Long-Term Safety and Efficacy of Plozasiran in Adults With Hypertriglyceridemia
Purpose
This is an open-label study to be conducted in adults with hypertriglyceridemia (HTG) and severe hypertriglyceridemia (SHTG). Each participant must have completed all required visits per protocol in the parent study AROAPOC3-2003 (USA and Canada participants only; NCT# 05413135), AROAPOC3-3001(Canada and Japan participants only; NCT05089084), AROAPOC3-3003 (NCT06347003), AROAPOC3-3004 (NCT06347016) or AROAPOC3-3009 (Argentina, Italy, South Africa, and Spain; NCT06347133). Subjects who previously met all eligibility requirements for AROAPOC3-3003 or AROAPOC3-3004 and were not permitted to proceed to randomization per the Sponsor's direction in order to prevent excessive over-enrollment may also be enrolled in this trial. The subjects must meet all other applicable eligibility criteria prior to enrollment and have an HbA1c results of <=10% within 30 days prior to Day 1. Subjects entering this OLE from AROAPOC3-2003 must meet the following additional criteria to be considered for enrollment in addition to applicable eligibility criteria: 1. HbA1c ≤10% within 30 days prior to Day 1 2. Completed AROAPOC3-2001 prior to entry into AROAPOC3-2003 AND fulfill either (c) or (d) 3. Baseline fasting TG level of ≥500 mg/dL and prior history of acute pancreatitis at the time of enrollment into AROAPOC3-2001 4. Baseline fasting TG level of ≥1000 mg/dL at the time of enrollment into AROAPOC3-2001 All eligible participants will receive plozasiran administered subcutaneously (SC) approximately every 3 months for 24 months. Participants will be counseled to remain on the specified low-fat diet throughout the study in accordance with local standard of care.
Condition
- Hypertriglyceridemia
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Adult males, or nonpregnant (who do not plan to become pregnant), nonlactating adult females, who are able and willing to provide written informed consent prior to the performance of any study-specific procedures - Completed all required study visits per protocol in the parent study - Female subjects of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 90 days after the End of Study (EOS) or the last dose of plozasiran, whichever is later. Male subjects must agree to use a condom during the study and for at least 90 days after the EOS or last dose of plozasiran whichever is later. Subjects must not donate sperm or eggs during the study and for at least 90 days after the EOS or last dose of plozasiran, whichever is later. Female subjects of childbearing potential on hormonal contraceptives must be stable on medication for >1 menstrual cycle prior to Day 1. - Subjects must be on standard of care lipid and TG-lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator, including an inability to safely administer or re-administer a specific drug because of fear, preference, genetic, clinical, or metabolic considerations, or due to a previous adverse reaction associated with, attributed to, or caused by specific drug) - If the subject has a medical history of clinical atherosclerotic cardiovascular disease (ASCVD) or elevated 10-year ASCVD risk (eg, ≥7.5% per American Heart Association/American College of Cardiology [AHA/ACC] risk calculator for subjects ≥40 years of age or Framingham risk score calculator for subjects under the age of 40), the subject must be on appropriate lipid-lowering therapy as per local standard of care (ie, including moderate-to-high intensity statin, as indicated). If the subject has diabetes: 1. Subject must be on optimized antidiabetic regimen as defined by the local standards, Investigator, and institutional practices 2. Subject must have no events of diabetic ketoacidosis, diabetic decompensation/ hyperosmolar hyperglycemic nonketotic coma, diabetes complications, recurrent infections, or hospitalization related to poor glycemic control within 24 weeks of the Day 1 visit - Willing to follow diet counseling and maintain a stable low-fat diet Subjects in the USA and Canada who completed protocol AROAPOC3-2003 meeting all eligibility criteria (with the exception of inclusion criteria #9 which is not applicable to these subjects) who also meet the following additional criteria may enroll in this trial: - HbA1c ≤10% within 30 days prior to Day 1 - Completed AROAPOC3-2001 prior to entry into AROAPOC3-2003 AND either (c) or (d) below: - Baseline fasting TG level of ≥500 mg/dL and prior history of acute pancreatitis at the time of enrollment into AROAPOC3-2001 - Baseline fasting TG level of ≥1000 mg/dL at the time of enrollment into AROAPOC3-2001 - Subjects who previously met all eligibility requirements for AROAPOC3-3003, or AROAPOC3-3004 and were not permitted to proceed to randomization per Sponsor's direction in order to prevent excessive over-enrollment may also be enrolled in this trial. These subjects must meet all eligibility criteria prior to enrollment (with the exception of inclusion criteria #2 and #8 which are not applicable to these subjects) and have an HbA1c ≤10% within 30 days of Day 1.
