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Atherosclerotic Cardiovascular DiseasePhase 2ORION-1NCT02597127

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

A Phase 2 study testing ALN-PCSSC and Normal Saline in people with Atherosclerotic Cardiovascular Disease and Familial Hypercholesterolemia, run by The Medicines Company at 54 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
ALN-PCSSC and Normal Saline
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
501 participants
Where
54 sitesin 5 countries
Study dates
Jan 2016to 7 Jun 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female participants ≥18 years of age.
  • 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]).
  • 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.
  • Fasting triglyceride <4.52 mmol/L (<400 mg/dL) at screening.
  • Calculated glomerular filtration rate 30 mL/min or higher by estimated glomerular filtration rate (eGFR) using standardized local clinical methodology.
  • Participants on statins should be receiving a maximally tolerated dose (investigator's discretion).
  • 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.
  • Willing and able to give informed consent before initiation of any study-related procedures and willing to comply with all required study procedures.

Who cannot join

  • 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.
  • 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.
  • New York Heart Association (NYHA) class II, III, or IV heart failure or last known left ventricular ejection fraction <30%.
  • Cardiac arrhythmia within 3 months prior to randomization that is not controlled by medication or via ablation.
  • Any history of hemorrhagic stroke.
  • Major adverse cardiac event within 6 months prior to randomization.
Show all 23Show fewer
  • Uncontrolled severe hypertension: systolic blood pressure >180 millimeters of mercury (mmHg) or diastolic blood pressure >110 mmHg prior to randomization despite anti-hypertensive therapy.
  • Poorly controlled Type 2 diabetes, such as, glycated hemoglobin A1c (HbA1c)>10.0% prior to randomization.
  • 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.
  • 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.
  • 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.
  • Males who are unwilling to use an acceptable method of birth control during the entire study period (such as, condom with spermicide).
  • Known history of alcohol and/or drug abuse within the last 5 years.
  • Treatment with other investigational medicinal products or devices within 30 days or five half˗lives, whichever is longer.
  • Use of other investigational medicinal products or devices during the course of the study.
  • 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)
  • Previous or current treatment (within 90 days of screening) with monoclonal antibodies directed at PCSK9.

Trial locations and contacts

54 sites in 5 countries.

54 sites in 5 countries

Netherlands14 sites

  • Amsterdam Medical Center

    Amsterdam, 1105 AZ

  • Deventer Ziekenhuis

    Deventer, 7416 SE

  • Andromed Eindhoven

    Eindhoven, 5611 NV

  • Admiraal de Ruyter Hospital, Cardiology

    Goes, 4462 RA

  • Bethesda Diabetes Research Center

    Hoogeveen, 7909 AA

  • Medisch Centrum Gorecht

    Hoogezand, 9603 AE

  • VOC Hoorn

    Hoorn, 0031229284320

  • Leids Universitair Medisch Centrum (LUMC)

    Leiden, 2333 ZA

  • Andromed Rotterdam

    Rotterdam, 3021 HC

  • Haga Hospital

    The Hague, 2545 CH

  • Diakonessenhuis, Vascular Policlinic

    Utrecht, 3582 KE

  • UMC Utrecht

    Utrecht, 3584 CX

  • VieCurie Venlo, Cardiology

    Venlo, 5912 BL

  • Albert Schweitzer Hospital, Cardiology

    Zwijndrecht, 3331 LZ

Other trials in Netherlands

United Kingdom14 sites

  • Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust

    Birmingham, B15 2TH

  • Edinburgh Royal Infirmary

    Edinburgh, EH16 4SA

  • The Royal Devon and Exeter NHS Trust

    Exeter, EX2 5DW

  • Fowey River Practice

    Fowey, PL23 1DT

  • Buckinghamshire NHS Trust

    High Wycombe, HP11 2TT

  • Oak Tree Surgery

    Liskeard, Oak Tree Surgery

  • Royal Free Hospital

    London, NW3 2QG

  • Central Manchester University Hospital NHS Foundation Trust

    Manchester, M13 9WL

  • The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital

    Newcastle upon Tyne, NE1 4LP

  • The Alverton Practice

    Penzance, TR18 4JH

  • Knowle House Surgery

    Plymouth, PL5 3JB

  • Brannel Surgery

    St Austell, St. Austell

  • Rame Medical Ltd (Rame Research)

