gene therapy study for children with cln5 batten disease

Conditions: Neuronal Ceroid Lipofuscinosis CLN5

Summary: this is a prospective, non-randomized, open-label, dose escalation study of a single administration of gene therapy in children who are 3 to 9 years old with neuronal ceroid lipofuscinosis (batten) subtype 5 (cln5) disease.

the study is a first in human (fih) open-label, dose escalation study designed to assess the safety and efficacy of administration of an adeno-associated viral vector serotype 9 (aav9) carrying the gene encoding human ceroid-lipofuscinosis neuronal protein 5 (cln5) in subjects with cln5 batten disease. the study treatment will be delivered via intracerebroventricular (icv) and intravitreal (ivt) injection on the same day. each participant will be followed for safety and efficacy for 5 years after treatment. efficacy assessments in this study will evaluate motor, language, visual and cognitive function.

Eligibility criteria:
inclusion criteria * age from 3 to 9 years (child) * molecular genetic diagnosis of the cln5 gene * confirmed clinical diagnosis of cln5 disease * impaired motor and/or language function and/or impaired visual acuity * written informed consent from parent or legal guardian and assent from study participant, if appropriate * able to comply with protocol required assessments (laboratory sample collection, lumbar puncture (lp), nerve conduction studies (ncs), magnetic resonance imaging (mri), etc.), which may require sedation or general anesthesia * able to walk with or without assistance (assistance may include a walker, braces, or with one hand held) * agree to reside within a 1-hour drive of the study site for at least 6 months following treatment (or a safely drivable distance for the study participant and caregivers according to investigator's discretion) exclusion criteria * has another neurologic disease or illness that may have caused cognitive decline before study entry * known pathogenic or clinically suspected variant in a seizure associated genetic mutation besides cln5 * any active infections or severe infections within the 30 days prior to study treatment administration * presence of a concomitant medical condition that precludes intracerebroventricular (icv) injection, lumbar puncture (lp), or use of anesthetics needed for study-related procedures * presence of any concomitant medical conditions that preclude intravitreal (ivt) administration * has status epilepticus that lasts longer than 5 minutes or having more than 1 seizure within a 5-minute period, without returning to a normal level of consciousness between episodes within 12 weeks before study treatment * total anti-aav9 antibody titer greater than 1:400 * any anticipated need for major surgery in the next 24 months * participation in an investigational new drug, investigational device exemption, or equivalent clinical study in the past 6 months * any prior participation in a study in which a gene therapy vector or stem cell transplantation was administered * participation in other investigational studies and non-interventional studies that have similar study assessments as this protocol while the study participant is enrolled in this study with the exception of sister studies sponsored by neurogene * history of or current chemotherapy, radiotherapy, or other immunosuppressive therapy within the past 3 months * use of prohibited medications * immunizations of any kind in the 45 days prior to study treatment * requiring daytime or nighttime ventilatory support at the time of screening * any item which would exclude the study participant from being able to undergo brain magnetic resonance imaging (mri) according to local institutional policy * known allergies or hypersensitivities to the required immunosuppression regime

Keywords: batten disease neuronal ceroid lipofuscinosis disease neuronal ceroid lipofuscinosis subtype 5 disease ncl gene therapy gene transfer cln5 cln