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Adult Subjects With Elevated Low-Density Lipoprotein-Cholesterol to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects

Primary Purpose

To Reduce the LDL-C Level in Hypercholesteremia Adult Patients, Combination for Subgroup High LDL-c Patients With Other Comorbidities

Status
Recruiting
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
RN0191 INJECTION
Sponsored by
Ikaria Bioscience Pty Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for To Reduce the LDL-C Level in Hypercholesteremia Adult Patients

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Male and female subjects, aged 18 to 60 years, inclusive. Body mass index between 18 and 32 kg/m2, inclusive, with body weight > 45 kg for females and >50 kg for males. Serum LDL-C ≥100mg/dL (2.6 mmol/L) at screening and Day -1. Fasting triglycerides < 400 mg/dL (<4.52 mmol/L) at screening and Day -1. Adequate complete blood counts (complete blood counts [CBCs]; if outside the reference range, CBC values that are not clinically relevant and are acceptable to the Investigator) Female subjects are eligible to participate if they are confirmed either not women of child-bearing potential (WOCBP), or have a negative urine pregnancy test at Day 1, are not breastfeeding, and willing and able to abide by the contraception guidelines. Male subjects who can produce viable sperm are eligible to participate if they agree to use an adequate method of contraception as per the contraceptive guidance from Screening (signing the ICF) until at least 3 months post dose. Subjects with a partner(s) who is (are) not of childbearing potential are exempt from these requirements. Male subjects with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile penetration. In addition, male subjects must refrain from donating sperm from Screening (signing the ICF) until at least 3 months post dose. Willing to comply with protocol required visit schedule and visit requirements and provide written informed consent Exclusion Criteria: Male and female subjects, aged 18 to 60 years, inclusive. Body mass index between 18 and 32 kg/m2, inclusive, with body weight > 45 kg for females and >50 kg for males . Serum LDL-C ≥100mg/dL (2.6 mmol/L) at screening and Day -1. Fasting triglycerides < 400 mg/dL (<4.52 mmol/L) at screening and Day -1. Adequate complete blood counts (complete blood counts [CBCs]; if outside the reference range, CBC values that are not clinically relevant and are acceptable to the Investigator). Female subjects are eligible to participate if they are confirmed either not women of child-bearing potential (WOCBP), or have a negative urine pregnancy test at Day 1, are not breastfeeding, and willing and able to abide by the contraception guidelines (signing the ICF). Male subjects who can produce viable sperm are eligible to participate if they agree to use an adequate method of contraception as per the contraceptive guidance in Appendix 3 from Screening (signing the ICF) until at least 3 months post dose. Subjects with a partner(s) who is (are) not of childbearing potential are exempt from these requirements. Male subjects with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile penetration. In addition, male subjects must refrain from donating sperm from Screening (signing the ICF) until at least 3 months post dose. Willing to comply with protocol required visit schedule and visit requirements and provide written informed consent.

Sites / Locations

  • Nucleus NetworksRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

Cohort 1 will be 25 mg RN0191 (or placebo)

Cohort 1 will be 100 mg RN0191 (or placebo)

Cohort 1 will be 300 mg RN0191 (or placebo)

Cohort 1 will be 500 mg RN0191 (or placebo)

Arm Description

Outcomes

Primary Outcome Measures

Exploratory objectives are presented in the body of the protocol.
• To determine the safety and tolerability of RN0191 administered as escalating single subcutaneously (SC) doses in adult subjects with elevated low-density lipoprotein-cholesterol

Secondary Outcome Measures

Full Information

First Posted
June 2, 2023
Last Updated
August 18, 2023
Sponsor
Ikaria Bioscience Pty Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05905068
Brief Title
Adult Subjects With Elevated Low-Density Lipoprotein-Cholesterol to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects
Official Title
A Phase 1, Randomized, Single-blinded, Placebo-controlled, Single-ascending-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of RN0191 in Adult Subjects With Elevated Low-Density Lipoprotein-Cholesterol
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 14, 2023 (Actual)
Primary Completion Date
July 27, 2024 (Anticipated)
Study Completion Date
July 27, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ikaria Bioscience Pty 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
Objectives: The primary and secondary objectives of the study are presented below. Exploratory objectives are presented in the body of the protocol. Primary: • To determine the safety and tolerability of RN0191 administered as escalating single subcutaneously (SC) doses in adult subjects with elevated low-density lipoprotein-cholesterol Secondary: To evaluate the single-dose pharmacokinetics (PK) of RN0191 in adult subjects with elevated low-density lipoprotein-cholesterol To evaluate the pharmacodynamic (PD) effect of RN0191 on serum levels of low-density lipoprotein-cholesterol (LDL-C) To evaluate the PD effect of RN0191 on plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9)
Detailed Description
This is a randomized, placebo-controlled, single ascending-dose (SAD) study of RN0191 administered SC to adult subjects with elevated low-density lipoprotein-cholesterol. Subjects who have signed an Ethics Committee (EC)-approved informed consent form (ICF) and have met all the protocol eligibility criteria during screening may be enrolled into the study. The study only has one part: SAD cohorts with Sentinel Dosing The starting dose for subjects in Cohort 1 will be 25 mg RN0191 (or placebo). The following are the planned dose levels for subsequent cohorts in the SAD phase: Cohort 2: 100 mg RN0191 or placebo Cohort 3: 300 mg RN0191 or placebo Cohort 4: 500 mg RN0191 or placebo

