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

Thalassemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03165864
• Other study ID #: ISIS 702843-CS1
• Status: Completed
• Phase: Phase 1
• Start date: May 9, 2017
• Est. completion date: September 25, 2018

Study information

• Verified date: January 2019
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: September 25, 2018
• Est. primary completion date: September 25, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Thalassemia

Intervention

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

Other:
• Placebo
Saline .9%

Locations

Country	Name	City	State
Australia	Nucleus Network	Melbourne	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacodynamics after single and multiple doses of IONIS TMPRSS6-Lrx (Changes in transferrin saturation)	Effects of IONIS TMPRSS6-Lrx on changes (absolute and percent) in transferrin saturation compared to baseline	Up to 148 Days
Other	Pharmacodynamics after single and multiple doses of IONIS TMPRSS6-Lrx (Changes in serum iron)	Effects of IONIS TMPRSS6-Lrx on changes (absolute and percent) in serum iron compared to baseline	Up to 148 Days
Other	Pharmacodynamics after single and multiple doses of IONIS TMPRSS6-Lrx (Changes in hepcidin levels)	Effects of IONIS TMPRSS6-Lrx on changes (absolute and percent) in hepcidin levels compared to baseline	Up to 148 Days
Primary	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	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
Secondary	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
Secondary	Pharmacokinetics after single and multiple doses of IONIS TMPRSS6-Lrx (Plasma terminal elimination half-life (t1/2?z)	The plasma pharmacokinetics (Plasma terminal elimination half-life (t1/2?z) of Ionis TMPRSS6-Lrx will be assessed following single and multiple dose SC administration	Up to 148 Days
Secondary	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
Secondary	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