Healthy ParticipantsPhase 1NCT05337878
A Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Pelacarsen (ISIS 681257) in Healthy Japanese Participants
A Phase 1 study testing Pelacarsen in people with Healthy Participants, run by Ionis Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
The purpose of the study is to assess the safety, tolerability, and pharmacokinetics (PK) of single and multiple subcutaneous (SC) doses of Pelacarsen (ISIS 681257) in healthy Japanese participants. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Participants
- What is being tested?
- Pelacarsen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Oct 2018to 18 Dec 2019
- 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
- Provided written informed consent (signed and dated) and any authorizations required by local law and was able to comply with all study requirements.
- Male and female of first-, second- or third-generation Japanese participants.
- Japanese healthy or obese male and female participants 18 to 65 years of age inclusive, and in good health as determined by past medical history, physical examination, vital signs, ECG and laboratory tests at screening.
- Participants weighed at least 45 kilograms (kg), healthy or obese with body mass index (BMI) ≤ 35.0 kilograms per meter square (kg/m^2).
- Participants had to have lipoprotein(a) (Lp[a]) ≥ 15 nanomole per liter (nmol/L) (8 milligram per deciliter [mg/dL]) at screening.
Who cannot join
- Clinically significant abnormalities in medical history including acute coronary syndrome, major surgery within 3 months of screening, planned surgery that would have occurred during the study or physical examination or other screening results such as ECGs findings at screening.
- Screening laboratory results as follows or any other clinically significant abnormalities in screening laboratory values that would have rendered a participant unsuitable for inclusion. If abnormal, the laboratory tests may have been repeated after consultation with the Sponsor Medical Monitor.
- Estimated glomerular filtration rate (eGFR) ˂ 60 milliliter per minute per 1.73 meter per square (mL/min/1.73m^2) (as determined by the Chronic Kidney Disease-Epidemiological Collaboration [CKD-EPI] Equation).
- Urine protein-to-creatinine ratio (UPCR) ≥ 200 milligram per gram (mg/g) or urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g.
- Alanine aminotransferase (ALT; serum glutamic pyruvic transaminase), aspartate aminotransferase (AST; serum glutamic oxaloacetic transaminase), bilirubin, alkaline phosphatase, serum creatinine, blood urea nitrogen > 1.5 × upper limit of normal (ULN) at screening excluded a participant from participation in the study.
- Fasting blood glucose > ULN. If elevated, hemoglobin A1c was checked and if < 6%, the participant could have been enrolled.
- Platelet count < 140,000 per microliter (/μL). 3. Active infection requiring systemic antiviral or antimicrobial therapy that would not have been completed prior to Day 1.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Double-blind, Placebo-controlled, Non-confirmatory Study to Assess Safety, Tolerability, PK, and PD of Single Ascending and Multiple Doses of ISIS 681257 in Healthy Japanese Participants
The purpose of the study is to assess the safety, tolerability, and pharmacokinetics (PK) of single and multiple subcutaneous (SC) doses of Pelacarsen (ISIS 681257) in healthy Japanese participants.
Read the detailed description
This was a randomized, placebo-controlled, participant and investigator-blinded, single ascending and multiple-dose study of Pelacrsen (ISIS 681257) in up to 29 healthy Japanese male and female participants. The study was conducted in two parts:1) Single ascending dose (SAD) including up to a 28-day screening period, a baseline period, dose with study drug on Day 1, a 2-day (48 hours) post-dose in-patient observation period, followed by an out-patient observation period up to Day 90; 2) Multiple doses (MD) including up to a 28-day screening period, a baseline period, dose with study drug up to Day 85, a 2-day (48 hours) post-dose in-patient observation period, followed by an out-patient observation period up to Day 204.
In the SAD period, participants were randomized to receive single dose of Pelacarsen or placebo.
Upon completion of the SAD period participants were randomized to receive multiple doses of Pelacarsen.
- Conditions
- Healthy Participants
- Being tested
- Placebo, Pelacarsen
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Pelacarsen-matching placebo administered by SC injection.
PelacarsenDrug
Also called AKCEA-APO(a)-LRx, TQJ230, ISIS 681257
Pelacarsen administered by SC injection.