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
To Reduce the LDL-C Level in Hypercholesteremia Adult Patients, Combination for Subgroup High LDL-c Patients With Other Comorbidities

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
This is a randomized, placebo-controlled, single ascending-dose (SAD) study of RN0191 administered SC to adult subjects with elevated low-density lipoprotein-cholesterol. Subjects who have signed an Ethics Committee (EC)-approved informed consent form (ICF) and have met all the protocol eligibility criteria during screening may be enrolled into the study. In this SAD study, adult subjects with elevated LDL-C will be enrolled in up to 4 cohorts. Each cohort will comprise 8 subjects randomized in a 3:1 ratio (1:1 ratio for sentinel subjects; 5:1 ratio for non-sentinel subjects) to receive a single dose of RN0191 (n=6) or placebo (n=2), respectively.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1 will be 25 mg RN0191 (or placebo)
Arm Type
Active Comparator
Arm Title
Cohort 1 will be 100 mg RN0191 (or placebo)
Arm Type
Active Comparator
Arm Title
Cohort 1 will be 300 mg RN0191 (or placebo)
Arm Type
Active Comparator
Arm Title
Cohort 1 will be 500 mg RN0191 (or placebo)
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
RN0191 INJECTION
Intervention Description
a sterile solution in each bottle for subcutaneous (SC) injection
Primary Outcome Measure Information:
Title
Exploratory objectives are presented in the body of the protocol.
Description
• To determine the safety and tolerability of RN0191 administered as escalating single subcutaneously (SC) doses in adult subjects with elevated low-density lipoprotein-cholesterol
Time Frame
For each subject in the study, the duration of the study clinic visits is approximately 21 weeks from screening to Day 85/EOS examination.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male and female subjects, aged 18 to 60 years, inclusive. Body mass index between 18 and 32 kg/m2, inclusive, with body weight > 45 kg for females and >50 kg for males. Serum LDL-C ≥100mg/dL (2.6 mmol/L) at screening and Day -1. Fasting triglycerides < 400 mg/dL (<4.52 mmol/L) at screening and Day -1. Adequate complete blood counts (complete blood counts [CBCs]; if outside the reference range, CBC values that are not clinically relevant and are acceptable to the Investigator) Female subjects are eligible to participate if they are confirmed either not women of child-bearing potential (WOCBP), or have a negative urine pregnancy test at Day 1, are not breastfeeding, and willing and able to abide by the contraception guidelines. Male subjects who can produce viable sperm are eligible to participate if they agree to use an adequate method of contraception as per the contraceptive guidance from Screening (signing the ICF) until at least 3 months post dose. Subjects with a partner(s) who is (are) not of childbearing potential are exempt from these requirements. Male subjects with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile penetration. In addition, male subjects must refrain from donating sperm from Screening (signing the ICF) until at least 3 months post dose. Willing to comply with protocol required visit schedule and visit requirements and provide written informed consent Exclusion Criteria: Male and female subjects, aged 18 to 60 years, inclusive. Body mass index between 18 and 32 kg/m2, inclusive, with body weight > 45 kg for females and >50 kg for males . Serum LDL-C ≥100mg/dL (2.6 mmol/L) at screening and Day -1. Fasting triglycerides < 400 mg/dL (<4.52 mmol/L) at screening and Day -1. Adequate complete blood counts (complete blood counts [CBCs]; if outside the reference range, CBC values that are not clinically relevant and are acceptable to the Investigator). Female subjects are eligible to participate if they are confirmed either not women of child-bearing potential (WOCBP), or have a negative urine pregnancy test at Day 1, are not breastfeeding, and willing and able to abide by the contraception guidelines (signing the ICF). Male subjects who can produce viable sperm are eligible to participate if they agree to use an adequate method of contraception as per the contraceptive guidance in Appendix 3 from Screening (signing the ICF) until at least 3 months post dose. Subjects with a partner(s) who is (are) not of childbearing potential are exempt from these requirements. Male subjects with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile penetration. In addition, male subjects must refrain from donating sperm from Screening (signing the ICF) until at least 3 months post dose. Willing to comply with protocol required visit schedule and visit requirements and provide written informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
jian jiang, MS
Phone
13916015172
Email
esther.jiang@ronatherapeutics.com
First Name & Middle Initial & Last Name or Official Title & Degree
dan xiang, MS
Email
dan.xiang@ronatherapeutics.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristi McLendon, MD
Organizational Affiliation
Nucleus Network
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nucleus Networks
City
Herston
State/Province
Brisbane
ZIP/Postal Code
4006
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristi McLendon, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Adult Subjects With Elevated Low-Density Lipoprotein-Cholesterol to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects

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