Batten DiseaseNCT03862274
Examining Developmental Outcomes of Children Diagnosed With CLN2 Disease
An observational study of Batten Disease and CLN2, run by Jessica Scherr at 1 site in United States.
Trial summary
The investigators propose a study to assess cognitive and developmental outcomes of patients with CLN2 that are untreated and receiving cerliponase alfa. This study aims to validate standardized assessment measures to establish a standard of care. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Batten Disease, CLN2, Neuronal Ceroid-Lipofuscinoses
- What is being tested?
- CLN2 Treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2018to Dec 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients that have a TPP1 enzyme deficiency and/or confirmed molecular diagnosis of pathogenic variants in the TPP1 gene are eligible to participate if they are untreated or are receiving cerliponase alfa.
Who may be able to join
- Patients that have a TPP1 enzyme deficiency
- Patients have confirmed molecular diagnosis of pathogenic variants in the TPP1 gene
- Patients that are enrolled in post-marketing studies will be allowed to enroll into the current study
Who cannot join
- Patients without a diagnosis of CLN2 and deficiency of TPP1
- Patients that are currently enrolled as part of a larger multi-center clinical trial
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Nationwide Children's Hospital
Columbus, Ohio, 43205
About this study
The investigators propose a study to assess cognitive and developmental outcomes of patients with CLN2 that are untreated and receiving cerliponase alfa. This study aims to validate standardized assessment measures to establish a standard of care. The secondary aim is to compare cognitive and developmental outcomes of patients with CLN2 that are receiving celiponase alfa to a natural history cohort. To accomplish specific aims of the study, the investigators will use a multi-method approach to collect retrospective data collected as standard of care and prospective developmental data in children with CLN2 disease. The investigators will use a combination of standardized measures that include direct assessment and parent report of child development. The investigators focus will also include multiple measures of development including language, motor, social-emotional, and adaptive functioning.
Read the detailed description
CLN2 disease is a predominantly late infantile form of neuronal ceroid lipofuscinosis and one of the many genetic isoforms of Batten disease. Mutations in the CLN2 gene are characterized by deficient lysosomal serine protease TPP1, an enzyme that metabolizes intracellular lysosomal storage materials. Accumulations of intracellular deposits occur over time and in many organs of individuals with CLN2 disease and lead to neurodegeneration and, eventually, death. CLN2 disease is an extremely rare genetic disease affecting around 1 per 200,000 live births. Symptoms emerge early in life typically between the ages of 2 and 4 years of age and include seizures, as well as loss of motor, language, and vision functioning. Development further declines in early childhood and by age 6 years, children with CLN2 are often unable to walk or sit unsupported and become blind. The progression of the disease is rapid with death typically occurring in mid-childhood between the ages of 10 and 15 years of age.
Recently, enzyme replacement therapy (ERT), cerliponase alfa, which is a recombinant form of human TPPI, was the first FDA-approved treatment to slow the progression of motor decline in children with CLN2. Cerliponase alfa is expected to restore TPP1 enzyme activity in the brain and alter neurodegeneration and disease progression. Animal models suggest promising treatment outcomes as cerliponase alfa significantly delayed the onset of clinical signs, preserved motor and cognitive function, and prolonged life. Initial results from a clinical trial further demonstrated that patients receiving cerliponase alfa had less motor declines, as measured by the CLN2 Clinical Rating Scale, compared to a natural history cohort. Despite these promising results, little is known about the trajectory of other developmental domains, including language, social-emotional, and adaptive functioning of children receiving cerliponase alfa. Likewise, the developmental trajectory of untreated patients with CLN2 is not well understood. Therefore, it is important to understand developmental outcomes and the progression of CLN2 in a natural history cohort in order to compare the effectiveness of treatment outcomes.
- Conditions
- Batten Disease, CLN2, Neuronal Ceroid-Lipofuscinoses
- Being tested
- CLN2 Treatment
- Medical subject headings
- Neuronal Ceroid-Lipofuscinoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CLN2 TreatmentOther
Patients that have a TPP1 enzyme deficiency and/or confirmed molecular diagnosis of pathogenic variants in the TPP1 gene are eligible to participate if they are receiving cerliponase alfa.
