HyperlipidemiasPhase 1NCT04606602
Study to Investigate Safety, Tolerability, PK and PD Response of SLN360 in Subjects With Elevated Lipoprotein(a)
A Phase 1 study testing SLN360 in people with Hyperlipidemias and Dyslipidemias, run by Silence Therapeutics plc at 8 sites in 4 countries.
Trial summary
This study will investigate the safety and tolerability of SLN360 in patients with elevated Lp(a). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyperlipidemias, Dyslipidemias, Elevated Lp(a)
- What is being tested?
- SLN360
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 8 sitesin 4 countries
- Study dates
- 18 Nov 2020to 23 Aug 2023
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Elevated plasma Lp(a) ≥ 150nmol/L.
- All subjects must agree to adhere to appropriate contraception requirements.
- Subjects must provide written informed consent and be able to comply with all study requirements.
- Body mass index of ≥ 18 kg/m2 and ≤ 45 kg/m2.
- For the MD part: confirmed history of stable atherosclerortic cardiovascular disease.
Who cannot join
- Single Ascending Dose only: any history of clinically overt cardiovascular disease, defined as acute coronary syndromes, myocardial infarction, stable angina, coronary or other revascularization, ischemic stroke or transient ischemic attack and atherosclerotic peripheral arterial disease.
- Multiple Dose only: recent history of acute cardiovascular disease events within 6 months of screening (including, but not limited to, acute myocardial infarction, unstable angina, acute stroke and acute limb ischemia).
- Moderate or severe hepatic cirrhosis with Child-Pugh grade B or C, or other current or previous liver disease.
- Active serious mental illness or psychiatric disorder, including but not limited to schizophrenia, bipolar disorder, or severe depression requiring current pharmacological intervention.
- Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrolment in the study or could interfere with the subject's participation in, or completion of the study.
- Subjects with previous or current use of medication or therapies significantly affecting Lp(a) level or hormone replacement therapy, unless on a stable dose for ≥ 8 weeks prior to screening
- History or clinical evidence of alcohol or illegal drug misuse within the 6 months before screening.
- History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc, or intolerance to s.c. injections.
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
United States4 sites
Metabolic and Atherosclerosis Research Center
Cincinnati, Ohio, 45227
Cleveland Clinic
Cleveland, Ohio, 44195
Jacksonville Center for Clinical Research Ltd.
Jacksonville, Florida, 32216
Progressive Medical Research
Port Orange, Florida, 32127
Australia2 sites
Monash Medical Centre
Clayton
Linear Clinical Research
Perth, Western Australia
About this study
Official title: A Randomised, Double-blind, Placebo Controlled, First-in-human Study to Investigate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Response of SLN360 in Subjects With Elevated Lipoprotein(a)
This study will investigate the safety and tolerability of SLN360 in patients with elevated Lp(a).
Read the detailed description
This first-in-human (FIH) study will investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of SLN360 after single ascending s.c. doses and multiple doses in healthy male and female subjects.
Up to 9 cohorts of 88 patients with elevated Lp(a) will be enrolled. Each patient will receive single or multiple doses of SLN360 or placebo given by subcutaneous (s.c) injection.
- Conditions
- Hyperlipidemias, Dyslipidemias, Elevated Lp(a)
- Being tested
- SLN360, Placebo
- Keywords
- Dyslipidemia, Dyslipoproteinemia, Hyperlipidemia, Hyperlipoproteinemia, Hyperlipoproteinemia (a), Lipoprotein, Lipoprotein (a)
- Medical subject headings
- Hyperlipidemias, Dyslipidemias, Hyperlipoproteinemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SLN360Drug
SLN360 for subcutaneous (s.c.) injection
PlaceboDrug
Sodium chloride for subcutaneous (s.c.) injection
| Study group | Role | What they receive |
|---|---|---|
| 30 mg | Experimental | Not described Receives: Drug: SLN360 |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| 100 mg | Experimental | Not described Receives: Drug: SLN360 |
| 300 mg | Experimental | Not described Receives: Drug: SLN360 |
| 600 mg | Experimental | Not described Receives: Drug: SLN360 |
| 900 mg | Experimental | Not described Receives: Drug: SLN360 |
| 100 mg multi dose | Experimental | Not described Receives: Drug: SLN360 |
| 200 mg multi dose | Experimental | Not described Receives: Drug: SLN360 |
| 300 mg multi dose | Experimental | Not described Receives: Drug: SLN360 |
| 600 mg multi dose | Experimental | Not described Receives: Drug: SLN360 |
| Placebo multi dose | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-emergent adverse events
safety and tolerability will be reported separately following single-dose administration.
