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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05539651




Registration number
NCT05539651
Ethics application status
Date submitted
22/08/2022
Date registered
14/09/2022
Date last updated
1/11/2023

Titles & IDs
Public title
A Single and Multiple Ascending Doses Study to Evaluate the Safety and Pharmacokinetics of RBD5044
Scientific title
A Randomized, Double-Blind, Placebo-Controlled Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of Subcutaneously Administered RBD5044 in Healthy Subjects
Secondary ID [1] 0 0
RBAP1101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Health Volunteer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RBD5044
Treatment: Drugs - Placebo

Experimental: RBD5044 SAD experimental group - Subjects in SAD experimental groups will receive a single subcutaneous injection of RBD5044 on Day 1.

Experimental: RBD5044 MAD experimental group - Subjects in MAD experimental groups will receive one subcutaneous injection of RBD5044 on Day 1 and another subcutaneous injection of RBD5044 on Day 29.

Placebo comparator: Placebo SAD group - Subjects in SAD placebo groups will receive a single subcutaneous injection of placebo on Day 1.

Placebo comparator: Placebo MAD group - Subjects in MAD placebo groups will receive one subcutaneous injection of placebo on Day 1 and another subcutaneous injection of placebo on Day 29.


Treatment: Drugs: RBD5044
Subcutaneously Administered RBD5044 in Healthy Subjects

Treatment: Drugs: Placebo
Subcutaneously Administered Placebo in Healthy Subjects
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0
Timepoint [1] 0 0
SAD: Up to 24 weeks; MAD: Up to 28 weeks
Secondary outcome [1] 0 0
To characterize the pharmacokinetic parameter Cmax of RBD5044 in healthy subjects
Timepoint [1] 0 0
SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
Secondary outcome [2] 0 0
To characterize the pharmacokinetic parameter Tmax of RBD5044 in healthy subjects
Timepoint [2] 0 0
SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
Secondary outcome [3] 0 0
To characterize the pharmacokinetic parameter AUC0-inf of RBD5044 in healthy subjects
Timepoint [3] 0 0
SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
Secondary outcome [4] 0 0
To characterize the pharmacokinetic parameter AUC0-t of RBD5044 in healthy subjects
Timepoint [4] 0 0
SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
Secondary outcome [5] 0 0
To characterize the pharmacokinetic parameter t1/2 of RBD5044 in healthy subjects
Timepoint [5] 0 0
SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
Secondary outcome [6] 0 0
To characterize the pharmacokinetic parameter ?z of RBD5044 in healthy subjects
Timepoint [6] 0 0
SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
Secondary outcome [7] 0 0
To characterize the pharmacokinetic parameter MRT of RBD5044 in healthy subjects
Timepoint [7] 0 0
SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
Secondary outcome [8] 0 0
To characterize the pharmacokinetic parameter CL/F of RBD5044 in healthy subjects
Timepoint [8] 0 0
SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
Secondary outcome [9] 0 0
To characterize the pharmacokinetic parameter Vz/F of RBD5044 in healthy subjects
Timepoint [9] 0 0
SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
Secondary outcome [10] 0 0
To evaluate the pharmacodynamics (PD) effect of RBD5044 on serum levels of APOC3 in healthy subjects
Timepoint [10] 0 0
SAD: Up to 24 weeks; MAD: Up to 28 weeks
Secondary outcome [11] 0 0
To evaluate the PD effect of RBD5044 on serum levels of triglyceride (TG) in healthy subjects.
Timepoint [11] 0 0
SAD: Up to 24 weeks; MAD: Up to 28 weeks

Eligibility
Key inclusion criteria
A subject will be eligible for inclusion in this study only if all of the following criteria are met:

1. Willing to comply with protocol required visit schedule and visit requirements and provide written informed consent.
2. Male and female subjects, aged 18 to 65 years (inclusive).
3. Body mass index between 18 and 32 kg/m2, inclusive.
4. Fasting TG = 0.9 mmol/L (80 mg/dL) and = 3.4 mmol/L (300 mg/dL) at screening.
5. Fasting LDL-C < 4.9 mmol/L (<190 mg/dL) at screening.
6. Healthy as determined by pre-study medical history, physical examination, clinical laboratory assessments, and 12-lead electrocardiogram (ECG).
7. Satisfy one of the following:

