Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 702843 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 IONIS TMPRSS6-Lrx Administered Subcutaneously for up to 44 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 Single and Multiple Doses of ISIS 702843 Administered Subcutaneously to Healthy Volunteers

Conditions
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Thalassemia

Intervention / Treatment
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* Drug: IONIS TMPRSS6-Lrx
* Other: 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 18-65 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 < 32 kg/m2 Exclusion Criteria: Clinically significant abnormalities in medical history or physical examination Clinically significant lab abnormalities that would render a subject unsuitable for inclusion Known history or positive test for HIV, HCV, or HBV Treatment with another Study Drug, biological agent, or device within one-month of Screening or 5 half-lives of investigational agent, whichever is longer Smoking > 10 cigarettes per day Regular excessive use of alcohol within 6 months of screening Current use of concomitant medications other than occasional acetaminophen (paracetamol) or ibuprofen unless approved by Sponsor Medical Monitor Considered unsuitable for inclusion by the Investigator or Sponsor

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: IONIS TMPRSS6-Lrx<br>Ascending single and multiple doses of IONIS TMPRSS6-Lrx administered subcutaneously | Drug: IONIS TMPRSS6-Lrx<br>* Ascending single and multiple doses of IONIS TMPRSS6-Lrx administered subcutaneously<br>|
| Placebo Comparator: Placebo<br>Saline .9% | Other: 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 TMPRSS6-Lrx | The safety and tolerability of single and multiple doses of IONIS TMPRSS6-Lrx will be assessed by determining the incidence, severity, and dose relationship of adverse events that are related to treatment with IONIS TMPRSS6-Lrx | Up to 148 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics after single and multiple doses of IONIS TMPRSS6-Lrx (maximum observed drug concentration or Cmax) | The plasma pharmacokinetics (maximum observed drug concentration or Cmax) of Ionis TMPRSS6-Lrx will be assessed following single and multiple dose SC administration | Up to 148 Days | 
| Pharmacokinetics after single and multiple doses of IONIS TMPRSS6-Lrx (time taken to reach maximal concentration or Tmax) | The plasma pharmacokinetics (time taken to reach maximal concentration or Tmax) of Ionis TMPRSS6-Lrx will be assessed following single and multiple dose SC administration | Up to 148 Days | 
| Pharmacokinetics after single and multiple doses of IONIS TMPRSS6-Lrx (Plasma terminal elimination half-life (t1/2λz) | The plasma pharmacokinetics (Plasma terminal elimination half-life (t1/2λz) of Ionis TMPRSS6-Lrx will be assessed following single and multiple dose SC administration | Up to 148 Days | 
| Pharmacokinetics after single and multiple doses of IONIS TMPRSS6-Lrx (Partial areas under the plasma concentration-time curve from zero time (predose) to selected times (t) after the subcutaneous administration (AUCt) | The plasma pharmacokinetics (Partial areas under the plasma concentration-time curve from zero time (predose) to selected times (t) after the subcutaneous administration (AUCt) of Ionis TMPRSS6-Lrx will be assessed following single and multiple dose SC administration | Up to 148 Days | 
| Pharmacokinetics after single and multiple doses of IONIS TMPRSS6-Lrx (Percentage of the administered dose excreted in urine (% Dose Excreted) | The plasma pharmacokinetics (Percentage of the administered dose excreted in urine (% Dose Excreted) of Ionis TMPRSS6-Lrx will be assessed following single and multiple dose SC administration | Up to 148 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thalassaemia, IONIS TMPRSS6-Lrx