| Study group | Role | What they receive |
|---|---|---|
| CLN2 Natural History Control Group | Patients that have a TPP1 enzyme deficiency and/or confirmed molecular diagnosis of pathogenic variants in the TPP1 gene are eligible to participate if they are untreated or not receiving cerliponase alfa. | |
| CLN2 Treatment Group | Patients that have a TPP1 enzyme deficiency and/or confirmed molecular diagnosis of pathogenic variants in the TPP1 gene are eligible to participate if they are receiving cerliponase alfa. Receives: Other: CLN2 Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Visual Reception Skills on the Mullen Scales of Early Learning
Changes in the Visual Reception subscale on the Mullen Scales of Early Learning will be assessed every 6 months. Visual reception skills are a measure of visual processing and problem solving. Raw scores will be used as a measure of visual receptions skills with scores ranging from 0 to 50. Higher scores indicate more visual reception skills.
Measured: up to 4 years
Changes in Fine Motor Skills on the Mullen Scales of Early Learning
Changes in the Fine Motor subscale on the Mullen Scales of Early Learning will be assessed every 6 months. Fine motor skills are a measure of fine motor coordination. Raw scores will be used as a measure of fine motor skills with scores ranging from 0 to 49. Higher scores indicate more fine motor skills.
Measured: up to 4 years
Changes in Receptive Language Skills on the Mullen Scales of Early Learning
Changes in the Receptive Language subscale on the Mullen Scales of Early Learning will be assessed every 6 months. Receptive language skills are a measure of the understanding of language. Raw scores will be used as a measure of receptive language skills with scores ranging from 0 to 48. Higher scores indicate more receptive language skills.
Measured: up to 4 years
Changes in Expressive Language Skills on the Mullen Scales of Early Learning
Changes in the Expressive Language subscale on the Mullen Scales of Early Learning will be assessed every 6 months. Expressive language skills are a measure of how an individual communicates. Raw scores will be used as a measure of expressive language skills with scores ranging from 0 to 50. Higher scores indicate more expressive language skills.
Measured: up to 4 years
Motor and Language Changes on the CLN2 disease rating scale
Change in motor and language subscales of the CLN2 disease rating scale. Ranges for scores are 0 to 6 with higher scores indicating more abilities in motor and language skill development.
Measured: up to 4 years
Secondary outcomes (2)
Changes in Receptive Language Skills on the Preschool Language Scales
Changes in the Receptive Language subscale on the Preschool Language Scales will be assessed every 6 months. Receptive language skills are a measure of the understanding of language. Raw scores will be used as a measure of receptive language skills with scores ranging from 0 to 65. Higher scores indicate more receptive language skills.
Measured: up to 4 years
Changes in Expressive Language Skills on the Preschool Language Scales
Changes in the Expressive Language subscale on the Preschool Language Scales will be assessed every 6 months. Expressive language skills are a measure of how an individual communicates. Raw scores will be used as a measure of expressive language skills with scores ranging from 0 to 67. Higher scores indicate more expressive language skills.
Measured: up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2019
- Study start1 Dec 2018
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Batten DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jessica Scherr
- Sponsor type
- University, hospital or other
- Collaborators
- BioMarin Pharmaceutical
- Responsible party
- Sponsor-investigator, Jessica Scherr, Nationwide Children's Hospital
- Investigators
- Jessica Scherr, PhD, Principal investigator, Nationwide Children's HospitalEmily de los Reyes, MD, Principal investigator, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03862274
- Sponsor's protocol ID
- IRB18-00464
- Status last verified
- Oct 2025
- First submitted
- 4 Jan 2019
- Last updated
- 24 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 23602993Schulz 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.
PubMed 29688815Wisniewski KE, Zhong N, Philippart M. Pheno/genotypic correlations of neuronal ceroid lipofuscinoses. Neurology. 2001 Aug 28;57(4):576-81. doi: 10.1212/wnl.57.4.576.
PubMed 11548735Worgall S, Kekatpure MV, Heier L, Ballon D, Dyke JP, Shungu D, Mao X, Kosofsky B, Kaplitt MG, Souweidane MM, Sondhi D, Hackett NR, Hollmann C, Crystal RG. Neurological deterioration in late infantile neuronal ceroid lipofuscinosis. Neurology. 2007 Aug 7;69(6):521-35. doi: 10.1212/01.wnl.0000267885.47092.40.
PubMed 17679671Williams RE, Aberg L, Autti T, Goebel HH, Kohlschutter A, Lonnqvist T. Diagnosis of the neuronal ceroid lipofuscinoses: an update. Biochim Biophys Acta. 2006 Oct;1762(10):865-72. doi: 10.1016/j.bbadis.2006.07.001. Epub 2006 Jul 12.
