Gene Therapy for Children With CLN3 Batten Disease

NCT03770572 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CLN-301
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1/2, open-label, single dose, dose-escalation clinical trial to evaluate the safety and efficacy of CLN-301 (previous NCH Code: scAAV9.P546.CLN3) delivered intrathecally into the lumbar spinal cord region of subjects with CLN3 Batten disease.

Conditions

CLN3; Batten Disease

Keywords

CLN3; Neuronal ceroid lipofuscinosis; NCL; Gene Transfer

Outcome Measures

Primary Outcomes (2)

• Safety evaluation based on the development of dose-limiting toxicity (DLT).

  The DLT is defined as any unanticipated AE that is considered related to CLN-301 and is Common Terminology Criteria for Adverse Events Grade 3 or higher.

  36 Months

• Efficacy: Change in rating as determined using the Unified Batten Disease Rating Scale (UBDRS) rating scale.

  The UBDRS is a clinical ratings instrument used specifically to assess motor, seizure, behavioral and functional capabilities. The "Physical Assessment" is a 20 item subscale that measures vision, speech, motor strength, gait, abnormal involuntary movements and balance. Each item has a score range of 0 to 4. The minimum score is 0 and the maximum score is 112. The items are summed up to obtain a total score.The higher the score, the more severe the disability and worse the outcome.

  36 months

Secondary Outcomes (3)

• QOL: Change in Quality of Life (QOL) as determined using the Pediatric Quality of Life (PedsQL™) scale.

  36 months

• Seizures: Change is seizure subscore as determined using Seizure subscale of the UBDRS scale.

  36 months

• Global impression: Change in disease severity using the UBDRS clinical global impression (CGI) subscale.

  36 months

Study Arms (2)

Cohort 1: CLN-301 Low-Dose

EXPERIMENTAL

No more than 5 mL of 6 x 1013 vg CLN-301 administered via intrathecal injection

Genetic: Low dose CLN-301

Cohort 2: CLN-301 High-Dose

EXPERIMENTAL

No more than 10 mL of 1.2 x 1014 vg of CLN-301 administered via intrathecal injection

Genetic: High dose CLN-301

Interventions

Low dose CLN-301 GENETIC

Subjects with diagnosis of CLN3 Batten disease will receive a single dose of CLN-301 at low dose

Cohort 1: CLN-301 Low-Dose

High dose CLN-301 GENETIC

Subjects with diagnosis of CLN3 Batten disease will receive a single dose of CLN-301 at high dose

Cohort 2: CLN-301 High-Dose

Eligibility Criteria

• Age: 3 Years - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diagnosis of CLN3 Batten disease determined by genotype available at screening by a College of American Pathologists/Clinical Laboratory Improvement Amendments (CAP/CLIA)-certified laboratory (or a non-US laboratory with an equivalent national accreditation/certification)
• Aged ≥ 3 to \< 11 years
• UBDRS physical impairment score of ≤ 7
• Able to walk independently at least 50 feet

You may not qualify if:

• Presence of another inherited neurologic or metabolic disease, eg, other forms of Batten disease (also known as neuronal ceroid lipofuscinosis; NCL) or seizures unrelated to CLN3 Batten disease (subjects with febrile seizures may be eligible at the discretion of the investigator)
• Presence of another neurological illness that may have caused cognitive decline (eg, trauma, meningitis, hemorrhage) before screening
• Active viral infection (includes HIV or serology positive for hepatitis B or C)
• Subjects with 2 consecutive aminotransaminase liver tests \> 3 times the upper limit of normal or \> 1.5 times the upper limit of normal if taking valproic acid at Visit 1 (screening/baseline)
• Subjects with anti-AAV9 antibody titers \> 1:400 as determined by ELISA (enzyme-linked immunosorbent assay) binding immunoassay
• Abnormal laboratory values considered clinically significant
• Presence of immunologic disease
• Has received stem cell or bone marrow transplantation
• Has received any form of organ transplant
• 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 investigator)
• Current use of cannabinoids and any by-products
• Contraindications for intrathecal administration of the product or lumbar puncture (for collection of CSF), such as bleeding disorders or other medical conditions (eg, spina bifida, meningitis, or clotting abnormalities)
• Contraindications for MRI scans (eg, cardiac pacemaker, metal fragment or chip in the eye, aneurysm clip in the brain)
• Poorly controlled seizures - intractable epilepsy
• Episode of generalized motor status epilepticus within 4 weeks before the Gene Transfer visit

Sponsors & Collaborators

• Alcyone Therapeutics, Inc: lead

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43201, United States

Location

Related Publications (9)

• 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

• Phillips SN, Benedict JW, Weimer JM, Pearce DA. CLN3, the protein associated with batten disease: structure, function and localization. J Neurosci Res. 2005 Mar 1;79(5):573-83. doi: 10.1002/jnr.20367.

