An Extension Trial of Inclisiran in Participants With Cardiovascular Disease and High Cholesterol
Condition: Atherosclerotic Cardiovascular Disease; Symptomatic Atherosclerosis; Type2 Diabetes; Familial Hypercholesterolemia
MeSH terms: Cardiovascular Diseases; Atherosclerosis; Hyperlipoproteinemia Type II; Hypercholesterolemia
Intervention: Inclisiran; Evolocumab
Intervention description: Inclisiran is a synthetic, chemically modified small interfering ribonucleic acid (siRNA) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) messenger ribonucleic acid (mRNA) with a covalently attached triantennary N-acetylgalactosamine (GalNAc) ligand.; Evolocumab is a fully human monoclonal antibody that inhibits PCSK9.
Intervention MeSH terms: Evolocumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 382.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This clinical study was designed to assess the efficacy, safety, and tolerability of
      long-term dosing of inclisiran and evolocumab given as subcutaneous injections in
      participants with high cardiovascular risk and elevated low-density lipoprotein cholesterol
      (LDL-C).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Completion of Study MDCO-PCS-15-01 and no contraindication to receiving inclisiran or
             evolocumab.

          2. 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.

          3. Willing to self-inject.

        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's] judgment).

          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. 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).

          4. Active liver disease defined as any known current infectious, neoplastic, or metabolic
             pathology of the liver; unexplained alanine aminotransferase (ALT) or aspartate
             aminotransferase (AST) elevation greater than 2 times upper limit of normal (ULN); or
             total bilirubin elevation greater than 1.5 times ULN at study entry visit.

          5. Females who are pregnant or nursing, or who are of childbearing potential and
             unwilling to use at least two methods of contraception (for example, oral
             contraceptives, barrier methods, approved contraceptive implant, long-term injectable
             contraception, intrauterine device) for the entire duration of the study. Exemptions
             from this criterion are

               -  Women >2 years postmenopausal (defined as 1 year or longer since their last
                  menstrual period) AND more than 55 years of age

               -  Postmenopausal women (as defined above) and less than 55 years old with a
                  negative pregnancy test within 24 hours of enrollment

               -  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 (that is, condom with spermicide).

          7. Treatment with investigational medicinal products other than inclisiran or devices
             within 30 days or five half˗lives, whichever is longer.

          8. Planned use of investigational medicinal products other than inclisiran or devices
             during the course of the study.

          9. Participants with a history of a serious hypersensitivity reaction to evolocumab or
             any of the excipients

         10. Previous or current treatment (within 90 days of study entry) with monoclonal
             antibodies directed towards PCSK9.

         11. 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 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).

               -  Involved with, or a relative of, someone directly involved in the conduct of the
                  study.

               -  Any known cognitive impairment (for example, Alzheimer's Disease).