| Study group | Role | What they receive |
|---|---|---|
| SAD: Placebo | Placebo comparator | Single dose of Pelacarsen-matching placebo administered by SC injection on Day 1 of single-dose treatment period. Receives: Drug: Placebo |
| SAD: Pelacarsen 20 milligrams (mg) | Experimental | Single dose of Pelacarsen, 20 mg, administered by SC injection on Day 1 of single-dose treatment period. Receives: Drug: Pelacarsen |
| SAD: Pelacarsen 40 mg | Experimental | Single dose of Pelacarsen, 40 mg, administered by SC injection on Day 1 of single-dose treatment period. Receives: Drug: Pelacarsen |
| SAD: Pelacarsen 80 mg | Experimental | Single dose of Pelacarsen, 80 mg, administered by SC injection on Day 1 of single-dose treatment period. Receives: Drug: Pelacarsen |
| MD: Placebo | Placebo comparator | Multiple doses of Pelacarsen-matching placebo administered by SC injection every 4 weeks, on Days 1, 29, 57 and 85 of multiple-dose treatment period. Receives: Drug: Placebo |
| MD: Pelacarsen 80 mg | Experimental | Multiple doses of Pelacarsen, 80 mg, administered by SC injection every 4 weeks, on Days 1, 29, 57 and 85 of multiple-dose treatment period. Receives: Drug: Pelacarsen |
What is being measured
The primary outcome is the main question the study is designed to answer.
SAD: Percentage of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Evaluation Parameters
Measured: Up to Day 90
SAD: Percentage of Participants With Adverse Events
Measured: Up to Day 90
SAD: Percentage of Participants With Serious Adverse Events
Measured: Up to Day 90
MAD: Percentage of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Evaluation Parameters
Measured: Up to Day 204
MAD: Percentage of Participants With Adverse Events
Measured: Up to Day 204
MAD: Percentage of Participants With Serious Adverse Events
Measured: Up to Day 204
Secondary outcomes (4)
Maximum Observed Drug Concentration (Cmax) in Plasma After Single Ascending Dose of Pelacarsen
Measured: Day 1: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 up to 168 hours post-dose
Area Under Curve (AUC) From Time Zero to the Last Quantifiable Concentration (AUClast) in Plasma After Single Ascending Dose of Pelacarsen
Measured: Day 1: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 up to 168 hours post-dose
Maximum Observed Drug Concentration (Cmax) in Plasma After Multiple Doses of Pelacarsen
Measured: Days 1 and 85: Pre-dose; 1, 2, 4, 8, 24 up to 168 hours post-dose
Area Under Curve (AUC) From Time Zero to the Last Quantifiable Concentration (AUClast) in Plasma After Multiple Doses of Pelacarsen
Measured: Days 1 and 85: Pre-dose; 1, 2, 4, 8, 24 up to 168 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2022
- Study start15 Oct 2018
- Primary completion18 Dec 2019
- Study completion18 Dec 2019
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 Healthy ParticipantsStudies 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
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 29 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
- NCT05337878
- Sponsor's protocol ID
- AKCEA-CS1
- Status last verified
- Apr 2022
- First submitted
- 13 Apr 2022
- Last updated
- 20 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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 37070852
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-blind, Placebo-controlled, Non-confirmatory Study to Assess Safety, Tolerability, PK, and PD of Single Ascending and Multiple Doses of ISIS 681257 in Healthy Japanese Participants
- ClinicalTrials.gov ID
- NCT05337878
- Acronym / sponsor ID
- AKCEA-CS1
- Conditions
- Healthy Participants
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Oct 2018 (actual)
- Primary completion
- 18 Dec 2019 (actual)
- Study completion
- 18 Dec 2019 (actual)
- First posted
- 20 Apr 2022 (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 of the study is to assess the safety, tolerability, and pharmacokinetics (PK) of single and multiple subcutaneous (SC) doses of Pelacarsen (ISIS 681257) in healthy Japanese participants.
Detailed description
This was a randomized, placebo-controlled, participant and investigator-blinded, single ascending and multiple-dose study of Pelacrsen (ISIS 681257) in up to 29 healthy Japanese male and female participants. The study was conducted in two parts:1) Single ascending dose (SAD) including up to a 28-day screening period, a baseline period, dose with study drug on Day 1, a 2-day (48 hours) post-dose in-patient observation period, followed by an out-patient observation period up to Day 90; 2) Multiple doses (MD) including up to a 28-day screening period, a baseline period, dose with study drug up to Day 85, a 2-day (48 hours) post-dose in-patient observation period, followed by an out-patient observation period up to Day 204.
In the SAD period, participants were randomized to receive single dose of Pelacarsen or placebo.
Upon completion of the SAD period participants were randomized to receive multiple doses of Pelacarsen.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| SAD: Placebo | Placebo comparator | Drug: PlaceboSingle dose of Pelacarsen-matching placebo administered by SC injection on Day 1 of single-dose treatment period. |
| SAD: Pelacarsen 20 milligrams (mg) | Experimental | Drug: PelacarsenSingle dose of Pelacarsen, 20 mg, administered by SC injection on Day 1 of single-dose treatment period. |
| SAD: Pelacarsen 40 mg | Experimental | Drug: PelacarsenSingle dose of Pelacarsen, 40 mg, administered by SC injection on Day 1 of single-dose treatment period. |
| SAD: Pelacarsen 80 mg | Experimental | Drug: PelacarsenSingle dose of Pelacarsen, 80 mg, administered by SC injection on Day 1 of single-dose treatment period. |
| MD: Placebo | Placebo comparator | Drug: PlaceboMultiple doses of Pelacarsen-matching placebo administered by SC injection every 4 weeks, on Days 1, 29, 57 and 85 of multiple-dose treatment period. |
| MD: Pelacarsen 80 mg | Experimental | Drug: PelacarsenMultiple doses of Pelacarsen, 80 mg, administered by SC injection every 4 weeks, on Days 1, 29, 57 and 85 of multiple-dose treatment period. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Provided written informed consent (signed and dated) and any authorizations required by local law and was able to comply with all study requirements.