Measured: Day 150
Incidence of treatment-emergent adverse events
safety and tolerability will be reported separately following multiple-dose administration.
Measured: Day 201
Secondary outcomes (4)
Pharmacokinetic: peak plasma concentration (Cmax)
safety and tolerability will be reported separately following single-dose and multiple-dose administration.
Measured: Day 150 and Day 201
Pharmacokinetic: area under the plasma concentration (AUC)
safety and tolerability will be reported separately following single-dose and multiple-dose administration.
Measured: Day 150 and Day 201
Pharmacokinetic: apparent total clearance from plasma after s.c injection (CL/F)
safety and tolerability will be reported separately following single-dose and multiple-dose administration.
Measured: Day 150 and Day 201
Pharmacodynamic: Change in Lp(a)
safety and tolerability will be reported separately following single-dose and multiple-dose administration.
Measured: Day 150 and Day 201
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2020
- Study start18 Nov 2020
- Primary completion23 Aug 2023
- Study completion23 Aug 2023
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 HyperlipidemiasStudies of the same condition, open and under way.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Silence Therapeutics plc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medpace, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04606602
- Sponsor's protocol ID
- SLN360-001
- Status last verified
- Aug 2024
- First submitted
- 7 Oct 2020
- Last updated
- 12 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Nissen SE, Wolski K, Balog C, Swerdlow DI, Scrimgeour AC, Rambaran C, Wilson RJ, Boyce M, Ray KK, Cho L, Watts GF, Koren M, Turner T, Stroes ES, Melgaard C, Campion GV. Single Ascending Dose Study of a Short Interfering RNA Targeting Lipoprotein(a) Production in Individuals With Elevated Plasma Lipoprotein(a) Levels. JAMA. 2022 May 3;327(17):1679-1687. doi: 10.1001/jama.2022.5050.
PubMed 35368052Nissen SE, Wolski K, Watts GF, Koren MJ, Fok H, Nicholls SJ, Rider DA, Cho L, Romano S, Melgaard C, Rambaran C. Single Ascending and Multiple-Dose Trial of Zerlasiran, a Short Interfering RNA Targeting Lipoprotein(a): A Randomized Clinical Trial. JAMA. 2024 May 14;331(18):1534-1543. doi: 10.1001/jama.2024.4504.
PubMed 38587822
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Placebo Controlled, First-in-human Study to Investigate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Response of SLN360 in Subjects With Elevated Lipoprotein(a)
- ClinicalTrials.gov ID
- NCT04606602
- Acronym / sponsor ID
- SLN360-001
- Conditions
- Hyperlipidemias, Dyslipidemias, Elevated Lp(a)
- Keywords
- Dyslipidemia, Dyslipoproteinemia, Hyperlipidemia, Hyperlipoproteinemia, Hyperlipoproteinemia (a), Lipoprotein, Lipoprotein (a)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Silence Therapeutics plcIndustry (pharma, biotech, devices)
- Collaborators
- Medpace, Inc.
- Study start
- 18 Nov 2020 (actual)
- Primary completion
- 23 Aug 2023 (actual)
- Study completion
- 23 Aug 2023 (actual)
- First posted
- 28 Oct 2020 (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.
This study will investigate the safety and tolerability of SLN360 in patients with elevated Lp(a).
Detailed description
This first-in-human (FIH) study will investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of SLN360 after single ascending s.c. doses and multiple doses in healthy male and female subjects.
