NCT02414594

Brief Summary

The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS APO(a)-LRx (ISIS 681257) given to healthy volunteer subjects.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Apr 2015

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 1, 2015

Completed
Same day until next milestone

Study Start

First participant enrolled

April 1, 2015

Completed
12 days until next milestone

First Posted

Study publicly available on registry

April 13, 2015

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2016

Completed
Last Updated

December 5, 2018

Status Verified

December 1, 2018

Enrollment Period

10 months

First QC Date

April 1, 2015

Last Update Submit

December 3, 2018

Conditions

Elevated Lipoprotein(a)

Outcome Measures

Primary Outcomes (3)

  • To evaluate the safety and tolerability of single and multiple doses of IONIS-APO(a)-LRx (incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters)

    The safety and tolerability of IONIS-APO(a)-LRx will be assessed by determining the incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters by dose. Safety results in subjects dosed with IONIS-APO(a)-LRx will be compared with those from subjects dosed with placebo.

    Up to 113 days

  • To evaluate the pharmacokinetics of single and multiple doses of IONIS-APO(a)-LRx (unconjugated and conjugated ASO)

    The plasma pharmacokinetics of IONIS-APO(a)-LRx (unconjugated and conjugated ASO) will be assessed following single and multiple-dose SC administration. The amount of ISIS-APO(a)-LRx excreted in urine at selected 24-hour intervals will also be determined.

    Up to 113 days

  • To evaluate the plasma pharmacodynamics of IONIS-APO(a)-LRx (Changes in plasma Lp(a) levels)

    Changes in plasma Lp(a) levels compared to baseline.

    Up to 113 days

Secondary Outcomes (8)

  • Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx

    Up to 113 days

  • Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx

    Up to 113 days

  • Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx

    Up to 113 days

  • Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx

    Up to 113 days

  • Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx

    Up to 113 days

  • +3 more secondary outcomes

Study Arms (2)

IONIS-APO(a)-LRx

EXPERIMENTAL

Drug: IONIS-APO(a)-LRx

Drug: IONIS-APO(a)-LRx

Placebo (Normal Saline)

PLACEBO COMPARATOR

Drug: Sterile Normal Saline (0.9% NaCl)

Drug: Sterile Normal Saline (0.9% NaCl)

Interventions

IONIS-APO(a)-LRxDRUG

Ascending single and multiple doses of IONIS-APO(a)-LRx by subcutaneous (SC) injection

IONIS-APO(a)-LRx
Sterile Normal Saline (0.9% NaCl)DRUG

Calculated volume to match active comparator

Placebo (Normal Saline)

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Must have given written informed consent and be able to comply with all study requirements
  • Healthy males or females aged 18-65 inclusive and weighing ≥ 50 kg 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 \< 35.0 kg/m2
  • Subjects must have Lp(a) ≥ 75 nanomoles/liter nmol/L (30 mg/dL) at Screening

You may not qualify if:

  • Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B
  • Treatment with another Study Drug, biological agent, or device within one-month of screening
  • Regular use of alcohol within 6 months of Screening
  • Use of concomitant drugs unless authorized by the Sponsor Medical Monitor
  • Smoking \> 10 cigarettes a day

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Clinical Site

Toronto, Ontario, M9L 3A2, Canada

Location

Related Publications (2)

  • Milosavljevic MN, Stefanovic SM, Pejcic AV. Potential Novel RNA-Targeting Agents for Effective Lipoprotein(a) Lowering: A Systematic Assessment of the Evidence From Completed and Ongoing Developmental Clinical Trials. J Cardiovasc Pharmacol. 2023 Jul 1;82(1):1-12. doi: 10.1097/FJC.0000000000001429.

    PMID: 37070852DERIVED

  • Viney NJ, van Capelleveen JC, Geary RS, Xia S, Tami JA, Yu RZ, Marcovina SM, Hughes SG, Graham MJ, Crooke RM, Crooke ST, Witztum JL, Stroes ES, Tsimikas S. Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials. Lancet. 2016 Nov 5;388(10057):2239-2253. doi: 10.1016/S0140-6736(16)31009-1. Epub 2016 Sep 21.

    PMID: 27665230DERIVED

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
OTHER
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 1, 2015

First Posted

April 13, 2015

Study Start

April 1, 2015

Primary Completion

February 1, 2016

Study Completion

February 1, 2016

Last Updated

December 5, 2018

Record last verified: 2018-12

Locations

CA(1)