Study of VSA001 Injection in Chinese Healthy Adult Volunteers

• ClinicalTrials.gov Identifier: NCT05757596
• Recruitment Status: Not yet recruiting
• First Posted: March 7, 2023
• Last Update Posted: March 7, 2023
• Sponsor: Visirna Therapeutics HK Limited
• Collaborator: Arrowhead Pharmaceuticals
• Information provided by (Responsible Party): Visirna Therapeutics HK Limited

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Healthy Adult Volunteers	Drug: VSA001 injection; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: June 1, 2023
• Estimated Primary Completion Date: December 1, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability [ Time Frame: 85 days ]

   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).

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

China, Beijing

Peking University Third Hospital

Beijing, Beijing, China

Contact: Cathy Wang, MD. cathy.wang@visirna.com

Contact: Ye Li, MD. ye.li@visirna.com

Principal Investigator: Fangfang Wang, MD.

Principal Investigator: Haiyan Li, MD.

Sponsors and Collaborators

Visirna Therapeutics HK Limited

Arrowhead Pharmaceuticals

More Information

• Responsible Party: Visirna Therapeutics HK Limited
• ClinicalTrials.gov Identifier: NCT05757596
• Other Study ID Numbers: VSA001-1001
• First Posted: March 7, 2023
• Last Update Posted: March 7, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No