Examining Developmental Outcomes of Children Diagnosed With CLN2 Disease
キーワード
概要
説明
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.
日付
最終確認済み: | 02/28/2019 |
最初に提出された: | 01/03/2019 |
提出された推定登録数: | 02/28/2019 |
最初の投稿: | 03/04/2019 |
最終更新が送信されました: | 02/28/2019 |
最終更新日: | 03/04/2019 |
実際の研究開始日: | 11/30/2018 |
一次完了予定日: | 12/31/2022 |
研究完了予定日: | 11/30/2023 |
状態または病気
介入/治療
Other: CLN2 Treatment Group
段階
アームグループ
腕 | 介入/治療 |
---|---|
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 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. |
適格基準
研究に適格な性別 | All |
サンプリング方法 | Non-Probability Sample |
健康なボランティアを受け入れる | はい |
基準 | 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 |
結果
主な結果の測定
1. Changes in Visual Reception Skills on the Mullen Scales of Early Learning [up to 4 years]
2. Changes in Fine Motor Skills on the Mullen Scales of Early Learning [up to 4 years]
3. Changes in Receptive Language Skills on the Mullen Scales of Early Learning [up to 4 years]
4. Changes in Expressive Language Skills on the Mullen Scales of Early Learning [up to 4 years]
5. Motor and Language Changes on the CLN2 disease rating scale [up to 4 years]
二次的な結果の測定
1. Changes in Receptive Language Skills on the Preschool Language Scales [up to 4 years]
2. Changes in Expressive Language Skills on the Preschool Language Scales [up to 4 years]