PubMed 16930952
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Examining Developmental Outcomes of Children Diagnosed With CLN2 Disease
- ClinicalTrials.gov ID
- NCT03862274
- Acronym / sponsor ID
- IRB18-00464
- Conditions
- Batten Disease, CLN2, Neuronal Ceroid-Lipofuscinoses
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Jessica ScherrUniversity, hospital or other
- Collaborators
- BioMarin Pharmaceutical
- Study start
- 1 Dec 2018 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 5 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators propose a study to assess cognitive and developmental outcomes of patients with CLN2 that are untreated and receiving cerliponase alfa. This study aims to validate standardized assessment measures to establish a standard of care. The secondary aim is to compare cognitive and developmental outcomes of patients with CLN2 that are receiving celiponase alfa to a natural history cohort. To accomplish specific aims of the study, the investigators will use a multi-method approach to collect retrospective data collected as standard of care and prospective developmental data in children with CLN2 disease. The investigators will use a combination of standardized measures that include direct assessment and parent report of child development. The investigators focus will also include multiple measures of development including language, motor, social-emotional, and adaptive functioning.
Detailed description
CLN2 disease is a predominantly late infantile form of neuronal ceroid lipofuscinosis and one of the many genetic isoforms of Batten disease. Mutations in the CLN2 gene are characterized by deficient lysosomal serine protease TPP1, an enzyme that metabolizes intracellular lysosomal storage materials. Accumulations of intracellular deposits occur over time and in many organs of individuals with CLN2 disease and lead to neurodegeneration and, eventually, death. CLN2 disease is an extremely rare genetic disease affecting around 1 per 200,000 live births. Symptoms emerge early in life typically between the ages of 2 and 4 years of age and include seizures, as well as loss of motor, language, and vision functioning. Development further declines in early childhood and by age 6 years, children with CLN2 are often unable to walk or sit unsupported and become blind. The progression of the disease is rapid with death typically occurring in mid-childhood between the ages of 10 and 15 years of age.
Recently, enzyme replacement therapy (ERT), cerliponase alfa, which is a recombinant form of human TPPI, was the first FDA-approved treatment to slow the progression of motor decline in children with CLN2. Cerliponase alfa is expected to restore TPP1 enzyme activity in the brain and alter neurodegeneration and disease progression. Animal models suggest promising treatment outcomes as cerliponase alfa significantly delayed the onset of clinical signs, preserved motor and cognitive function, and prolonged life. Initial results from a clinical trial further demonstrated that patients receiving cerliponase alfa had less motor declines, as measured by the CLN2 Clinical Rating Scale, compared to a natural history cohort. Despite these promising results, little is known about the trajectory of other developmental domains, including language, social-emotional, and adaptive functioning of children receiving cerliponase alfa. Likewise, the developmental trajectory of untreated patients with CLN2 is not well understood. Therefore, it is important to understand developmental outcomes and the progression of CLN2 in a natural history cohort in order to compare the effectiveness of treatment outcomes.
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CLN2 Natural History Control Group | – | –Patients that have a TPP1 enzyme deficiency and/or confirmed molecular diagnosis of pathogenic variants in the TPP1 gene are eligible to participate if they are untreated or not receiving cerliponase alfa. |
| CLN2 Treatment Group | – | Other: CLN2 TreatmentPatients that have a TPP1 enzyme deficiency and/or confirmed molecular diagnosis of pathogenic variants in the TPP1 gene are eligible to participate if they are receiving cerliponase alfa. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients that have a TPP1 enzyme deficiency and/or confirmed molecular diagnosis of pathogenic variants in the TPP1 gene are eligible to participate if they are untreated or are receiving cerliponase alfa.
Key inclusion criteria (3 listed)
- Patients that have a TPP1 enzyme deficiency
- Patients have confirmed molecular diagnosis of pathogenic variants in the TPP1 gene
- Patients that are enrolled in post-marketing studies will be allowed to enroll into the current study
Key exclusion criteria (2 listed)
- Patients without a diagnosis of CLN2 and deficiency of TPP1
- Patients that are currently enrolled as part of a larger multi-center clinical trial
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CLN2 TreatmentPatients that have a TPP1 enzyme deficiency and/or confirmed molecular diagnosis of pathogenic variants in the TPP1 gene are eligible to participate if they are receiving cerliponase alfa. | Other | CLN2 Treatment Group |
Primary outcome
Changes in Visual Reception Skills on the Mullen Scales of Early Learning
Time frame: up to 4 years
Changes in the Visual Reception subscale on the Mullen Scales of Early Learning will be assessed every 6 months. Visual reception skills are a measure of visual processing and problem solving. Raw scores will be used as a measure of visual receptions skills with scores ranging from 0 to 50. Higher scores indicate more visual reception skills.
