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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
The Medicines Company
ClinicalTrials.gov Identifier:
NCT02597127
First received: November 3, 2015
Last updated: May 5, 2017
Last verified: September 2016
  Purpose
This study is a Phase II, placebo-controlled, double-blind, randomized trial in 480 subjects with atherosclerotic cardiovascular disease (ASCVD) or ASCVD-risk equivalents (eg, 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 Intervention Phase
Atherosclerotic Cardiovascular Disease Familial Hypercholesterolemia Diabetes Drug: ALN-PCSSC Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by The Medicines Company:

Primary Outcome Measures:
  • Percentage change in LDL-C from baseline to Day 180. [ Time Frame: Baseline to 180 days ]

Enrollment: 501
Study Start Date: January 2016
Estimated Study Completion Date: August 2017
Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ALN-PCSSC 200mg (bi-annual dosing)
ALN-PCSSC 200mg s.c. administration once at day 1
Drug: ALN-PCSSC
ALN-PCSSC is a small interfering RNA that inhibits PCSK9 synthesis and is given as subcutaneous injections
Other Name: PCSK9 synthesis inhibitor
Experimental: ALN-PCSSC 300mg (bi-annual dosing)
ALN-PCSSC 300mg s.c. administration once at day 1
Drug: ALN-PCSSC
ALN-PCSSC is a small interfering RNA that inhibits PCSK9 synthesis and is given as subcutaneous injections
Other Name: PCSK9 synthesis inhibitor
Experimental: ALN-PCSSC 500mg (bi-annual dosing)
ALN-PCSSC 500 mg s.c. administration once at day 1
Drug: ALN-PCSSC
ALN-PCSSC is a small interfering RNA that inhibits PCSK9 synthesis and is given as subcutaneous injections
Other Name: PCSK9 synthesis inhibitor
Placebo Comparator: Normal Saline (bi-annual dosing)
Saline s.c. administration once at day 1
Drug: ALN-PCSSC
ALN-PCSSC is a small interfering RNA that inhibits PCSK9 synthesis and is given as subcutaneous injections
Other Name: PCSK9 synthesis inhibitor
Experimental: ALN-PCSSC 100mg (quarterly dosing)
ALN-PCSSC 100mg s.c. administration twice at day 1 and day 90
Drug: ALN-PCSSC
ALN-PCSSC is a small interfering RNA that inhibits PCSK9 synthesis and is given as subcutaneous injections
Other Name: PCSK9 synthesis inhibitor
Experimental: ALN-PCSSC 200mg (quarterly dosing)
ALN-PCSSC 200mg s.c. administration twice at day 1 and day 90
Drug: ALN-PCSSC
ALN-PCSSC is a small interfering RNA that inhibits PCSK9 synthesis and is given as subcutaneous injections
Other Name: PCSK9 synthesis inhibitor
Experimental: ALN-PCSSC 300mg (quarterly dosing)
ALN-PCSSC 300mg s.c. administration twice at day 1 and day 90
Drug: ALN-PCSSC
ALN-PCSSC is a small interfering RNA that inhibits PCSK9 synthesis and is given as subcutaneous injections
Other Name: PCSK9 synthesis inhibitor
Placebo Comparator: Normal Saline (quarterly dosing)
Saline s.c. administration twice at day 1 and day 90
Drug: ALN-PCSSC
ALN-PCSSC is a small interfering RNA that inhibits PCSK9 synthesis and is given as subcutaneous injections
Other Name: PCSK9 synthesis inhibitor

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  1. Male or female subjects ≥18 years of age.
  2. History of ASCVD or ASCVD-risk equivalents (symptomatic atherosclerosis, Type 2 diabetes, familial hypercholesterolemia, including subjects whose 10-year risk of a cardiovascular [CV] event assessed by Framingham Risk Score (by Framingham Risk Score >20%) or equivalent has a target LDL-C of < 100mg/dL)
  3. Serum LDL-C ≥1.8 mmol/L (≥70 mg/dL) for ASCVD subjects or ≥2.6 mmol/L (≥100 mg/dL) for ASCVD-risk equivalent subjects 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. Subjects on statins should be receiving a maximally tolerated dose (investigator's discretion)
  7. Subjects 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 subject 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 mmHg or diastolic blood pressure >110 mmHg prior to randomization despite anti-hypertensive therapy.
  8. Poorly controlled Type 2 diabetes, ie, 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), 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 subject is shorter than the duration of the trial (eg, 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 (ie, 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:

    • Inappropriate for this study, including subjects 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 subjects whose cooperation is doubtful due to drug abuse or alcohol dependency).
    • 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).
    • 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.
    • Involved with, or a relative of, someone directly involved in the conduct of the study.
    • Any known cognitive impairment (eg, Alzheimer's disease)
  17. Previous or current treatment (within 90 days of screening) with monoclonal antibodies directed at PCSK9.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02597127

  Show 54 Study Locations
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
  More Information

Publications:
ALN TTRSC-001; EudraCT 2012 004203 12
ALN-TTRSC-002; EudraCT 2013 002856 33
Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr, Tomaselli GF; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S1-45. doi: 10.1161/01.cir.0000437738.63853.7a. Epub 2013 Nov 12. Erratum in: Circulation. 2015 Dec 22;132(25):e396. Circulation. 2014 Jun 24;129(25 Suppl 2):S46-8.
World Health Organization Cardiovascular Statistics, 2011, http://www.who.int/mediacentre/factsheets/fs317/en/index.html

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT02597127     History of Changes
Other Study ID Numbers: MDCO-PCS-15-01
Study First Received: November 3, 2015
Last Updated: May 5, 2017

Additional relevant MeSH terms:
Cardiovascular Diseases
Hypercholesterolemia
Hyperlipoproteinemia Type II
Atherosclerosis
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on June 27, 2017