C3 Glomerulopathy, IgA Nephropathy
Conditions
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.
Interventions
DRUGARO-C3
ARO-C3 for sc injection
DRUGPlacebo
sterile normal saline (0.9% NaCl) for sc injection
Sponsors
Arrowhead Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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/
Design outcomes
Primary
| 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
| 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 |
Countries
Australia, Georgia, Germany, New Zealand, South Korea, Thailand, United Kingdom
Outcome results
None listed