Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ionis AGT-LRx in Healthy Volunteers

A Blinded, Placebo-Controlled, Dose-Escalation, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ISIS 757456 Administered Subcutaneously to Healthy Volunteers

The purpose is to assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS AGT-LRx in up to 82 Healthy Volunteers

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: Ionis AGT-LRx

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5V 2T3
      • Syneos Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• 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 18-60 inclusive and weighing ≥ 50 kg 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/m
• Agree to conduct at home blood pressure monitoring (in triplicate using study provided device) every morning and every evening throughout study participation for Single-Dose Cohort subjects and every morning for Multiple-Dose Cohort subjects

Exclusion Criteria:

• Treatment with another Study Drug, biological agent, or device within one-month of Screening
• Subject with borderline orthostatic hypotension defined as a fall in systolic blood pressure of ≥ 17 mmHg or diastolic blood pressure of ≥ 7 mmHg when they assume a standing position (within 3 minutes of standing up)
• Use of nicotine-containing products or illicit drugs
• Considered unsuitable for inclusion by the Principal Investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Saline .9%	Drug: Placebo; Saline .9%
EXPERIMENTAL: Ionis AGT-LRx; Ascending single and multiple doses of Ionis AGT-LRx administered subcutaneously.	Drug: Ionis AGT-LRx; Ascending single and multiple doses of Ionis AGT-LRx administered subcutaneously

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 IONIS AGT-LRx	The safety and tolerability of single and multiple doses of IONIS AGT-LRx will be assessed by determining the incidence, severity, and dose relationship of adverse events that are related to treatment with IONIS AGT-LRx	Up to 127 days
Any observed changes in Blood Pressure measurements, ECGs, or laboratory tests from baseline	The safety and tolerability of single and multiple doses of IONIS AGT-LRx will be assessed by reviewing any observed changes in Blood Pressure measurements, physical exam, and laboratory tests from baseline by dose. Results in subjects dosed with IONIS AGT-LRx will be compared with those from subjects dosed with placebo.	Up to 127 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics after single and multiple doses of IONIS AGT-LRx	The plasma pharmacokinetics (concentration-time results) of IONIS AGT-LRx will be assessed following single and multiple dose SC administration	Up to 127 days
Pharmacodynamics of IONIS AGT-LRx (Changes in plasma AGT Levels)	Effects of IONIS AGT-LRx on changes in AGT plasma protein compared to baseline.	Up to 127 days

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Morgan ES, Tami Y, Hu K, Brambatti M, Mullick AE, Geary RS, Bakris GL, Tsimikas S. Antisense Inhibition of Angiotensinogen With IONIS-AGT-LRx: Results of Phase 1 and Phase 2 Studies. JACC Basic Transl Sci. 2021 May 3;6(6):485-496. doi: 10.1016/j.jacbts.2021.04.004. eCollection 2021 Jun.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 5, 2017
• Primary Completion (ACTUAL): March 29, 2018
• Study Completion (ACTUAL): August 1, 2018

Study Registration Dates

• First Submitted: March 6, 2017
• First Submitted That Met QC Criteria: March 29, 2017
• First Posted (ACTUAL): April 5, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 21, 2018
• Last Update Submitted That Met QC Criteria: August 20, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Healthy Volunteers, IONIS AGT-Lrx
• Other Study ID Numbers: ISIS 757456-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