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

NCT07264166 | Enrolling By Invitation

• 1 other identifier: HHI-HIE-OBS-2025-001
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

Hypoxic-Ischemic Encephalopathy; HIE; Cerebral Palsy; quadriplegia; hypoxic brain injury; stroke; ischemic injury; hypoxic brain damage; spastic diplegia; Chronic Hypoxic Ischemic Encephalopathy; Neonatal Hypoxic Ischemic Encephalopathy; Anoxic Brain Injury; Ischemic Brain Injury; Spastic Cerebral Palsy; Quadriplegic Cerebral Palsy; Pediatric Brain Injury; Perinatal Brain Injury; Global Cerebral Ischemia; Observational Registry; Real World Evidence; Real World Data; Multinational Registry; Observational Study; Neurodevelopmental Disorders; Epilepsy; Pediatric Epilepsy; Seizure Disorder; Epileptic Seizures; Refractory Epilepsy; Drug Resistant Epilepsy

Outcome Measures

Primary Outcomes (1)

• Change in Gross Motor Function Measure (GMFM-66/88) Score From Baseline to 12 Months

  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 Outcomes (6)

• Change in Cognitive Performance (Bayley Scales) From Baseline

  Baseline to 12 months and 24 months

• Change in Seizure Frequency

  Baseline to 12 months and 24 months

• Change in Spasticity Using the Modified Ashworth Scale (MAS)

  Baseline to 12 months

• Change in Quality of Life (PedsQL Caregiver-Reported Score)

  Baseline to 12 months and 24 months

• Change in MRI/DTI Biomarkers of White-Matter Integrity

  Baseline to 12 months

Other Outcomes (5)

• Change in Caregiver Burden Score

  Baseline to 12 months and 24 months

• Incidence of Adverse Events and Serious Adverse Events

  Treatment through 24-month follow-up

• Change in Functional Communication (PEDI-CAT / CP-CHILD)

  Baseline to 12 months

Study Arms (1)

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.

Eligibility Criteria

• Age: 2 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Healing Hope International: lead

Study Sites (1)

Stem Solutions

Monterrey, Nuevo León, 64000, Mexico

Location

Related Publications (2)

• Lindvall O, Bjorklund A. Cell replacement therapy: helping the brain to repair itself. NeuroRx. 2004 Oct;1(4):379-81. doi: 10.1602/neurorx.1.4.379. No abstract available.

  PMID: 15717041 BACKGROUND

• Douglas-Escobar M, Weiss MD. Hypoxic-ischemic encephalopathy: a review for the clinician. JAMA Pediatr. 2015 Apr;169(4):397-403. doi: 10.1001/jamapediatrics.2014.3269.

  PMID: 25685948 BACKGROUND

MeSH Terms

Conditions

Hypoxia, Brain; Hypoxia-Ischemia, Brain; Cerebral Palsy; Quadriplegia; Stroke; Neurodevelopmental Disorders; Epilepsy; Seizures; Drug Resistant Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Ischemia; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Brain Damage, Chronic; Paralysis; Neurologic Manifestations; Mental Disorders

Study Officials

• Dr. Anna Lara Kattan, MD: Regenerative Medicine

  Stem Solutions

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Clinical Research

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: December 4, 2025
• Study Start: March 1, 2026
• Primary Completion (Estimated): January 1, 2032
• Study Completion (Estimated): June 15, 2032
• Last Updated: March 23, 2026

Record last verified: 2026-03

Locations

ME (1)