Intravitreal ERT to Prevent Retinal Disease Progression in Children With CLN2

NCT05152914 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00001444
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I/II randomized, masked, clinical trial to determine the safety and efficacy of intravitreal administration of cerliponase alfa.

Conditions

Neuronal Ceroid Lipofuscinosis Type 2

Outcome Measures

Primary Outcomes (1)

• Monitoring for the development of unacceptable toxicity.

  Based on the development of unacceptable toxicity, defined as the occurrence of any Grade 3 or higher, unanticipated, treatment related toxicity.

  2 years

Secondary Outcomes (2)

• Efficacy of intravitreal cerliponase alfa to stabilize fundoscopic features.

  2 years

• Efficacy of intravitreal cerliponase alfa to stabilize retinal architecture.

  2 years

Study Arms (1)

Intervention

EXPERIMENTAL

Drug: Cerliponase Alfa

Interventions

Cerliponase Alfa DRUG

Brineura is a hydrolytic lysosomal N-terminal tripeptidyl peptidase indicated to slow the loss of ambulation in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) deficiency.

Also known as: Brineura

Intervention

Eligibility Criteria

• Age: 24 Months - 72 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Genotypic confirmation of classical CLN2 Batten's disease from a CLIA certified lab.
• Enzyme level deficiency of tripeptidyl-peptidase
• Minimum age requirement: 24 months of age at enrollment
• Maximum age requirement: 72 months of age at enrollment
• Currently receiving intraventricular cerliponase alfa
• Willing to participate in the proposed study visits over the 2-year period
• Minimum central retinal thickness (CRT) of 140μm based upon OCT assessment
• Clear ocular media
• No ocular pathology present to account for vision loss other than optic atrophy and pigmentary retinopathy that is felt to be due to the CLN2 disease process

You may not qualify if:

• Any opacities in the clear ocular media including vitreous debris.
• History of ocular trauma or prior ocular surgery.
• Episode of generalized motor status epilepticus within four weeks before the First Dose visit
• Severe infection (e.g., upper respiratory tract infection, pneumonia, pyelonephritis, or meningitis) within four weeks before the First Dose visit (enrollment may be postponed)
• Those with a history of bleeding disorders.
• History of or current chemotherapy, radiotherapy or other immunosuppression therapy within the past 30 days (corticosteroid treatment may be permitted at the discretion of the PI)
• Has a medical condition, or extenuating circumstance that, in the opinion of the investigator, might compromise the subject's ability to comply with the protocol required testing or procedures or compromise the subject's wellbeing, safety, or clinical interpretability

Sponsors & Collaborators

• David L Rogers, MD: lead

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Related Publications (4)

• Schulz A, Kohlschutter A, Mink J, Simonati A, Williams R. NCL diseases - clinical perspectives. Biochim Biophys Acta. 2013 Nov;1832(11):1801-6. doi: 10.1016/j.bbadis.2013.04.008. Epub 2013 Apr 17.

  PMID: 23602993 BACKGROUND

• Sleat DE, Donnelly RJ, Lackland H, Liu CG, Sohar I, Pullarkat RK, Lobel P. Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis. Science. 1997 Sep 19;277(5333):1802-5. doi: 10.1126/science.277.5333.1802.

  PMID: 9295267 BACKGROUND

• Schulz A, Ajayi T, Specchio N, de Los Reyes E, Gissen P, Ballon D, Dyke JP, Cahan H, Slasor P, Jacoby D, Kohlschutter A; CLN2 Study Group. Study of Intraventricular Cerliponase Alfa for CLN2 Disease. N Engl J Med. 2018 May 17;378(20):1898-1907. doi: 10.1056/NEJMoa1712649. Epub 2018 Apr 24.

  PMID: 29688815 BACKGROUND

• Gardner E, Bailey M, Schulz A, Aristorena M, Miller N, Mole SE. Mutation update: Review of TPP1 gene variants associated with neuronal ceroid lipofuscinosis CLN2 disease. Hum Mutat. 2019 Nov;40(11):1924-1938. doi: 10.1002/humu.23860. Epub 2019 Jul 26.

  PMID: 31283065 BACKGROUND

MeSH Terms

Conditions

Neuronal Ceroid-Lipofuscinoses

Interventions

cerliponase alfa

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• David Rogers, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief of the Department of Ophthalmology

Study Record Dates

• First Submitted: November 29, 2021
• First Posted: December 10, 2021
• Study Start: November 1, 2021
• Primary Completion: March 4, 2026
• Study Completion (Estimated): March 6, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

US (1)