    Torpoint, PL11 2TB

  • Worcestershire Acute NHS Trust

    Worcester, WR5 1DD

Other trials in United Kingdom

Canada12 sites

  • Brampton Research Associates

    Brampton, Ontario, L6Z 4N5

  • ECOGENE-21 Clinical Trials Center

    Chicoutimi, Quebec, G7H 7K9

  • Lawson Health Research Institute

    London, Ontario, N6C 2R5

  • Clinic Sante Cardio MC

    Montreal, Quebec, H1T 3Y7

  • Institut de Recherches Cliniques de Montreal

    Montreal, Quebec, H2W 1R7

  • Université Laval Quebec

    Québec, Quebec, G1V 4G5

  • Clinique des maladies lipidique Quebec

    Québec, Quebec, 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, J1H 5N4

  • Eastern Regional Health Authority, Patient Research Centre

    St. John's, Newfoundland and Labrador, A1B 3V6

  • St. Michael's Hospital

    Toronto, Ontario, M5C 2T2

  • St. Paul's Hospital

    Vancouver, British Columbia, V6Z 1Y6

  • St. Boniface Hospital

    Winnipeg, Manitoba, R2H 2A6

Other trials in Canada

United States8 sites

  • Amarillo Heart Clinical Research Institute, Inc.

    Amarillo, Texas, 79106

  • Metabolic And Atherosclerosis Research Center

    Cincinnati, Ohio, 45227

  • Sterling Research Group

    Cincinnati, Ohio, 45246

  • Wellmont CVA Heart Institute

    Greeneville, Tennessee, 37745

  • Midwest Institute For Clinical Research

    Indianapolis, Indiana, 46260

  • Jacksonville Center for Clinical Research

    Jacksonville, Florida, 32216

  • Mount Sinai Icahn School of Medicine

    New York, New York, 10029

  • National Clinical Research, Inc.

    Richmond, Virginia, 23294

Other trials in United States

Germany6 sites

  • Medical University Berlin

    Berlin, 12203

  • Medical Center Essen

    Essen, 45355

  • University Hospital Frankfurt

    Frankfurt, 60590

  • University Heart Center Hamburg

    Hamburg, 20251

  • Medical University Hospital Heidelberg, Internal medicine III

    Heidelberg, 69120

  • Technical University Munich, German Heart Center

    Munich, 80636

Other trials in Germany

About this study

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

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).

Read the 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
Being tested
ALN-PCSSC, Normal Saline
Medical subject headings
Atherosclerosis, Hyperlipoproteinemia Type II, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ALN-PCSSCDrug

    Also called PCSK9 synthesis inhibitor, Inclisiran

    ALN-PCSSC is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis and is given as SC injections

  • Normal SalineDrug

    Saline (sterile, normal, 0.9%) solution given as SC injections

Study groups in NCT02597127
Study groupRoleWhat they receive
ALN-PCSSC 200 mg (bi-annual dosing)ExperimentalALN-PCSSC 200 milligram (mg) SC administration once at Day 1
Receives: Drug: ALN-PCSSC
ALN-PCSSC 300 mg (bi-annual dosing)ExperimentalALN-PCSSC 300 mg SC administration once at Day 1
Receives: Drug: ALN-PCSSC
ALN-PCSSC 500 mg (bi-annual dosing)ExperimentalALN-PCSSC 500 mg SC administration once at Day 1
Receives: Drug: ALN-PCSSC
Normal Saline (bi-annual dosing)Placebo comparatorSaline SC administration once at Day 1
Receives: Drug: Normal Saline
ALN-PCSSC 100 mg (quarterly dosing)ExperimentalALN-PCSSC 100 mg SC administration twice at Day 1 and Day 90
Receives: Drug: ALN-PCSSC
ALN-PCSSC 200 mg (quarterly dosing)ExperimentalALN-PCSSC 200 mg SC administration twice at Day 1 and Day 90
Receives: Drug: ALN-PCSSC
ALN-PCSSC 300 mg (quarterly dosing)ExperimentalALN-PCSSC 300 mg SC administration twice at Day 1 and Day 90
Receives: Drug: ALN-PCSSC
Normal Saline (quarterly dosing)Placebo comparatorSaline SC administration twice at Day 1 and Day 90
Receives: Drug: Normal Saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage Change in LDL-C From Baseline to Day 180

    Percent Change in LDL-C (beta-quantification) from Baseline to Day 180 in MITT Population

    Measured: Baseline to 180 days

Secondary outcomes (9)

  1. Percentage Change in LDL-C From Baseline to Day 90

    Percent Change in LDL-C (beta-quantification) from Baseline to Day 90 in MITT Population

    Measured: Baseline to 90 days

  2. Percent Change From Baseline In LDL-C Levels At 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.

    Measured: Baseline, 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

    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.