Changes in Fine Motor Skills on the Mullen Scales of Early Learning
Time frame: up to 4 years
Changes in the Fine Motor subscale on the Mullen Scales of Early Learning will be assessed every 6 months. Fine motor skills are a measure of fine motor coordination. Raw scores will be used as a measure of fine motor skills with scores ranging from 0 to 49. Higher scores indicate more fine motor skills.
Changes in Receptive Language Skills on the Mullen Scales of Early Learning
Time frame: up to 4 years
Changes in the Receptive Language subscale on the Mullen Scales of Early Learning will be assessed every 6 months. Receptive language skills are a measure of the understanding of language. Raw scores will be used as a measure of receptive language skills with scores ranging from 0 to 48. Higher scores indicate more receptive language skills.
Changes in Expressive Language Skills on the Mullen Scales of Early Learning
Time frame: up to 4 years
Changes in the Expressive Language subscale on the Mullen Scales of Early Learning will be assessed every 6 months. Expressive language skills are a measure of how an individual communicates. Raw scores will be used as a measure of expressive language skills with scores ranging from 0 to 50. Higher scores indicate more expressive language skills.
Motor and Language Changes on the CLN2 disease rating scale
Time frame: up to 4 years
Change in motor and language subscales of the CLN2 disease rating scale. Ranges for scores are 0 to 6 with higher scores indicating more abilities in motor and language skill development.
2 secondary outcomes
Changes in Receptive Language Skills on the Preschool Language Scales
Time frame: up to 4 years
Changes in Expressive Language Skills on the Preschool Language Scales
Time frame: up to 4 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2025.
- Background: PubMed 23602993Schulz 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.
- Background: PubMed 29688815Schulz 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.
- Background: PubMed 11548735Wisniewski KE, Zhong N, Philippart M. Pheno/genotypic correlations of neuronal ceroid lipofuscinoses. Neurology. 2001 Aug 28;57(4):576-81. doi: 10.1212/wnl.57.4.576.
- Background: PubMed 17679671Worgall S, Kekatpure MV, Heier L, Ballon D, Dyke JP, Shungu D, Mao X, Kosofsky B, Kaplitt MG, Souweidane MM, Sondhi D, Hackett NR, Hollmann C, Crystal RG. Neurological deterioration in late infantile neuronal ceroid lipofuscinosis. Neurology. 2007 Aug 7;69(6):521-35. doi: 10.1212/01.wnl.0000267885.47092.40.
- Background: PubMed 16930952Williams RE, Aberg L, Autti T, Goebel HH, Kohlschutter A, Lonnqvist T. Diagnosis of the neuronal ceroid lipofuscinoses: an update. Biochim Biophys Acta. 2006 Oct;1762(10):865-72. doi: 10.1016/j.bbadis.2006.07.001. Epub 2006 Jul 12.
- Individual participant dataSharing planned: No
Related trials for Batten Disease
RecruitingObservational study
Clinical and Neuropsychological Investigations in Batten Disease
Neuronal Ceroid Lipofuscinosis, Neuronal Ceroid Lipofuscinosis CLN1
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Not yet recruitingPhase 3
Study With Batten-1 (Miglustat Liquid Formulation) to Treat Ceroid Lipofuscinosis Neuronal 3 (CLN3) Disease
CLN3
RecruitingPhase 1/2
A Registrational Study of TTX-381 to Treat Vision Loss in CLN2 Disease
Neuronal Ceroid Lipofuscinosis Type 2
RecruitingObservational study
Investigations of Juvenile Neuronal Ceroid Lipofuscinosis
Juvenile Neuronal Ceroid Lipofuscinosis (CLN3), Batten Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jessica Scherr, PhD principal investigator
Nationwide Children's Hospital
Emily de los Reyes, MD principal investigator
Nationwide Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Batten Disease and CLN2, run by Jessica Scherr at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 24 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Visual Reception Skills on the Mullen Scales of Early Learning (time frame: up to 4 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03862274, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2025.