Clinical trial NCT06760455: A Safety and Tolerability Study of BPR-30221616 Injection in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Participants
Lead sponsor: Chengdu Brilliant Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-01-06
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Participants With Adverse Events (AE)
timeFrame: Up to Day 360
measure: Incidence of Participants With Serious Adverse Events (SAE)
timeFrame: Up to Day 360
measure: Incidence of Participants With Clinically Significant laboratory tests, electrocardiogram (ECG), physical examination, vital signs
timeFrame: Up to Day 360
Secondary outcomes:
measure: Maximum plasma concentration （Cmax）of BPR-30221616
timeFrame: Day 1 through to Day 3
measure: Time to maximum plasma concentration（Tmax） of BPR-30221616
timeFrame: Day 1 through to Day 3
measure: Area under the plasma concentration-time curve（AUC）of BPR-30221616
timeFrame: Day 1 through to Day 3
measure: Elimination rate constant (λz) of BPR-30221616
timeFrame: Day 1 through to Day 3
measure: Elimination half-life (t1/2) of BPR-30221616
timeFrame: Day 1 through to Day 3
measure: Apparent volume of distribution during terminal phase (Vz/F) of BPR-30221616
timeFrame: Day 1 through to Day 3
measure: Clearance (CL/F) of BPR-30221616
timeFrame: Day 1 through to Day 3
measure: Mean residence time from zero to infinity (MRT0-∞) of BPR-30221616
timeFrame: Day 1 through to Day 3
measure: Cumulative amount of the dose excreted unchanged in urine (Ae) of BPR-30221616
timeFrame: Day 1 through to Day 3
measure: Cumulative fraction of the dose excreted unchanged in urine (Fe) of BPR-30221616
timeFrame: Day 1 through to Day 3
measure: Renal clearance(CLr) of BPR-30221616
timeFrame: Day 1 through to Day 3
measure: Effect of BPR-30221616 on serum transthyretin（TTR） levels as measured by reduction from baseline in serum TTR
timeFrame: Day 1 through to Day 540
measure: Number of participants who develop serum anti-BPR-30221616 antibodies
timeFrame: Day 1 through to Day 360
Other outcomes:
measure: Effect of BPR-30221616 on serum Vitamin A levels as measured by reduction from baseline in serum Vitamin A
timeFrame: Day 1 through to Day 540
measure: Effect of BPR-30221616 on serum Retinol-Binding Protein（RBP） levels as measured by reduction from baseline in serum RBP
timeFrame: Day 1 through to Day 540
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
References: