SYNTHETIC DOUBLE-STRANDED SIRNA OLIGONUCLEOTIDE DIRECTED AGAINST APOLIPOPROTEIN C-III MRNA AND COVALENTLY LINKED TO A LIGAND CONTAINING THREE N-ACETYLGALACTOSAMINE RESIDUES for Hypertriglyceridemia

Inclusion criteria

• {"criterion_text":"- 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"}
• {"criterion_text":"- Completed all required study visits per protocol in the parent study (i.e. AROAPOC3-3001 [Canada and Japan only], AROAPOC3-3003, AROAPOC3-3004, or AROAPOC3-3009)."}
• {"criterion_text":"- 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 EOS or the last dose of IMP, whichever is later. Male subjects must agree to use a condom during the study and for at least 90 days after the EOS or the last dose of IMP, 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 IMP, whichever is later. Female subjects of childbearing potential on hormonal contraceptives must be stable on the medication for >1 menstrual cycle prior to Day 1 (V1)."}

Exclusion criteria

• {"criterion_text":"- Subject was permanently discontinued from receiving IMP in the parent study due to elevated AST or ALT or due to HbA1c elevation that did not respond to antidiabetic regimen."}
• {"criterion_text":"- Subject withdrew consent for continued study treatment in the parent study"}
• {"criterion_text":"- Known hypersensitivity to the active substance or to any of the excipients of plozasiran"}
• {"criterion_text":"- Any new condition or worsening of existing condition (eg, renal, hematologic, gastrointestinal, endocrine, cardiovascular, pulmonary, immunologic, psychiatric) 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."}
• {"criterion_text":"- Unwilling to limit alcohol consumption to within moderate limits for the duration of the study. Moderate limits are defined as follows: no more than 14 units per week (1 unit approximately corresponds to 80 mL of wine, 200 mL of beer, or 25 mL of 40% alcohol)."}

Primary endpoints

• {"endpoint_text":"- Subject incidence of treatment-emergent adverse events (TEAEs)","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Change and percent change from baseline over time in fasting TG levels","definition_or_measurement_approach":"Change and percent change from baseline over time in fasting triglyceride (TG) levels"}
• {"endpoint_text":"- Change and percent change from baseline over time in APOC3","definition_or_measurement_approach":"Change and percent change from baseline over time in APOC3"}
• {"endpoint_text":"- Change and percent change from baseline over time in remnant cholesterol","definition_or_measurement_approach":"Change and percent change from baseline over time in remnant cholesterol"}
• {"endpoint_text":"- Change and percent change from baseline over time in fasting non-HDL-C","definition_or_measurement_approach":"Change and percent change from baseline over time in fasting non-HDL cholesterol"}
• {"endpoint_text":"- Change and percent change from baseline over time in fasting HDL-C","definition_or_measurement_approach":"Change and percent change from baseline over time in fasting HDL cholesterol"}
• {"endpoint_text":"- Change and percent change from baseline over time in fasting total Apo B","definition_or_measurement_approach":"Change and percent change from baseline over time in fasting total apolipoprotein B"}
• {"endpoint_text":"- Change and percent change from baseline over time in fasting LDL-C using ultracentrifugation","definition_or_measurement_approach":"Change and percent change from baseline over time in fasting LDL-C measured using ultracentrifugation"}
• {"endpoint_text":"- Change from baseline over time in hemoglobin A1c (HbA1c)","definition_or_measurement_approach":"Change from baseline over time in HbA1c"}
• {"endpoint_text":"- Subject incidence of emergent apheresis","definition_or_measurement_approach":"Incidence of emergent apheresis procedures in subjects"}
• {"endpoint_text":"- Adjudicated MACE event rates during the treatment period","definition_or_measurement_approach":"Adjudicated major adverse cardiovascular event (MACE) rates during treatment period (events adjudicated)"}
• {"endpoint_text":"- Incidence and titers of ADA to plozasiran in those receiving plozasiran over time","definition_or_measurement_approach":"Incidence and titers of anti-drug antibodies (ADA) to plozasiran over time in subjects receiving plozasiran"}
• {"endpoint_text":"- Adjudicated AP event rate during the treatment period.","definition_or_measurement_approach":"Adjudicated acute pancreatitis (AP) event rate during the treatment period"}

Primary sponsor

Full Name

Arrowhead Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

IQVIA Limited

Responsibilities

Codes: 1,10,11,12,13,2,5,6,8

Name

Phlexglobal Limited

Responsibilities

eTMF

Name

Sharp Clinical Services LLC

Responsibilities

13

Name

Medidata Solutions Inc.

Responsibilities

7

Name

Almac Clinical Technologies LLC

Responsibilities

3

Name

Cisys Inc.

Responsibilities

Electronic Adjudication System (EAS) Vendor for adjudication services

Third parties

• {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Canada","full_name":"Charles River Laboratories Montreal ULC","duties_or_roles":"Antibody testing","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"1,10,11,12,13,2,5,6,8","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Phlexglobal Limited","duties_or_roles":"eTMF","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Sharp Clinical Services LLC","duties_or_roles":"13","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Manufacturing Packaging Farmaca (MPF) B.V.","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cisys Inc.","duties_or_roles":"Electronic Adjudication System (EAS) Vendor for adjudication services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"3","organisation_type":"Pharmaceutical company"}