Study of ARO-ANG3 in Adults With Mixed Dyslipidemia (ARCHES-2)

Arrowhead Pharmaceuticals

Status and phase: Active, not recruiting; Phase 2

Conditions: Mixed Dyslipidemia

Treatments: Drug: Placebo; Drug: ARO-ANG3

Study type: Interventional

Funder types: Industry

Identifiers

NCT04832971

AROANG3-2001

Details and patient eligibility

About

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.

Enrollment: 204 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Based on medical history, evidence of 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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204 participants in 4 patient groups, including a placebo group

ARO-ANG3 50 mg

Experimental group

Description:

Two doses of ARO-ANG3 by subcutaneous (sc) injection at Day 1 and Week 12 during double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.

Treatment:

Drug: ARO-ANG3

ARO-ANG3 100 mg

Experimental group

Description:

Two doses of ARO-ANG3 bysc injection at Day 1 and Week 12 during double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.

Treatment:

Drug: ARO-ANG3

ARO-ANG3 200 mg

Experimental group

Description:

Two doses of ARO-ANG3 by sc injection at Day 1 and Week 12 during double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.

Treatment:

Drug: ARO-ANG3

Placebo

Placebo Comparator group

Description:

Calculated volume to match active treatment by sc injection at Day 1 and Week 12 during the double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.

Treatment:

Drug: Placebo

Drug: ARO-ANG3