A study to understand the safety and effectivness of ARO-APOC3 in Adults with Severe Hypertriglyceridemia
- Conditions
- Severe HypertriglyceridemiaMedDRA version: 20.1Level: LLTClassification code 10020870Term: HypertriglyceridemiaSystem Organ Class: 100000004861Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2021-000687-30-DE
- Lead Sponsor
- Arrowhead Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 216
To be eligible for enrollment, participants must meet all the following inclusion criteria:
1. Males or nonpregnant (who do not plan to become pregnant), nonlactating females =18 years of age;
2. Based on medical history, prior evidence of fasting triglycerides (TG) =500 mg/dL (5.65 mmol/L);
3. A mean fasting TG =500 mg/dL (5.65 mmol/L) and =4000 mg/dL (45.2 mmol/L) collected at two separate and consecutive visits at least 7 days apart and no more than 17 days apart during the Screening period;
4. If the participant has a medical history of clinical ASCVD or elevated 10-year ASCVD risk (eg, =7.5% per American Heart Association/American College of Cardiology [ACC/AHA] risk calculator for subjects >40 years of age or Framingham risk score calculator for subjects under the age of 40) then the participant must be on appropriate lipid-lowering therapy as per local standard of care (ie, including moderate-to-high intensity statin, as indicated) prior to collection of qualifying TG levels;
5. Able and willing to provide written informed consent prior to the performance of any study specific procedures;
6. Willing to follow diet counseling and maintain a stable diet as per Investigator judgment based on local standard of care;
7. Participants of childbearing potential must agree to use highly effective contraception, during the study and for at least 24 weeks following the last dose of IP. Males must not donate sperm during the study and for at least 24 weeks following the or last dose of IP;
8. Women of childbearing potential on hormonal contraceptives must be stable on the medication for >2 menstrual cycles prior to Day 1; and
9. Participants on any of the following medications must be on a stable regimen for the specified duration prior to collection of Screening Visit (S2) laboratory tests and for the duration of study participation:
Medication: Time on stable regimen prior to collection of Screening Visit (S2) laboratory tests
• Lipid lowering therapies (including statins): = 4 weeks
• Beta-blockers, thiazide diuretics: = 4 weeks
• Fibrates: = 6 weeks
• PCSK9 inhibitors: = 8 weeks
• Retinoids: = 8 weeks
• Atypical antipsychotics: = 12 weeks
• Diabetes mellitus medications: = 12 weeks
• Anticoagulation therapy: = 12 weeks
• Thyroid hormone replacement therapy: = 12 weeks
• Testosterone replacement therapy: = 16 weeks
• Oral estrogens, tamoxifen, raloxifene: = 16 weeks
• Immunosuppressants: = 24 weeks
NOTE: All laboratory tests used as inclusion criteria will be assessed by a central laboratory and may be repeated once and the repeat value may be used for inclusion purposes. Local laboratory testing may be permitted in limited circumstances and only with prior Sponsor approval.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 172
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 44
1. Current use, or use within the last 365 days from Day 1, of any hepatocyte targeted siRNA or antisense oligonucleotide molecule;
2. Active pancreatitis within 12 weeks prior to Day 1;
3. Known genetically confirmed diagnosis of Familial Chylomicronemia Syndrome
4. Any planned bariatric surgery or similar procedures to induce weight loss during the period starting at consent through the end of study (EOS);
5. History of major surgery within 12 weeks of Day 1 or planned major surgery during the study;
6. Planned coronary intervention (such as stent placement or heart bypass) during the study;
7. History of acute coronary syndrome event within 24 weeks of Day 1;
8. New York Heart Association (NYHA) Class II, III, or IV heart failure or last known ejection fraction of <30%;
9. Uncontrolled hypertension (blood pressure >160/100 mmHg at Screening); participant may be rescreened once hypertension is controlled;
10. History of hemorrhagic stroke within 24 weeks of Day 1;
11. History of bleeding diathesis or coagulopathy;
12. Current diagnosis of nephrotic syndrome;
13. Any of the following laboratory values at Screening:
a. Hepatic: ALT or AST >2× ULN at Screening,
b. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (using the Modification of Diet in Renal Disease [MDRD] equation) at Screening ,
c. Glycosylated hemoglobin (HbA1c) >9.0% (or >75 mmol/mol International Federation of Clinical Chemistry [IFCC] units) at Screening ;
d. Spot urine protein/spot urine creatinine ratio >3 grams per day;
e. Clinically significant abnormality in prothrombin time (PT), activated partial thromboplastin time (aPTT), or international normalized ratio (INR);
14. Use of any of the following:
a. Systemic use of corticosteroids or anabolic steroids within 4 weeks prior to Day 1 or planned use during the study (stable doses of testosterone replacement therapy >16 weeks prior to Screening [visit S2] is permitted for a documented history of hypogonadism [low testosterone] as verified in subject health records)
b. Plasma apheresis within 4 weeks prior to Day 1 or planned during the study;
15. Blood donation of 50 to 499 mL within 4 weeks of Screening (visit S2) laboratory collection or of >499 mL within 8 weeks of Screening (visit S2) laboratory collection;
16. Known history of human immunodeficiency virus infection;
17. Seropositive (hepatitis B surface antigen [HBsAg] +) for hepatitis B virus (HBV) or hepatitis C virus (HCV) (HCV seropositivity requires positive test for antibodies confirmed with positive test for HCV RNA);
18. Clinical evidence of uncontrolled hypothyroidism or hyperthyroidism as per Investigator’s judgment;
19. History of malignancy within the last 2 years prior to the date of consent requiring systemic treatment except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer. Currently receiving systemic cancer treatment(s) or, in the Investigator's opinion, at risk of relapse for recent cancer;
20. Use of an investigational agent or device within 30 days or within 5 half-lives, based on plasma pharmacokinetics (PK) (whichever is longer) prior to Day 1 or current participation in an interventional investigational study. Participants previously exposed to ARO APOC3, or ARO-ANG3 will require a washout period of at least 1 year from last dose;
21. Unwilling to limit alcohol consumption to within moderate limits for t
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the study is to evaluate the safety and efficacy of ARO-APOC3 in adults with Severe Hypertriglyceridemia (SHTG) and to select a dosing regimen for later stage clinical studies in this patient population.;Secondary Objective: Not Applicable;Primary end point(s): The primary endpoint of the study is:<br>• Percent change from baseline at Week 24 in fasting TG.;Timepoint(s) of evaluation of this end point: 24 Weeks
- Secondary Outcome Measures
Name Time Method