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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Donidalorsen; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M9L 3A2
      • Ionis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Donidalorsen; Ascending single and multiple doses of Donidalorsen administered subcutaneously	Drug: Donidalorsen; Donidalorsen administered subcutaneously; Other Names: ISIS 721744; IONIS-PKK-LRx
Placebo Comparator: Placebo (sterile saline 0.9%); Calculated volume to match active comparator	Drug: Placebo; Saline .9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events that are related to treatment with Donidalorsen	The safety and tolerability of multiple doses of Donidalorsen will be assessed by determining the incidence, severity, and dose relationship of adverse events that are related to treatment with Donidalorsen.	Up to 176 days
Peak plasma Concentration (Cmax) of Donidalorsen	Maximum Donidalorsen plasma concentration, Cmax (ug/mL) will be assessed following SC administration	Up to 176 days
Time to peak plasma Concentration (Tmax) of Donidalorsen	Time to peak Donidalorsen plasma concentration, Tmax (hours) will be assessed following SC administration	Up to 176 days
Effects of Donidalorsen on plasma PKK concentration	Effects of Donidalorsen on plasma PKK concentration after multiple doses of Donidalorsen compared to baseline	Up to 176 days

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2017
• Primary Completion (Actual): October 9, 2018
• Study Completion (Actual): October 9, 2018

Study Registration Dates

• First Submitted: August 17, 2017
• First Submitted That Met QC Criteria: August 23, 2017
• First Posted (Actual): August 28, 2017

Study Record Updates

• Last Update Posted (Actual): August 4, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: IONIS PKK-LRx
• Other Study ID Numbers: ISIS 721744-CS1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes