{"id":162,"date":"2022-10-14T16:27:40","date_gmt":"2022-10-14T16:27:40","guid":{"rendered":"https:\/\/brineurahcp-dev-001.azurewebsites.net\/en-us\/brineura\/?page_id=162"},"modified":"2026-03-11T12:52:17","modified_gmt":"2026-03-11T12:52:17","slug":"study-design","status":"publish","type":"page","link":"https:\/\/hcp.biomarin.com\/en-us\/brineura\/study-design\/","title":{"rendered":"Study Design"},"content":{"rendered":"<div id=\"acf-block-6480d91c30e99\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-6480d91c30ec2\" class=\"block-wysiwyg\">\n            <h1>Brineura\u00ae (cerliponase alfa) clinical studies: design and demographics<\/h1>\n<p>&nbsp;<\/p>\n<h3 class=\"p1\">Trials 1 and 2<\/h3>\n<h2>Brineura was assessed over 96 weeks in a nonrandomized, single-arm study with extension vs a natural history cohort<sup>1,2<\/sup><\/h2>\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"new\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<figure id=\"acf-block-6480d91c31203\">\n    <div class=\"image image-align-left\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/brineura\/wp-content\/uploads\/sites\/2\/2025\/10\/table.png?v=0.32\" alt=\"\" \/>            <\/div>\n    <\/figure>\n\n<div id=\"acf-block-6480d91c31242\" class=\"block-wysiwyg\">\n            <ul>\n<li>24 patients, aged 3 to 8 years, were treated with Brineura<sup>\u00ae<\/sup> (cerliponase alfa) 300 mg administered every other week for 48 weeks and continued during the extension period<sup>1<\/sup>\n<ul>\n<li>1 patient withdrew after week 1 due to inability to continue with study procedures<sup>1<\/sup><\/li>\n<li>Brineura-treated patients were compared to an independent natural history cohort that included 42 patients who satisfied inclusion criteria for the clinical study<sup>1<\/sup><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>Learn more about the natural history of CLN2 disease at <a href=\"http:\/\/www.cln2connection.com\/overview\/natural-history\/\" target=\"_blank\" rel=\"noopener\"><strong>CLN2Connection.com\u00a0&gt;<\/strong><\/a><\/p>\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-6480d91c3125c\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-6480d91c31279\" class=\"block-wysiwyg\">\n            <h2>The clinical study was designed to assess disease progression using the CLN2 Clinical Rating Scale<sup>1<\/sup><\/h2>\n<ul>\n<li>CLN2 Clinical Rating Scale has multiple domains including Motor and Language domains, each with a 0-to-3 score (the highest possible combined score is 6)<sup>1<\/sup>\n<ul>\n<li>Each score represents a range of function<sup>1<\/sup><\/li>\n<li>Only the Motor domain was used to assess disease progression<sup>1<\/sup><\/li>\n<li>Due to the inability to establish comparability for the CLN2 Language domain ratings between the clinical study with extension and the natural history cohort, efficacy of Brineura for the Language domain cannot be established<sup>1<\/sup><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n    <\/div>\n\n<figure id=\"acf-block-6480d91c312a2\">\n    <div class=\"image image-rounded image-align-left\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/brineura\/wp-content\/uploads\/sites\/2\/2022\/10\/chart4.svg\" alt=\"motor function\" \/>            <\/div>\n            <figcaption>Adapted from: Steinfeld R, et al. <em>Am J Med Genet<\/em>. 2002:112:347-354.<br \/>\n*In some children, motor development was never completely normal.\n<\/figcaption>\n    <\/figure>\n\n<div id=\"acf-block-6480d91c312b7\" class=\"block-wysiwyg\">\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-6480d91c312bf\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-6480d91c312cf\" class=\"block-wysiwyg\">\n            <h2>Baseline demographics of enrolled population<sup>1,3<\/sup><\/h2>\n    <\/div>\n\n<figure id=\"acf-block-6480d91c312ed\">\n    <div class=\"image image-rounded image-align-left\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/brineura\/wp-content\/uploads\/sites\/2\/2026\/01\/Characteristics_no-background_3_edits@2x_rt4.png?v=0.32\" alt=\"\" \/>            <\/div>\n    <\/figure>\n\n<div id=\"acf-block-6480d91c326a7\" class=\"block-wysiwyg\">\n            <p><small>*Enrolled patient had a single dose and withdrew consent due to inability to comply with study procedures.<sup>1<\/sup><\/small><br \/>\n<small><sup>\u2020<\/sup>Baseline score was last measurement before 300 mg dose.<sup>3<\/sup><\/small><br \/>\n<small><sup>\u2021<\/sup>Similar distribution to natural history control group.<sup>3<\/sup><\/small><br \/>\n<small><sup>\u00a7<\/sup>Common alleles are c.622C&gt;T and c.509-1G&gt;C.<sup>5<\/sup><br \/>\n<\/small><br \/>\n<small><\/small><\/p>\n<p class=\"p1\"><small>ITT, intent-to-treat;<\/small> <small>SD, standard deviation.<\/small><\/p>\n<ul>\n<li>Patients were evaluated for efficacy if they had a combined Motor plus Language CLN2 score of less than 6 at screening<sup>1<\/sup>\n<ul>\n<li>Two patients with a combined Motor plus Language score of 6 (grossly normal for both domains) were excluded from the efficacy analysis; they maintained that score throughout the study period<sup>1<\/sup><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-68f1ec2b872d1\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-68f1ec2b874a2\" class=\"block-wysiwyg\">\n            <h3>Trial 3<\/h3>\n<h2 class=\"p1\">Phase 2 study of Brineura for CLN2 disease in a cohort including patients &lt;3 years of age<sup>1,4<\/sup><\/h2>\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-68f1ee0bc9959\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-68f1ec2b874ee\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<figure id=\"acf-block-68f1ec2b876d8\">\n    <div class=\"image image-rounded image-align-left\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/brineura\/wp-content\/uploads\/sites\/2\/2026\/01\/study_design1_rt4.jpg?v=0.32\" alt=\"\" \/>            <\/div>\n    <\/figure>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-699811d85331f\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-699811d853475\" class=\"block-wysiwyg\">\n            <ul>\n<li>Trial 3 was a Phase 2, open label clinical study that enrolled 14 symptomatic and presymptomatic CLN2 patients less than 18 years of age\n<ul>\n<li>The trial enrolled 14 patients ranging in age from 1 to 6 years at baseline, including 8 patients less than 3 years of age<\/li>\n<\/ul>\n<\/li>\n<li>Thirteen of the 14 Brineura-treated patients were matched with up to 3 natural history comparators on the basis of age within 3 months, equal CLN2 Motor score, and genotype (0, 1, or 2 key mutations)<\/li>\n<\/ul>\n<p><small>*Matched on the basis of baseline age (within 3 months); genotype (equal number of common alleles c.622C&gt;T, c.509.1G); and baseline motor-language score (exact match).<sup>4<\/sup><\/small><br \/>\n<small><sup>\u2020<\/sup>Dose adjusted for patients aged &lt;2 years.<sup>4<\/sup><\/small><\/p>\n<p><small>QoW, every other week.<\/small><\/p>\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-68f1ef21ee421\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-68f1ef21ee604\" class=\"block wrapped-content block-zero-top block-tight-bottom\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-68f1ef21ee5bc\" class=\"block-wysiwyg\">\n            <h2><b>Patient disposition, demographics, and baseline characteristics<sup>4<\/sup><\/b><\/h2>\n    <\/div>\n\n<figure id=\"acf-block-68f1ef21ee7db\">\n    <div class=\"image image-rounded image-align-left\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/brineura\/wp-content\/uploads\/sites\/2\/2025\/11\/Disposition.png?v=0.32\" alt=\"\" \/>            <\/div>\n            <figcaption><p>*One patient discontinued study to receive Brineura commercially.<\/p>\n<p>Max, maximum; Min, minimum; SD, standard deviation.<\/p>\n<\/figcaption>\n    <\/figure>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-6480d91c32725\" class=\"block cards cards-3-col\">\n\t<div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t\t<div class=\"cards-title\">\n\t\t\t    \t\t\t\t\t\t\t<\/div>\n\t\t\t<div class=\"cards-wrapper\">\n\t\t\t    \n<div id=\"acf-block-6480d91c3275c\" class=\"card card-fixed-button\" data-muted-autoplay=\"false\">\n        <div class=\"card-content\">\n                            <h4>Connect with BioMarin to register for Brineura updates\n<\/h4>\n        \n                                                                                                                                                                                                                                                                                    \n                                                                                        <\/div>\n                                <div class=\"card-actions\">\n                            \n                            <p><a class=\"button button-arrow\" href=\"https:\/\/hcp.biomarin.com\/en-us\/brineura\/register\/\" target=\"_self\">Register Now<\/a><\/p>\n                                                                                    <\/div>\n<\/div>\n\n<div id=\"acf-block-6480d91c327a4\" class=\"card card-fixed-button\" data-muted-autoplay=\"false\">\n        <div class=\"card-content\">\n                            <h4>Brineura safety was evaluated in 38 patients with CLN2 disease across multiple clinical studies\n<\/h4>\n        \n                                                                                                                                                                                                                                                                                    \n                                                                                        <\/div>\n                                <div class=\"card-actions\">\n                            \n                            <p><a class=\"button button-arrow\" href=\"https:\/\/hcp.biomarin.com\/en-us\/brineura\/safety\/\" target=\"_self\">See Safety Profile<\/a><\/p>\n                                                                                    <\/div>\n<\/div>\n\n<div id=\"acf-block-6480d91c327bf\" class=\"card