Elevated Lipoprotein(a)Phase 1NCT02414594
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS APO(a)-LRx in Healthy Volunteers With Elevated Lipoprotein(a)
A Phase 1 study testing IONIS-APO(a)-LRx and Sterile Normal Saline (0.9% NaCl) in people with Elevated Lipoprotein(a), run by Ionis Pharmaceuticals, Inc. at 1 site in Canada.
Trial summary
The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS APO(a)-LRx (ISIS 681257) given to healthy volunteer subjects. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Elevated Lipoprotein(a)
- What is being tested?
- IONIS-APO(a)-LRx and Sterile Normal Saline (0.9% NaCl)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2015to Feb 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
- Considered unsuitable for inclusion by the Principal Investigator
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Blinded, Placebo-Controlled, Dose-Escalation, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ISIS 681257 Administered Subcutaneously to Healthy Volunteers With Elevated Lipoprotein(a)
The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS APO(a)-LRx (ISIS 681257) given to healthy volunteer subjects.
- Conditions
- Elevated Lipoprotein(a)
- Being tested
- IONIS-APO(a)-LRx, Sterile Normal Saline (0.9% NaCl)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IONIS-APO(a)-LRxDrug
Ascending single and multiple doses of IONIS-APO(a)-LRx by subcutaneous (SC) injection
Sterile Normal Saline (0.9% NaCl)Drug
Calculated volume to match active comparator
| Study group | Role | What they receive |
|---|---|---|
| IONIS-APO(a)-LRx | Experimental | Drug: IONIS-APO(a)-LRx Receives: Drug: IONIS-APO(a)-LRx |
| Placebo (Normal Saline) | Placebo comparator | Drug: Sterile Normal Saline (0.9% NaCl) Receives: Drug: Sterile Normal Saline (0.9% NaCl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Up to 113 days
Secondary outcomes (8)
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
Effects of IONIS-APO(a)-LRx on changes in levels of oxidized phospholipids associated with apoB-100 compared to baseline.
Measured: Up to 113 days
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
Effects of IONIS-APO(a)-LRx on changes in levels of oxidized phospholipids associated with apo(a) compared to baseline.
Measured: Up to 113 days
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
Effects of IONIS-APO(a)-LRx on changes in Lp-PLA2 compared to baseline.
Measured: Up to 113 days
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
Effects of IONIS-APO(a)-LRx on changes in sPLA2 compared to baseline.
Measured: Up to 113 days
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
Effects of IONIS-APO(a)-LRx on changes in apo(a) isoform size compared to baseline.
Measured: Up to 113 days
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
Effects of ISIS-APO(a)-LRx on changes in lipid panel compared to baseline.
Measured: Up to 113 days
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
Effects of IONIS-APO(a)-LRx on changes in systemic markers of inflammation compared to baseline.
Measured: Up to 113 days
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
Effects of IONIS-APO(a)-LRx on changes in plasminogen/coagulation compared to baseline.
Measured: Up to 113 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2015 (estimated)
- Study startApr 2015
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Elevated Lipoprotein(a)Studies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Akcea Therapeutics
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02414594
- Sponsor's protocol ID
- IONIS-APO(a)-LRx
- Status last verified
- Dec 2018
- First submitted
- 1 Apr 2015
- Last updated
- 5 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 37070852Viney 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.
PubMed 27665230
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Blinded, Placebo-Controlled, Dose-Escalation, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ISIS 681257 Administered Subcutaneously to Healthy Volunteers With Elevated Lipoprotein(a)
- ClinicalTrials.gov ID
- NCT02414594
- Acronym / sponsor ID
- IONIS-APO(a)-LRx
- Conditions
- Elevated Lipoprotein(a)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Akcea Therapeutics
- Study start
- Apr 2015
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 13 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS APO(a)-LRx (ISIS 681257) given to healthy volunteer subjects.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IONIS-APO(a)-LRx | Experimental | Drug: IONIS-APO(a)-LRxDrug: IONIS-APO(a)-LRx |
| Placebo (Normal Saline) | Placebo comparator | Drug: Sterile Normal Saline (0.9% NaCl)Drug: Sterile Normal Saline (0.9% NaCl) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IONIS-APO(a)-LRxAscending single and multiple doses of IONIS-APO(a)-LRx by subcutaneous (SC) injection | Drug | IONIS-APO(a)-LRx |
| Sterile Normal Saline (0.9% NaCl)Calculated volume to match active comparator | Drug | Placebo (Normal Saline) |
Primary outcome
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)
Time frame: Up to 113 days
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.
To evaluate the pharmacokinetics of single and multiple doses of IONIS-APO(a)-LRx (unconjugated and conjugated ASO)
Time frame: Up to 113 days
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.
To evaluate the plasma pharmacodynamics of IONIS-APO(a)-LRx (Changes in plasma Lp(a) levels)
Time frame: Up to 113 days
Changes in plasma Lp(a) levels compared to baseline.
8 secondary outcomes
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
Time frame: Up to 113 days
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
Time frame: Up to 113 days
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
Time frame: Up to 113 days
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
Time frame: Up to 113 days
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
Time frame: Up to 113 days
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
Time frame: Up to 113 days
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
Time frame: Up to 113 days
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
Time frame: Up to 113 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2018.
- Derived from this study: PubMed 37070852Milosavljevic 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.
- Derived from this study: PubMed 27665230Viney 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IONIS-APO(a)-LRx and Sterile Normal Saline (0.9% NaCl) in people with Elevated Lipoprotein(a), run by Ionis Pharmaceuticals, Inc. at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: Up to 113 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02414594, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2018.