    Measured: Baseline, Day 180, Day 210

  4. Number of Participants With Individual Responsiveness as Measured By LDL-C Levels at Day 90 and 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.

    Measured: Day 90, Day 180

  5. Number of Participants With Greater Or Equal To 50% LDL-C Reduction From Baseline At 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.

    Measured: Baseline, Day 180

  6. Percentage Change in PCSK9 Levels From Baseline at 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.

    Measured: Baseline, Day 180

  7. Percentage Change in Other Lipids and Apolipoproteins From Baseline to 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.

    Measured: Baseline, Day 180

  8. Number of Participants Who Attained Global Lipid Modification Targets for Level of Atherosclerotic Cardiovascular Disease Risk

    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.

    Measured: Baseline, Day 180

  9. Percentage Change in Other Lipids and Inflammatory Markers From Baseline to 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.

    Measured: Baseline, Day 180

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2015 (estimated)
  2. Study startJan 2016
  3. Primary completion7 Jun 2017
  4. Study completion7 Jun 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
501 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02597127
Sponsor's protocol ID
MDCO-PCS-15-01
Acronym
ORION-1
Status last verified
Apr 2019
First submitted
3 Nov 2015
Last updated
17 May 2019
Data monitoring committee
Yes

Publications

  • Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derre A, Villeger L, Farnier M, Beucler I, Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin P, Weissenbach J, Prat A, Krempf M, Junien C, Seidah NG, Boileau C. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003 Jun;34(2):154-6. doi: 10.1038/ng1161.

    PubMed 12730697

  • Ashwell G, Morell AG. The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins. Adv Enzymol Relat Areas Mol Biol. 1974;41(0):99-128. doi: 10.1002/9780470122860.ch3. No abstract available.

    PubMed 4609051

  • Banerjee Y, Shah K, Al-Rasadi K. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med. 2012 Jun 21;366(25):2425-6; author reply 2426. doi: 10.1056/NEJMc1204929. No abstract available.

    PubMed 22716984

  • Milazzo L, Antinori S. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med. 2012 Jun 21;366(25):2425; author reply 2426. doi: 10.1056/NEJMc1204929. No abstract available.

    PubMed 22716983

  • Cholesterol Treatment Trialists' (CTT) Collaboration; Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010 Nov 13;376(9753):1670-81. doi: 10.1016/S0140-6736(10)61350-5. Epub 2010 Nov 8.

    PubMed 21067804

  • Coelho T, Adams D, Silva A, Lozeron P, Hawkins PN, Mant T, Perez J, Chiesa J, Warrington S, Tranter E, Munisamy M, Falzone R, Harrop J, Cehelsky J, Bettencourt BR, Geissler M, Butler JS, Sehgal A, Meyers RE, Chen Q, Borland T, Hutabarat RM, Clausen VA, Alvarez R, Fitzgerald K, Gamba-Vitalo C, Nochur SV, Vaishnaw AK, Sah DW, Gollob JA, Suhr OB. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med. 2013 Aug 29;369(9):819-29. doi: 10.1056/NEJMoa1208760.

    PubMed 23984729

  • Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006 Mar 23;354(12):1264-72. doi: 10.1056/NEJMoa054013.

    PubMed 16554528

  • Davidson MH, Maki KC, Pearson TA, Pasternak RC, Deedwania PC, McKenney JM, Fonarow GC, Maron DJ, Ansell BJ, Clark LT, Ballantyne CM. Results of the National Cholesterol Education (NCEP) Program Evaluation ProjecT Utilizing Novel E-Technology (NEPTUNE) II survey and implications for treatment under the recent NCEP Writing Group recommendations. Am J Cardiol. 2005 Aug 15;96(4):556-63. doi: 10.1016/j.amjcard.2005.04.019.

    PubMed 16098311

  • 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.

    PubMed 23083772

  • Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001 May 24;411(6836):494-8. doi: 10.1038/35078107.

    PubMed 11373684

  • 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.

    PubMed 12842255

  • 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.

    PubMed 21122640

  • 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.

    PubMed 16703508

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ALN-PCSSC and Normal Saline in people with Atherosclerotic Cardiovascular Disease and Familial Hypercholesterolemia, run by The Medicines Company at 54 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 54 sites in Netherlands, United Kingdom, Canada, United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage Change in LDL-C From Baseline to Day 180 (time frame: Baseline to 180 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02597127, which also lists 42 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2019.

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