Primary Hyperoxaluria Type 1 (PH1)
Conditions
Keywords
PH1, Primary hyperoxaluria, AGXT, CRISPR, Gene Editing, Pharmacokinetics, Pharmacodynamics, ABO-101, redePHine
Brief summary
The goal of the redePHine study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABO-101 in participants with primary hyperoxaluria type 1 (PH1). The trial will consist of 2 Study Periods. During the first Study Period, there will be 2 parts. In Part A, adult participants will be treated with a single ascending dose to identify a recommended dose. In Part B, pediatric participants will be treated with the recommended dose. Following the first Study Period, participants will start Study Period 2, a long-term monitoring program to comply with local and national requirements.
Interventions
DRUGABO-101
Intravenous (IV) infusion
Sponsors
Arbor Biotechnologies
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single ascending dose escalation/adaptive design, followed by single dose expansion
Eligibility
Sex/Gender
ALL
Age
6 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria for Parts A and B * Documentation of PH1 as determined by genetic analysis confirming pathogenic mutations in the alanine-glyoxylate aminotransferase (AGXT) gene (valid historical laboratory data will be reviewed and approved by the Sponsor) * Age at time of signing the informed consent/assent form: * Part A: ≥18 years to ≤64 years * Part B: ≥6 years to \<18 years * 24-hour UOx ≥0.7 mmol/24 hours/1.73 m² * eGFR ≥30 mL/min/1.73m² * Weight ≤90 kg Key
Exclusion criteria
for Parts A and B * Confirmed diagnosis of primary hyperoxaluria type 2 or type 3 * History of a liver, kidney or combined liver/kidney transplant * Currently on dialysis * Participant has previously used (within past 24 months) or is currently receiving an approved or investigational urinary oxalate lowering RNA interference (RNAi) or siRNA therapy * Female participants who are pregnant or breastfeeding (or are planning either during the first 12 months)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of treatment-emergent adverse events (TEAEs), including ABO-101-related TEAEs and serious adverse events (SAEs) | Up to 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Percent change in 24-hour urinary oxalate excretion (UOx) from Baseline to Month 6 | Up to 6 months |
| Absolute change in UOx corrected for body surface area | Up to 6 months |
| Percent change in plasma glycolate from Baseline to Month 6 | Up to 6 months |
| Changes in estimated glomerular filtration rate (eGFR) from Baseline to Month 12 and Month 24 | Up to 24 months |
| Plasma concentrations for LNP lipids, Cas12i2 mRNA, and guide RNA (gRNA) | Up to 6 months |
| Urine concentrations for LNP lipids | Up to 6 months |
| Antidrug antibodies to ABO-101 and anti-Cas protein antibodies | Up to 6 months |
Countries
France, Germany, Tunisia, United Kingdom, United States
Contacts
CONTACTDaniel Ory, MD
STUDY_DIRECTORWinston Yan, MD, PhD
Arbor Biotechnologies
Outcome results
None listed