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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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C3 Glomerulopathy, IgA Nephropathy

Intervention / Treatment
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* Drug: ARO-C3
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 
| Pharmacodynamics (PD): Change From Baseline in Complement 3 (C3) up to Day 169 |  | Baseline, through Day 169 (EOS) | 
| PD: Percent Change From Baseline in C3 up to Day 169 |  | Baseline, through Day 169 (EOS) |