Study of VSA001 Injection in Chinese Healthy Adult Volunteers

A Phase 1 Clinical Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Effects of a Single Dose of VSA001 Injection in Chinese Healthy Adult Volunteers

This is a phase 1, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics effects of a single dose of VSA001 injection in Chinese healthy adult volunteers. Eligible enrolled participants will initially receive VSA001 injection at the assigned dose level.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Adult Volunteers
• Intervention / Treatment: Drug: VSA001 injection; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Peking University Third Hospital
      • Contact: Cathy Wang, MD.; Email: cathy.wang@visirna.com
      • Contact: Ye Li, MD.; Email: ye.li@visirna.com
      • Principal Investigator: Fangfang Wang, MD.
      • Principal Investigator: Haiyan Li, MD.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The subjects voluntarily participate in this study who are able to read, understand, and sign the ICF before participation; and have a full understanding of the content, process and possible adverse reactions of the study and are able to complete the study in accordance with the requirements of the protocol.
2. Healthy male and female subjects aged between 18 and 55 years (both inclusive) at the time of informed consent.
3. Body mass index (BMI) = weight (kg)/height (m)2, within the range of 19.0-30.0 kg/m2 (both inclusive), and body weight no less than 50 kg.
4. In good general health and without clinically significant abnormalities as judged by the investigator, based on medical history, physical examination, vital signs, 12-lead ECG, and laboratory results.
5. Negative serum pregnancy test within 72 h prior to initiation of study treatment in all premenopausal females and females who have been amenorrheic for less than 12 months. (Serum pregnancy test is not required for females who have undergone surgical sterilization, such as hysterectomy and/or bilateral oophorectomy, or those who have not experienced menses for 12 consecutive months and are judged to be postmenopausal based on factors such as age and castration therapy).
6. Subjects and their partners must agree to use adequate contraceptive methods prior to initiation of study treatment, during the study, and for at least 3 months after discontinuation of study treatment.
7. Fasting serum TGs >80 mg/dL (>0.903 mmol/L) at screening.

Exclusion Criteria:

1. History or presence of significant or clinically significant diseases/abnormality, including but not limited to cardiac/cardiovascular, respiratory, endocrine, gastrointestinal, renal, hepatic, gallbladder, dermatological, hematological, immunological, neurologic, or psychiatric diseases/abnormality, or the disease that, in the judgement of the investigator, present a safety concern or affects the pharmacokinetic evaluation.
2. A family history of congenital long QT syndrome, Brugada syndrome or unexplained sudden cardiac death.
3. Subjects who are with acute exacerbation of any significant acute or chronic disease as judged by the investigator.
4. AST and ALT >2×upper limit of normal (ULN) , or total bilirubin >ULN at screening.
5. Serum creatinine estimated eGFR < 60 ml/min/1.73 m2 per MDRD formula.
6. Cardiac troponin (troponin I) above ULN at Screening.
7. Fasting serum TGs >300 mg/dL (>3.38 mmol/L) at screening.
8. Presence of other conditions or treatments that may affect the study results and interfere with the subject's participation in the study as assessed by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: VSA001 injection; A single dose of active drug (VSA001, low or high dose) will be administered by subcutaneous injection on Day 1.	Drug: VSA001 injection; The active drug is VSA001 injection. The active pharmaceutical ingredient (API) contained in VSA001 is a synthetic, double-stranded, hepatocyte targeted NAG-conjugated RNAi.
Placebo Comparator: Placebo; The placebo is normal saline (0.9%) administered subcutaneously; volume matched to the corresponding VSA001 dose volume.	Drug: Placebo; 0.9% Saline, volume matched

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Incidence, frequency, and severity of adverse events (AEs) and serious adverse events (SAEs), and the relationship with VSA-01001. Clinically significant abnormalities in laboratory tests, vital signs, physical examination, 12-lead electrocardiograms (ECG).	85 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics parameter: Cmax	Maximum plasma concentration (Cmax)	48 hours
Pharmacokinetics parameter: Tmax	Time to maximum plasma concentration (Tmax)	48 hours
Pharmacokinetics parameter: AUC0-t	Area under the plasma concentration-time curve from the time 0 to the last quantifiable time point (AUC0-t).	48 hours
Pharmacokinetics parameter: t1/2	Half-life (t1/2).	48 hours
Pharmacokinetics parameter: CL/F	Apparent clearance (CL/F).	48 hours
Pharmacokinetics parameter: Vz/F	Apparent volume of distribution (Vz/F).	48 hours
Pharmacodynamic (PD) parameters	Change from baseline over time in fasting serum APOC3 and triglycerides (TGs).	85 days

Collaborators and Investigators

• Sponsor: Visirna Therapeutics HK Limited
• Collaborators: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2023
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: February 14, 2023
• First Submitted That Met QC Criteria: February 23, 2023
• First Posted (Estimate): March 7, 2023

Study Record Updates

• Last Update Posted (Estimate): March 7, 2023
• Last Update Submitted That Met QC Criteria: February 23, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: VSA001-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No