A Phase 1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-C3 in Adult Healthy Volunteers and in Adult Patients With Complement-Mediated Renal Disease
- Conditions
- complement-mediated renal diseaseMedDRA version: 23.0Level: PTClassification code: 10083522Term: Immune-mediated renal disorder Class: 100000004857Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- CTIS2023-506690-36-00
- Lead Sponsor
- Arrowhead Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 69
Able and willing to provide written informed consent prior to the performance of any study-specific procedures, Subjects 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 last dose of study drug, whichever is later. Subjects 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 (see Appendix 1 for details). Subjects of childbearing potential on hormonal contraceptives must be stable on the medication for >2 menstrual cycles prior to Day 1., Willing and able to comply with all study visits and study requirements, No abnormal finding of clinical relevance at the Screening evaluation that in the opinion of the Investigator could adversely impact subject safety during the study or adversely impact study results, Pre-study renal biopsy with source verifiable record confirming diagnosis of C3G within the last 3 years prior to Day 1 (Cohort 7 only) OR confirming IgAN with presence of C3 (Cohort 8 only) within 5 years prior to Day 1., Clinical evidence of ongoing disease based on significant proteinuria defined as persistent proteinuria >750 mg/day based on verifiable records and confirmed on a valid 24-hour UPE during Screening, Estimated glomerular filtration rate =30 mL/min/1.73m2 calculated by Chronic Kidney Disease Epidemiology Collaboration creatinine equation (CKD-EPI) at Screening and currently not on dialysis, Must have stable or worsening renal disease, on stable and optimized treatment, in the opinion of the Investigator, for at least 90 days prior to the first dose of ARO-C3 and willing to stay on a stable standard of care regimen for duration of the study; treatments may include, but are not limited to, immunosuppressive agents, anti-hypertensives, and/or anti-proteinurics, Subjects must have been on a maximally recommended or tolerated dose of an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for at least 90 days prior to receiving first ARO-C3 dose unless contraindicated due to documented intolerance or allergy, Vaccinated for N. meningitidis types A, C, W, Y, and B, S. pneumoniae, and Hib within the past 2 years based on source verifiable medical records or willing to receive vaccination 2 weeks prior to administration of the study drug with a meningococcal booster and second pneumococcal vaccine on Day 57. Only subjects who are documented nonresponders to these vaccinations based on verifiable medical records can be exempted from the vaccine requirements per discretion of the PI, A negative test result from a coronavirus disease 2019 (COVID-19) polymerase chain reaction (PCR) or other approved test from an appropriate sample (based on local standard of care) during the Screening period OR proof of vaccination with available COVID-19 vaccines based on local vaccine recommendations and guidelines, Males or non-pregnant, non-lactating female volunteers 18 to 70 years of age, Subjects with a body mass index (BMI) between 18.0 and 35.0 kg/m2, inclusive. Subjects who have a BMI outside of this range may be allowed into the study at the discretion of the Investigator
Human immunodeficiency virus (HIV) infection, as shown by the presence of anti-HIV antibody (seropositive), Renal biopsy showing interstitial fibrosis/tubular atrophy of more than 50%, Monoclonal gammopathy of undetermined significance (MGUS) as confirmed by the measurement of serum free light chains or other investigation as per local standard of care, History of major surgery within 90 days of Screening, The use of inhibitors of complement factors including ravulizumab, eculizumab, pegcetacoplan, or factor D or B inhibitors within 12 weeks or 5 half-lives (whichever is longer) prior to Screening, History of systemic manifestation of IgA disease including Henoch-Schonlein purpura, Have used other monoclonal antibody therapies for treatment of IgAN including belimumab within 90 days or rituximab within 180 days of Day 1, History of recurrent or chronic infections including infections caused by encapsulated bacterial organisms or viruses including herpes zoster or herpes simplex, The presence of fever >38 °C (100.4 °F) or history of an active bacterial, viral, or fungal infection within 14 days prior to treatment administration, Uncontrolled hypertension (blood pressure >160/100 mm Hg at Screening), A history of torsades de pointes, ventricular rhythm disturbances (e.g., ventricular tachycardia or fibrillation), pathologic sinus bradycardia (<50 beats per minute [bpm] with symptoms), heart block (excluding first-degree block, being PR interval prolongation only), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG. Subjects with a history of atrial arrhythmias should be discussed with the Medical Monitor., Known or suspected hereditary complement deficiency or other primary immunodeficiency syndrome based on medical history, Symptomatic heart failure (per New York Heart Association guidelines), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction <20%, transient ischemic attack, or cerebrovascular accident) within 180 days prior to study entry, History of malignancy including multiple myeloma within the last 2 years except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer. Subjects with other curatively treated malignancies who have no evidence of metastatic disease and >2-year disease-free interval may be entered following approval by the Medical Monitor, History of bone marrow, hematopoietic stem cell, or solid organ (including kidney) transplantation, Regular use of alcohol within 30 days prior to the Screening Visit (i.e., more than 14 units of alcohol per week [1 unit=150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]), A 12-lead ECG at Screening with abnormalities that may compromise subject’s safety in this study per Investigator’s discretion, including but not limited to heart block (second degree or higher grade), prolonged QTc (>450 ms by either Bazett or Fredericia correction method), clinically significant atrial arrhythmias, new ST segment elevation or depression, or new Q wave on ECG., 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, Blood donation (500 mL) within 7 days prior to study drug administration. Donation or loss of whole blood (excluding the volume of blood that will be drawn during the Screening procedures of this study) prior to administratio
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method