* Females: must be non-pregnant and non-lactating; surgically sterile, post-menopausal, abstinent, or if engaged in sexual relations of child-bearing potential, the subject is using an acceptable contraceptive method (refer to Section 4.6.3) for four weeks before, during, and for at least 6 months after the last dose of study drug administration.
* Males: must be surgically sterile, abstinent, or if engaged in sexual relations of child-bearing potential, the subject is utilizing an acceptable contraceptive method (refer to Section 4.6.3)) during and for at least 6 months after the last dose of study drug administration.
8. Non-smokers and non-nicotine users for at least 90 days before screening
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
A subject meeting any of the following exclusion criteria will not be allowed to participate in this study:

1. Any uncontrolled or serious disease, or any medical or surgical condition, may interfere with participation in the clinical study and/or put the subject at significant risk (according to the investigator's judgment) if he/she participates in the clinical study.
2. History or presence of cardiovascular disease (including peripheral artery and cerebrovascular disease).
3. Systolic blood pressure (SBP) > 140 mmHg and/or diastolic blood pressure (DBP) > 90 mmHg after 10 minutes of supine rest, unless determined by the investigator to be not clinically relevant.
4. Diagnosis of diabetes mellitus.
5. Received any medication or nutraceutical to alter serum lipids within 30 days before screening.
6. Active serious mental illness or psychiatric disorder, including but not limited to schizophrenia, bipolar disorder, or severe depression, which require current pharmacological intervention.
7. Alanine aminotransferase (ALT) and/or total bilirubin are above the upper limit of normal reference range (ULN); no investigator discretion and repeat assessments are allowed.
8. Aspartate aminotransferase (AST), alkaline phosphatase (ALP), or gamma-glutamyl transferase (GGT) > 2 × ULN (no investigator discretion); or, if AST, ALP, or GGT > ULN, but = 2 × ULN and considered clinically relevant by the investigator.
9. Used prescription drugs within 14 days or 7 half-lives (whichever is longer) before the first dose of study drug.
10. Used over-the-counter medication, excluding routine vitamins, within 7 days before the first dose of the study drug, unless determined by the investigator to be not clinically relevant, and unlikely to impact blood lipids level.
11. Received an investigational product within 30 days or 7 half-lives (whichever is longer) before the first dose of the study drug or are in the follow-up of another clinical study. If subjects used advanced therapy (ASO/siRNA/gene therapy/cell therapy), it should be judged by the investigator.
12. Hepatitis B virus, hepatitis C virus, human immunodeficiency virus (HIV), syphilis infection, or positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus antibody (HCVAb), HIV antibody (HIVAb), treponema pallidum antibody (TP-Ab) at screening.
13. Clinically significant illness within 7 days before the first dose of the study drug.
14. Consume more than 14 (female) or 21 (male) units of alcohol per week (unit: 1 glass of wine [125 mL] = 1 measure of spirits = ½ pint of beer) within the 12 months before screening or positive screen for alcohol abuse.
15. History or clinical evidence of drug abuse within the 12 months before screening or positive screen for drug abuse. Drug abuse is defined as compulsive, repetitive, and/or chronic use of drugs or other substances with or without problems related to their use and/or where stopping or a dose reduction will lead to withdrawal symptoms.
16. Donated more than 500 mL of blood within 90 days before the first dose of the study drug.
17. History of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc).
18. History of intolerance to subcutaneous (SC) injection or relevant abdominal scarring (surgical, burns, etc.).
19. Any conditions which would make the subject unsuitable for enrollment or could interfere with the subject's participation in or completion of the study in the opinion of the investigator.

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

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2024
Actual
Sample size
Target
72
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Q-Pharm Pty Limited - Brisbane
Recruitment postcode(s) [1] 0 0
- Brisbane

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Suzhou Ribo Life Science Co. Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a randomized, double-blind, placebo-controlled phase I study to evaluate the safety, tolerability, PK profiles and PD effect of single and multiple ascending doses of subcutaneously administered RBD5044 in healthy subjects. The study will be performed in 2 phases: single ascending dose (SAD) phase and multiple ascending doses (MAD) phase in healthy subjects. There are 6 cohorts in SAD phases, the dose levels are 5mg, 20mg, 60mg, 90mg, 120mg and 150mg. There are 3 cohorts in MAD phases, the dose levels are 60mg, 90mg and 120mg.The decision to escalate to subsequent dose levels will be made by the SRC based on the review of all available safety information, including AEs, ECGs, vital signs, and clinical laboratory test results in each cohort.
Trial website
https://clinicaltrials.gov/study/NCT05539651
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
Richard Friend, Dr.
Address 0 0
Country 0 0
Phone 0 0
+61 403 415 925
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05539651