Severe Hypertriglyceridemia
Conditions
Brief summary
The purpose of AROAPOC3-2001 is to evaluate the efficacy and safety of ARO-APOC3 in participants with severe hypertriglyceridemia. Participants will receive 2 subcutaneous injections of ARO-APOC3.
Interventions
DRUGARO-APOC3
2 doses of ARO-APOC3 by subcutaneous (sc) injection
DRUGPlacebo
calculated volume to match active treatment by sc injection
Sponsors
Arrowhead Pharmaceuticals
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Based on medical history, evidence of triglycerides (TG) ≥ 500 mg/dL and ≤ 4000 mg/dL at Screening * Fasting TG ≥ 500 mg/dL at Screening * Willing to follow diet counseling per Investigator judgment based on local standard of care * Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception * Willing to provide written informed consent and to comply with study requirements
Exclusion criteria
* Active pancreatitis within 12 weeks prior to first dose * Any planned bariatric surgery or similar procedures to induce weight loss from consent to end of study * Acute coronary syndrome event within 24 weeks of first dose * Major surgery within 12 weeks of first dose * Planned coronary intervention (e.g., stent placement or heart bypass) or any non-cardiac major surgical procedure throughout the study * Uncontrolled hypertension * Human immunodeficiency virus (HIV) infection, seropositive for Hepatitis B (HBV), seropositive for Hepatitis C (HCV) * Uncontrolled hypothyroidism or hyperthyroidism * Hemorrhagic stroke within 24 weeks of first dose * Malignancy within the last 2 years prior to date of consent requiring systemic treatment (some exceptions apply) Note: additional inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline at Week 24 in Fasting Triglycerides (TG) | Baseline, Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline Over Time Through Week 48 in Fasting TG | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET) | — |
| Percent Change From Baseline at Week 24 in Apolipoprotein (Apo)C-III | Baseline, Week 24 | — |
| Percent Change From Baseline Over Time Through Week 48 in ApoC-III | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET) | — |
| Percent Change From Baseline at Week 24 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) | Baseline, Week 24 | — |
| Percent Change From Baseline Over Time Through Week 48 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET) | — |
| Percent Change From Baseline at Week 24 in Fasting High-Density Lipoprotein Cholesterol (HDL-C) | Baseline, Week 24 | — |
| Percent Change From Baseline Over Time Through Week 48 in Fasting HDL-C | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET) | — |
| Percent Change From Baseline at Week 24 in Fasting Total Apolipoprotein B (ApoB) | Baseline, Week 24 | — |
| Percent Change From Baseline Over Time Through Week 48 in Fasting Total ApoB | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET) | — |
| Percent Change From Baseline at Week 24 in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C) | Baseline, Week 24 | LDL-C analyses used both Martin-Hopkins methodology and ultracentrifugation. The Martin-Hopkins formula is a method for calculating LDL-C that improves accuracy by using an adjustable factor for estimating very-low-density lipoprotein (VLDL) cholesterol cholesterol based on triglyceride and non-HDL cholesterol levels. |
| Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET) | LDL-C analyses used both Martin-Hopkins methodology (MHM) and ultracentrifugation (UC). The Martin-Hopkins formula is a method for calculating LDL-C that improves accuracy by using an adjustable factor for estimating very-low-density lipoprotein (VLDL) cholesterol cholesterol based on triglyceride and non-HDL cholesterol levels. |
| Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12 | Day 1: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose; Week 12: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose | — |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From first dose of study drug up to Week 48 | An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with this treatment. A serious AE (SAE) is an AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is a medically important event or reaction. TEAEs are AEs that occur following investigational product (IP) administration or a pre-existing condition exacerbated following IP administration. |
Countries
Australia, Canada, Germany, Hungary, Netherlands, New Zealand, Poland, United States
Participant flow
Recruitment details
There were 76 study centers in 8 countries (Australia, Canada, Germany, Hungary, The Netherlands, New Zealand, Poland, and the United States \[US\]).
Pre-assignment details
Participants who met all the protocol eligibility criteria during Screening were enrolled and randomly assigned to treatment in a double-blind fashion. Participants were randomly assigned 3:1 to receive 1 of 3 ARO-APOC3 dosing regimens (ARO-APOC3 10 mg, 25 mg, or 50 mg) or matched placebo.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 55.8 years STANDARD_DEVIATION 11.22 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race/Ethnicity, Customized Other, Not Specified | 0 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants |
| Race/Ethnicity, Customized White | 56 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 178 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 61 | 0 / 54 | 0 / 55 | 0 / 56 |
| other Total, other adverse events | 44 / 61 | 44 / 54 | 36 / 55 | 50 / 56 |
| serious Total, serious adverse events | 10 / 61 | 4 / 54 | 2 / 55 | 7 / 56 |
Outcome results
None listed