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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 702843 Administered Subcutaneously to Healthy Volunteers

Primary Purpose

Thalassemia

Status
Completed
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
IONIS TMPRSS6-Lrx
Placebo
Sponsored by
Ionis Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thalassemia focused on measuring Thalassaemia, IONIS TMPRSS6-Lrx

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Nucleus Network

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

IONIS TMPRSS6-Lrx

Placebo

Arm Description

Ascending single and multiple doses of IONIS TMPRSS6-Lrx administered subcutaneously

Saline .9%

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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
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
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
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

Full Information

First Posted
May 18, 2017
Last Updated
January 17, 2019
Sponsor
Ionis Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03165864
Brief Title
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 702843 Administered Subcutaneously to Healthy Volunteers
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
May 9, 2017 (Actual)
Primary Completion Date
September 25, 2018 (Actual)
Study Completion Date
September 25, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ionis Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose is to assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS TMPRSS6-Lrx Administered Subcutaneously for up to 44 Healthy Volunteers

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thalassemia
Keywords
Thalassaemia, IONIS TMPRSS6-Lrx

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IONIS TMPRSS6-Lrx
Arm Type
Experimental
Arm Description
Ascending single and multiple doses of IONIS TMPRSS6-Lrx administered subcutaneously
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Saline .9%
Intervention Type
Drug
Intervention Name(s)
IONIS TMPRSS6-Lrx
Intervention Description
Ascending single and multiple doses of IONIS TMPRSS6-Lrx administered subcutaneously
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Saline .9%
Primary Outcome Measure Information:
Title
Incidence and severity of adverse events that are related to treatment with IONIS TMPRSS6-Lrx
Description
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
Time Frame
Up to 148 Days
Secondary Outcome Measure Information:
Title
Pharmacokinetics after single and multiple doses of IONIS TMPRSS6-Lrx (maximum observed drug concentration or Cmax)
Description
The plasma pharmacokinetics (maximum observed drug concentration or Cmax) of Ionis TMPRSS6-Lrx will be assessed following single and multiple dose SC administration
Time Frame
Up to 148 Days
Title
Pharmacokinetics after single and multiple doses of IONIS TMPRSS6-Lrx (time taken to reach maximal concentration or Tmax)
Description
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
Time Frame
Up to 148 Days
Title
Pharmacokinetics after single and multiple doses of IONIS TMPRSS6-Lrx (Plasma terminal elimination half-life (t1/2λz)
Description
The plasma pharmacokinetics (Plasma terminal elimination half-life (t1/2λz) of Ionis TMPRSS6-Lrx will be assessed following single and multiple dose SC administration
Time Frame
Up to 148 Days
Title
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)
Description
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
Time Frame
Up to 148 Days
Title
Pharmacokinetics after single and multiple doses of IONIS TMPRSS6-Lrx (Percentage of the administered dose excreted in urine (% Dose Excreted)
Description
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
Time Frame
Up to 148 Days
Other Pre-specified Outcome Measures:
Title
Pharmacodynamics after single and multiple doses of IONIS TMPRSS6-Lrx (Changes in transferrin saturation)
Description
Effects of IONIS TMPRSS6-Lrx on changes (absolute and percent) in transferrin saturation compared to baseline
Time Frame
Up to 148 Days
Title
Pharmacodynamics after single and multiple doses of IONIS TMPRSS6-Lrx (Changes in serum iron)
Description
Effects of IONIS TMPRSS6-Lrx on changes (absolute and percent) in serum iron compared to baseline
Time Frame
Up to 148 Days
Title
Pharmacodynamics after single and multiple doses of IONIS TMPRSS6-Lrx (Changes in hepcidin levels)
Description
Effects of IONIS TMPRSS6-Lrx on changes (absolute and percent) in hepcidin levels compared to baseline
Time Frame
Up to 148 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Facility Information:
Facility Name
Nucleus Network
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
VIC 3004
Country
Australia

12. IPD Sharing Statement

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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 702843 Administered Subcutaneously to Healthy Volunteers

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