Healthy VolunteersPhase 1NCT03101878
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ionis AGT-LRx in Healthy Volunteers
A Phase 1 study testing Ionis AGT-LRx in people with Healthy Volunteers, 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 AGT-LRx in up to 82 Healthy Volunteers Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Ionis AGT-LRx
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteCanada
- Study dates
- 5 Apr 2017to 1 Aug 2018
- 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 60 years
- All sexes
- Healthy volunteers accepted
- 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 18-60 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 kg/m
- Agree to conduct at home blood pressure monitoring (in triplicate using study provided device) every morning and every evening throughout study participation for Single-Dose Cohort subjects and every morning for Multiple-Dose Cohort subjects
Who cannot join
- Treatment with another Study Drug, biological agent, or device within one-month of Screening
- Subject with borderline orthostatic hypotension defined as a fall in systolic blood pressure of ≥ 17 mmHg or diastolic blood pressure of ≥ 7 mmHg when they assume a standing position (within 3 minutes of standing up)
- Use of nicotine-containing products or illicit drugs
- 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 757456 Administered Subcutaneously to Healthy Volunteers
The purpose is to assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS AGT-LRx in up to 82 Healthy Volunteers
- Conditions
- Healthy Volunteers
- Being tested
- Ionis AGT-LRx, Placebo
- Keywords
- Healthy Volunteers, IONIS AGT-Lrx
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ionis AGT-LRxDrug
Ascending single and multiple doses of Ionis AGT-LRx administered subcutaneously
PlaceboDrug
Saline .9%
| Study group | Role | What they receive |
|---|---|---|
| Ionis AGT-LRx | Experimental | Ascending single and multiple doses of Ionis AGT-LRx administered subcutaneously. Receives: Drug: Ionis AGT-LRx |
| Placebo | Placebo comparator | Saline .9% Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of adverse events that are related to treatment with IONIS AGT-LRx
The safety and tolerability of single and multiple doses of IONIS AGT-LRx will be assessed by determining the incidence, severity, and dose relationship of adverse events that are related to treatment with IONIS AGT-LRx
Measured: Up to 127 days
Any observed changes in Blood Pressure measurements, ECGs, or laboratory tests from baseline
The safety and tolerability of single and multiple doses of IONIS AGT-LRx will be assessed by reviewing any observed changes in Blood Pressure measurements, physical exam, and laboratory tests from baseline by dose. Results in subjects dosed with IONIS AGT-LRx will be compared with those from subjects dosed with placebo.
Measured: Up to 127 days
Secondary outcomes (2)
Pharmacokinetics after single and multiple doses of IONIS AGT-LRx
The plasma pharmacokinetics (concentration-time results) of IONIS AGT-LRx will be assessed following single and multiple dose SC administration
Measured: Up to 127 days
Pharmacodynamics of IONIS AGT-LRx (Changes in plasma AGT Levels)
Effects of IONIS AGT-LRx on changes in AGT plasma protein compared to baseline.
Measured: Up to 127 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2017
- Study start5 Apr 2017
- Primary completion29 Mar 2018
- Study completion1 Aug 2018
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 Healthy VolunteersStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03101878
- Sponsor's protocol ID
- ISIS 757456-CS1
- Status last verified
- Aug 2018
- First submitted
- 6 Mar 2017
- Last updated
- 21 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Lidani KCF, Trainor PJ, Buscaglia R, Foster K, Jaramillo S, Michael K, Landry AP, Michos ED, Ouyang P, Morgan ES, Tsimikas S, DeFilippis AP. Circulating Levels of Angiotensinogen, Sex Hormones, and Hormone Therapy-The Multi-Ethnic Study of Atherosclerosis (MESA). J Clin Hypertens (Greenwich). 2025 Jun;27(6):e70083. doi: 10.1111/jch.70083.
PubMed 40556120Morgan ES, Tami Y, Hu K, Brambatti M, Mullick AE, Geary RS, Bakris GL, Tsimikas S. Antisense Inhibition of Angiotensinogen With IONIS-AGT-LRx: Results of Phase 1 and Phase 2 Studies. JACC Basic Transl Sci. 2021 May 3;6(6):485-496. doi: 10.1016/j.jacbts.2021.04.004. eCollection 2021 Jun.
PubMed 34222719
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 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 757456 Administered Subcutaneously to Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03101878
- Acronym / sponsor ID
- ISIS 757456-CS1
- Conditions
- Healthy Volunteers
- Keywords
- Healthy Volunteers, IONIS AGT-Lrx
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 5 Apr 2017 (actual)
- Primary completion
- 29 Mar 2018 (actual)
- Study completion
- 1 Aug 2018 (actual)
- First posted
- 5 Apr 2017 (actual)
- 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 AGT-LRx in up to 82 Healthy Volunteers
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ionis AGT-LRx | Experimental | Drug: Ionis AGT-LRxAscending single and multiple doses of Ionis AGT-LRx administered subcutaneously. |
| Placebo | Placebo comparator | Drug: PlaceboSaline .9% |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- 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 18-60 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 kg/m
Key exclusion criteria (4 listed)
- Treatment with another Study Drug, biological agent, or device within one-month of Screening
- Subject with borderline orthostatic hypotension defined as a fall in systolic blood pressure of ≥ 17 mmHg or diastolic blood pressure of ≥ 7 mmHg when they assume a standing position (within 3 minutes of standing up)
- Use of nicotine-containing products or illicit drugs
- Considered unsuitable for inclusion by the Principal Investigator
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 AGT-LRxAscending single and multiple doses of Ionis AGT-LRx administered subcutaneously | Drug | Ionis AGT-LRx |
| PlaceboSaline .9% | Drug | Placebo |
Primary outcome
Incidence and severity of adverse events that are related to treatment with IONIS AGT-LRx
Time frame: Up to 127 days
The safety and tolerability of single and multiple doses of IONIS AGT-LRx will be assessed by determining the incidence, severity, and dose relationship of adverse events that are related to treatment with IONIS AGT-LRx
Any observed changes in Blood Pressure measurements, ECGs, or laboratory tests from baseline
Time frame: Up to 127 days
The safety and tolerability of single and multiple doses of IONIS AGT-LRx will be assessed by reviewing any observed changes in Blood Pressure measurements, physical exam, and laboratory tests from baseline by dose. Results in subjects dosed with IONIS AGT-LRx will be compared with those from subjects dosed with placebo.
2 secondary outcomes
Pharmacokinetics after single and multiple doses of IONIS AGT-LRx
Time frame: Up to 127 days
Pharmacodynamics of IONIS AGT-LRx (Changes in plasma AGT Levels)
Time frame: Up to 127 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 21 Aug 2018.
- Derived from this study: PubMed 40556120Lidani KCF, Trainor PJ, Buscaglia R, Foster K, Jaramillo S, Michael K, Landry AP, Michos ED, Ouyang P, Morgan ES, Tsimikas S, DeFilippis AP. Circulating Levels of Angiotensinogen, Sex Hormones, and Hormone Therapy-The Multi-Ethnic Study of Atherosclerosis (MESA). J Clin Hypertens (Greenwich). 2025 Jun;27(6):e70083. doi: 10.1111/jch.70083.
- Derived from this study: PubMed 34222719Morgan ES, Tami Y, Hu K, Brambatti M, Mullick AE, Geary RS, Bakris GL, Tsimikas S. Antisense Inhibition of Angiotensinogen With IONIS-AGT-LRx: Results of Phase 1 and Phase 2 Studies. JACC Basic Transl Sci. 2021 May 3;6(6):485-496. doi: 10.1016/j.jacbts.2021.04.004. eCollection 2021 Jun.
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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 AGT-LRx in people with Healthy Volunteers, 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 4 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 21 Aug 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?
Incidence and severity of adverse events that are related to treatment with IONIS AGT-LRx (time frame: Up to 127 days). The study lists 2 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 NCT03101878, 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 21 Aug 2018.