada, British Columbia

St. Paul's Hospital

Vancouver, British Columbia, Canada, V6Z 1Y6

Canada, Manitoba

St. Boniface Hospital

Winnipeg, Manitoba, Canada, R2H 2A6

Canada, Newfoundland and Labrador

Eastern Regional Health Authority, Patient Research Centre

St. Johns, Newfoundland and Labrador, Canada, A1B 3V6

Canada, Ontario

Brampton Research Associates

Brampton, Ontario, Canada, L6Z 4N5

Lawson Health Research Institute

London, Ontario, Canada, N6C 2R5

St. Michael's Hospital

Toronto, Ontario, Canada, M5C 2T2

Canada, Quebec

ECOGENE-21 Clinical Trials Center

Chicoutimi, Quebec, Canada, G7H 7K9

Clinic Sante Cardio MC

Montreal, Quebec, Canada, H1T 3Y7

Institut de Recherches Cliniques de Montreal

Montreal, Quebec, Canada, H2W 1R7

Université Laval Quebec

Quebec City, Quebec, Canada, G1V 4G5

Clinique des maladies lipidique Quebec

Quebec City, Quebec, Canada, G1V 4W2

Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke (CIUSSS de l'Estrie - CHUS)

Sherbrooke, Quebec, Canada, J1H 5N4

Germany

Medical University Berlin

Berlin, Germany, 12203

Medical Center Essen

Essen, Germany, 45355

University Hospital Frankfurt

Frankfurt, Germany, 60590

University Heart Center Hamburg

Hamburg, Germany, 20251

Medical University Hospital Heidelberg, Internal medicine III

Heidelberg, Germany, 69120

Technical University Munich, German Heart Center

Munich, Germany, 80636

Netherlands

Amsterdam Medical Center

Amsterdam, Netherlands, 1105 AZ

Haga Hospital

Den Haag, Netherlands, 2545 CH

Deventer Ziekenhuis

Deventer, Netherlands, 7416 SE

Andromed Eindhoven

Eindhoven, Netherlands, 5611 NV

Admiraal de Ruyter Hospital, Cardiology

Goes, Netherlands, 4462 RA

Bethesda Diabetes Research Center

Hoogeveen, Netherlands, 7909 AA

Medisch Centrum Gorecht

Hoogezand, Netherlands, 9603 AE

VOC Hoorn

Hoorn, Netherlands, 0031229284320

Leids Universitair Medisch Centrum (LUMC)

Leiden, Netherlands, 2333 ZA

Andromed Rotterdam

Rotterdam, Netherlands, 3021 HC

Diakonessenhuis, Vascular Policlinic

Utrecht, Netherlands, 3582 KE

UMC Utrecht

Utrecht, Netherlands, 3584 CX

VieCurie Venlo, Cardiology

Venlo, Netherlands, 5912 BL

Albert Schweitzer Hospital, Cardiology

Zwijndrecht, Netherlands, 3331 LZ

United Kingdom

Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom, B15 2TH

Edinburgh Royal Infirmary

Edinburgh, United Kingdom, EH16 4SA

The Royal Devon and Exeter NHS Trust

Exeter, United Kingdom, EX2 5DW

Fowey River Practice

Fowey, United Kingdom, PL23 1DT

Buckinghamshire NHS Trust

High Wycombe, United Kingdom, HP11 2TT

Oak Tree Surgery

Liskeard, United Kingdom, Oak Tree Surgery

Royal Free Hospital

London, United Kingdom, NW3 2QG

Central Manchester University Hospital NHS Foundation Trust

Manchester, United Kingdom, M13 9WL

The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital

Newcastle upon Tyne, United Kingdom, NE1 4LP

The Alverton Practice

Penzance, United Kingdom, TR18 4JH

Knowle House Surgery

Plymouth, United Kingdom, PL5 3JB

Brannel Surgery

St. Austell, United Kingdom, St. Austell

Rame Medical Ltd (Rame Research)

Torpoint, United Kingdom, PL11 2TB

Worcestershire Acute NHS Trust

Worcester, United Kingdom, WR5 1DD

Sponsors and Collaborators

The Medicines Company

Investigators

• Principal Investigator: Kausik K Ray, MD; Department of Public Health and Primary Care, Imperial College London, Reynolds Building

  Study Documents (Full-Text)

Documents provided by The Medicines Company:

Study Protocol  [PDF] April 12, 2016

Statistical Analysis Plan  [PDF] January 11, 2016

More Information

Publications:

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Dias CS, Shaywitz AJ, Wasserman SM, Smith BP, Gao B, Stolman DS, Crispino CP, Smirnakis KV, Emery MG, Colbert A, Gibbs JP, Retter MW, Cooke BP, Uy ST, Matson M, Stein EA. Effects of AMG 145 on low-density lipoprotein cholesterol levels: results from 2 randomized, double-blind, placebo-controlled, ascending-dose phase 1 studies in healthy volunteers and hypercholesterolemic subjects on statins. J Am Coll Cardiol. 2012 Nov 6;60(19):1888-98. doi: 10.1016/j.jacc.2012.08.986. Epub 2012 Oct 17.

