A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults with Severe Hypertriglyceridemia
- Conditions
- dyslipidaemiaSevere Hypertriglyceridemia10013317
- Registration Number
- NL-OMON54297
- Lead Sponsor
- Arrowhead Pharmaceuticals
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 10
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, evidence of triglycerides fasting (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 14 days apart during the Screening period.
4. If the participant has a medical history of clinical atherosclerotic
cardiovascular disease (ASCVD) or those with elevated 10-year ASVCD risk (e.g.,
>=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) must be on appropriate
lipid-lowering therapy as per local standard of care (i.e., 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.
Exclusion Criteria:
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 the study;
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 (sitting blood pressure >160/100 mmHg at
Screening); participant may be re-screened 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. HbA1c >9.0% (or >75 mmol/mol [IFCC] units) at screening;
d. Spot urine protein/spot urine creatinine ratio >3 grams per day;
e. Clinically significant abnormality in PT, aPTT, or 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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint of the study is:<br /><br>• Percent change from baseline at Week 24 in fasting TG. </p><br>
- Secondary Outcome Measures
Name Time Method <p>The following are the secondary endpoints to be evaluated in this study:<br /><br>• Percent change over time through Week 48 in fasting TG;<br /><br>• Percent change from baseline at Week 24 and over time through Week 48 in<br /><br>apolipoprotein (Apo)C-III;<br /><br>• Percent change from baseline at Week 24 and over time through Week 48 in<br /><br>fasting non high-density lipoprotein-cholesterol (non HDL-C);<br /><br>• Percent change from baseline at Week 24 and over time through Week 48 in<br /><br>fasting HDL C;<br /><br>• Percent change from baseline at Week 24 and over time through Week 48 in<br /><br>fasting total ApoB;<br /><br>• Percent change from baseline at Week 24 and over time through Week 48 in<br /><br>fasting low density lipoprotein-cholesterol (LDL C) using ultracentrifugation;<br /><br>• Change from baseline in plasma concentrations of ARO-APOC3 over time through<br /><br>Week 12; and<br /><br>• The frequency and severity of AEs and SAEs over time through Week 48.</p><br>