Study of ARO-C3 in Adult Healthy Volunteers and Patients With Complement Mediated Renal Disease

A Phase 1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and/or Pharmacodynamics of ARO-C3 in Adult Healthy Volunteers and in Adult Patients With Complement-Mediated Renal Disease

The purpose of AROC3-1001 is to evaluate the safety, tolerability, pharmacokinetics and/or pharmacodynamics in adult healthy volunteers (HVs) and in adult patients with complement-mediated renal disease (C3 Glomerulopathy [C3G] and IgA Nephropathy [IgAN]). In Part 1 of the study, HVs will receive either one or two doses of ARO-C3 or placebo. In Part 2 of the study, adult patients with C3G/IgAN will receive 3 open-label doses of ARO-C3. Dose levels in Part 2 will be determined based on cumulative safety and pharmacodynamic data from Part 1.

Study Overview

• Status: Completed
• Conditions: IgA Nephropathy; C3 Glomerulopathy
• Intervention / Treatment: Drug: ARO-C3; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Research Site 1
    • Concord, New South Wales, Australia, 2139
      • Research Site 3
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Research Site 2
• Georgia
  • Tbilisi, Georgia, 0112
    • Research Site 2
• Germany
  • Cologne, Germany, 50937
    • Research Site 2
  • Erlangen, Germany, 91054
    • Research Site 4
• New Zealand
  • Auckland, New Zealand, 1010
    • Research Site
• South Korea
  • Daegu, South Korea, 42601
    • Research Site 3
  • Soeul, South Korea, 03722
    • Research Site 6
  • Soeul, South Korea, 05030
    • Research Site 8
  • Busan
    • Gamcheon, Busan, South Korea, 49267
      • Research Site 1
    • Haeundae, Busan, South Korea, 48108
      • Research Site 2
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, South Korea, 10444
      • Research Site 4
• Thailand
  • Bangkok, Thailand, 10400
    • Research Site 2
  • Chiang Mai, Thailand, 50200
    • Research Site 3
• United Kingdom
  • Oxford, United Kingdom, OX3 7LE
    • Research Site 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria (All Participants):

• Willing to provide written informed consent and to comply with study requirements
• Female participants must be non-pregnant/non-lactating
• Healthy volunteers must be willing to be vaccinated with a meningococcal and pneumococcal vaccine. C3G and IgAN participants must have been vaccinated or willing to undergo vaccination
• All participants must be willing to be vaccinated or have a history of vaccination for Haemophilus influenzae
• Body Mass Index (BMI) between 18.0 and 35.0 kg/m2
• 12-lead electrocardiogram (ECG) at Screening with no abnormalities that may compromise participant's safety at discretion of investigator
• Participants of childbearing potential must use highly effective contraception during the study and for at least 12 weeks following the end of the study or last dose of study drug, whichever is later. Males must not donate sperm during the study and for at least 12 weeks following the end of the study or last dose of study drug, whichever is later.
• No abnormal finding of clinical relevance at the Screening evaluation that, in the opinion of the investigator, could adversely impact participant safety or study results

Inclusion Criteria (C3G and IgAN Participants):

• Diagnosis of C3G or IgAN
• Clinical evidence of ongoing disease based on significant proteinuria
• Estimated glomerular filtration rate ≥30 mL/Min/1.73 m2 at Screening and currently not on dialysis
• Must be on a maximally recommended or tolerated dose of an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)

Exclusion Criteria (All Participants):

• Seropositive for human immunodeficiency virus (HIV) infection,hepatitis B virus, or hepatitis C virus
• History of recurrent or chronic infections
• Uncontrolled hypertension
• Regular use of alcohol within 30 days prior to Screening
• Use of illicit drugs within 1 year prior to Screening or positive urine drug screen at Screening
• History of meningococcal infection
• History of asplenia or splenectomy
• Known contraindication or history of anaphylactic reaction to any vaccine or vaccine component or prophylactic antibiotics planned for use in the study
• Any medical or surgical condition that, in the opinion of the investigator, would expose the participant to a significant safety risk or compromise the results of the study

Note: Additional Inclusion/Exclusion criteria may apply per protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARO-C3 (Healthy Volunteers); 1 or 2 doses of ARO-C3 by subcutaneous (sc) injection	Drug: ARO-C3; ARO-C3 for sc injection
Placebo Comparator: Placebo (Healthy Volunteers); placebo calculated volume to match active treatment by sc injection	Drug: Placebo; sterile normal saline (0.9% NaCl) for sc injection
Experimental: ARO-C3 (Adult Patients with C3G or IgAN); 3 doses of ARO-C3 by sc injection	Drug: ARO-C3; ARO-C3 for sc injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Adverse Events (AEs) and/or Serious Adverse Events (SAEs) at Day 169	up to day 169 (End of Study [EOS])

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (PK) of ARO-C3: Maximum Observed Plasma Concentration (Cmax)	up to 48 hours post-dose
PK of ARO-C3: Area under the Plasma Concentration Versus Time Curve from Zero to 24Hours (AUC0-24)	up to 48 hours post-dose
PK of ARO-C3: Area Under the Plasma Versus Time Concentration Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)	up to 48 hours post-dose
PK of ARO-C3: Area Under the Plasma Concentration Versus Time Curve from Zero Extrapolated to Infinity (AUCinf) PK of ARO-C3:	up to 48 hours post-dose
PK of ARO-C3: Terminal Elimination Half-Life (t1/2)	up to 48 hours post-dose
PK of ARO-C3: Apparent Total Body Clearance of ARO-C3 from Plasma (CL)	up to 48 hours post-dose
PK of ARO-C3: Volume of Distribution (Vz/F)	up to 48 hours post-dose

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Publications and helpful links

General Publications

• Tunnicliffe DJ, Reid S, Craig JC, Samuels JA, Molony DA, Strippoli GF. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev. 2024 Feb 1;2(2):CD003962. doi: 10.1002/14651858.CD003962.pub3.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Actual): September 10, 2025
• Study Completion (Actual): September 10, 2025

Study Registration Dates

• First Submitted: October 8, 2021
• First Submitted That Met QC Criteria: October 8, 2021
• First Posted (Actual): October 19, 2021

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Glomerulonephritis, IGA
• Other Study ID Numbers: AROC3-1001; 2023-506690-36-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes