Aardvark Therapeutics secured U.S. IRB approval to amend its Phase 3 HERO protocol, lowering the minimum enrollment age from 10 to 7 for patients with Prader–Willi syndrome (PWS) and hyperphagia. The 90-patient, randomized, double-blind, placebo-controlled study spans the U.S., Australia, Canada, the U.K., and South Korea, with a primary endpoint of change in the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) at Week 12 and secondary clinician and caregiver global severity measures. The company continues to guide to topline data in the third quarter of 2026 and offers an open-label extension to completers.
The move is as much about strategy as access. In a rare pediatric condition where hyperphagia manifests early, expanding eligibility should broaden the screenable pool, de-risk accrual timelines, and strengthen external validity for a potential pediatric-inclusive label. Given ARD-101’s Orphan Drug and Rare Pediatric Disease designations, demonstrating benefit in younger cohorts could also enhance regulatory and commercial positioning, including potential eligibility for a Rare Pediatric Disease Priority Review Voucher if approved. Beyond PWS dynamics, the amendment aligns with a broader sponsor playbook: adjust inclusion criteria mid-trial to sustain momentum without inflating sample size or prolonging study duration.
Operationally, U.S. sites can now re-engage pre-screen failures aged 7 to 9 and refresh outreach to pediatric PWS clinics and advocacy networks. The caregiver-reported HQ-CT is well-suited to younger participants, but sites will need rapid retraining on rater consistency across age bands and updates to informed consent/assent workflows. Safety oversight may tighten for growth and gastrointestinal monitoring in younger children, especially given ARD-101’s gut-restricted mechanism as a TAS2R agonist that stimulates enteroendocrine signaling, including GLP-1 and CCK. Ex-U.S. sites will move at the pace of local ethics approvals, likely shifting short-term enrollment weight to the U.S. and requiring close coordination on supply, scheduling, and centralized ePRO integration for caregivers.
For CROs and vendors, the amendment underscores rising demand for pediatric-ready operational infrastructure: age-appropriate ePRO interfaces, caregiver engagement tools, and rater calibration across developmental stages. Regulators gain data more aligned to real-world use, but will expect clarity on age stratification, exposure duration, and any growth or developmental signals in safety readouts. For patients and families, earlier eligibility increases access but complicates retention and placebo tolerance in younger children, making site-level support and flexible visit schedules critical in a short, 12-week pivotal window.
What to watch next: whether Aardvark formalizes age-based stratification or covariate adjustments in the statistical plan to manage added heterogeneity, and whether any interim operational signals trigger sample size re-estimation to preserve power. The sensitivity of HQ-CT to detect change over 12 weeks in a mixed-age cohort will be pivotal, as will alignment between caregiver and clinician global severity measures. Ex-U.S. approvals for the amendment will influence geographic enrollment mix and the Q3 2026 readout cadence. If efficacy and tolerability are consistent across ages, Aardvark can credibly pursue a pediatric-inclusive label and later combination positioning alongside GLP-1–based regimens; if variability emerges in the younger subset, expect calls for additional data or postmarketing commitments that could extend timelines.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
