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

IgA Nephropathy Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05083364
• Other study ID #: AROC3-1001
• Status: Recruiting
• Phase: Phase 1
• Start date: February 2, 2022
• Est. completion date: June 2025

Study information

• Verified date: April 2024
• Source: Arrowhead Pharmaceuticals
• Contact: Clinical Operations Lead
• Phone: 626-304-3400
• Email: ARO-C3[@]arrowheadpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: June 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• C3 Glomerulopathy
• Glomerulonephritis, IGA
• IgA Nephropathy

Intervention

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

Locations

Country	Name	City	State
Australia	Research Site 1	Camperdown	New South Wales
Australia	Research Site 2	Clayton	Victoria
Australia	Research Site 3	Concord	New South Wales
Georgia	Research Site 1	Tbilisi
Georgia	Research Site 2	Tbilisi
Georgia	Research Site 3	Tbilisi
Germany	Research Site 2	Cologne
Germany	Research Site 4	Erlangen
Germany	Research Site 3	Halle
Germany	Research Site 1	Mainz
Korea, Republic of	Research Site 3	Daegu
Korea, Republic of	Research Site 1	Gamcheon	Busan
Korea, Republic of	Research Site 4	Goyang-si	Gyeonggi-do
Korea, Republic of	Research Site 2	Haeundae	Busan
Korea, Republic of	Research Site 5	Seongnam	Gyeonggi-do
Korea, Republic of	Research Site 6	Soeul
Korea, Republic of	Research Site 7	Soeul
Korea, Republic of	Research Site 8	Soeul
New Zealand	Research Site	Auckland
Thailand	Research Site 1	Bangkok
Thailand	Research Site 2	Bangkok
Thailand	Research Site 4	Bangkok
Thailand	Research Site 3	Chiang Mai
United Kingdom	Research Site 5	Cambridge
United Kingdom	Research Site 2	Coventry
United Kingdom	Research Site 1	Leicester
United Kingdom	Research Site 3	Liverpool
United Kingdom	Research Site 6	Newcastle
United Kingdom	Research Site 4	Oxford

Sponsors (1)

Lead Sponsor	Collaborator
Arrowhead Pharmaceuticals

Countries where clinical trial is conducted

Australia,  Georgia,  Germany,  Korea, Republic of,  New Zealand,  Thailand,  United Kingdom, 

Outcome

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