Data from Pharmawand - Curated by EPG Health - Date added 12 January 2019
Aeglea BioTherapeutics, Inc. announced the design of its global pivotal Phase III PEACE (Pegzilarginase Effect on Arginase 1 Deficiency Clinical Endpoints) trial to evaluate the safety and efficacy of pegzilarginase, the Company’s lead investigational therapy, in patients with Arginase 1 Deficiency (ARG1-D). The Company has aligned the trial design and endpoints with input from the FDA and the European Medicines Agency (EMA), and plans to conduct a single, global pivotal trial to support registration. Aeglea expects to dose the first patient in the PEACE trial in the second quarter of 2019 and expects topline data will be available in the first quarter of 2021.
PEACE is a global, randomized, double-blind trial designed to assess the effects of treatment with pegzilarginase versus placebo over 24 weeks with a primary endpoint of statistically significant plasma arginine reduction from baseline. The primary endpoint is intended to assess the effectiveness of pegzilarginase in lowering plasma arginine levels given the evidence that improved plasma arginine control has the potential to improve the clinical status and slow disease progression in patients with ARG1-D. Secondary endpoints assessing changes in clinically meaningful outcomes including mobility, adaptive behavior, safety and pharmacokinetics will be used to describe the broader impact of pegzilarginase relative to placebo on multiple aspects of ARG1-D.
The company plans to enroll 30 (pediatric and adult) patients with ARG1-D. Patients enrolled in the trial will be randomized on a two-to-one basis to receive weekly infusions of pegzilarginase (0.1 mg/kg), or placebo for the double-blind treatment period of 24 weeks. Dose adjustments during this period can be made to optimize plasma arginine control for levels outside the range of 50 to 150 µM. Patients will be considered eligible for the PEACE trial if they exhibit average plasma arginine of greater than 250 µM, are greater than two years of age and have a deficit in mobility or adaptive behavior. All assessments and dose adjustments will be conducted in a blinded fashion at pre-specified intervals. Patients will remain on current disease management for the duration of the Phase III PEACE trial.
In addition, the Phase III PEACE trial will evaluate pegzilarginase relative to placebo through a multi-dimensional assessment of clinical outcome. Measures of clinical outcome are defined as a patient exhibiting improvement from baseline in mobility (2 Minute Walk Test or Functional Mobility Assessment) or adaptive behavior (Vineland Adaptive Behavior Scale). Additional secondary endpoints include a response rate for each individual assessment, the total number of mobility and adaptive behavior responses per patient, the proportion of patients with plasma arginine below medical guidance of 200 µM, safety and pharmacokinetics.
Throughout the PEACE trial, patients will be monitored for adverse events. Upon completion of the 24-week treatment period, patients will qualify to participate in a long-term extension study of pegzilarginase.