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A Single and Multiple Ascending Doses Phase I Study to Evaluate the Safety and Pharmacokinetics of RBD4059 in Healthy Subjects

Primary Purpose

Healthy Volunteers

Status
Recruiting
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
RBD4059
Placebo
Sponsored by
Suzhou Ribo Life Science Co. Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Healthy Volunteers

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Male and female (non-childbearing potential only), aged 18 to 65 years, inclusive. Body mass index (BMI) between 18 and 32 kg/m2, inclusive. APTT, Prothrombin time(PT), INR, thrombin time (TT),FXI activity must be within the normal reference range (as per the local laboratory reference range) at screening . Adequate complete blood counts (CBCs) and platelet are within the normal reference range (If CBCs are outside the reference range, unless not clinically significant determined by the Investigator ). Healthy as determined by pre-study medical history, vital signs, physical examination, clinical laboratory assessments, and 12-lead electrocardiogram (ECG). Subjects who are willing to cooperate with the study staff, comply with the study requirements, complete the study according to the relevant procedures specified in the protocol, and correctly understand and sign the informed consent form in writing. Exclusion Criteria: Any uncontrolled or serious disease that may interfere with participation in the clinical study and/or put the subject at significant risk (according to Investigator's judgment) if he/she participates in the clinical study. History or presence of cardiovascular disease (including peripheral artery and cerebrovascular disease). Systolic blood pressure (SBP) is less than 90 or greater than 140 mmHg and/or diastolic blood pressure (DBP) is less than 40 or greater than 90 mmHg after 10 minutes of supine rest, unless determined by the Investigator to be not clinically significant. Diagnosis of diabetes mellitus, history of gestational diabetes that is fully resolved is not permitted. 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. Note: additional inclusion/exclusion criteria may apply, per protocol.

Sites / Locations

  • Q-Pharm Pty LimitedRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Arm Label

RBD4059 SAD experimental group

RBD4059 MAD experimental group

Placebo SAD group

Placebo MAD group

Arm Description

Subjects in SAD experimental groups will receive a single subcutaneous injection of RBD4059 on Day 1.

Subjects in MAD experimental groups will receive one subcutaneous injection of RBD4059 on Day 1 and another subcutaneous injection of RBD4059 on Day 29.

Subjects in SAD placebo groups will receive a single subcutaneous injection of placebo on Day 1.

Subjects in MAD placebo groups will receive one subcutaneous injection of placebo on Day 1 and another subcutaneous injection of placebo on Day 29.

Outcomes

Primary Outcome Measures

Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0
Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0

Secondary Outcome Measures

To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:Cmax
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:Tmax
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:AUC0-t
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:AUC0-inf
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:t1/2
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:MRT
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:λz
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:CL/F
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:Vz
To evaluate the pharmacodynamics (PD) effect of RBD4059 on levels of Coagulation factor XI (FXI) antigen in healthy subjects.
To evaluate the pharmacodynamics (PD) effect of RBD4059 on levels of FXI activity in healthy subjects.
To evaluate the pharmacodynamics (PD) effect of RBD4059 on levels of Activated partial thromboplastin time (APTT) in healthy subjects.

Full Information

First Posted
November 21, 2022
Last Updated
October 19, 2023
Sponsor
Suzhou Ribo Life Science Co. Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05653037
Brief Title
A Single and Multiple Ascending Doses Phase I Study to Evaluate the Safety and Pharmacokinetics of RBD4059 in Healthy Subjects
Official Title
A Randomized, Single-blind, Placebo-Controlled Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of Subcutaneously Administered RBD4059 in Healthy Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 21, 2023 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Suzhou Ribo Life Science Co. Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a Randomized, Single-blind, Placebo-Controlled Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of Subcutaneously Administered RBD4059 in Healthy Subjects. The study will be performed in 2 phases: single ascending dose (SAD) phase and multiple ascending doses (MAD) phase in healthy subjects. The decision to escalate to subsequent dose levels will be made by the SRC based on the review of all available safety information and PK/PD data in each cohort. RBD4059, a GalNAc conjugated siRNA, is an FXI-targeted new molecular entity independently developed by Ribo using its proprietary siRNA delivery system - RIBO-GalSTARTM.
Detailed Description
RBD4059, a GalNAc conjugated siRNA, is an FXI-targeted new molecular entity independently developed by Ribo using its proprietary siRNA delivery system - RIBO-GalSTARTM. As a GalNAc-based liver targeting delivery system, RIBO-GalSTARTM incorporates a unique technology for the delivery of oligonucleotide therapeutics for various targets and indications associated with the liver, thus enabling highly specific and highly durable enrichment of the siRNA in hepatocytes, the primary source of FXI. RBD4059 is, therefore, proposed to be a novel effective and durable antithrombotic treatment, with low bleeding risk via inhibition of FXI activity and prolongation of APTT.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Volunteers

