Study of ARO-C3 in Adult Healthy Volunteers and Patients With Paroxysmal Nocturnal Hemoglobinuria and Complement-Mediated Renal Disease
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
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
- 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
- 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)]
Eligibility Criteria
Criteria
Inclusion Criteria (All Participants):
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Willing to provide written informed consent and to comply with study requirements
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Female participants must be non-pregnant/non-lactating
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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
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All participants must be willing to be vaccinated or have a history of vaccination for Haemophilus influenzae
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Body Mass Index (BMI) between 18.0 and 35.0 kg/m2
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12-lead electrocardiogram (ECG) at Screening with no abnormalities that may compromise participant's safety at discretion of investigator
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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.
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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):
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Diagnosis of C3G or IgAN
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Clinical evidence of ongoing disease based on significant proteinuria
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Estimated glomerular filtration rate ≥40 mL/Min/1.73 m2 at Screening and currently not on dialysis
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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):
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Seropositive for human immunodeficiency virus (HIV) infection,hepatitis B virus, or hepatitis C virus
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History of recurrent or chronic infections
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Uncontrolled hypertension
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Regular usee of alcohol within 30 days prior to Screening
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Use of illicit drugs within 1 year prior to Screening or positive urine drug screen at Screening
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History of meningococcal infection
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History of asplenia or splenectomy
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Known contraindication or history of anaphylactic reaction to any vaccine or vaccine component or prophylactic antibiotics planned for use in the study
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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 | |
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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.- AROC3-1001