Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000439640
Ethics application status
Approved
Date submitted
11/04/2023
Date registered
1/05/2023
Date last updated
13/04/2024
Date data sharing statement initially provided
1/05/2023
Date results information initially provided
13/04/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Evaluate SGB-3403 in Healthy Volunteers
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered SGB-3403 in Healthy Volunteers
Secondary ID [1] 309354 0
SGB-3403-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypercholesterolemia 329561 0
Condition category
Condition code
Cardiovascular 326490 326490 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SGB-3403
Other interventions - Placebo
4 Cohorts: 30mg, 100mg, 300mg, 500mg and 800mg
The duration of administration: single dose
SGB-3403 will be administered via subcutaneous injection by a registered nurse
The used and/or partially used vials can be disposed of per local practice. If the used and/or partially used vials cannot be disposed of at the site, they will be returned, along with the unused vials, to the sponsor or its agent after receipt of written authorization from the Sponsor.
Intervention code [1] 325788 0
Treatment: Drugs
Comparator / control treatment
Sodium chloride injection (0.9% w/v) will be administered via subcutaneous injection.
Control group
Placebo

Outcomes
Primary outcome [1] 334333 0
Safety and tolerability will be assessed by the incidence of adverse events assessed by triplicate 12-lead ECG (heart rate, PR interval, QRS interval, HR, QT, and QTc interval), physical examination (includes, at a minimum head, eyes, ears, nose, throat, neck, and lymph nodes, and the cardiovascular, dermatological, musculoskeletal, respiratory, gastrointestinal, and neurological systems), vital signs assessed by vital signs monitor (vital signs monitor can simultaneously monitor blood pressure, heart rate, respiratory rate, and temperature), blood monitoring and by collection of a blood sample for assessment of chemistry and hematology, serology (HIV, HBsAg, HBV, Syphilis, and HCV), coagulation and urine sample for urinalysis. Adverse effects will be coded using the latest version of MedDRA, summaries will be based on treatment-emergent adverse events and will be evaluated and documented using NCI-CTCAE-V5.0 and Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA 2007). The safety laboratory data will be summarized by visit and by treatment group, along with changes from baseline.
Timepoint [1] 334333 0
Baseline, 2, 3, 5, 8, 15, 22, 29, 43, and 57 days post-intervention commencement
Secondary outcome [1] 420281 0
Pharmacokinetic parameters analysis includes, but is not limited to:
1. Maximum Observed Plasma Concentration (Cmax) of Drug prototypes and Potential Metabolites
2. Time to maximum plasma concentration (Tmax)
3. Area Under the Concentration-time Curve (AUC0-168) and of Drug prototypes and Potential Metabolites
4. Area under the plasma concentration versus time curve from zero to infinity (AUC0-inf)
5. Terminal elimination half-life (t½)
6. Urine concentration up to 48 hours post a single subcutaneous dose
7. The cumulative amount of drug excreted in urine (Ae)
8. Fraction of drug recovered in urine (Fe)
9. Clearance (CLr)
Timepoint [1] 420281 0
0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, 168h post-dose
Secondary outcome [2] 420282 0
The pharmacodynamic (PD) effect of SGB-3403 on serum levels of low-density lipoprotein cholesterol (LDL-C) will be assessed by blood sample detection.
Timepoint [2] 420282 0
Screening, predose, 2, 3, 5, 8, 15, 22, 29, 43, 57, 71, 85 days post-dose, LDL-C level has not returned to =80% of baseline. Subjects will return to the clinical study site for PD monitoring visits every 4 ± 1 weeks until LDL-C level returns to = 80% of baseline. PD follow-up will not exceed 180 days after the last study drug administration.
Secondary outcome [3] 421214 0
The pharmacodynamic (PD) effect of SGB-3403 on serum levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) will be assessed by blood sample detection.
Timepoint [3] 421214 0
Screening, predose, 2, 3, 5, 8, 15, 22, 29, 43, 57, 71, 85 days post-dose, LDL-C level has not returned to =80% of baseline. Subjects will return to the clinical study site for PD monitoring visits every 4 ± 1 weeks until LDL-C level returns to = 80% of baseline. PD follow-up will not exceed 180 days after the last study drug administration.
Secondary outcome [4] 421215 0
The pharmacodynamic (PD) effect of SGB-3403 on total cholesterol (TC), very low-density lipoprotein cholesterol (VLDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apolipoprotein B, apolipoprotein A1, triglycerides, and lipoprotein (a) will be assessed by blood sample detection.
Timepoint [4] 421215 0
Screening, predose, 2, 3, 5, 8, 15, 22, 29, 43, 57, 71, 85 days post-dose, LDL-C level has not returned to =80% of baseline. Subjects will return to the clinical study site for PD monitoring visits every 4 ± 1 weeks until LDL-C level returns to = 80% of baseline. PD follow-up will not exceed 180 days after the study drug administration.
Secondary outcome [5] 421216 0
The immunogenicity will be assessed by anti-therapeutic drug antibody (ADA) positive blood samples. Confirmed Anti-therapeutic drug antibody (ADA) positive samples would be further tested for neutralizing antibodies if necessary
Timepoint [5] 421216 0
Predose, 29 days post-dose.

