Severe HypertriglyceridemiaPhase 2SHASTA-2NCT04720534
Study to Evaluate ARO-APOC3 in Adults With Severe Hypertriglyceridemia
A Phase 2 study testing ARO-APOC3 in people with Severe Hypertriglyceridemia, run by Arrowhead Pharmaceuticals at 74 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Hypertriglyceridemia
- What is being tested?
- ARO-APOC3
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 229 participants
- Where
- 74 sitesin 8 countries
- Study dates
- 31 May 2021to 31 Aug 2023
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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/exclusion criteria may apply per protocol
Trial locations and contacts
74 sites in 8 countries.
74 sites in 8 countries
United States33 sites
Research Site 17
Arlington Heights, Illinois, 60005
Research Site 2
Beverly Hills, California, 90211
Research Site 5
Boca Raton, Florida, 33434
Research Site 36
Chattanooga, Tennessee, 37421
Research Site 31
Dayton, Ohio, 45419
Research Site 16
Dunwoody, Georgia, 30338
Research Site 30
Fargo, North Dakota, 58104
Research Site 6
Fort Lauderdale, Florida, 33308
Research Site 32
Franklin, Ohio, 45005
Research Site 35
Greenville, South Carolina, 29607
Research Site 38
Houston, Texas, 77030
Research Site 39
Houston, Texas, 77099
Research Site 22
Kalispell, Montana, 59901
Research Site 24
Las Vegas, Nevada, 89121
Research Site 18
Lexington, Kentucky, 40503
Research Site 25
Long Island City, New York, 11106
Research Site 41
Manassas, Virginia, 20110
Research Site 33
Maumee, Ohio, 43537
Research Site 10
Miami, Florida, 33144
Research Site 9
Miami, Florida, 33144
Research Site 11
Miami, Florida, 33155
Research Site 8
Miami, Florida, 33173
Research Site 12
Miami Springs, Florida, 33166
Research Site 20
Minneapolis, Minnesota, 55455
Research Site 29
Morehead City, North Carolina, 28557
Research Site 26
New Windsor, New York, 12553
Research Site 27
New York, New York, 10029
Research Site 34
Oklahoma City, Oklahoma, 73135
Research Site 23
Omaha, Nebraska, 68114
Research Site 4
Palm Springs, California, 92292
Research Site 14
Port Orange, Florida, 32127
Research Site 40
San Antonio, Texas, 78249
Research Site 21
Tupelo, Mississippi, 38801
Poland10 sites
Research Site 74
Bydgoszcz, 85-605
Research Site 75
Elblag, 82-300
Research Site 76
Gdynia, 81-157
Research Site 77
Łęczyca, 99-100
Research Site 83
Lodz, 94-048
Research Site 78
Oświęcim, 32-600
Research Site 79
Poznan, 61-655
Research Site 80
Puławy, 24-100
Research Site 81
Rzeszów, 35-055
Research Site 82
Wołomin, 05-200
Hungary9 sites
Research Site 57
Baja, 6500
Research Site 58
Baja, 6500
Research Site 59
Balatonföldvár, H-8230
Research Site 60
Békéscsaba, 5600
Research Site 61
Debrecen, 4032
Research Site 62
Gyöngyös, 3200
Research Site 63
Komárom, 2921
Research Site 65
Nyíregyháza, 4400
Research Site 64
Nyíregyháza, 4405
Australia6 sites
Research Site 46
Adelaide, South Australia, 5000
Research Site 44
Brisbane, Queensland, 4064
Research Site 42
Camperdown, New South Wales, 2050
Research Site 47
Clayton, Victoria, 3168
Research Site 43
Perth, Nedlands, 6009
Research Site 45
Sippy Downs, Queensland, 4556
Canada6 sites
Research Site 52
Chicoutimi, Quebec, G7H5H6
Research Site 49
Concord, Ontario, L4K 4M2
Research Site 53
Greenfield, Quebec, J4V2G8
Research Site 50
London, Ontario, N6A 5A5
Research Site 54
Montreal, Quebec, H2W2T2
Research Site 51
Toronto, Ontario, M4G 3E8
New Zealand5 sites
Research Site 69
Christchurch, 8011
Research Site 73
Grafton, Auckland, 1010
Research Site 70
Hamilton, 3200
Research Site 71
Papatoetoe, 2025
Research Site 72
Rotorua, 3010
Netherlands3 sites
Research Site 66
Amsterdam, 1105 AZ
Research Site 67
Dordrecht, 3318 AT
Research Site 68
Sneek, 08601
About this study
Official title: A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults With Severe Hypertriglyceridemia
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.
- Conditions
- Severe Hypertriglyceridemia
- Being tested
- ARO-APOC3, Placebo
- Medical subject headings
- Hypertriglyceridemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARO-APOC3Drug
2 doses of ARO-APOC3 by subcutaneous (sc) injection
PlaceboDrug
calculated volume to match active treatment by sc injection
| Study group | Role | What they receive |
|---|---|---|
| Placebo, Day 1 and Week 12 | Experimental | Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections. Receives: Drug: Placebo |
| ARO-APOC3 10 mg | Experimental | Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections. Receives: Drug: ARO-APOC3 |
| ARO-APOC3 25 mg | Experimental | Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections. Receives: Drug: ARO-APOC3 |
| ARO-APOC3 50 mg | Experimental | Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections. Receives: Drug: ARO-APOC3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline at Week 24 in Fasting Triglycerides (TG)
Measured: Baseline, Week 24
Secondary outcomes (13)
Percent Change From Baseline Over Time Through Week 48 in Fasting TG
Measured: 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
Measured: Baseline, Week 24
Percent Change From Baseline Over Time Through Week 48 in ApoC-III
Measured: 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)
Measured: Baseline, Week 24
Percent Change From Baseline Over Time Through Week 48 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C)
Measured: 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)
Measured: Baseline, Week 24
Percent Change From Baseline Over Time Through Week 48 in Fasting HDL-C
Measured: 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)
Measured: Baseline, Week 24
Percent Change From Baseline Over Time Through Week 48 in Fasting Total ApoB
Measured: 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)
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.
Measured: Baseline, Week 24
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C
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.
Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12
Measured: 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)
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.
Measured: From first dose of study drug up to Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2021
- Study start31 May 2021
- Primary completion9 Mar 2023
- Study completion31 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Severe HypertriglyceridemiaStudies of the same condition, open and under way.
- More trials run by Arrowhead PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 229 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arrowhead Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04720534
- Sponsor's protocol ID
- AROAPOC3-2001
- Acronym
- SHASTA-2
- Status last verified
- Mar 2026
- First submitted
- 19 Jan 2021
- Last updated
- 24 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Gaudet D, Pall D, Watts GF, Nicholls SJ, Rosenson RS, Modesto K, San Martin J, Hellawell J, Ballantyne CM. Plozasiran (ARO-APOC3) for Severe Hypertriglyceridemia: The SHASTA-2 Randomized Clinical Trial. JAMA Cardiol. 2024 Jul 1;9(7):620-630. doi: 10.1001/jamacardio.2024.0959.
PubMed 38583092