Study of ARO-ANG3 in Healthy Volunteers and in Dyslipidemic Patients

Conditions

Dyslipidemias, Familial Hypercholesterolemia, Hypertriglyceridemia

Brief summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetcs and pharmacodynamics of single- and multiple doses of ARO-ANG3 in healthy adult volunteers and in dyslipidemic patients including familial hypercholesterolemia and severe hypertriglyceridemia.

Watts GF, Scott R, Sullivan D, Baker J, Clifton P, Hamilton J, Given B, Melquist S, Zhou R, Gaudet D, Goldberg IJ, Knowles JW, Leeper NJ, Hegele RA, Ballantyne CM.

2026-04-07

10.1038/s41591-026-04307-8

RNA interference targeting ANGPTL3 for triglyceride and cholesterol lowering: phase 1 basket trial cohorts.

Watts GF, Schwabe C, Scott R, Gladding PA, Sullivan D, Baker J, Clifton P, Hamilton J, Given B, Melquist S, Zhou R, Chang T, San Martin J, Gaudet D, Goldberg IJ, Knowles JW, Hegele RA, Ballantyne CM.

2023-08-2569 citations

10.1038/s41591-023-02494-2

Abstract 15751: Pharmacodynamic Effect of ARO-ANG3, an Investigational RNA Interference Targeting Hepatic Angiopoietin-like Protein 3, in Patients With Hypercholesterolemia

Gerald F. Watts, Christian Schwabe, Russell Scott, Patrick Gladding, David Sullivan et al. (18 authors)

Circulation2020-11-1740 citations

10.1161/circ.142.suppl_3.15751

Interventions

DRUGARO-ANG3

single or multiple doses of ARO-ANG3 by subcutaneous (sc) injections

DRUGsterile normal saline (0.9% NaCl)

calculated volume to match active treatment

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Yes

Inclusion criteria

* Women of child bearing 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 * On a stable diet for at least 4 weeks with no plans to significantly alter diet or weight over course of study * Normal electrocardiogram (ECG) at Screening

Exclusion criteria

* Clinically significant health concerns * Regular use of alcohol within one month prior to Screening * Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study * Recent use of illicit drugs * Use of more than two tobacco/nicotine containing or cannabis products per month within 6 months prior to drug administration (applicable only to Normal Healthy Volunteers) NOTE: additional inclusion/

Design outcomes

Primary

Measure	Time frame
Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment	Up to 113 (+/- 3 days) post-dose

Secondary

Measure	Time frame
PK of ARO-ANG3: Terminal Elimination Half-Life (t1/2)	Single dose phase: Up to 48 hours post-dose
Pharmacokinetics (PK) of ARO-ANG3: Maximum Observed Plasma Concentration (Cmax)	Single dose phase: Up to 48 hours post-dose
PK of ARO-ANG3: Time to Maximum Plasma Concentration (Tmax)	Single dose phase: Up to 48 hours post-dose
PK of ARO-ANG3: Area Under the Plasma Concentration Versus Time Curve From Zero to infinity (AUCinf)	Single dose phase: Up to 48 hours post-dose
Reduction in Fasting Serum ANGPTL3 from Pre-Dose Baseline	Baseline, Up to Day 113 (+/- 3 days)
PK of ARO-ANG3: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)	Single dose phase: Up to 48 hours post-dose

Countries

Australia, New Zealand

Outcome results

None listed