A Single and Multiple Ascending Doses Study to Evaluate the Safety, Tolerability and Pharmacokinetics of RBD7022

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hyperlipemia

Intervention / Treatment
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* Drug: RBD7022
* Drug: RBD7022
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RBD7022 SAD experimental group<br>Subjects in SAD experimental groups will receive a single subcutaneous injection of RBD7022 on Day 0. | Drug: RBD7022<br>* Subcutaneously Administered RBD7022 in Healthy Subjects.<br>|
| Experimental: RBD7022 MAD experimental group<br>Subjects in MAD experimental groups will receive one subcutaneous injection of RBD7022 on Day 0 and another subcutaneous injection of RBD7022 on Day 28. | Drug: RBD7022<br>* Subcutaneously Administered RBD7022 in Healthy Subjects.<br>|
| Placebo Comparator: Placebo SAD group<br>Subjects in SAD placebo groups will receive a single subcutaneous injection of placebo on Day 0. | Drug: Placebo<br>* Subcutaneously Administered Placebo in Healthys Subject.<br>|
| Placebo Comparator: Placebo MAD group<br>Subjects in MAD placebo groups will receive one subcutaneous injection of placebo on Day 0 and another subcutaneous injection of placebo on Day 28 . | Drug: Placebo<br>* Subcutaneously Administered Placebo in Healthys Subject.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0 | 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 | SAD up to Day 180; MAD up to Day 208 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The serum LDL-C level after subject dosing RBD7022 | measure the LDL-C level in blood by lab examination and eveluate the effect of RBD7022 on Circulating LDL-c Levels (Determination of % Lowering of LDL-c to treatment/Baseline LDL-c Level) | SAD up to Day 180; MAD up to Day 208 | 
| The serum PCSK9 level after subject dosing RBD7022 | measure the pcsk9 level in blood by lab examination and eveluate the effect of RBD7022 on Circulating PCSK9 Levels (Determination of % Lowering of PCSK9 to treatment/Baseline PCSK9 Level). | SAD up to Day 180; MAD up to Day 208 | 
| Other blood lipoprotein and lipid parameters besides LDL-c | measure other blood lipoprotein and lipid parameters besides LDL-c in blood by lab examination and eveluate % change and absolute change in other lipoprotein and lipid parameters（TC、TG、Lp (a)、HDL-C、non HDL-C、Apo B、Apo A1、Apo A 1/ Apo B ratio） from baseline up to Day 208 | SAD up to Day 180; MAD up to Day 208 | 
| The effect of RBD7022 monotherapy or RBD7022 combination with statin in patients with elevated LDL-C | measure the LDL-C and pcsk9 level in blood by lab examination and assess % change and absolute change in LDL-c and PCSK9 from baseline up to Day 208 | SAD up to Day 180; MAD up to Day 208 | 
| To characterize the pharmacokinetic parameter Cmax | Plasma Maximum concentration (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 Tmax | Time to maximum concentration (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 | 
| To characterize the pharmacokinetic parameter AUC0-t | Area under the concentration-time curve from 0 to the collection time t (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 | 
| To characterize the pharmacokinetic parameter t1/2 | Half-Life (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 | Elimination rate constant (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 CL/F | Oral clearance (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 | 
| To characterize the pharmacokinetic parameter Vz/F | Volume of distribution in the terminal elimination period (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 | Area under the concentration-time curve from 0 to infinity | 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 |