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

• ClinicalTrials.gov Identifier: NCT03165864
• Recruitment Status: Completed
• First Posted: May 24, 2017
• Last Update Posted: January 22, 2019
• Sponsor: Ionis Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Ionis Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: May 18, 2017
• First Posted Date: May 24, 2017
• Last Update Posted Date: January 22, 2019
• Actual Study Start Date: May 9, 2017
• Actual Primary Completion Date: September 25, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 22, 2017)

Incidence and severity of adverse events that are related to treatment with IONIS TMPRSS6-Lrx [ Time Frame: Up to 148 Days ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 22, 2017)

• Pharmacokinetics after single and multiple doses of IONIS TMPRSS6-Lrx (maximum observed drug concentration or Cmax) [ Time Frame: Up to 148 Days ]
  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) [ Time Frame: Up to 148 Days ]
  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) [ Time Frame: Up to 148 Days ]
  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) [ Time Frame: Up to 148 Days ]
  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) [ Time Frame: Up to 148 Days ]
  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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: May 22, 2017)

• Pharmacodynamics after single and multiple doses of IONIS TMPRSS6-Lrx (Changes in transferrin saturation) [ Time Frame: Up to 148 Days ]
  Effects of IONIS TMPRSS6-Lrx on changes (absolute and percent) in transferrin saturation compared to baseline
• Pharmacodynamics after single and multiple doses of IONIS TMPRSS6-Lrx (Changes in serum iron) [ Time Frame: Up to 148 Days ]
  Effects of IONIS TMPRSS6-Lrx on changes (absolute and percent) in serum iron compared to baseline
• Pharmacodynamics after single and multiple doses of IONIS TMPRSS6-Lrx (Changes in hepcidin levels) [ Time Frame: Up to 148 Days ]
  Effects of IONIS TMPRSS6-Lrx on changes (absolute and percent) in hepcidin levels compared to baseline

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• 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
• 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Thalassemia

Intervention

• Drug: IONIS TMPRSS6-Lrx
  Ascending single and multiple doses of IONIS TMPRSS6-Lrx administered subcutaneously
• Other: Placebo
  Saline .9%

Study Arms

• Experimental: IONIS TMPRSS6-Lrx
  Ascending single and multiple doses of IONIS TMPRSS6-Lrx administered subcutaneously
  Intervention: Drug: IONIS TMPRSS6-Lrx
• Placebo Comparator: Placebo
  Saline .9%
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 31, 2018): 36
• Original Estimated Enrollment (submitted: May 22, 2017): 44
• Actual Study Completion Date: September 25, 2018
• Actual Primary Completion Date: September 25, 2018 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia

Administrative Information

• NCT Number: NCT03165864
• Other Study ID Numbers: ISIS 702843-CS1
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Ionis Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Ionis Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Ionis Pharmaceuticals, Inc.
• Verification Date: January 2019