Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS-APO(a)Rx in Participants With High Lipoprotein(a)
Condition: Elevated Lipoprotein(a)
Intervention: ISIS-APO(a)Rx; Placebo
Intervention description: ISIS-APO(a)Rx subcutaneously: 100 mg on Days 1, 8, 15, and 22; 200 mg on Days 29, 36, 43, and 50 unless down-titrated; and 300 mg on Days 57, 64, 71, and 78 unless down-titrated.; Normal saline as Placebo, subcutaneously on Days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: High Lipoprotein(a)

Summary:

      The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of
      ISIS-APO(a)Rx given to participants with high lipoprotein(a) for 12 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males or females aged 18-65 inclusive

          -  Females must be non-pregnant and non-lactating, and either surgically sterile (e.g.,
             tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or
             post-menopausal (defined as 12 months of spontaneous amenorrhea without an alternative
             medical cause and follicle-stimulating hormone (FSH) levels in the postmenopausal
             range for the laboratory involved)

          -  Males must be surgically sterile, abstinent or if engaged in sexual relations with a
             female of child-bearing potential, the participant must be using an acceptable
             contraceptive method from the time of signing the informed consent form until at least
             16 weeks after the last dose of Study Drug

          -  Body mass index (BMI) ≤40 kg/m2

          -  Lipoprotein(a) ≥50 and <175 mg/dL at time of screening (Cohort A)

          -  Lipoprotein(a) ≥175 mg/dL at time of screening (Cohort B)

        Exclusion Criteria:

          -  Clinically significant abnormalities in medical history (e.g., documented previous
             myocardial infarction, percutaneous coronary intervention (PCI), or major surgery
             within 3 months of screening, planned surgery that would occur during the study) or
             physical examination at screening

          -  Clinically significant abnormalities in screening laboratory values that would render
             a participant unsuitable for inclusion

          -  Active infection requiring systemic antiviral or antimicrobial therapy that will not
             be completed prior to Study Day 1

          -  Known history or positive test for human immunodeficiency virus (HIV), hepatitis C, or
             chronic hepatitis B

          -  Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or
             carcinoma in situ of the cervix that has been successfully treated

          -  History of bleeding diathesis or coagulopathy

          -  Recent history of, or current drug or alcohol abuse

          -  Participant with Lp(a) ≥50 and <175 mg/dL may not receive concomitant niacin therapy
             during the period 8 weeks prior to screening through the end of the Post-Treatment
             Evaluation Period

          -  Use of statins, ezetimibe or fibrates unless on a stable regimen for at least 8 weeks
             prior to dosing and will remain on a stable regimen for the duration of the study

          -  Use of lipid or Lp(a)-specific apheresis within 4 weeks prior to Screening through the
             end of the Post-Treatment Evaluation Period

          -  Use of concomitant drugs (including herbal or over-the-counter (OTC) medications other
             than ibuprofen, Benadryl or topical steroids) unless authorized by the Sponsor Medical
             Monitor

          -  Blood donation of 50-499 mL within 30 days of screening or of >499 mL within 8 weeks
             of screening

          -  Have any other conditions, which, in the opinion of the Investigator would make the
             participant unsuitable for inclusion, or could interfere with the participant
             participating in or completing the study