card-fixed-button\" data-muted-autoplay=\"false\">\n        <div class=\"card-content\">\n                            <h4>Download helpful materials for you and your patients\n<\/h4>\n        \n                                                                                                                                                                                                                                                                                    \n                                                                                        <\/div>\n                                <div class=\"card-actions\">\n                            \n                            <p><a class=\"button button-arrow\" href=\"https:\/\/hcp.biomarin.com\/en-us\/brineura\/resources\/\" target=\"_self\">View Resources<\/a><\/p>\n                                                                                    <\/div>\n<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n<div id=\"acf-block-6480d91c327f2\" class=\"block call-to-action call-to-action-no-overlay\">\n    <div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t\t<div class=\"box\" style=\"\">\n\t\t\t\t<div class=\"overlay\"><\/div>\n\t\t\t\t<div class=\"cta-content\">\n\t\t\t\t    \t\t\t\t\t<div class=\"cta-content-main\">\n                        <div class=\"content-block\">\n\t\t\t\t\t        \t\t\t\t\t        \t\t\t\t\t\t        <h2 class=\"h3\">Brineura Efficacy Results\n<\/h2>\n\t\t\t\t\t\t    \t\t\t\t\t\t    \t\t\t\t\t\t        <p>The efficacy of Brineura was assessed in multiple clinical trials including in children below 3 years of age.<\/p>\n\t\t\t\t\t\t    \t\t\t\t\t    <\/div>\n\t\t\t\t\t                                <div class=\"content-block\">\n                                <p><a class=\"button button-ghost button-arrow\" href=\"https:\/\/hcp.biomarin.com\/en-us\/brineura\/results\/\" target=\"_self\">Next Section<\/a><\/p>\n                            <\/div>\n\t\t\t\t\t                        <\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n<div id=\"acf-block-6480d91c32b65\" class=\"block references\">\n    <div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t    \t\t\t    <h4>References:\n<\/h4>\n\t\t\t\t\t\t                <ol>\n                                                                                                                        <li><span>Brineura [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2024.\n<\/span><\/li>\n                                                                                                                                                <li><span>Data on file, BioMarin Pharmaceutical Inc.\n<\/span><\/li>\n                                                                                                                                                <li><span>Schulz A, Ajayi T, Specchio N, et al. Study of Intraventricular Cerliponase Alfa for CLN2 Disease. <em>N Engl J Med<\/em>. 2018;378(20):1898-1907.\n<\/span><\/li>\n                                                                                                                                                <li><span>Schulz A, de los Reyes E, Specchio N, et al. Cerliponase alfa for the treatment of CLN2 disease in a patient cohort including children under 3 years of age. Poster presented at: 20th Annual WORLD Symposium: February 4-9, 2024; San Diego, CA.\n<\/span><\/li>\n                                                                                                                                                <li><span>Fietz M, AlSayed M, Burke D, et al. Diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): expert recommendations for early detection and laboratory diagnosis. <em>Mol Genet Metab<\/em>. 2016;119:160-167.\n<\/span><\/li>\n                                                            <\/ol>\n\t\t\t\t\t<\/div>\n\t<\/div>\n<\/div>","protected":false},"excerpt":{"rendered":"","protected":false},"author":4,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"class_list":["post-162","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Study Design - BioMarin Brineura HCP EN-US<\/title>\n<meta name=\"description\" content=\"Brineura\u00ae (cerliponase alfa) clinical studies: design and demographics\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/hcp.biomarin.com\/en-us\/brineura\/study-design\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Study design\" \/>\n<meta property=\"og:description\" content=\"Brineura\u00ae (cerliponase alfa) clinical studies: design and demographics\" \/>\n<meta property=\"og:url\" content=\"https:\/\/hcp.biomarin.com\/en-us\/brineura\/study-design\/\" \/>\n<meta property=\"og:site_name\" content=\"BioMarin Brineura HCP EN-US\" \/>\n<meta property=\"article:modified_time\" content=\"2026-03-11T12:52:17+00:00\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/hcp.biomarin.com\\\/en-us\\\/brineura\\\/study-design\\\/\",\"url\":\"https:\\\/\\\/hcp.biomarin.com\\\/en-us\\\/brineura\\\/study-design\\\/\",\"name\":\"Study Design - 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