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

Sponsor
Arrowhead Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05083364
Collaborator
(none)
62
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Study Details

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 paroxysmal nocturnal hemoglobinuria (PNH) and adult patients with complement-mediated renal disease (C3 Glomerulopathy [C3G] and IgA Nephropathy [IgAN]). In Part 1 of the study, HVs will receive a single dose of ARO-C3 or placebo. In Part 2 of the study, adult patients with PNH or C3G/IgAN will receive 2 open-label doses of ARO-C3. Dose levels in Part 2 will be determined based on cumulative safety and pharmacodynamic data from Part 1.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
62 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
Quadruple (Participant, Care Provider, 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 PNH, C3G or IgAN is open-label and there is no masking.
Primary Purpose:
Treatment
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 Paroxysmal Nocturnal Hemoglobinuria and Adult Patients With Complement-Mediated Renal Disease
Actual Study Start Date :
Feb 2, 2022
Anticipated Primary Completion Date :
Mar 1, 2024
Anticipated Study Completion Date :
Jun 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: ARO-C3 (Healthy Volunteers)

1 dose of ARO-C3 by subcutaneous (sc) injection

Drug: ARO-C3
ARO-C3 for sc injection

Placebo Comparator: Placebo (Healthy Volunteers)

placebo calculated volume to match active treatment by sc injection

Drug: Placebo
sterile normal saline (0.9% NaCl) for sc injection

Experimental: ARO-C3 (Adult Patients with C3G or IgAN)

2 doses of ARO-C3 by sc injection

Drug: ARO-C3
ARO-C3 for sc injection

Experimental: ARO-C3 (Adult Patients with PNH)

2 doses of ARO-C3 by sc injection

Drug: ARO-C3
ARO-C3 for sc injection

Outcome Measures

Primary Outcome Measures

  1. 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

  1. Pharmacokinetics (PK) of ARO-C3: Maximum Observed Plasma Concentration (Cmax) [up to 48 hours post-dose]

  2. PK of ARO-C3: Area under the Plasma Concentration Versus Time Curve from Zero to 24Hours (AUC0-24) [up to 48 hours post-dose]

  3. 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]

  4. 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]

  5. PK of ARO-C3: Terminal Elimination Half-Life (t1/2) [up to 48 hours post-dose]

  6. PK of ARO-C3: Apparent Total Body Clearance of ARO-C3 from Plasma (CL) [up to 48 hours post-dose]

  7. PK of ARO-C3: Volume of Distribution (Vz/F) [up to 48 hours post-dose]

  8. Pharmacodynamics (PD): Change From Baseline in Complement 3 (C3) up to Day 169 [Baseline, through Day 169 (EOS)]

  9. PD: Percent Change From Baseline in C3 up to Day 169 [Baseline, through Day 169 (EOS)]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts 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. 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Research Site 3 Busan Korea, Republic of 48108
2 Research Site 4 Busan Korea, Republic of 48108
3 Research Site 1 Busan Korea, Republic of 49267
4 Research Site 2 Busan Korea, Republic of 49267
5 Research Site 5 Daegu Korea, Republic of 42601
6 Research Site 6 Daegu Korea, Republic of 42601
7 Research Site 8 Gyeonggi-do Korea, Republic of 10444
8 Research Site 9 Gyeonggi-do Korea, Republic of 10444
9 Research Site 7 Gyeonggi-do Korea, Republic of 13496
10 Research Site 10 Incheon Korea, Republic of 21565
11 Research Site 11 Seoul Korea, Republic of 6591
12 Research Site 12 Soeul Korea, Republic of 5505
13 Research Site Auckland New Zealand 1010
14 Research Site 1 Bangkok Thailand 10330
15 Research Site 3 Bangkok Thailand 10400
16 Research Site 2 Bangkok Thailand 10700
17 Research Site 4 Chiang Mai Thailand 50200
18 Research Site 5 Chiang Mai Thailand 50200
19 Research Site 6 Hat Yai Thailand 90110

Sponsors and Collaborators

  • Arrowhead Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Arrowhead Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT05083364
Other Study ID Numbers:
  • AROC3-1001
First Posted:
Oct 19, 2021
Last Update Posted:
Aug 9, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 9, 2022