Age-related Macular Degeneration
Conditions
Brief summary
This study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses of ARO-033 compared to placebo in adult normal healthy volunteers (NHVs) and the safety, tolerability, PK, PD, and efficacy of multiple doses of ARO-033 in participants with age-related macular degeneration (AMD).
Interventions
DRUGARO-033
ARO-033 will be administered as a subcutaneous (SC) injection per schedule specified in the arm description.
DRUGPlacebo
Placebo matching to ARO-033 will be administered as SC injection per schedule specified in the arm description.
Sponsors
Arrowhead Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * NHV cohorts only: Adults 18 to 65 years of age who are not pregnant, not breastfeeding, and do not plan to become pregnant (or impregnate their partners) during the study and for at least 90 days following the end of the study. * AMD cohorts only: Adults ≥50 years of age who are not pregnant, not breastfeeding, and do not plan to become pregnant (or impregnate their partners) during the study and for at least 90 days following the end of the study. * Body mass index (BMI) between 18.0 and 35.0 kilograms (kg)/square meter (m\^2), inclusive. * No abnormal finding of clinical relevance at the Screening evaluation that in the opinion of the Investigator could adversely impact participant's safety during the study or adversely impact study results. * AMD cohorts only: A clinical diagnosis of AMD in both eyes as determined by the Investigator and confirmed by the central reading center. Key
Exclusion criteria
All Cohorts: * Human immunodeficiency virus (HIV) infection, as shown by the presence of anti-HIV antibody (seropositive). * Seropositive for hepatitis B virus (HBV) (hepatitis B surface antigen positive at screening) or hepatitis C virus (HCV) (HCV antibody positive with reflex confirmation using HCV RNA amplification at Screening). Cured HCV (positive antibody test without detectable HCV RNA) is permitted if HCV RNA has been negative for at least 2 years. * Uncontrolled hypertension (resting systolic blood pressure ≥160 millimeters of mercury \[mmHg\] or diastolic blood pressure ≥95 mmHg, confirmed by repeat measurement, at Screening). * Evidence of clinically significant immunocompromising condition (for example, primary immunodeficiency syndrome, aplastic anemia, known or suspected complement factor deficiency, or any other condition resulting in significantly impaired immune response as evidenced by recurrent infections), or recent/ongoing treatment with immunosuppressive agents. * History of major surgery within 90 days of Screening. * Use of an investigational agent or device within 30 days or 5 half-lives (whichever is longer) prior to dosing or current participation in an investigational study. Participants recently participating in studies involving investigational agents with prolonged therapeutic effect (such as ribonucleic acid interference \[RNAi\] therapeutics, cell or gene therapies) and whose last dose was less than 12 months prior to the first dose of study intervention, should be discussed with the Medical Monitor. * Any medical condition or clinically significant laboratory abnormality at Screening that in the opinion of the Investigator should exclude the participant from participation, preclude safe and successful completion of the study, or confound study results. AMD Cohorts Only: * Any ocular condition in the study eye that may be expected to progress and that may affect central vision or otherwise be a confounding factor during the study, as determined by the Investigator. * Atrophic retinal disease due to causes other than AMD (for example, drug-induced, Stargardt disease, cone rod dystrophy) in either eye. Note: Other protocol-defined inclusion and
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to Day 337 |
Secondary
| Measure | Time frame |
|---|---|
| Maximum Observed Plasma Concentration (Cmax) of ARO-033 | SAD: Predose (0 hour) up to 48 hours postdose (Day 1 up to Day 3); MAD: Predose up to 18 hours postdose (Days 1 and 29), 24 hours postdose (Days 2 and 30), and 48 hours postdose (Days 3 and 31); AMD cohorts: Up to 4 hours postdose (Days 1 and 29) |
| Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUC0-t) of ARO-033 | SAD: Predose (0 hour) up to 48 hours postdose (Day 1 up to Day 3); MAD: Predose up to 18 hours postdose (Days 1 and 29), 24 hours postdose (Days 2 and 30), and 48 hours postdose (Days 3 and 31); AMD cohorts: Up to 4 hours postdose (Days 1 and 29) |
| NHV Cohorts Only: Amount of ARO-033 Excreted in the Urine From Time 0 to 24 Hours After Dosing (Ae) | SAD: Predose (0 hour) up to 8 hours postdose (Day 1), and up to 24 hours postdose (Day 2); MAD: Predose (0 hour) up to 8 hours postdose (Days 1 and 29) |
Countries
New Zealand
Contacts
CONTACTMedical Monitor
Outcome results
None listed