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

NCT03101878 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ISIS 757456-CS1
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Volunteers

Keywords

Healthy Volunteers, IONIS AGT-Lrx

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Pharmacokinetics after single and multiple doses of IONIS AGT-LRx

  Up to 127 days

• Pharmacodynamics of IONIS AGT-LRx (Changes in plasma AGT Levels)

  Up to 127 days

Study Arms (2)

Ionis AGT-LRx

EXPERIMENTAL

Ascending single and multiple doses of Ionis AGT-LRx administered subcutaneously.

Drug: Ionis AGT-LRx

Placebo

PLACEBO COMPARATOR

Saline .9%

Drug: Placebo

Interventions

Ionis AGT-LRx DRUG

Ascending single and multiple doses of Ionis AGT-LRx administered subcutaneously

Ionis AGT-LRx

Placebo DRUG

Saline .9%

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (1)

Syneos Health

Toronto, Ontario, M5V 2T3, Canada

Location

Related Publications (1)

• 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.

  PMID: 34222719 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: April 5, 2017
• Study Start: April 5, 2017
• Primary Completion: March 29, 2018
• Study Completion: August 1, 2018
• Last Updated: August 21, 2018

Record last verified: 2018-08

Locations

CA (1)