Study of ARO-C3 in Adult Healthy Volunteers and Patients With Complement Mediated Renal Disease
Primary Purpose
C3 Glomerulopathy, IgA Nephropathy
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ARO-C3
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for C3 Glomerulopathy
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. PNH, 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 (PNH Participants):
- Diagnosis of PNH
Inclusion Criteria (C3G and IgAN Participants):
- Diagnosis of C3G or IgAN
- Clinical evidence of ongoing disease based on significant proteinuria
- Estimated glomerular filtration rate ≥40 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 usee 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
Sites / Locations
- Research Site 1
- Research Site 2Recruiting
- Research Site 1Recruiting
- Research Site 2Recruiting
- Research Site 4Recruiting
- Research Site 5Recruiting
- Research Site 3Recruiting
- Research SiteRecruiting
- Research Site 1Recruiting
- Research Site 2Recruiting
- Research Site 3Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Experimental
Arm Label
ARO-C3 (Healthy Volunteers)
Placebo (Healthy Volunteers)
ARO-C3 (Adult Patients with C3G or IgAN)
Arm Description
1 or 2 doses of ARO-C3 by subcutaneous (sc) injection
placebo calculated volume to match active treatment by sc injection
3 doses of ARO-C3 by sc injection
Outcomes
Primary Outcome Measures
Number of Participants with Adverse Events (AEs) and/or Serious Adverse Events (SAEs) at Day 169
Secondary Outcome Measures
Pharmacokinetics (PK) of ARO-C3: Maximum Observed Plasma Concentration (Cmax)
PK of ARO-C3: Area under the Plasma Concentration Versus Time Curve from Zero to 24Hours (AUC0-24)
PK of ARO-C3: Area Under the Plasma Versus Time Concentration Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)
PK of ARO-C3: Area Under the Plasma Concentration Versus Time Curve from Zero Extrapolated to Infinity (AUCinf) PK of ARO-C3:
PK of ARO-C3: Terminal Elimination Half-Life (t1/2)
PK of ARO-C3: Apparent Total Body Clearance of ARO-C3 from Plasma (CL)
PK of ARO-C3: Volume of Distribution (Vz/F)
Pharmacodynamics (PD): Change From Baseline in Complement 3 (C3) up to Day 169
PD: Percent Change From Baseline in C3 up to Day 169
Full Information
NCT ID
NCT05083364
First Posted
October 8, 2021
Last Updated
July 26, 2023
Sponsor
Arrowhead Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT05083364
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 2, 2022 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
June 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arrowhead Pharmaceuticals
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
C3 Glomerulopathy, IgA Nephropathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ARO-C3 (Healthy Volunteers)
Arm Type
Experimental
Arm Description
1 or 2 doses of ARO-C3 by subcutaneous (sc) injection
Arm Title
Placebo (Healthy Volunteers)
Arm Type
Placebo Comparator
Arm Description
placebo calculated volume to match active treatment by sc injection
Arm Title
ARO-C3 (Adult Patients with C3G or IgAN)
Arm Type
Experimental
Arm Description
3 doses of ARO-C3 by sc injection
Intervention Type
Drug
Intervention Name(s)
ARO-C3
Intervention Description
ARO-C3 for sc injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
sterile normal saline (0.9% NaCl) for sc injection
Primary Outcome Measure Information:
Title
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])
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK) of ARO-C3: Maximum Observed Plasma Concentration (Cmax)
Time Frame
up to 48 hours post-dose
Title
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
Title
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
Title
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
Title
PK of ARO-C3: Terminal Elimination Half-Life (t1/2)
Time Frame
up to 48 hours post-dose
Title
PK of ARO-C3: Apparent Total Body Clearance of ARO-C3 from Plasma (CL)
Time Frame
up to 48 hours post-dose
Title
PK of ARO-C3: Volume of Distribution (Vz/F)
Time Frame
up to 48 hours post-dose
Title
Pharmacodynamics (PD): Change From Baseline in Complement 3 (C3) up to Day 169
Time Frame
Baseline, through Day 169 (EOS)
Title
PD: Percent Change From Baseline in C3 up to Day 169
Time Frame
Baseline, through Day 169 (EOS)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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 ≥40 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Operations Lead
Phone
626-304-3400
Email
ARO-C3@arrowheadpharma.com
Facility Information:
Facility Name
Research Site 1
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
Research Site 2
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Individual Site Status
Recruiting
Facility Name
Research Site 1
City
Gamcheon
State/Province
Busan
ZIP/Postal Code
49267
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Research Site 2
City
Haeundae
State/Province
Busan
ZIP/Postal Code
48108
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Research Site 4
City
Goyang-si
State/Province
Gyeonggi-do
ZIP/Postal Code
10444
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Research Site 5
City
Seongnam
State/Province
Gyeonggi-do
ZIP/Postal Code
13496
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Research Site 3
City
Daegu
ZIP/Postal Code
42601
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Research Site
City
Auckland
ZIP/Postal Code
1010
Country
New Zealand
Individual Site Status
Recruiting
Facility Name
Research Site 1
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Individual Site Status
Recruiting
Facility Name
Research Site 2
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Individual Site Status
Recruiting
Facility Name
Research Site 3
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of ARO-C3 in Adult Healthy Volunteers and Patients With Complement Mediated Renal Disease
We'll reach out to this number within 24 hrs