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

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: Ionis AGT-LRx; Drug: Placebo

• Registration Number: NCT03101878
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-03-06
• Study First Submitted QC: 2017-03-29
• Study Start: 2017-04-05
• Study First Posted: 2017-04-05
• Primary Completion: 2018-03-29
• Status Verified: 2018-08
• Study Completion: 2018-08-01
• Last Update Submitted: 2018-08-20
• Last Update Posted: 2018-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 62

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ionis AGT-LRx	Ionis AGT-LRx	Ascending single and multiple doses of Ionis AGT-LRx administered subcutaneously.
Placebo	Placebo	Saline .9%

Primary Outcome Measures

Name	Time	Method
Incidence and severity of adverse events that are related to treatment with IONIS AGT-LRx	Up to 127 days	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
Any observed changes in Blood Pressure measurements, ECGs, or laboratory tests from baseline	Up to 127 days	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Syneos Health; 🇨🇦 Toronto, Ontario, Canada