Exclusion Criteria
- Subject was permanently discontinued from receiving plozasiran in the parent study due to elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or due to HbA1c elevation that did not respond to antidiabetic regimen - Subject withdrew consent for continued study treatment in the parent study - Known hypersensitivity to the active substance or to any of the excipients of plozasiran - Known hypersensitivity to the active substance or to any of the excipients of plozasiran - Any new condition or worsening of existing condition or any other situation that in the Investigator's judgment, would make the subject unsuitable for enrollment, could interfere with the subject participating in or completing the study, would make it difficult to comply with protocol requirements, or put the subject at an additional safety risk - Unwilling to limit alcohol consumption to within moderate limits for the duration of the study. - Poorly controlled glycemia (ie, HbA1c >10%) based upon the most recent HbA1c level reported in the parent trial prior to Day 1 - Acute pancreatitis within 4 weeks prior to Day 1 - Use of any hepatocyte-targeted siRNA that targets lipids and/or triglycerides within 365 days before Day 1 (except plozasiran or inclisiran, which are permitted). Administration of inclisiran must be separated from administration of plozasiran by at least 4 weeks throughout the treatment period - Use of any other hepatocyte targeted siRNA or antisense oligonucleotide molecule within 60 days or within 5 half-lives before Day 1 based on plasma PK, whichever is longer. - Use of an investigational agent (other than plozasiran) or device within 30 days or within 5 half-lives, based on plasma PK, whichever is longer, prior to Day 1 (V1) or current participation in an interventional investigational study. - Recent unstable or symptomatic cardiac arrhythmia (including any associated medication changes) within 90 days prior to Day 1. Individuals with stable well-controlled atrial arrhythmias will be allowed to participate in the study. - Uncontrolled hypertension (ie, seated systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg) at Day 1; subject may be re-evaluated when hypertension is controlled. Note: Other inclusion/exclusion criteria may apply per protocol
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Plozasiran Injection |
8 doses of plozasiran (ARO-APOC3) administered by subcutaneous (SC) injection |
|
Recruiting Locations
Research Site 21
Bakersfield, California 93311
Bakersfield, California 93311
Research Site 9
Beverly Hills, California 90211
Beverly Hills, California 90211
Research Site 11
Canoga Park, California 91303
Canoga Park, California 91303
Research Site 40
Garden Grove, California 92844
Garden Grove, California 92844
Research Site 235
Huntington Beach, California 92648
Huntington Beach, California 92648
Research Site 236
Lake Forest, California 92630
Lake Forest, California 92630
Research Site 39
Lincoln, California 95648
Lincoln, California 95648
Research Site 34
Oxnard, California 93030
Oxnard, California 93030
Research Site 229
Palm Springs, California 92262
Palm Springs, California 92262
Research Site 155
Fort Lauderdale, Florida 33308
Fort Lauderdale, Florida 33308
Research Site 14
Hialeah, Florida 33016
Hialeah, Florida 33016
Research Site 154
Miami, Florida 33144
Miami, Florida 33144
Research Site 1
Miami Lakes, Florida 33014
Miami Lakes, Florida 33014
Research Site 162
Mt. Dora, Florida 32757
Mt. Dora, Florida 32757
Research Site 42
Mt. Dora, Florida 32757
Mt. Dora, Florida 32757
Research Site 38
North Miami, Florida 33162
North Miami, Florida 33162
Research Site 159
Orlando, Florida 32825
Orlando, Florida 32825
Research Site 41
Orlando, Florida 32825
Orlando, Florida 32825
