Clinical trial NCT06471543: Study of RN0361in Adult Healthy Subjects and Adult Hypertriglyceridemic Subjects
Official title: A Phase 1, Randomized, Placebo-controlled, Single Ascending Dose and Phase 2 Randomized, Placebo Controlled, Parallel-Group, Single-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamic Effects, and Immunogenicity of RN0361 in Adult Healthy Subjects and Hypertriglyceridemic Subjects
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hypertriglyceridemia
Familial Chylomicronemia Syndrome
Lead sponsor: Ikaria Bioscience Pty Ltd
Sponsor class: INDUSTRY
First posted: 2024-06-24
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
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 evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of single doses of RN0361 in Adult healthy subjects and Adult Hypertriglyceridemic Subjects.


Eligibility criteria: Phase I：

Inclusion Criteria:

* Willing to provide written informed consent before any study-specific procedures.
* Comply with the study requirements and restrictions as listed in the Informed Consent Form and the protocol.
* Fasting serum triglyceride levels \> 80 mg/dL and fasting LDL-C ≥70 mg/dL at screening
* Female participants must either be nonchildbearing or, if of childbearing potential, not pregnant, not breastfeeding, and using effective contraception. Male participants must use condoms and ensure their partners use contraception if they are of childbearing potential.
* Participants must avoid sperm or egg donation during the study

Exclusion Criteria:

* History or presence of any serious or uncontrolled disease
* clinically significant health concerns
* Recent vaccination with live vaccines, except for influenza, or plans to receive such during the study.
* Positive tests for alcohol or drugs of abuse at screening.
* History of multiple drug allergies or allergic reactions to specific components used in the study.

Phase II:

Inclusion Criteria:

* Willing to provide written informed consent before any study-specific procedures.
* Comply with the study requirements and restrictions as listed in the Informed Consent Form and the protocol.
* Fasting serum triglyceride levels ≥ 300 mg/dL at screening
* Female participants must either be nonchildbearing or, if of childbearing potential, not pregnant, not breastfeeding, and using effective contraception. Male participants must use condoms and ensure their partners use contraception if they are of childbearing potential.

Exclusion Criteria:

* History or presence of any serious or uncontrolled disease
* Active pancreatitis within 12 weeks prior to Day 1
* Uncontrolled hypertension (sitting blood pressure) \>160/100 mm Hg
* Uncontrolled diabetes
* Symptomatic heart failure (NYHA II-IV)
* Positive serologic test of HBV, HCV, or HIV
* Alcohol or drugs abuse
* History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
* History of intolerance to SC injection or relevant abdominal scarring (surgical, burns, etc)
* History of malignancy within the last 2 years prior to the date of consent

Note: Additional inclusion/exclusion ceiteria may apply, per protocol.

Primary outcomes:
measure: Number and incidence of adverse events (AEs)/serious adverse events (SAEs) possibly or probably related to treatment of RN0361 in adult healthy subjects.
timeFrame: Up to Day85
measure: Absolute and percent change from baseline in APOC3 and fasting triglycerides (TG) in subjects with HTG
timeFrame: Up to Day183
Secondary outcomes:
measure: Plasma pharmacokinetics (PK) parameters (Cmax) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects.
timeFrame: Up to 48 hours post-dose
measure: Plasma pharmacokinetics (PK) parameters (Tmax) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects.
timeFrame: Up to 48 hours post-dose
measure: Plasma pharmacokinetics (PK) parameters (AUC 0-24) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects.
timeFrame: Up to 48 hours post-dose
measure: Plasma pharmacokinetics (PK) parameters (t1/2) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects.
timeFrame: Up to 48 hours post-dose
measure: Plasma pharmacokinetics (PK) parameters (AUC0-inf) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects.
timeFrame: Up to 48 hours post-dose
measure: Plasma pharmacokinetics (PK) parameters (Vz/F) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects.
timeFrame: Up to 48 hours post-dose
measure: Plasma pharmacokinetics (PK) parameters (λz) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects.
timeFrame: Up to 48 hours post-dose
measure: Urine pharmacokinetics (PK) parameters (CLR) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects.
timeFrame: Up to Day 85
measure: Urine pharmacokinetics (PK) parameters (Aet) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects.
timeFrame: Up to Day 85
measure: Urine pharmacokinetics (PK) parameters (Aeu) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects.
timeFrame: Up to Day 85
measure: Urine pharmacokinetics (PK) parameters (FE) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects.
timeFrame: Up to Day 85
measure: Absolute and percent change from baseline in APOC3 in adult healthy subjects.
timeFrame: Up to Day 85
measure: Absolute and percent change from baseline in TG in adult healthy subjects.
timeFrame: Up to Day 85
measure: Number and incidence of adverse events (AEs)/serious adverse events (SAEs) possibly or probably related to treatment of RN0361 in subjects with HTG.
timeFrame: Up to Day 183
measure: Absolute and percent change from baseline in remnant cholesterol and VLDL-C in subjects with HTG.
timeFrame: Up to Day 183
Other outcomes:
Locations:
city: Lilburn
country: United States
facility: Lifeline Primary Care/Avacare
state: Georgia
city: Versailles
country: United States
facility: Versailles Family Medicine / Avacare
state: Kentucky
city: Dilworth
country: United States
facility: Axis Clinicals USA
state: Minnesota
city: Webster
country: United States
facility: Tranquil
state: Texas
city: Pleasant View
country: United States
facility: Ogden Clinic, Mountain View / Avacare
state: Utah
city: Morayfield
country: Australia
facility: University of the Sunshine Coast Clinical Trials
state: Queensland
city: Sippy Downs
country: Australia
facility: University of the Sunshine Coast Clinical Trials, Sippy Downs
state: Queensland
city: Altona N.
country: Australia
facility: Altona Clinical Research
state: Victoria
city: Melbourne
country: Australia
facility: Nucleus Network Melbourne
state: Victoria
Study officials:
References: