This is a Phase 1 single-blind, placebo-controlled, dose-escalation study designed to evaluate the safety of AD-NP1, a humanized monoclonal antibody targeting human ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1). The study aims to assess the maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of AD-NP1 in healthy volunteers. Participants will be randomized to receive either AD-NP1 or placebo, with safety and efficacy monitored in accordance with Good Clinical Practice (GCP) guidelines. The study also seeks to explore changes in health-related quality of life (HRQOL) during the trial.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
36
AD-NP1 is a humanized monoclonal antibody targeting the catalytic domain of human ENPP1. It is administered intravenously at escalating doses (30 mg/kg, 40 mg/kg, 60 mg/kg, and 100 mg/kg).
Placebo is a normal saline solution administered intravenously in volumes matched to the corresponding AD-NP1 doses (30 mg/kg, 40 mg/kg, 60 mg/kg, and 100 mg/kg)
UCLA Clinical and Translational Research Center
Los Angeles, California, United States
Safety and tolerability of escalating doses of a single IV dose of AD-NP1
Assessed by the incidence of treatment-related Adverse Events (AEs) using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Time frame: Day of infusion (Day 0) to 28 days post-dose
Maximum Tolerated Dose of AD-NP1
To be determined based on dose limiting toxicities (DLTs) and adverse events
Time frame: Day of infusion (Day 0) to 28 days post-dose
Maximum Plasma Concentration (Cmax) as a pharmacokinetics (PK) parameter
Peak plasma concentration obtained directly from the experimental data points, to be measured in Nanograms per milliliter (ng/mL)
Time frame: Baseline (pre-dose) up to Day 60 post-dose
Time to Maximum Plasma Concentration (Tmax) as a pharmacokinetics (PK) parameter
Tmax presents the time at which Cmax is observed, to be measured in hours (h) and minutes (m)
Time frame: Baseline (pre-dose) up to Day 60 post-dose
Apparent Volume of Distribution (Vd) as a pharmacokinetics (PK) parameter
Volume of distribution calculated during the terminal elimination phase following administration, to be measured in Liters (L) or Liters per kilogram (L/kg)
Time frame: Baseline (pre-dose) up to Day 60 post-dose
Area Under the Plasma Concentration-Time Curve (AUC) as a pharmacokinetics (PK) parameter
AUC calculated using the linear-log trapezoidal rule from time zero (pre-dose) to the last quantifiable concentration point to be measured in Nanogram x hours per milliliter (ng \* h/mL)
Time frame: Baseline (Pre-dose), 30 minutes, 1, 2, 4, 6 hours, and Days 1, 3, 7, 14, 28, 60 post-dose.
Terminal Elimination Half-life (T(1/2)) as a pharmacokinetics (PK) parameter
The rate at which Ad-NP1 is cleared from the systemic plasma circulation, to be measured in Liters per hour (L/h) or Milliliters per minute per kilogram (mL/min/kg)
Time frame: Baseline (pre-dose) up to Day 60 post-dose
Total Body Clearance (CL) as a pharmacokinetics (PK) parameter
The rate at which AD-NP1 is cleared from the systemic plasma circulation, to be measured in Liters per hour (L/h) or Milliliters per minute per kilogram (mL/min/kg)
Time frame: Baseline (pre-dose) up to Day 60 post-dose
Plasma Uridine Concentration
Plasma concentrations of uridine will be quantified using Liquid Chromatography-Mass Spectrometry (LC/MS).
Time frame: Baseline (pre-dose), and Days 1, 3, 7, 14, and 28 post-dose.
Plasma Cytidine Concentration
Plasma concentrations of cytidine will be quantified using Liquid Chromatography-Mass Spectrometry (LC/MS)
Time frame: Baseline (pre-dose), and Days 1, 3, 7, 14, and 28 post-dose.
Plasma Orotidine Concentration
Plasma concentrations of orotidine will be quantified using Liquid Chromatography-Mass Spectrometry (LC/MS)
Time frame: Baseline (pre-dose), and Days 1, 3, 7, 14, and 28 post-dose.
Plasma Adenine Concentration
Plasma concentrations of adenine will be quantified using Liquid Chromatography-Mass Spectrometry (LC/MS)
Time frame: Baseline (pre-dose), and Days 1, 3, 7, 14, and 28 post-dose.
Plasma Carbamoyl Aspartate Concentration
Plasma concentrations of carbamoyl aspartate will be quantified using Liquid Chromatography-Mass Spectrometry (LC/MS).
Time frame: Baseline (pre-dose), and Days 1, 3, 7, 14, and 28 post-dose.
Immunogenicity of a single IV dose of AD-NP1
Determined by measuring levels of circulating anti-drug antibody in blood samples
Time frame: Baseline (pre-dose) and Days 1, 7, 14, 28, 90, and 180 post-dose
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