Eligibility
Key inclusion criteria
1. Male and female subjects aged 18 to 55 years are included.
2. Body mass index between 18 and 32 kg/m2, inclusive.
3. COVID-19 test negative before being admitted to the clinical study site.
4. Subjects and partners must agree to use 2 methods of highly effective contraception from signing informed consent until completion of the follow-up visit or postdose 90 days (whichever is longer).
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. The positive result of hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), human immunodeficiency virus (HIV) antibody, or syphilis at screening.
2. Alanine aminotransferase (ALT), total bilirubin (TBIL), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or gamma-glutamyl transferase (GGT) greater than or equal to 2 × ULN; or, if AST, ALP, or GGT greater than or equal to 1 × ULN, but less than or equal to 2 × ULN and considered clinically relevant by the Investigator.
3. History of multiple drug allergies or allergic reactions to an oligonucleotide or N acetylgalactosamine (GalNAc).
4. History of intolerance to subcutaneous (SC) injection or relevant abdominal scarring (surgical, burns, etc.)
5. Received an investigational agent (including PCSK9 inhibitors) within 30 days or 5 half-lives (whichever is longer) before the first dose of the study drug or are in another clinical study.
6. History or clinical evidence of drug abuse within the 12 months before screening or positive screen for drugs of abuse.
7. Alcohol consumption greater than 14 standard drinks per week within one month before screening or positive screen for an alcohol breath test (1 standard drink equal to 10 grams of alcohol).
8. Regular tobacco use equal to 5 cigarettes per day within 6 months before screening.
9. Donate more than 500 mL of blood within 90 days before the first dose of the study drug.

Study design
Purpose of the study
Treatment
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 assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
strategic decision of the sponsor
Date of first participant enrolment
Anticipated
1/06/2023
Actual
19/05/2023
Date of last participant enrolment
Anticipated
16/08/2023
Actual
14/06/2023
Date of last data collection
Anticipated
30/11/2023
Actual
Sample size
Target
37
Accrual to date
Final
13
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 313554 0
Commercial sector/Industry
Name [1] 313554 0
Sanegene Bio Australia Pty Ltd
Country [1] 313554 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Sanegene Bio Australia Pty Ltd
Address
LEVEL 7, 330 COLLINS STREET, MELBOURNE VIC 3000
Country
Australia
Secondary sponsor category [1] 315332 0
Other Collaborative groups
Name [1] 315332 0
Novotech (Australia) Pty Ltd
Address [1] 315332 0
Level 3, 235 Pyrmont Street, Pyrmont, NSW 2009, Australia (Novotech)
Country [1] 315332 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312735 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 312735 0
123 Glen Osmond Road Eastwood SA 5063
Ethics committee country [1] 312735 0
Australia
Date submitted for ethics approval [1] 312735 0
29/03/2023
Approval date [1] 312735 0
10/05/2023
Ethics approval number [1] 312735 0
EC00458

Summary
Brief summary
This is a Randomized, Double-blind, Placebo-controlled, Single Ascending Dose (SAD) Study evaluating the safety, tolerability, Pharmacokinetics and Pharmacodynamics of SGB-3403 subcutaneously administered in Healthy Subjects.
The primary purpose of this study is to evaluate the safety and tolerability of SGB-3403 when administered subcutaneously as a single ascending dose in healthy volunteers. The secondary purpose of this study is to characterize and evaluate the pharmacokinetics and pharmacodynamic effect of SGB-3403 following subcutaneous administration.
The SAD phase will enroll 37 healthy participants to be split into 5 cohorts. Cohort 1 will comprise 5 subjects (3 active, 2 placeboes) whilst the remaining 4 cohorts of the SAD phase will consist of 8 participants (6 active, 2 placeboes). Single doses of 30, 100, 300, 500, and 800 mg of SBG-3403 administered subcutaneously will be evaluated. Participants will complete a total of 3 overnight stays [admission on D-1 to post-dose on D3, followed by 9 follow-up visits on Day 5, Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71, and Day 85, then every 4 weeks until LDL-C level returns to = 80% of baseline, but not exceed 180 days after the last study drug administration..
Each cohort commences only if previously collected data, including PK data (if available), does not highlight safety concerns after consultation with the Safety Review Committee (SRC). Following the starting dose of SGB-3403, decisions regarding dose escalation will be based on safety and tolerability assessments, PK data (if available), and reviewed SRC. Safety assessments will include monitoring of Adverse Events (AEs), vital signs (blood pressure, pulse rate, respiratory rate, and body temperature), clinical laboratory findings, 12-lead electrocardiograms (ECGs), and physical examination.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 125718 0
Dr Christopher Argent
Address 125718 0
Scientia, Bright Building, Level 5, Corner High & Avoca Street, Randwick NSW 2031, Australia
Country 125718 0
Australia
Phone 125718 0
+61 02 9382 5844
Fax 125718 0
Email 125718 0
christopher.argent@scientiaclinicalresearch.com.au
Contact person for public queries
Name 125719 0
Ms Sue Thackwray
Address 125719 0
Novotech (Australia) Pty Ltd, Level 2, 381 MacArthur Avenue Hamilton Queensland 4007 Australia
Country 125719 0
Australia
Phone 125719 0
+61 731376231
Fax 125719 0
Email 125719 0
Sue.Thackwray@novotech-cro.com
Contact person for scientific queries
Name 125720 0
Ms Sue Thackwray
Address 125720 0
Novotech (Australia) Pty Ltd, Level 2, 381 MacArthur Avenue Hamilton Queensland 4007 Australia
Country 125720 0
Australia
Phone 125720 0
+61 731376231
Fax 125720 0
Email 125720 0
Sue.Thackwray@novotech-cro.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.