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Foley KA, Simpson RJ Jr, Crouse JR 3rd, Weiss TW, Markson LE, Alexander CM. Effectiveness of statin titration on low-density lipoprotein cholesterol goal attainment in patients at high risk of atherogenic events. Am J Cardiol. 2003 Jul 1;92(1):79-81. doi: 10.1016/s0002-9149(03)00474-0. No abstract available.

Foody JM, Sajjan SG, Hu XH, Ramey DR, Neff DR, Tershakovec AM, Tomassini JE, Wentworth C, Tunceli K. Loss of early gains in low-density lipoprotein cholesterol goal attainment among high-risk patients. J Clin Lipidol. 2010 Mar-Apr;4(2):126-32. doi: 10.1016/j.jacl.2010.01.007. Epub 2010 Feb 6.

ALN TTRSC-001; EudraCT 2012 004203 12

ALN-TTRSC-002; EudraCT 2013 002856 33

Geisbert TW, Hensley LE, Kagan E, Yu EZ, Geisbert JB, Daddario-DiCaprio K, Fritz EA, Jahrling PB, McClintock K, Phelps JR, Lee AC, Judge A, Jeffs LB, MacLachlan I. Postexposure protection of guinea pigs against a lethal ebola virus challenge is conferred by RNA interference. J Infect Dis. 2006 Jun 15;193(12):1650-7. doi: 10.1086/504267. Epub 2006 May 10.

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Nag SS, Daniel GW, Bullano MF, Kamal-Bahl S, Sajjan SG, Hu H, Alexander C. LDL-C goal attainment among patients newly diagnosed with coronary heart disease or diabetes in a commercial HMO. J Manag Care Pharm. 2007 Oct;13(8):652-63. doi: 10.18553/jmcp.2007.13.8.652.

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wright RS, Collins MG, Stoekenbroek RM, Robson R, Wijngaard PLJ, Landmesser U, Leiter LA, Kastelein JJP, Ray KK, Kallend D. Effects of Renal Impairment on the Pharmacokinetics, Efficacy, and Safety of Inclisiran: An Analysis of the ORION-7 and ORION-1 Studies. Mayo Clin Proc. 2020 Jan;95(1):77-89. doi: 10.1016/j.mayocp.2019.08.021. Epub 2019 Oct 17.

Ray KK, Stoekenbroek RM, Kallend D, Nishikido T, Leiter LA, Landmesser U, Wright RS, Wijngaard PLJ, Kastelein JJP. Effect of 1 or 2 Doses of Inclisiran on Low-Density Lipoprotein Cholesterol Levels: One-Year Follow-up of the ORION-1 Randomized Clinical Trial. JAMA Cardiol. 2019 Nov 1;4(11):1067-1075. doi: 10.1001/jamacardio.2019.3502.

Leiter LA, Teoh H, Kallend D, Wright RS, Landmesser U, Wijngaard PLJ, Kastelein JJP, Ray KK. Inclisiran Lowers LDL-C and PCSK9 Irrespective of Diabetes Status: The ORION-1 Randomized Clinical Trial. Diabetes Care. 2019 Jan;42(1):173-176. doi: 10.2337/dc18-1491. Epub 2018 Nov 28.

Ray KK, Stoekenbroek RM, Kallend D, Leiter LA, Landmesser U, Wright RS, Wijngaard P, Kastelein JJP. Effect of an siRNA Therapeutic Targeting PCSK9 on Atherogenic Lipoproteins: Prespecified Secondary End Points in ORION 1. Circulation. 2018 Sep 25;138(13):1304-1316. doi: 10.1161/CIRCULATIONAHA.118.034710.

Ray KK, Landmesser U, Leiter LA, Kallend D, Dufour R, Karakas M, Hall T, Troquay RP, Turner T, Visseren FL, Wijngaard P, Wright RS, Kastelein JJ. Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol. N Engl J Med. 2017 Apr 13;376(15):1430-1440. doi: 10.1056/NEJMoa1615758. Epub 2017 Mar 17.

• Responsible Party: The Medicines Company
• ClinicalTrials.gov Identifier: NCT02597127
• Other Study ID Numbers: MDCO-PCS-15-01
• First Posted: November 5, 2015
• Results First Posted: May 17, 2019
• Last Update Posted: May 17, 2019
• Last Verified: April 2019

Additional relevant MeSH terms:

Cardiovascular Diseases; Atherosclerosis; Hyperlipoproteinemia Type II; Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Hyperlipoproteinemias; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases