Elevated Triglycerides (TG)Phase 1NCT02900027
Safety, Tolerability, PK, and Pharmacodynamics(PD) of IONIS APOCIII-LRx in Healthy Volunteers With Elevated Triglycerides
A Phase 1 study testing APOC-III-L-Rx in people with Elevated Triglycerides (TG), 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 APOC-III-LRx 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 Triglycerides (TG)
- What is being tested?
- APOC-III-L-Rx
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2016to 30 Apr 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 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
- 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 Fasting TG ≥ 90 mg/dL or ≥ 200 mg/dL depending on Cohort assignment
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 excessive 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: Placebo-Controlled, Dose-Escalation Study to Assess Safety, Tolerability, PK and PD of a GalNAc3 Conjugated Antisense Oligonucleotide Targeting ApoC-III, Administered Subcutaneously to Healthy Volunteers With Elevated Triglycerides
The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS APOC-III-LRx given to healthy volunteer subjects.
- Conditions
- Elevated Triglycerides (TG)
- Being tested
- APOC-III-L-Rx, Placebo Comparator
- Medical subject headings
- Hypertriglyceridemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APOC-III-L-RxDrug
Ascending single and multiple doses of IONIS-APOC-III-LRx by subcutaneous (SC) injection
Placebo ComparatorDrug
Sterile Normal Saline (0.9% NaCl) calculated volume to match active comparator
| Study group | Role | What they receive |
|---|---|---|
| IONIS-APOC-III-LRx | Experimental | Ascending single and multiple doses of IONIS-APOC-III-LRx by subcutaneous (SC) injection Receives: Drug: Placebo Comparator |
| Placebo (Normal Saline) | Placebo comparator | Sterile Normal Saline (0.9% NaCl) calculated volume to match active comparator Receives: Drug: APOC-III-L-Rx |
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- APOC-III-LRx - (incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters)
The safety and tolerability of IONIS- APOC-III-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 APOC-III-LRx will be compared with those from subjects dosed with placebo.
Measured: Up to 183 days
Secondary outcomes (4)
To evaluate the plasma pharmacokinetics of single and multiple doses of IONIS- APOC-III-LRx
The maximum area under the curve (AUC) of IONIS- APOC-III-LRx will be assessed following single and multiple- dose SC administration
Measured: Up to 183 days
To evaluate the urine pharmacokinetics of single and multiple doses of IONIS¬-APOC-III-LRx
The amount of IONIS-APOC-III-LRx excreted in urine at selected 24-hour intervals [Ae0-24h] will be determined.
Measured: Up to 183 days
To evaluate the plasma pharmacokinetics of single and multiple doses of IONIS- APOC-III-LRx
The maximum plasma concentration (Cmax) of IONIS- APOC-III-LRx will be assessed following single and multiple- dose SC administration
Measured: Up to 183 Days
To evaluate the plasma pharmacokinetics of single and multiple doses of IONIS- APOC-III-LRx
The maximum time to Cmax (Tmax) of IONIS- APOC-III-LRx will be assessed following single and multiple-dose SC administration
Measured: Up to 183 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2016 (estimated)
- Study startSep 2016
- Primary completion30 Apr 2018
- Study completion30 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Elevated Triglycerides (TG)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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Akcea Therapeutics
- Responsible party
- Sponsor
- Investigators
- Janice Faulknor, Principal investigator, BioPharma Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02900027
- Sponsor's protocol ID
- IONIs-ApoCIII-LRx
- Status last verified
- May 2018
- First submitted
- 23 Aug 2016
- Last updated
- 22 May 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Alexander VJ, Xia S, Hurh E, Hughes SG, O'Dea L, Geary RS, Witztum JL, Tsimikas S. N-acetyl galactosamine-conjugated antisense drug to APOC3 mRNA, triglycerides and atherogenic lipoprotein levels. Eur Heart J. 2019 Sep 1;40(33):2785-2796. doi: 10.1093/eurheartj/ehz209.
PubMed 31329855
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Placebo-Controlled, Dose-Escalation Study to Assess Safety, Tolerability, PK and PD of a GalNAc3 Conjugated Antisense Oligonucleotide Targeting ApoC-III, Administered Subcutaneously to Healthy Volunteers With Elevated Triglycerides
- ClinicalTrials.gov ID
- NCT02900027
- Acronym / sponsor ID
- IONIs-ApoCIII-LRx
- Conditions
- Elevated Triglycerides (TG)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Akcea Therapeutics
- Study start
- Sep 2016 (actual)
- Primary completion
- 30 Apr 2018 (actual)
- Study completion
- 30 Apr 2018 (actual)
- First posted
- 14 Sep 2016 (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 APOC-III-LRx given to healthy volunteer subjects.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IONIS-APOC-III-LRx | Experimental | Drug: Placebo ComparatorAscending single and multiple doses of IONIS-APOC-III-LRx by subcutaneous (SC) injection |
| Placebo (Normal Saline) | Placebo comparator | Drug: APOC-III-L-RxSterile Normal Saline (0.9% NaCl) calculated volume to match active comparator |
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
- 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 excessive 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 |
|---|---|---|
| APOC-III-L-RxAscending single and multiple doses of IONIS-APOC-III-LRx by subcutaneous (SC) injection | Drug | Placebo (Normal Saline) |
| Placebo ComparatorSterile Normal Saline (0.9% NaCl) calculated volume to match active comparator | Drug | IONIS-APOC-III-LRx |
Primary outcome
To evaluate the safety and tolerability of single and multiple doses of IONIS- APOC-III-LRx - (incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters)
Time frame: Up to 183 days
The safety and tolerability of IONIS- APOC-III-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 APOC-III-LRx will be compared with those from subjects dosed with placebo.
4 secondary outcomes
To evaluate the plasma pharmacokinetics of single and multiple doses of IONIS- APOC-III-LRx
Time frame: Up to 183 days
To evaluate the urine pharmacokinetics of single and multiple doses of IONIS¬-APOC-III-LRx
Time frame: Up to 183 days
To evaluate the plasma pharmacokinetics of single and multiple doses of IONIS- APOC-III-LRx
Time frame: Up to 183 Days
To evaluate the plasma pharmacokinetics of single and multiple doses of IONIS- APOC-III-LRx
Time frame: Up to 183 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 22 May 2018.
- Derived from this study: PubMed 31329855Alexander VJ, Xia S, Hurh E, Hughes SG, O'Dea L, Geary RS, Witztum JL, Tsimikas S. N-acetyl galactosamine-conjugated antisense drug to APOC3 mRNA, triglycerides and atherogenic lipoprotein levels. Eur Heart J. 2019 Sep 1;40(33):2785-2796. doi: 10.1093/eurheartj/ehz209.
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.
Janice Faulknor principal investigator
BioPharma Services
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 APOC-III-L-Rx in people with Elevated Triglycerides (TG), 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 22 May 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- APOC-III-LRx - (incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters) (time frame: Up to 183 days). 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 NCT02900027, which also lists 1 linked publication.
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 22 May 2018.