Clinical trial NCT05083364: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: C3 Glomerulopathy
IgA Nephropathy
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-10-19
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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 ≥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

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs) and/or Serious Adverse Events (SAEs) at Day 169
timeFrame: up to day 169 (End of Study [EOS])
Secondary outcomes:
measure: Pharmacokinetics (PK) of ARO-C3: Maximum Observed Plasma Concentration (Cmax)
timeFrame: up to 48 hours post-dose
measure: PK of ARO-C3: Area under the Plasma Concentration Versus Time Curve from Zero to 24Hours (AUC0-24)
timeFrame: up to 48 hours post-dose
measure: PK of ARO-C3: Area Under the Plasma Versus Time Concentration Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)
timeFrame: up to 48 hours post-dose
measure: PK of ARO-C3: Area Under the Plasma Concentration Versus Time Curve from Zero Extrapolated to Infinity (AUCinf) PK of ARO-C3:
timeFrame: up to 48 hours post-dose
measure: PK of ARO-C3: Terminal Elimination Half-Life (t1/2)
timeFrame: up to 48 hours post-dose
measure: PK of ARO-C3: Apparent Total Body Clearance of ARO-C3 from Plasma (CL)
timeFrame: up to 48 hours post-dose
measure: PK of ARO-C3: Volume of Distribution (Vz/F)
timeFrame: up to 48 hours post-dose
measure: Pharmacodynamics (PD): Change From Baseline in Complement 3 (C3) up to Day 169
timeFrame: Baseline, through Day 169 (EOS)
measure: PD: Percent Change From Baseline in C3 up to Day 169
timeFrame: Baseline, through Day 169 (EOS)
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Research Site 1
state: New South Wales
city: Concord
country: Australia
facility: Research Site 3
state: New South Wales
city: Clayton
country: Australia
facility: Research Site 2
state: Victoria
city: Tbilisi
country: Georgia
facility: Research Site 2
city: Tbilisi
country: Georgia
facility: Research Site 3
city: Cologne
country: Germany
facility: Research Site 2
city: Erlangen
country: Germany
facility: Research Site 4
city: Mainz
country: Germany
facility: Research Site 1
city: Gamcheon
country: Korea, Republic of
facility: Research Site 1
state: Busan
city: Haeundae
country: Korea, Republic of
facility: Research Site 2
state: Busan
city: Goyang-si
country: Korea, Republic of
facility: Research Site 4
state: Gyeonggi-do
city: Daegu
country: Korea, Republic of
facility: Research Site 3
city: Soeul
country: Korea, Republic of
facility: Research Site 6
city: Soeul
country: Korea, Republic of
facility: Research Site 8
city: Soeul
country: Korea, Republic of
facility: Research Site 7
city: Auckland
country: New Zealand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site 2
city: Bangkok
country: Thailand
facility: Research Site 4
city: Chiang Mai
country: Thailand
facility: Research Site 3
city: Leicester
country: United Kingdom
facility: Research Site 1
city: Newcastle
country: United Kingdom
facility: Research Site 6
city: Oxford
country: United Kingdom
facility: Research Site 4
Study officials:
References: