Clinical Trials/NCT05539651

NCT05539651

Completed

Phase 1

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

Suzhou Ribo Life Science Co. Ltd.1 site in 1 country72 target enrollmentNovember 10, 2022

ConditionsHealth Volunteer

InterventionsRBD5044 Placebo

DrugsRBD5044 Placebo

Overview

Phase: Phase 1
Intervention: RBD5044
Conditions: Health Volunteer
Sponsor: Suzhou Ribo Life Science Co. Ltd.
Enrollment: 72
Locations: 1
Primary Endpoint: Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

November 10, 2022

End Date

October 30, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Suzhou Ribo Life Science Co. Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•A subject will be eligible for inclusion in this study only if all of the following criteria are met:
•Willing to comply with protocol required visit schedule and visit requirements and provide written informed consent.
•Male and female subjects, aged 18 to 65 years (inclusive).
•Body mass index between 18 and 32 kg/m2, inclusive.
•Fasting TG ≥ 0.9 mmol/L (80 mg/dL) and ≤ 3.4 mmol/L (300 mg/dL) at screening.
•Fasting LDL-C \< 4.9 mmol/L (\<190 mg/dL) at screening.
•Healthy as determined by pre-study medical history, physical examination, clinical laboratory assessments, and 12-lead electrocardiogram (ECG).
•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.

Exclusion Criteria

•A subject meeting any of the following exclusion criteria will not be allowed to participate in this study:
•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.
•History or presence of cardiovascular disease (including peripheral artery and cerebrovascular disease).
•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.
•Diagnosis of diabetes mellitus.
•Received any medication or nutraceutical to alter serum lipids within 30 days before screening.
•Active serious mental illness or psychiatric disorder, including but not limited to schizophrenia, bipolar disorder, or severe depression, which require current pharmacological intervention.
•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.
•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.
•Used prescription drugs within 14 days or 7 half-lives (whichever is longer) before the first dose of study drug.

Arms & Interventions

RBD5044 SAD experimental group

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

Intervention: RBD5044

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.

Intervention: RBD5044

Placebo SAD group

Subjects in SAD placebo groups will receive a single subcutaneous injection of placebo on Day 1.

Intervention: Placebo

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.

Intervention: Placebo

Outcomes

Primary Outcomes

Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0

Time Frame: SAD: Up to 24 weeks; MAD: Up to 28 weeks

The investigator will make an assessment of intensity for each AE and SAE reported during the study according to CTCAE V5.0

Secondary Outcomes

To characterize the pharmacokinetic parameter MRT of RBD5044 in healthy subjects(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)
To characterize the pharmacokinetic parameter Vz/F of RBD5044 in healthy subjects(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)
To characterize the pharmacokinetic parameter Cmax of RBD5044 in healthy subjects(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)
To characterize the pharmacokinetic parameter Tmax of RBD5044 in healthy subjects(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)
To characterize the pharmacokinetic parameter AUC0-inf of RBD5044 in healthy subjects(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)
To characterize the pharmacokinetic parameter AUC0-t of RBD5044 in healthy subjects(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)
To characterize the pharmacokinetic parameter t1/2 of RBD5044 in healthy subjects(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)
To evaluate the pharmacodynamics (PD) effect of RBD5044 on serum levels of APOC3 in healthy subjects(SAD: Up to 24 weeks; MAD: Up to 28 weeks)
To evaluate the PD effect of RBD5044 on serum levels of triglyceride (TG) in healthy subjects.(SAD: Up to 24 weeks; MAD: Up to 28 weeks)
To characterize the pharmacokinetic parameter λz of RBD5044 in healthy subjects(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)
To characterize the pharmacokinetic parameter CL/F of RBD5044 in healthy subjects(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)