A Safety and Tolerability Study of BPR-30221616 Injection in Healthy Subjects

A Single-center, Double-blind, Placebo-controlled, Dose-escalation Phase I Clinical Study to Evaluate the Safety and Tolerability of BPR-30221616 Injection in Healthy Subjects

The purpose of this study is to determine the safety, tolerability, pharmacokinetics、 pharmacodynamics and immunogenicity of BPR-30221616 in healthy subjects.

Study Overview

• Status: Recruiting
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: BPR-30221616 Injection; Drug: Sodium Chloride Injection

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Principal Investigator; Phone Number: China/Beijing+010-69154796; Email: hanxiaohong@pumch.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Xiaohong Han; Phone Number: 8613810659230; Email: hanxiaohong@pumc.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male and female healthy subjects.
• Age 18 to 65 years.
• Male weight ≥ 50.0 kg ，female weight ≥ 45.0 kg ， BMI ≥18.0 and ≤30.0 kg/m^2.
• Females must be non-pregnant and non-lactating.
• Subjects must give informed consent prior to the trial and willing to give written informed consent form.
• Subjects who can communicate reliably with the investigator and comply with all study requirements .

Exclusion Criteria:

• Subjects who have a clinically relevant history or presence of neurological,respiratory, gastrointestinal, cardiovascular, haematological, immunological, genitourinary,hepatic,renal, musculoskeletal diseases， or considered unfit for the study by the investigator with new disease within the 7 days prior to dose administration.
• Subjects with a history of serious mental illness.
• Clinically-significant (CS) abnormalities in physical examination, vital signs, electrocardiogram, clinical laboratory examination , chest radiograph and abdominal ultrasound at screening visit.
• Alanine aminotransferase (ALT) >1.5× normal upper limit (ULN), or aspartate aminotransferase (AST) >1.5×ULN, or total bilirubin >1.5×ULN at screening visit.
• Glomerular filtration rate (eGFR) <90mL/min/1.73m2 at screening visit.
• Vitamin A level < lower limit of normal (LLN) at screening visit.
• Uncontrolled ventricular arrhythmias, or co-morbidities that may cause prolonged QT.
• Known history of allergic reactions to 2 or more drugs or to N-acetylated galactosamine (GalNAc) or oligonucleotides.
• Subjects who had undergone major surgery within 6 months prior to screening or planned to undergo surgery during the study period, and who had previously undergone surgery that would affect drug absorption, distribution, metabolism, or excretion (except surgery for appendicitis).
• Alcoholic or regular drinking within the 6 months of randomization; Or a positive baseline alcohol breath test.
• Subjects who have a history of drug abuse within the 12 months of screening or have a positive baseline drug screening result.
• Smoking >5 cigarettes a day.
• Known human immunodeficiency virus (HIV) ,Treponema pallidum Antibody (TP-Ab),hepatitis B surface antigen (HBsAg)or hepatitis C virus (HCV) infection at screening visit.
• Subjects who have donated 400 mL or more of blood within the 3 months prior to dose administration or plan to donate until 6 months after dose administration.
• From the signing of informed consent, throughout the study until 12 months after dose administration , unwilling to use appropriate and effective contraceptions.
• Received an investigational agent or device intervention within 3 months of screening.
• Received prescription drugs within 4 weeks of randomization.
• Received over-the-counter drugs(unless deemed not clinically relevant by the investigator) within 7 days of randomization.
• Received any oligonucleotides[including small interfering ribonucleic acid(siRNA) and antisense oligonucleotides].
• Intolerance to subcutaneous injection.
• Had a special diet (such as grapefruit and products containing grapefruit, chocolate, any food containing caffeine or rich in xanthines (such as animal liver)) or had strenuous activity within 48 hours prior to dose administration , or with other factors affecting drug absorption, distribution, metabolism, excretion.
• Any physical or mental illness or condition that, as determined by the study physician, is likely to increase the risk of the study, interfere with the subject's adherence to the protocol, or interfere with the subject's completion of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BPR-30221616 Injection	Drug: BPR-30221616 Injection; BPR-30221616 will be administered by subcutaneous (SC) injection
Placebo Comparator: Sodium Chloride Injection	Drug: Sodium Chloride Injection; Sodium Chloride Injection will be administered by SC injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Participants With Adverse Events (AE)	Up to Day 360
Incidence of Participants With Serious Adverse Events (SAE)	Up to Day 360
Incidence of Participants With Clinically Significant laboratory tests, electrocardiogram (ECG), physical examination, vital signs	Up to Day 360

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum plasma concentration （Cmax）of BPR-30221616	Day 1 through to Day 3
Time to maximum plasma concentration（Tmax） of BPR-30221616	Day 1 through to Day 3
Area under the plasma concentration-time curve（AUC）of BPR-30221616	Day 1 through to Day 3
Elimination rate constant (λz) of BPR-30221616	Day 1 through to Day 3
Elimination half-life (t1/2) of BPR-30221616	Day 1 through to Day 3
Apparent volume of distribution during terminal phase (Vz/F) of BPR-30221616	Day 1 through to Day 3
Clearance (CL/F) of BPR-30221616	Day 1 through to Day 3
Mean residence time from zero to infinity (MRT0-∞) of BPR-30221616	Day 1 through to Day 3
Cumulative amount of the dose excreted unchanged in urine (Ae) of BPR-30221616	Day 1 through to Day 3
Cumulative fraction of the dose excreted unchanged in urine (Fe) of BPR-30221616	Day 1 through to Day 3
Renal clearance(CLr) of BPR-30221616	Day 1 through to Day 3
Effect of BPR-30221616 on serum transthyretin（TTR） levels as measured by reduction from baseline in serum TTR	Day 1 through to Day 540
Number of participants who develop serum anti-BPR-30221616 antibodies	Day 1 through to Day 360

Other Outcome Measures

Outcome Measure	Time Frame
Effect of BPR-30221616 on serum Vitamin A levels as measured by reduction from baseline in serum Vitamin A	Day 1 through to Day 540
Effect of BPR-30221616 on serum Retinol-Binding Protein（RBP） levels as measured by reduction from baseline in serum RBP	Day 1 through to Day 540

Collaborators and Investigators

• Sponsor: Chengdu Brilliant Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2025
• Primary Completion (Estimated): January 24, 2026
• Study Completion (Estimated): December 5, 2026

Study Registration Dates

• First Submitted: December 19, 2024
• First Submitted That Met QC Criteria: January 3, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 8, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: BPR-30221616-Ⅰ-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No