Familial Chylomicronemia Syndrome, Hypertriglyceridemia
Conditions
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.
Interventions
DRUGRN0361
Placebo
Sponsors
Ikaria Bioscience Pty Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and incidence of adverse events (AEs)/serious adverse events (SAEs) possibly or probably related to treatment of RN0361 in adult healthy subjects. | Up to Day85 | Phase 1 |
| Absolute and percent change from baseline in APOC3 and fasting triglycerides (TG) in subjects with HTG | Up to Day183 | Phase 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Up to 48 hours post-dose | Phase 1 |
| Plasma pharmacokinetics (PK) parameters (t1/2) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects. | Up to 48 hours post-dose | Phase 1 |
| Plasma pharmacokinetics (PK) parameters (AUC0-inf) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects. | Up to 48 hours post-dose | Phase 1 |
| Plasma pharmacokinetics (PK) parameters (Vz/F) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects. | Up to 48 hours post-dose | Phase 1 |
| Plasma pharmacokinetics (PK) parameters (λz) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects. | Up to 48 hours post-dose | Phase 1 |
| Urine pharmacokinetics (PK) parameters (CLR) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects. | Up to Day 85 | Phase 1 |
| Plasma pharmacokinetics (PK) parameters (Cmax) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects. | Up to 48 hours post-dose | Phase 1 |
| Urine pharmacokinetics (PK) parameters (Aeu) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects. | Up to Day 85 | Phase 1 |
| Urine pharmacokinetics (PK) parameters (FE) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects. | Up to Day 85 | Phase 1 |
| Absolute and percent change from baseline in APOC3 in adult healthy subjects. | Up to Day 85 | Phase 1 |
| Absolute and percent change from baseline in TG in adult healthy subjects. | Up to Day 85 | Phase 1 |
| Number and incidence of adverse events (AEs)/serious adverse events (SAEs) possibly or probably related to treatment of RN0361 in subjects with HTG. | Up to Day 183 | Phase 2 |
| Absolute and percent change from baseline in remnant cholesterol and VLDL-C in subjects with HTG. | Up to Day 183 | Phase 2 |
| Urine pharmacokinetics (PK) parameters (Aet) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects. | Up to Day 85 | Phase 1 |
| Plasma pharmacokinetics (PK) parameters (Tmax) of a single ascending SC dose of RN0361 and its metabolite AS3'N-1 in adult healthy subjects. | Up to 48 hours post-dose | Phase 1 |
Countries
Australia, United States
Outcome results
None listed