A study to evaluate the effect of ALN-PCSSC treatment on low-density lipoprotein cholesterol levels

Phase 1

• Conditions: Hypercholesterolemia; MedDRA version: 20.1Level: LLTClassification code 10020604Term: HypercholesterolemiaSystem Organ Class: 100000004861; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2015-003772-74-DE
• Lead Sponsor: The Medicines Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-10-23
• Last Update Posted: 24 September 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 480

Inclusion Criteria

1. Male or female subjects 18 years of age or older, and of any race.
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 or equivalent has a target LDL-C of < 100mg/dL) and receiving maximum-tolerated lipid-lowering therapy
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 the maximally tolerated dose
7. Subjects on lipid-lowering therapies (such as statins 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 written and informed consent before initiation of any study-related procedures and willing to comply with all required study procedures.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 240
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 240

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 Failure 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 (MACE) 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 II diabetes, ie, 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 one 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). 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.
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:
a. Inappropriate for this study, including subjects who are unable to communicate or to cooperate with the investigator.
b. 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).
c. 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).
d. Have any medical or surgical condition, which in the opinion of the investigator would put the subject at increased

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified