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

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

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Ionis AGT-LRx
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ionis AGT-LRx<br>Ascending single and multiple doses of Ionis AGT-LRx administered subcutaneously. | Drug: Ionis AGT-LRx<br>* Ascending single and multiple doses of Ionis AGT-LRx administered subcutaneously<br>|
| Placebo Comparator: Placebo<br>Saline .9% | Drug: Placebo<br>* Saline .9%<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteers, IONIS AGT-Lrx