Research Site 16
Tamarac, Florida 33321
Tamarac, Florida 33321
Research Site 18
Tampa, Florida 33614
Tampa, Florida 33614
Research Site 237
Lawrenceville, Georgia 30044
Lawrenceville, Georgia 30044
Research Site 17
Park Ridge, Illinois 60068
Park Ridge, Illinois 60068
Research Site 167
Elkhart, Indiana 46514-2487
Elkhart, Indiana 46514-2487
Research Site 43
Elkhart, Indiana 46514
Elkhart, Indiana 46514
Research Site 157
Indianapolis, Indiana 46290
Indianapolis, Indiana 46290
Research Site 28
Overland Park, Kansas 66211
Overland Park, Kansas 66211
Research Site 23
Topeka, Kansas 66606
Topeka, Kansas 66606
Research Site 12
Annapolis, Maryland 21401
Annapolis, Maryland 21401
Research Site 166
Baltimore, Maryland 21229
Baltimore, Maryland 21229
Research Site 44
Baltimore, Maryland 21229
Baltimore, Maryland 21229
Research Site 30
Flint, Michigan 48532
Flint, Michigan 48532
Research Site 33
Jackson, Mississippi 39202
Jackson, Mississippi 39202
Research Site 32
Olive Branch, Mississippi 38654
Olive Branch, Mississippi 38654
Research Site 2
Jefferson City, Missouri 65109
Jefferson City, Missouri 65109
Research Site 232
St Louis, Missouri 63136
St Louis, Missouri 63136
Research Site 29
Fremont, Nebraska 68025
Fremont, Nebraska 68025
Research Site 3
Omaha, Nebraska 68144
Omaha, Nebraska 68144
Research Site 165
Summit, New Jersey 07901
Summit, New Jersey 07901
Research Site 77
Summit, New Jersey 07901
Summit, New Jersey 07901
Research Site 156
Long Island City, New York 11106
Long Island City, New York 11106
Research Site 72
Long Island City, New York 11106
Long Island City, New York 11106
Research Site 233
New York, New York 10016
New York, New York 10016
Research Site 228
New York, New York 10029
New York, New York 10029
Research Site 37
Asheboro, North Carolina 27203
Asheboro, North Carolina 27203
Research Site 36
Morehead City, North Carolina 28557
Morehead City, North Carolina 28557
Research Site 169
Wilmington, North Carolina 28401
Wilmington, North Carolina 28401
Research Site 22
Beavercreek, Ohio 45431
Beavercreek, Ohio 45431
Research Site 234
Columbus, Ohio 43214
Columbus, Ohio 43214
Research Site 164
Norman, Oklahoma 73072
Norman, Oklahoma 73072
Research Site 76
Norman, Oklahoma 73072
Norman, Oklahoma 73072
Research Site 31
Oklahoma City, Oklahoma 73112
Oklahoma City, Oklahoma 73112
Research Site 26
Horsham, Pennsylvania 19044
Horsham, Pennsylvania 19044
Research Site 8
Newport, Pennsylvania 17074
Newport, Pennsylvania 17074
Research Site 231
Philadelphia, Pennsylvania 19104
Philadelphia, Pennsylvania 19104
Research Site 238
Fort Mill, South Carolina 29707
Fort Mill, South Carolina 29707
Research Site 27
El Paso, Texas 19044
El Paso, Texas 19044
Research Site 160
Fort Worth, Texas 76132
Fort Worth, Texas 76132
Research Site 158
Houston, Texas 77061
Houston, Texas 77061
Research Site 73
Houston, Texas 77061
Houston, Texas 77061
Research Site 163
Houston, Texas 77090
Houston, Texas 77090
Research Site 75
Houston, Texas 77090
Houston, Texas 77090
Research Site 24
Houston, Texas 77095
Houston, Texas 77095
Research Site 230
Missouri City, Texas 77459
Missouri City, Texas 77459
Research Site 161
Plano, Texas 75093
Plano, Texas 75093
Research Site 74
Plano, Texas 75093
Plano, Texas 75093
Research Site 168
San Antonio, Texas 78230
San Antonio, Texas 78230
Research Site 13
Sugar Land, Texas 77479
Sugar Land, Texas 77479
Research Site 170
Tomball, Texas 77375
Tomball, Texas 77375
Research Site 25
Victoria, Texas 77901
Victoria, Texas 77901
Research Site 15
Bountiful, Utah 84010
Bountiful, Utah 84010
Research Site 35
St. George, Utah 84790
St. George, Utah 84790
Research Site 10
Manassas, Virginia 20110
Manassas, Virginia 20110
More Details
- Status
- Recruiting
- Sponsor
- Arrowhead Pharmaceuticals