Intranasal AAV9-PHP.eB Gene Therapy in Cerebral Palsy (CP) & Hypoxic Ischemic Encephalopathy (HIE) (GEN-HOPE)

March 18, 2026 updated by: Tamara C Tamas, Healing Hope International

Healing Hope International Multinational Observational Registry Evaluating Intranasal 15-Gene AAV9-PHP.eB Therapy and Functional Outcomes in Participants With Cerebral Palsy & Chronic Hypoxic-Ischemic Encephalopathy (HIE) (GEN-HOPE Study)

This international study, organized by Healing Hope International, is an observational registry designed to collect real-world data on participants 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 participants 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 participants with chronic HIE. Results will guide future clinical trial development and help define safe and effective standards of care for regenerative neurologic therapies.

Study Overview

Status

Enrolling by invitation

Conditions

Detailed Description

The GEN HOPE Study is a multinational, real world observational registry coordinated by Healing Hope International to characterize reported safety events and functional outcomes in participants with chronic hypoxic ischemic encephalopathy (HIE), a condition commonly presenting as cerebral palsy, who have received intranasal 15-gene AAV9-PHP.eB gene therapy 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, antiinflammatory 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 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 deidentified 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 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 participants affected by HIE worldwide.

Study Type

Observational

Enrollment (Estimated)

25

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • Nuevo León
      • Monterrey, Nuevo León, Mexico, 64000
        • Stem Solutions

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The study population consists of patients aged 2 to 60 years with chronic hypoxic-ischemic encephalopathy (HIE) who have undergone or are undergoing intranasal 15-gene AAV9-PHP.eB gene therapy at participating international clinical sites.

Participants typically present with moderate to severe motor and cognitive impairments resulting from neonatal brain injury. Most rely on rehabilitative therapies such as occupational, physical, or speech therapy, and many have comorbid spasticity, seizure disorders, or feeding and respiratory challenges.

Families voluntarily enroll to share functional, cognitive, imaging, and quality-of-life outcomes following the therapy, allowing the registry to capture real-world data from diverse treatment centers. Enrollment is open to patients meeting medical stability criteria and caregiver consent requirements, regardless of geographic origin, socioeconomic background, or previous therapy history.

No healthy volunteers are included.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intranasal 15-Gene AAV9-PHP.eB Therapy Cohort
This cohort includes patients 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Gross Motor Function Measure (GMFM-66/88) Score From Baseline to 12 Months
Time Frame: Baseline to 12 months after treatment
Assesses change in overall motor ability using the Gross Motor Function Measure (GMFM-66/88), a validated scale for patients with cerebral palsy and/or hypoxic ischemic injury. Measures performance in lying, sitting, crawling, standing, and walking domains. Higher scores indicate greater motor function.
Baseline to 12 months after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Spasticity Using the Modified Ashworth Scale (MAS)
Time Frame: Baseline to 12 months
Measures tone and resistance in major muscle groups using the Modified Ashworth Scale (0 = no increase in tone; 4 = rigid in flexion or extension). Lower scores indicate reduced spasticity.
Baseline to 12 months
Change in MRI/DTI Biomarkers of White-Matter Integrity
Time Frame: Baseline to 12 months
Quantitative analysis of fractional anisotropy and mean diffusivity from diffusion tensor imaging (DTI) in periventricular and cortical regions. Increases in fractional anisotropy and cortical thickness suggest structural neurorepair.
Baseline to 12 months
Change in Cognitive Performance (Bayley Scales) From Baseline
Time Frame: Baseline to 12 months and 24 months
Assesses change in cognitive performance using the Bayley Scales of Infant and Toddler Development (Bayley-III or Bayley-IV) for participants aged 2-4 years. Composite cognitive scores range from 40-160 (mean 100, SD 15), with higher scores indicating improved cognitive and developmental function.
Baseline to 12 months and 24 months
Change in Seizure Frequency
Time Frame: Baseline to 12 months and 24 months
Monthly caregiver-reported seizure logs and medication records are collected to quantify changes in seizure frequency. Reduction in seizure rate indicates improvement in neuronal stability and anti-inflammatory response. Seizure frequency is a count measure-no minimum/maximum scale required.
Baseline to 12 months and 24 months
Change in Quality of Life (PedsQL Caregiver-Reported Score)
Time Frame: Baseline to 12 months and 24 months

Assesses child and caregiver quality of life using the Pediatric Quality of Life Inventory (PedsQL).

Scale range: 0-100, with higher scores indicating improved perceived quality of life.
Baseline to 12 months and 24 months
Change in Cognitive Performance (WISC-V) From Baseline
Time Frame: Baseline to 12 months and 24 months
Assesses change in cognitive performance using the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V) for participants aged 5-10 years. Full Scale IQ scores range from 40-160, with higher scores indicating improved cognitive function.
Baseline to 12 months and 24 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Caregiver Burden Score
Time Frame: Baseline to 12 months and 24 months
Measured using the Caregiver Strain Index (CSI). Lower scores indicate reduced physical, emotional, and time-related burden associated with caregiving.
Baseline to 12 months and 24 months
Incidence of Adverse Events and Serious Adverse Events
Time Frame: Treatment through 24-month follow-up
Safety endpoints include frequency and severity of adverse events, infections, seizure exacerbations, or hospitalization following gene therapy administration.
Treatment through 24-month follow-up
Change in Functional Communication (PEDI-CAT / CP-CHILD)
Time Frame: Baseline to 12 months
Evaluates communication and social interaction using validated scales (PEDI-CAT Communication Domain and CP-CHILD). Higher scores indicate improved communication function.
Baseline to 12 months
Change in Anti-AAV9-PHP.eB Antibody Titers
Time Frame: Baseline to 6 months post-treatment
Quantifies humoral immune response to AAV9-PHP.eB using ELISA or equivalent assays where available.
Baseline to 6 months post-treatment
Change in Laboratory Safety Parameters During Rapamycin Use
Time Frame: Baseline, Weeks 2, 4, 8, and 12
Assesses the number of participants who develop laboratory abnormalities while receiving adjunctive rapamycin. Monitored parameters include complete blood count (CBC), liver enzymes (AST, ALT), renal function markers (creatinine, BUN), and lipid profile (LDL, HDL, triglycerides). Abnormalities are defined according to site-specific laboratory reference ranges. The outcome is reported as the number of participants exhibiting at least one laboratory value outside the normal range.
Baseline, Weeks 2, 4, 8, and 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Healing Hope International

Investigators

  • Principal Investigator: Dr. Anna Lara Kattan, MD: Regenerative Medicine, Stem Solutions

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2026

Primary Completion (Estimated)

January 1, 2032

Study Completion (Estimated)

June 15, 2032

Study Registration Dates

First Submitted

November 24, 2025

First Submitted That Met QC Criteria

November 24, 2025

First Posted (Actual)

December 4, 2025

Study Record Updates

Last Update Posted (Actual)

March 23, 2026

Last Update Submitted That Met QC Criteria

March 18, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HHI-HIE-OBS-2025-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Individual participant data will not be publicly shared because the registry collects information from medically fragile children with hypoxic-ischemic encephalopathy across international sites. The data contain potentially identifiable clinical and imaging information that cannot be fully anonymized without risk of re-identification.

De-identified, aggregate-level results and statistical summaries will be made available through peer-reviewed publications, conference presentations, and registry updates. Access to limited, de-identified datasets for qualified researchers may be considered under controlled data-use agreements and ethics committee approval.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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