A Randomized, Single Blind, Placebo Controlled, Single Center Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Pharmacodynamics of Single and Multiple Ascending Doses of Subcutaneously Administered RBD7022 in Participants With Normal or Elevated LDL-c Cholesterol
Overview
- Phase
- Phase 1
- Intervention
- RBD7022
- Conditions
- Hyperlipemia
- Sponsor
- Suzhou Ribo Life Science Co. Ltd.
- Enrollment
- 80
- 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
Brief Summary
This is a randomized, single blind, placebo controlled, single center phase I study to evaluate the safety, tolerability, pharmacokinetics, and preliminary pharmacodynamics of single and multiple ascending doses of subcutaneously administered RBD7022 in participants with normal or elevated LDL-c cholesterol. The study will be performed in 2 phases: single ascending dose (SAD) phase and multiple ascending doses (MAD) phase in participants. The decision to escalate to subsequent dose levels will be made by the SRC based on the review of all available safety information in each cohort.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female subjects, aged 18 to 65 years, inclusive
- •Body mass index between 17 and 28 kg/m2 , inclusive
- •LDL-C normal or elevated at screening and baseline.
- •Willing to comply with protocol required visit schedule and visit requirements and provide written informed consent.
- •The clinical laboratory examination of the subjects was within the normal range, or abnormal but had no clinical significance as judged by the investigators, and did not affect the study results;
- •Vital signs, physical examination, ECG, ultrasound showed normal or abnormal but no clinically significant as determined by the investigator.
Exclusion Criteria
- •With a clear history of primary diseases of major organs, the subject is not suitable to participate in this study considered by the investigator;
- •Diagnosis of diabetes mellitus;
- •Pregnant or breastfeeding women;
- •Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrollment or could interfere with the subject's participation in or completion of the study.
Arms & Interventions
RBD7022 SAD experimental group
Subjects in SAD experimental groups will receive a single subcutaneous injection of RBD7022 on Day 0.
Intervention: RBD7022
RBD7022 MAD experimental group
Subjects in MAD experimental groups will receive one subcutaneous injection of RBD7022 on Day 0 and another subcutaneous injection of RBD7022 on Day 28.
Intervention: RBD7022
Placebo SAD group
Subjects in SAD placebo groups will receive a single subcutaneous injection of placebo on Day 0.
Intervention: Placebo
Placebo MAD group
Subjects in MAD placebo groups will receive one subcutaneous injection of placebo on Day 0 and another subcutaneous injection of placebo on Day 28 .
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0
Time Frame: SAD up to Day 180; MAD up to Day 208
By the examination of vital signs, physical examination, 12-lead electrocardiogram (ECG), and laboratory examination, 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 CL/F(SAD: within 60 min before dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24, 48 and 72 hours after dosing; MAD: within 60 minutes before day 0 and day 28 dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24 ,48 and 72 hours after Day 0 and day 28 dosing)
- The serum LDL-C level after subject dosing RBD7022(SAD up to Day 180; MAD up to Day 208)
- To characterize the pharmacokinetic parameter Cmax(SAD: within 60 min before dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24, 48 and 72 hours after dosing; MAD: within 60 minutes before day 0 and day 28 dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24 ,48 and 72 hours after Day 0 and day 28 dosing)
- To characterize the pharmacokinetic parameter AUC0-t(SAD: within 60 min before dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24, 48 and 72 hours after dosing; MAD: within 60 minutes before day 0 and day 28 dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24 ,48 and 72 hours after Day 0 and day 28 dosing)
- The effect of RBD7022 monotherapy or RBD7022 combination with statin in patients with elevated LDL-C(SAD up to Day 180; MAD up to Day 208)
- To characterize the pharmacokinetic parameter Tmax(SAD: within 60 min before dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24, 48 and 72 hours after dosing; MAD: within 60 minutes before day 0 and day 28 dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24 ,48 and 72 hours after Day 0 and day 28 dosing)
- The serum PCSK9 level after subject dosing RBD7022(SAD up to Day 180; MAD up to Day 208)
- Other blood lipoprotein and lipid parameters besides LDL-c(SAD up to Day 180; MAD up to Day 208)
- To characterize the pharmacokinetic parameter t1/2(SAD: within 60 min before dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24, 48 and 72 hours after dosing; MAD: within 60 minutes before day 0 and day 28 dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24 ,48 and 72 hours after Day 0 and day 28 dosing)
- To characterize the pharmacokinetic parameter λz(SAD: within 60 min before dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24, 48 and 72 hours after dosing; MAD: within 60 minutes before day 0 and day 28 dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24 ,48 and 72 hours after Day 0 and day 28 dosing)
- To characterize the pharmacokinetic parameter Vz/F(SAD: within 60 min before dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24, 48 and 72 hours after dosing; MAD: within 60 minutes before day 0 and day 28 dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24 ,48 and 72 hours after Day 0 and day 28 dosing)
- To characterize the pharmacokinetic parameter AUC0-inf(SAD: within 60 min before dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24, 48 and 72 hours after dosing; MAD: within 60 minutes before day 0 and day 28 dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24 ,48 and 72 hours after Day 0 and day 28 dosing)