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Trial record 2 of 9 for:    TPP1

Examining Developmental Outcomes of Children Diagnosed With CLN2 Disease

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ClinicalTrials.gov Identifier: NCT03862274
Recruitment Status : Recruiting
First Posted : March 5, 2019
Last Update Posted : March 5, 2019
Sponsor:
Collaborator:
BioMarin Pharmaceutical
Information provided by (Responsible Party):
Jessica Scherr, Nationwide Children's Hospital

Brief 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. 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.

Condition or disease Intervention/treatment
Batten Disease CLN2 Neuronal Ceroid-Lipofuscinoses Other: CLN2 Treatment

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.


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Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Case-Control
Time Perspective: Other
Official Title: Examining Developmental Outcomes of Children Diagnosed With CLN2 Disease
Actual Study Start Date : December 1, 2018
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : December 2023


Group/Cohort Intervention/treatment
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.
Other: CLN2 Treatment
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.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.


Secondary Outcome Measures :
  1. Changes in Receptive Language Skills on the Preschool Language Scales [ Time Frame: up to 4 years ]
    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.

  2. Changes in Expressive Language Skills on the Preschool Language Scales [ Time Frame: up to 4 years ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
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.
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Patients without a diagnosis of CLN2 and deficiency of TPP1
  • Patients that are currently enrolled as part of a larger multi-center clinical trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03862274


Contacts
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Contact: Jessica Scherr, PhD 614-355-7500 jessica.scherr@nationwidechildrens.org
Contact: Emily de los Reyes, MD 614-722-4625 Emily.delosReyes@nationwidechildrens.org

Locations
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United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Jessica Scherr, PhD    614-355-7500 ext 38230    jessica.scherr@nationwidechildrens.org   
Contact: Emily de los Reyes, MD       Emily.delosReyes@nationwidechildrens.org   
Principal Investigator: Jessica Scherr, PhD         
Principal Investigator: Emily de los Reyes, MD         
Sponsors and Collaborators
Jessica Scherr
BioMarin Pharmaceutical
Investigators
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Principal Investigator: Jessica Scherr, PhD Nationwide Children's Hospital
Principal Investigator: Emily de los Reyes, MD Nationwide Children's Hospital

Publications:
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Responsible Party: Jessica Scherr, Principal Investigator, Nationwide Children's Hospital
ClinicalTrials.gov Identifier: NCT03862274     History of Changes
Other Study ID Numbers: IRB18-00464
First Posted: March 5, 2019    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neuronal Ceroid-Lipofuscinoses
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Lipid Metabolism Disorders
Metabolic Diseases