Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Donidalorsen (IONIS-PKK-LRx) Administered Subcutaneously to 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 Donidalorsen administered subcutaneously to Healthy Volunteers

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Placebo
* Drug: Donidalorsen


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 18-65 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Donidalorsen<br>Ascending single and multiple doses of Donidalorsen administered subcutaneously | Drug: Donidalorsen<br>* Donidalorsen administered subcutaneously<br>* Other names: IONIS-PKK-LRx;|
| Placebo Comparator: Placebo (sterile saline 0.9%)<br>Calculated volume to match active comparator | 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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IONIS PKK-LRx