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
Participant
Allocation
Randomized
Enrollment
64 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
RBD4059 SAD experimental group
Arm Type
Experimental
Arm Description
Subjects in SAD experimental groups will receive a single subcutaneous injection of RBD4059 on Day 1.
Arm Title
RBD4059 MAD experimental group
Arm Type
Experimental
Arm Description
Subjects in MAD experimental groups will receive one subcutaneous injection of RBD4059 on Day 1 and another subcutaneous injection of RBD4059 on Day 29.
Arm Title
Placebo SAD group
Arm Type
Placebo Comparator
Arm Description
Subjects in SAD placebo groups will receive a single subcutaneous injection of placebo on Day 1.
Arm Title
Placebo MAD group
Arm Type
Placebo Comparator
Arm Description
Subjects in MAD placebo groups will receive one subcutaneous injection of placebo on Day 1 and another subcutaneous injection of placebo on Day 29.
Intervention Type
Drug
Intervention Name(s)
RBD4059
Intervention Description
Subcutaneously Administered RBD4059 in Healthy Subjects.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Subcutaneously Administered Placebo in Healthys Subject.
Primary Outcome Measure Information:
Title
Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0
Time Frame
SAD: Up to Day 169 ;
Title
Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0
Time Frame
MAD: Up to Day 197
Secondary Outcome Measure Information:
Title
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:Cmax
Time Frame
Up to 48 hours post-dose
Title
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:Tmax
Time Frame
Up to 48 hours post-dose
Title
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:AUC0-t
Time Frame
Up to 48 hours post-dose
Title
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:AUC0-inf
Time Frame
Up to 48 hours post-dose
Title
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:t1/2
Time Frame
Up to 48 hours post-dose
Title
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:MRT
Time Frame
Up to 48 hours post-dose
Title
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:λz
Time Frame
Up to 48 hours post-dose
Title
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:CL/F
Time Frame
Up to 48 hours post-dose
Title
To characterize the pharmacokinetics (PK) of RBD4059 in healthy subjects:Vz
Time Frame
Up to 48 hours post-dose
Title
To evaluate the pharmacodynamics (PD) effect of RBD4059 on levels of Coagulation factor XI (FXI) antigen in healthy subjects.
Time Frame
SAD: Up to Day 169 ; MAD: Up to Day 197
Title
To evaluate the pharmacodynamics (PD) effect of RBD4059 on levels of FXI activity in healthy subjects.
Time Frame
SAD: Up to Day 169 ; MAD: Up to Day 197
Title
To evaluate the pharmacodynamics (PD) effect of RBD4059 on levels of Activated partial thromboplastin time (APTT) in healthy subjects.
Time Frame
SAD: Up to Day 169 ; MAD: Up to Day 197

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male and female (non-childbearing potential only), aged 18 to 65 years, inclusive. Body mass index (BMI) between 18 and 32 kg/m2, inclusive. APTT, Prothrombin time(PT), INR, thrombin time (TT),FXI activity must be within the normal reference range (as per the local laboratory reference range) at screening . Adequate complete blood counts (CBCs) and platelet are within the normal reference range (If CBCs are outside the reference range, unless not clinically significant determined by the Investigator ). Healthy as determined by pre-study medical history, vital signs, physical examination, clinical laboratory assessments, and 12-lead electrocardiogram (ECG). Subjects who are willing to cooperate with the study staff, comply with the study requirements, complete the study according to the relevant procedures specified in the protocol, and correctly understand and sign the informed consent form in writing. Exclusion Criteria: Any uncontrolled or serious disease that may interfere with participation in the clinical study and/or put the subject at significant risk (according to Investigator's judgment) if he/she participates in the clinical study. History or presence of cardiovascular disease (including peripheral artery and cerebrovascular disease). Systolic blood pressure (SBP) is less than 90 or greater than 140 mmHg and/or diastolic blood pressure (DBP) is less than 40 or greater than 90 mmHg after 10 minutes of supine rest, unless determined by the Investigator to be not clinically significant. Diagnosis of diabetes mellitus, history of gestational diabetes that is fully resolved is not permitted. 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. Note: additional inclusion/exclusion criteria may apply, per protocol.
Facility Information:
Facility Name
Q-Pharm Pty Limited
City
Brisbane
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Priyanka meet
Phone
+61 430 316 033
Email
p.meet@nucleusnetwork.com.au

12. IPD Sharing Statement

Learn more about this trial

A Single and Multiple Ascending Doses Phase I Study to Evaluate the Safety and Pharmacokinetics of RBD4059 in Healthy Subjects

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