Up to 9 cohorts of 88 patients with elevated Lp(a) will be enrolled. Each patient will receive single or multiple doses of SLN360 or placebo given by subcutaneous (s.c) injection.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| 30 mg | Experimental | Drug: SLN360 |
| Placebo | Placebo comparator | Drug: Placebo |
| 100 mg | Experimental | Drug: SLN360 |
| 300 mg | Experimental | Drug: SLN360 |
| 600 mg | Experimental | Drug: SLN360 |
| 900 mg | Experimental | Drug: SLN360 |
| 100 mg multi dose | Experimental | Drug: SLN360 |
| 200 mg multi dose | Experimental | Drug: SLN360 |
| 300 mg multi dose | Experimental | Drug: SLN360 |
| 600 mg multi dose | Experimental | Drug: SLN360 |
| Placebo multi dose | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Elevated plasma Lp(a) ≥ 150nmol/L.
- All subjects must agree to adhere to appropriate contraception requirements.
- Subjects must provide written informed consent and be able to comply with all study requirements.
- Body mass index of ≥ 18 kg/m2 and ≤ 45 kg/m2.
- For the MD part: confirmed history of stable atherosclerortic cardiovascular disease.
Key exclusion criteria (8 listed)
- Single Ascending Dose only: any history of clinically overt cardiovascular disease, defined as acute coronary syndromes, myocardial infarction, stable angina, coronary or other revascularization, ischemic stroke or transient ischemic attack and atherosclerotic peripheral arterial disease.
- Multiple Dose only: recent history of acute cardiovascular disease events within 6 months of screening (including, but not limited to, acute myocardial infarction, unstable angina, acute stroke and acute limb ischemia).
- Moderate or severe hepatic cirrhosis with Child-Pugh grade B or C, or other current or previous liver disease.
- Active serious mental illness or psychiatric disorder, including but not limited to schizophrenia, bipolar disorder, or severe depression requiring current pharmacological intervention.
- Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrolment in the study or could interfere with the subject's participation in, or completion of 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 |
|---|---|---|
| SLN360SLN360 for subcutaneous (s.c.) injection | Drug | 100 mg, 100 mg multi dose, 200 mg multi dose, 30 mg, 300 mg, 300 mg multi dose, 600 mg, 600 mg multi dose, 900 mg |
| PlaceboSodium chloride for subcutaneous (s.c.) injection | Drug | Placebo, Placebo multi dose |
Primary outcome
Incidence of treatment-emergent adverse events
Time frame: Day 150
safety and tolerability will be reported separately following single-dose administration.
Incidence of treatment-emergent adverse events
Time frame: Day 201
safety and tolerability will be reported separately following multiple-dose administration.
4 secondary outcomes
Pharmacokinetic: peak plasma concentration (Cmax)
Time frame: Day 150 and Day 201
Pharmacokinetic: area under the plasma concentration (AUC)
Time frame: Day 150 and Day 201
Pharmacokinetic: apparent total clearance from plasma after s.c injection (CL/F)
Time frame: Day 150 and Day 201
Pharmacodynamic: Change in Lp(a)
Time frame: Day 150 and Day 201
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 12 Aug 2024.
- Results publication: PubMed 35368052Nissen SE, Wolski K, Balog C, Swerdlow DI, Scrimgeour AC, Rambaran C, Wilson RJ, Boyce M, Ray KK, Cho L, Watts GF, Koren M, Turner T, Stroes ES, Melgaard C, Campion GV. Single Ascending Dose Study of a Short Interfering RNA Targeting Lipoprotein(a) Production in Individuals With Elevated Plasma Lipoprotein(a) Levels. JAMA. 2022 May 3;327(17):1679-1687. doi: 10.1001/jama.2022.5050.
- Results publication: PubMed 38587822Nissen SE, Wolski K, Watts GF, Koren MJ, Fok H, Nicholls SJ, Rider DA, Cho L, Romano S, Melgaard C, Rambaran C. Single Ascending and Multiple-Dose Trial of Zerlasiran, a Short Interfering RNA Targeting Lipoprotein(a): A Randomized Clinical Trial. JAMA. 2024 May 14;331(18):1534-1543. doi: 10.1001/jama.2024.4504.
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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.
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SLN360 in people with Hyperlipidemias and Dyslipidemias, run by Silence Therapeutics plc at 8 sites in 4 countries.
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 8 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 12 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Australia, Netherlands, United Kingdom. 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 of treatment-emergent adverse events (time frame: Day 150). 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 NCT04606602, 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 12 Aug 2024.