- Male and female of first-, second- or third-generation Japanese participants.
- Japanese healthy or obese male and female participants 18 to 65 years of age inclusive, and in good health as determined by past medical history, physical examination, vital signs, ECG and laboratory tests at screening.
- Participants weighed at least 45 kilograms (kg), healthy or obese with body mass index (BMI) ≤ 35.0 kilograms per meter square (kg/m^2).
- Participants had to have lipoprotein(a) (Lp[a]) ≥ 15 nanomole per liter (nmol/L) (8 milligram per deciliter [mg/dL]) at screening.
Key exclusion criteria (7 listed)
- Clinically significant abnormalities in medical history including acute coronary syndrome, major surgery within 3 months of screening, planned surgery that would have occurred during the study or physical examination or other screening results such as ECGs findings at screening.
- Screening laboratory results as follows or any other clinically significant abnormalities in screening laboratory values that would have rendered a participant unsuitable for inclusion. If abnormal, the laboratory tests may have been repeated after consultation with the Sponsor Medical Monitor.
- Estimated glomerular filtration rate (eGFR) ˂ 60 milliliter per minute per 1.73 meter per square (mL/min/1.73m^2) (as determined by the Chronic Kidney Disease-Epidemiological Collaboration [CKD-EPI] Equation).
- Urine protein-to-creatinine ratio (UPCR) ≥ 200 milligram per gram (mg/g) or urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g.
- Alanine aminotransferase (ALT; serum glutamic pyruvic transaminase), aspartate aminotransferase (AST; serum glutamic oxaloacetic transaminase), bilirubin, alkaline phosphatase, serum creatinine, blood urea nitrogen > 1.5 × upper limit of normal (ULN) at screening excluded a participant from participation in the study.
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 |
|---|---|---|
| PlaceboPelacarsen-matching placebo administered by SC injection. | Drug | MD: Placebo, SAD: Placebo |
| PelacarsenAlso: AKCEA-APO(a)-LRx, TQJ230, ISIS 681257Pelacarsen administered by SC injection. | Drug | MD: Pelacarsen 80 mg, SAD: Pelacarsen 20 milligrams (mg), SAD: Pelacarsen 40 mg, SAD: Pelacarsen 80 mg |
Primary outcome
SAD: Percentage of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Evaluation Parameters
Time frame: Up to Day 90
SAD: Percentage of Participants With Adverse Events
Time frame: Up to Day 90
SAD: Percentage of Participants With Serious Adverse Events
Time frame: Up to Day 90
MAD: Percentage of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Evaluation Parameters
Time frame: Up to Day 204
MAD: Percentage of Participants With Adverse Events
Time frame: Up to Day 204
MAD: Percentage of Participants With Serious Adverse Events
Time frame: Up to Day 204
4 secondary outcomes
Maximum Observed Drug Concentration (Cmax) in Plasma After Single Ascending Dose of Pelacarsen
Time frame: Day 1: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 up to 168 hours post-dose
Area Under Curve (AUC) From Time Zero to the Last Quantifiable Concentration (AUClast) in Plasma After Single Ascending Dose of Pelacarsen
Time frame: Day 1: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 up to 168 hours post-dose
Maximum Observed Drug Concentration (Cmax) in Plasma After Multiple Doses of Pelacarsen
Time frame: Days 1 and 85: Pre-dose; 1, 2, 4, 8, 24 up to 168 hours post-dose
Area Under Curve (AUC) From Time Zero to the Last Quantifiable Concentration (AUClast) in Plasma After Multiple Doses of Pelacarsen
Time frame: Days 1 and 85: Pre-dose; 1, 2, 4, 8, 24 up to 168 hours post-dose
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 20 Apr 2022.
- 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.
- Individual participant dataSharing planned: No
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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 Pelacarsen in people with Healthy Participants, run by Ionis Pharmaceuticals, Inc. at 1 site in United States.
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 5 inclusion and 7 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 20 Apr 2022. 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 United States. 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?
SAD: Percentage of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Evaluation Parameters (time frame: Up to Day 90). The study lists 6 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 NCT05337878, 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 20 Apr 2022.