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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06209177




Registration number
NCT06209177
Ethics application status
Date submitted
5/01/2024
Date registered
17/01/2024
Date last updated
24/04/2024

Titles & IDs
Public title
Study of ARO-CFB in Adult Healthy Volunteers and Patients With Complement-Mediated Kidney Disease
Scientific title
A Phase 1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ARO-CFB in Adult Healthy Volunteers and Adult Patients With Complement-Mediated Kidney Disease
Secondary ID [1] 0 0
AROCFB-1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
IgA Nephropathy 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ARO-CFB
Treatment: Drugs - Placebo

Experimental: ARO-CFB (Healthy Volunteers) - 1 or 2 doses of ARO-CFB by subcutaneous (sc) injection

Experimental: Placebo (Healthy Volunteers) - placebo calculated volume to match active treatment by sc injection

Experimental: ARO-CFB (Adult Patients with IgAN) - 3 doses of ARO-CFB by sc injection


Treatment: Drugs: ARO-CFB
ARO-CFB for sc injection

Treatment: Drugs: Placebo
sterile normal saline (0.9% NaCl for sc injection)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Part 1: up to Day 169 (End of Study [EOS]); Part 2: up to Day 225 (EOS)
Secondary outcome [1] 0 0
Change from Baseline in Serum Complement Factor B (CFB) and Its Breakdown Products Ba and Bb
Timepoint [1] 0 0
Part 1: up to Day 169 (End of Study [EOS]); Part 2: up to Day 225 (EOS)
Secondary outcome [2] 0 0
Pharmacokinetics (PK) of ARO-CFB: Maximum Observed Plasma Concentration (Cmax)
Timepoint [2] 0 0
Part 1 only: up to 48 hours postdose
Secondary outcome [3] 0 0
PK of ARO-CFB: Time to Maximum Observed Plasma Concentration (Tmax)
Timepoint [3] 0 0
Part 1 only: up to 48 hours post-dose
Secondary outcome [4] 0 0
PK of ARO-CFB: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)
Timepoint [4] 0 0
Part 1 only: up to 48 hours post-dose
Secondary outcome [5] 0 0
PK of ARO-CFB: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)
Timepoint [5] 0 0
Part 1 only: up to 48 hours post-dose
Secondary outcome [6] 0 0
PK of ARO-CFB: Area Under the Plasma Concentration Versus Time Curve from Zero Extrapolated to Infinity (AUCinf)
Timepoint [6] 0 0
Part 1 only: up to 48 hours post-dose
Secondary outcome [7] 0 0
PK of ARO-CFB: Terminal Elimination Half-Life (t1/2)
Timepoint [7] 0 0
Part 1 only: up to 48 hours post-dose
Secondary outcome [8] 0 0
PK of ARO-CFB: Apparent Clearance (CL/F)
Timepoint [8] 0 0
Part 1 only: up to 48 hours post-dose
Secondary outcome [9] 0 0
PK of ARO-CFB: Volume of Distribution (Vz/F)
Timepoint [9] 0 0
Part 1 only: up to 48 hours post-dose
Secondary outcome [10] 0 0
PK of ARO-CFB: Amount of Drug Recovered in Urine Over Zero - 24 Hours Post-dose (Ae)
Timepoint [10] 0 0
Part 1 only: up to 24 hours post-dose
Secondary outcome [11] 0 0
PK of ARO-CFB: Fraction of Drug Excreted Unchanged (fe)
Timepoint [11] 0 0
Part 1 only: up to 24 hours post-dose
Secondary outcome [12] 0 0
PK of ARO-CFB: Renal Clearance (CLr)
Timepoint [12] 0 0
Part 1 only: up to 24 hours post-dose
Secondary outcome [13] 0 0
Percent Change from Baseline in Serum Complement Factor B (CFB) and Its Breakdown Products Ba and Bb
Timepoint [13] 0 0
Part 1: up to Day 169 (End of Study [EOS]); Part 2: up to Day 225 (EOS)

Eligibility
Key inclusion 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. 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 type B

- Body Mass Index (BMI) between 18.0 and 35.0 kg/m2

- Participants of childbearing potential must agree to use highly effective
contraception in addition to a condom during the study and for at least 90 days
following the end of the study or the last dose of study drug, whichever is later.
Participants must not donate sperm or eggs during the study and for at least 90 days
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 adversely
impact study results.

Inclusion Criteria (IgAN Participants):

- Diagnosis of IgA Nephropathy based on renal biopsy within 5 years

- Clinical evidence of ongoing disease based on significant proteinuria

- Estimated glomerular filtration rate =30 mL/min/1.73m2 at Screening and currently not
on dialysis

- Must have stable or worsening renal disease, on stable and optimized treatment for at
least 30 days prior to Screening and willing to stay on a stable standard of care
regimen for the duration of the study

- Must be on a maximally recommended or tolerated dose of an angiotensin-converting
enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria (All Cohorts):

- History of recurrent or chronic infections including infections caused by encapsulated
bacterial organisms or viruses

- History of active bacterial, viral, or fungal infection within 14 days prior to
treatment administrations

- Seropositive for Human immunodeficiency virus (HIV), hepatitis B virus (HBV) or
hepatitis C virus (HCV)

- History of meningococcal infection

- History of asplenia

- History of severe aplastic anemia or concurrent severe aplastic anemia

- Known or suspected hereditary complement deficiency or other primary immunodeficiency
syndrome

- History of diabetes mellitus (Type 1 or Type 2)

- Uncontrolled hypertension

Exclusion Criteria (IgAN Participants):

- Nephrotic syndrome or rapidly progressive glomerulonephritis

- Suspicion for secondary etiologies of IgAN

- Evidence of non-IgAN kidney disease on renal biopsy

- Renal biopsy showing interstitial fibrosis/tubular atrophy of more than 50%

- Use of complement inhibitors or monoclonal antibody therapies for treatment of IgAN

Note: Additional Inclusion/Exclusion criteria may apply per protocol

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/04/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2027
Actual
Sample size
Target
66
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Arrowhead Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of AROCFB-1001 is to evaluate the safety, tolerability, pharmacokinetics and
pharmacodynamics of ARO-CFB Injection in adult healthy volunteers (HVs) and in adult patients
with complement-mediated kidney disease (IgA Nephropathy [IgAN]). In Part 1 of the study, HVs
will receive either one or two doses of ARO-CFB or placebo. In Part 2 of the study, adult
patients with IgAN will receive 3 open-label doses of ARO-CFB. Dose levels in Part 2 will be
determined based on cumulative safety and pharmacodynamic data from Part 1.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06209177
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Medical Monitor
Address 0 0
Country 0 0
Phone 0 0
626-696-4702
Fax 0 0
Email 0 0
gshekhtman@arrowheadpharma.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06209177