  PMID: 15657902 BACKGROUND

• Munroe PB, Mitchison HM, O'Rawe AM, Anderson JW, Boustany RM, Lerner TJ, Taschner PE, de Vos N, Breuning MH, Gardiner RM, Mole SE. Spectrum of mutations in the Batten disease gene, CLN3. Am J Hum Genet. 1997 Aug;61(2):310-6. doi: 10.1086/514846.

  PMID: 9311735 BACKGROUND

• Drack AV, Mullins RF, Pfeifer WL, Augustine EF, Stasheff SF, Hong SD. Immunosuppressive Treatment for Retinal Degeneration in Juvenile Neuronal Ceroid Lipofuscinosis (Juvenile Batten Disease). Ophthalmic Genet. 2015;36(4):359-64. doi: 10.3109/13816810.2014.886271. Epub 2014 Feb 19.

  PMID: 24547931 BACKGROUND

• Kwon JM, Adams H, Rothberg PG, Augustine EF, Marshall FJ, Deblieck EA, Vierhile A, Beck CA, Newhouse NJ, Cialone J, Levy E, Ramirez-Montealegre D, Dure LS, Rose KR, Mink JW. Quantifying physical decline in juvenile neuronal ceroid lipofuscinosis (Batten disease). Neurology. 2011 Nov 15;77(20):1801-7. doi: 10.1212/WNL.0b013e318237f649. Epub 2011 Oct 19.

  PMID: 22013180 BACKGROUND

• Adams HR, Mink JW; University of Rochester Batten Center Study Group. Neurobehavioral features and natural history of juvenile neuronal ceroid lipofuscinosis (Batten disease). J Child Neurol. 2013 Sep;28(9):1128-36. doi: 10.1177/0883073813494813.

  PMID: 24014508 BACKGROUND

• Ostergaard JR, Rasmussen TB, Molgaard H. Cardiac involvement in juvenile neuronal ceroid lipofuscinosis (Batten disease). Neurology. 2011 Apr 5;76(14):1245-51. doi: 10.1212/WNL.0b013e31821435bd.

  PMID: 21464428 BACKGROUND

• Cotman SL, Vrbanac V, Lebel LA, Lee RL, Johnson KA, Donahue LR, Teed AM, Antonellis K, Bronson RT, Lerner TJ, MacDonald ME. Cln3(Deltaex7/8) knock-in mice with the common JNCL mutation exhibit progressive neurologic disease that begins before birth. Hum Mol Genet. 2002 Oct 15;11(22):2709-21. doi: 10.1093/hmg/11.22.2709.

  PMID: 12374761 BACKGROUND

• Johnson TB, Brudvig JJ, Likhite S, Pratt MA, White KA, Cain JT, Booth CD, Timm DJ, Davis SS, Meyerink B, Pineda R, Dennys-Rivers C, Kaspar BK, Meyer K, Weimer JM. Early postnatal administration of an AAV9 gene therapy is safe and efficacious in CLN3 disease. Front Genet. 2023 Mar 24;14:1118649. doi: 10.3389/fgene.2023.1118649. eCollection 2023.

  PMID: 37035740 DERIVED

MeSH Terms

Conditions

Neuronal Ceroid-Lipofuscinoses

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

• Kathrin C Meyer, PhD

  Alcyone Therapeutics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single Treatment Group (AAV9-CLN3) - 2 Cohort Assignment (Low-dose, High-dose) Dose escalation in this study will begin with low-dose, determined to be the minimal efficacious dose as determined in non-clinical studies. Dose escalation to a high-dose (2x the minimally effective dose (MED) as evaluated in Cohort 1) will proceed as part of Cohort 2 of the study upon demonstration of safety of the low-dose in Cohort 1 of the study.

Study Record Dates

• First Submitted: December 7, 2018
• First Posted: December 10, 2018
• Study Start: November 13, 2018
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2029
• Last Updated: August 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)