Clinical trial NCT06839235: Phase 1/2 Study of ABO-101 in Primary Hyperoxaluria Type 1 (redePHine)
Official title: A Phase 1/2 Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of ABO-101 in Participants With Primary Hyperoxaluria Type 1 (PH1)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Primary Hyperoxaluria Type 1 (PH1)
Keywords: PH1
Primary hyperoxaluria
AGXT
CRISPR
Gene Editing
Pharmacokinetics
Pharmacodynamics
ABO-101
redePHine
Lead sponsor: Arbor Biotechnologies
Sponsor class: INDUSTRY
First posted: 2025-02-21
Enrollment: 23
Sex: ALL
Minimum age (years): 6
Maximum age (years): 64
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Single ascending dose escalation/adaptive design, followed by single dose expansion
Primary purpose: TREATMENT

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.


Eligibility 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)

Primary outcomes:
measure: Incidence and severity of treatment-emergent adverse events (TEAEs), including ABO-101-related TEAEs and serious adverse events (SAEs)
timeFrame: Up to 6 months
Secondary outcomes:
measure: Percent change in 24-hour urinary oxalate excretion (UOx) from Baseline to Month 6
timeFrame: Up to 6 months
measure: Absolute change in UOx corrected for body surface area
timeFrame: Up to 6 months
measure: Percent change in plasma glycolate from Baseline to Month 6
timeFrame: Up to 6 months
measure: Changes in estimated glomerular filtration rate (eGFR) from Baseline to Month 12 and Month 24
timeFrame: Up to 24 months
measure: Plasma concentrations for LNP lipids, Cas12i2 mRNA, and guide RNA (gRNA)
timeFrame: Up to 6 months
measure: Urine concentrations for LNP lipids
timeFrame: Up to 6 months
measure: Antidrug antibodies to ABO-101 and anti-Cas protein antibodies
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: St. Paul
country: United States
facility: Nucleus Network
state: Minnesota
Study officials:
affiliation: Arbor Biotechnologies
name: Winston Yan, MD, PhD
role: STUDY_DIRECTOR
References: