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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04606602




Registration number
NCT04606602
Ethics application status
Date submitted
7/10/2020
Date registered
28/10/2020
Date last updated
3/10/2023

Titles & IDs
Public title
Study to Investigate Safety, Tolerability, PK and PD Response of SLN360 in Subjects With Elevated Lipoprotein(a)
Scientific 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)
Secondary ID [1] 0 0
SLN360-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hyperlipidemias 0 0
Dyslipidemias 0 0
Elevated Lp(a) 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Blood 0 0 0 0
Other blood disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SLN360
Treatment: Drugs - Placebo

Experimental: 30 mg -

Placebo Comparator: Placebo -

Experimental: 100 mg -

Experimental: 300 mg -

Experimental: 600 mg -

Experimental: 900 mg -

Experimental: 100 mg multi dose -

Experimental: 200 mg multi dose -

Experimental: 300 mg multi dose -

Experimental: 600 mg multi dose -

Placebo Comparator: Placebo multi dose -


Treatment: Drugs: SLN360
SLN360 for subcutaneous (s.c.) injection

Treatment: Drugs: Placebo
Sodium chloride for subcutaneous (s.c.) injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of treatment-emergent adverse events
Timepoint [1] 0 0
Day 150
Primary outcome [2] 0 0
Incidence of treatment-emergent adverse events
Timepoint [2] 0 0
Day 201
Secondary outcome [1] 0 0
Pharmacokinetic: peak plasma concentration (Cmax)
Timepoint [1] 0 0
Day 150 and Day 201
Secondary outcome [2] 0 0
Pharmacokinetic: area under the plasma concentration (AUC)
Timepoint [2] 0 0
Day 150 and Day 201
Secondary outcome [3] 0 0
Pharmacokinetic: apparent total clearance from plasma after s.c injection (CL/F)
Timepoint [3] 0 0
Day 150 and Day 201
Secondary outcome [4] 0 0
Pharmacodynamic: Change in Lp(a)
Timepoint [4] 0 0
Day 150 and Day 201

Eligibility
Key inclusion criteria
Inclusion criteria:

- 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- 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.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/11/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/08/2023
Sample size
Target
Accrual to date
Final
70
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Linear Clinical Research - Perth
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton
Recruitment postcode(s) [1] 0 0
- Perth
Recruitment postcode(s) [2] 0 0
- Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Ohio
Country [3] 0 0
Netherlands
State/province [3] 0 0
Amsterdam
Country [4] 0 0
United Kingdom
State/province [4] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Silence Therapeutics plc
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Medpace, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study will investigate the safety and tolerability of SLN360 in patients with elevated
Lp(a).
Trial website
https://clinicaltrials.gov/ct2/show/NCT04606602
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04606602