Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Donidalorsen (IONIS-PKK-LRx) Administered Subcutaneously to Healthy Volunteers

A Double-Blind, Placebo-Controlled, Dose-Escalation Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 721744, an Antisense Oligonucleotide Inhibitor of PKK, Administered Subcutaneously to Healthy Volunteers

The purpose is to assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Donidalorsen administered subcutaneously to Healthy Volunteers

Inclusion Criteria:

• Must have given written informed consent and be able to comply with all study requirements
• Healthy males or females aged 18-65 inclusive at the time of Informed Consent
• Females must be non-pregnant and non-lactating, and either surgically sterile or post- menopausal
• Males must be surgically sterile, abstinent or using an acceptable contraceptive method
• BMI <35 kg/m2

Exclusion Criteria:

• Clinically-significant abnormalities in medical history including acute coronary syndrome, major surgery within 3 months of Screening, planned surgery that would occur during the study or physical examination or other screening results such as ECGs at Screening
• Clinically significant hematologic, chemistry, and urine abnormalities
• Treatment with another Study Drug, biological agent, or device within 4 weeks of Screening
• History of bleeding diathesis or coagulopathy
• Smoking >10 cigarettes per day
• Considered unsuitable for inclusion by the Principal Investigator
• Current use of concomitant medications (including herbal or OTC medications) unless approved by Sponsor Medical Monitor
• Known history or positive test for HIV, hepatitis C or chronic hepatitis B
• Blood donation within 30 days of screening