Phase 2
N=204
Study of ARO-ANG3 in Adults With Mixed Dyslipidemia
Mixed Dyslipidemia
Bottom Line
View on ClinicalTrials.gov: NCT04832971 ↗Enrolled (actual)
204
Serious AEs
8.6%
Results posted
Jan 2024
Primary outcome: Primary: Percent Change From Baseline in Fasting TG at Week 24 — 7.55; -43.67; -49.01; -55.57 percentage change — p=<.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- ARO-ANG3 (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Arrowhead Pharmaceuticals
- Primary completion
- Aug 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Fasting TG at Week 24 |
7.55; -43.67; -49.01; -55.57 | <.0001 sig |
| SECONDARY Percent Change From Baseline in Fasting TG Over Time |
7.00; -41.52; -52.22; -56.21; 13.58; -41.01 | <.0001 sig |
| SECONDARY Percent Change From Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24 |
4.2; -25.1; -24.6; -32.2 | <.0001 sig |
| SECONDARY Percent Change From Baseline in Fasting Non-HDL-C Over Time |
5.2; -23.5; -25.3; -32.9; 3.7; -24.4 | <.0001 sig |
| SECONDARY Percent Change From Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24 |
2.27; -16.40; -12.91; -19.64 | <.0001 sig |
| SECONDARY Percent Change From Baseline in Fasting Total ApoB Over Time |
2.57; -14.00; -11.71; -18.47; 1.51; -15.85 | <.0001 sig |
| SECONDARY Percent Change From Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24 |
5.0; -11.0; -4.3; -15.1 | 0.0138 sig |
| SECONDARY Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time |
5.1; -8.3; -3.4; -13.7; 3.7; -10.1 | 0.0192 sig |
| SECONDARY Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24 |
1.24; -53.02; -68.52; -72.45 | <.0001 sig |
| SECONDARY Percent Change From Baseline in ANGPTL3 Over Time |
5.54; -62.11; -75.25; -79.15; 2.97; -56.09 | <.0001 sig |
| SECONDARY Percent Change From Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24 |
3.1; -9.0; -18.5; -21.5 | 0.0039 sig |
| SECONDARY Percent Change From Baseline in Fasting HDL-C Over Time |
-0.3; -13.9; -25.5; -24.8; 0.4; -14.5 | 0.0003 sig |
| SECONDARY Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period |
0.0000; 2.6685; 0.0000; 57.6941; 63.5267; 154.7823 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24 |
30; 37; 29; 39; 3; 3 | — |
| SECONDARY Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period |
35; 40; 34; 42; 8; 12 | — |
| SECONDARY Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period |
10; 27; 13; 30; 10; 31 | — |
| SECONDARY Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period |
-10.02; -34.78; -2.09; -39.64; 7.87; -51.88 | — |
| SECONDARY Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period |
6.70; -19.95; -5.02; -16.02; -2.53; -23.12 | — |
| SECONDARY Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period |
6.57; -13.49; -10.22; -7.48; -3.88; -11.77 | — |
| SECONDARY Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period |
16.61; -7.68; -1.59; 4.59; 4.13; -2.82 | — |
| SECONDARY Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period |
3.41; -41.57; 4.47; -56.81; 0.79; -59.24 | — |
| SECONDARY Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period |
13.70; 1.67; 7.70; -12.88; 4.80; -11.26 | — |
Summary
The purpose of AROANG3-2001 is to evaluate the efficacy and safety of ARO-ANG3 in participants with mixed dyslipidemia. Participants will initially receive 2 subcutaneous injections of ARO-ANG3 or placebo. Participants who complete the double-blind treatment period may opt to continue in an open-label extension during which they will receive up to 8 doses of ARO-ANG3.
Eligibility Criteria
Inclusion Criteria
- Based on medical history, evidence of triglycerides (TG) ≥ 150 mg/dL but ≤ 499 mg/dL
- Fasting levels at Screening of LDL-C ≥ 70 mg/dL OR non-HDL-C ≥ 100 mg/dL after at least 4 weeks of stable diet and stable optimal statin therapy
- Mean fasting TG ≥ 150 mg/dL and ≤ 499 mg/dL during Screening collected at two separate and consecutive visits and at least 7 days apart and not more than 17 days apart
- Willing to follow diet counseling and maintain a stable diet per Investigator judgment based on local standard of care
- Participants of childbearing potential must agree to use highly-effective contraception during the study and for at least 24 weeks from last dose of study medication
- Women of childbearing potential must have a negative pregnancy test and cannot be breastfeeding
- Women of childbearing potential on hormonal contraceptives must be stable on the medication for ≥ 2 menstrual cycles prior to Day 1
- Men must not donate sperm during the study and for at least 24 weeks following the last dose of study medication
- Able and willing to provide written informed consent and to comply with study requirements
Exclusion Criteria
- Current use or use within 365 days from Day 1 of any hepatocyte targeted siRNA or antisense oligonucleotide molecule
- Active pancreatitis within 12 weeks prior to Day 1
- Any planned bariatric surgery or similar procedures to induce weight loss from consent to end of study
- Acute coronary syndrome event within 24 weeks of Day 1
- Major surgery within 12 weeks of Day 1 or planned surgery during the study
- Planned coronary intervention (e.g., stent placement or heart bypass) during the study
- Uncontrolled hypertension
- Human immunodeficiency virus (HIV) infection, seropositive for Hepatitis B (HBV), seropositive for Hepatitis C (HCV)
- Uncontrolled hypothyroidism or hyperthyroidism
- Hemorrhagic stroke within 24 weeks of Day 1
- History of bleeding diathesis or coagulopathy
- Current diagnosis of nephrotic syndrome
- Systemic use of corticosteroids or anabolic steroids within 4 weeks prior to Day 1 or planned use during the study
- Malignancy within the last 2 years prior to date of consent requiring systemic treatment (some exceptions apply)
Note: additional inclusion/exclusion criteria may apply per protocol
Data sourced from ClinicalTrials.gov (NCT04832971). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.