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

• ClinicalTrials.gov Identifier: NCT05083364
• Recruitment Status: Recruiting
• First Posted: October 19, 2021
• Last Update Posted: April 15, 2024
• Sponsor: Arrowhead Pharmaceuticals
• Information provided by (Responsible Party): Arrowhead Pharmaceuticals

Tracking Information

• First Submitted Date: October 8, 2021
• First Posted Date: October 19, 2021
• Last Update Posted Date: April 15, 2024
• Actual Study Start Date: February 2, 2022
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 8, 2021): Number of Participants with Adverse Events (AEs) and/or Serious Adverse Events (SAEs) at Day 169 [ Time Frame: up to day 169 (End of Study [EOS]) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 8, 2021)

• Pharmacokinetics (PK) of ARO-C3: Maximum Observed Plasma Concentration (Cmax) [ Time Frame: up to 48 hours post-dose ]
• PK of ARO-C3: Area under the Plasma Concentration Versus Time Curve from Zero to 24Hours (AUC0-24) [ Time Frame: 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) [ Time Frame: 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: [ Time Frame: up to 48 hours post-dose ]
• PK of ARO-C3: Terminal Elimination Half-Life (t1/2) [ Time Frame: up to 48 hours post-dose ]
• PK of ARO-C3: Apparent Total Body Clearance of ARO-C3 from Plasma (CL) [ Time Frame: up to 48 hours post-dose ]
• PK of ARO-C3: Volume of Distribution (Vz/F) [ Time Frame: up to 48 hours post-dose ]
• Pharmacodynamics (PD): Change From Baseline in Complement 3 (C3) up to Day 169 [ Time Frame: Baseline, through Day 169 (EOS) ]
• PD: Percent Change From Baseline in C3 up to Day 169 [ Time Frame: Baseline, through Day 169 (EOS) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of ARO-C3 in Adult Healthy Volunteers and Patients With Complement Mediated Renal Disease
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Part 1, participants are randomized to receive either ARO-C3 or placebo. Participants,care providers, investigator and outcomes assessors are all blinded to treatment assignment. Part 2 in patients with C3G or IgAN is open-label and there is no masking.

Primary Purpose: Treatment

Condition

• C3 Glomerulopathy
• IgA Nephropathy

Intervention

• Drug: ARO-C3
  ARO-C3 for sc injection
• Drug: Placebo
  sterile normal saline (0.9% NaCl) for sc injection

Study Arms

• Experimental: ARO-C3 (Healthy Volunteers)
  1 or 2 doses of ARO-C3 by subcutaneous (sc) injection
  Intervention: Drug: ARO-C3
• Placebo Comparator: Placebo (Healthy Volunteers)
  placebo calculated volume to match active treatment by sc injection
  Intervention: Drug: Placebo
• Experimental: ARO-C3 (Adult Patients with C3G or IgAN)
  3 doses of ARO-C3 by sc injection
  Intervention: Drug: ARO-C3

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 6, 2023): 60
• Original Estimated Enrollment (submitted: October 8, 2021): 62
• Estimated Study Completion Date: June 2025
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Clinical Operations Lead; 626-304-3400; ARO-C3@arrowheadpharma.com

• Listed Location Countries: Australia, Georgia, Germany, Korea, Republic of, New Zealand, Thailand, United Kingdom
• Removed Location Countries: Spain

Administrative Information

• NCT Number: NCT05083364
• Other Study ID Numbers: AROC3-1001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Arrowhead Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Arrowhead Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Arrowhead Pharmaceuticals
• Verification Date: April 2024