International Observational Study of Intranasal 15-Gene AAV9-PHP.eB Therapy for Children With Chronic Hypoxic-Ischemic Encephalopathy (Cerebral Palsy) (GEN-HOPE)

Healing Hope International

Status: Begins enrollment in a year or more

Conditions: Cerebral Palsy Spastic Diplegia; Hypoxic Ischemic Encephalopathy of Newborn; Cerebral Palsy; Hypoxic Ischaemic Encephalopathy Due to Cardiac Arrest; Cerebral Palsy Hemiparetic Cerebral Palsy Spasticity Gait Disorders, Neurologic Postural Balance Impairment; Hypoxic Ischaemic Encephalopathy (HIE); Cerebral Palsy (CP); Cerebral Palsy Quadriplegic; Hypoxic Brain Damage

Study type: Observational

Funder types: Other

Identifiers

NCT07264166

HHI-HIE-OBS-2025-001

Details and patient eligibility

About

This international study, organized by Healing Hope International, is an observational registry designed to collect real-world data on children living with chronic hypoxic-ischemic encephalopathy (HIE) who receive an emerging intranasal gene therapy based on the AAV9-PHP.eB viral vector.

The investigational therapy delivers a panel of 15 restorative genes that support brain repair, reduce inflammation, promote myelination, and improve neural communication. It is administered intranasally in one or three sessions by participating international clinical teams. Because the therapy is already being offered abroad, this registry does not assign treatment but instead follows children who have received it as part of their existing medical care.

The GEN-HOPE Study aims to understand how this gene therapy affects movement, cognition, spasticity, and seizure frequency over time. Families and clinicians will share outcomes such as changes in gross motor function (GMFM-66/88), cognitive assessments (Bayley or WISC tests), and quality-of-life measures. Information on safety, laboratory results, MRI findings, and caregiver-reported experiences will also be collected.

By combining data from multiple countries, the registry seeks to evaluate whether this novel gene-based approach can meaningfully improve daily function and comfort for children with chronic HIE. Results will guide future clinical-trial development and help define safe and effective standards of care for regenerative neurologic therapies.

Full description

The GEN-HOPE Study is a multinational, real-world observational registry coordinated by Healing Hope International to evaluate the safety and functional outcomes of a 15-gene AAV9-PHP.eB intranasal gene therapy administered to children with chronic hypoxic-ischemic encephalopathy (HIE) outside the United States.

This registry does not assign or direct any medical intervention. Instead, it prospectively collects standardized clinical and caregiver-reported data from participating international sites where the therapy is already being used under local medical supervision. The aim is to document the naturalistic course of recovery following treatment and to generate evidence that may inform the design of future controlled trials.

The investigational therapy uses an AAV9-PHP.eB viral vector optimized for central nervous system delivery through the nasal mucosa. The 15-gene panel encodes factors related to neuronal plasticity, white-matter repair, anti-inflammatory modulation, metabolic and vascular support, and cellular longevity. Dosing schedules vary by site (single-session or three-session delivery), and some centers administer short-term rapamycin as an adjunctive immunomodulator.

Participants are children aged 2-65 years who have documented chronic HIE, stable baseline medical status, and caregiver consent to share outcome data. Key assessments include gross motor function (GMFM-66/88), cognitive and language evaluations (Bayley-III/IV or WISC-V), spasticity and seizure frequency, and quality-of-life and caregiver burden metrics. Whenever available, MRI/DTI data and laboratory monitoring are recorded. Follow-up intervals occur at approximately 3, 6, 12, 18, and 24 months post-treatment.

Data are analyzed using target-trial emulation and propensity-weighted methods to estimate treatment effects compared with matched external controls receiving standard care. The primary outcome is change in GMFM-66/88 score at 12 months. Secondary outcomes include cognitive performance, seizure burden, quality of life, and safety parameters.

All information is de-identified and stored in a secure international database compliant with data-protection and ethical-governance standards. Oversight is provided by an independent Data and Safety Monitoring Board (DSMB) with expertise in pediatric neurology, statistics, and gene-therapy safety.

The GEN-HOPE Study seeks to accelerate understanding of gene-based neurorestorative strategies and to establish a transparent evidence base supporting compassionate-use access, long-term safety monitoring, and eventual clinical-trial harmonization for children affected by HIE worldwide.

Enrollment: 25 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age 2 to 65 years, at the time of enrollment.
2. Documented diagnosis of chronic hypoxic-ischemic encephalopathy (HIE), confirmed by medical history, MRI findings, or neonatal records.
3. Stable medical condition for at least 6 months prior to enrollment (no major surgeries or hospitalizations related to HIE within that period).
4. Baseline Gross Motor Function Measure (GMFM-66 or GMFM-88) score between 40% and 70%, representing moderate functional impairment.
5. Completion or active receipt of intranasal 15-gene AAV9-PHP.eB therapy at a participating international clinical site under local physician supervision.
6. Parent(s) or legal guardian(s) willing and able to provide written informed consent for participation in the observational registry and data sharing.
7. Access to clinical follow-up and ability to participate in scheduled assessments or data submissions at 3, 6, 12, 18, and 24 months after treatment.

Exclusion criteria

1. Active systemic infection, immune deficiency, or ongoing use of immunosuppressive agents (other than short-term rapamycin used per treating physician's protocol).
2. Known positive anti-AAV9 neutralizing antibody titer at baseline exceeding threshold values that may preclude effective vector transduction (if testing performed locally).
3. Uncontrolled seizure activity exceeding five episodes per day at baseline despite medical therapy.
4. Known or suspected malignancy, severe hepatic or renal dysfunction, or other conditions that would confound safety monitoring.
5. Previous gene therapy or investigational stem cell therapy within the past 12 months.
6. Known pregnancy or breastfeeding in post-pubertal female participants.
7. Any condition that, in the opinion of the local investigator or registry sponsor, may interfere with participation, data reliability, or patient safety.

Trial design

25 participants in 1 patient group

Intranasal 15-Gene AAV9-PHP.eB Therapy Cohort

Description:

This cohort includes children diagnosed with chronic hypoxic-ischemic encephalopathy (HIE) who receive an intranasal 15-gene AAV9-PHP.eB therapy as part of their existing medical care at participating international sites.