[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT05898620":3,"trial-entities:NCT05898620":219,"trial-summary:NCT05898620":223},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":20,"study_type":33,"primary_purpose":34,"phases":35,"enrollment_info":37,"interventions":40,"primary_outcomes":50,"secondary_outcomes":55,"sex":56,"minimum_age":57,"maximum_age":58,"healthy_volunteers":59,"eligibility_criteria":60,"std_ages":73,"locations":77,"central_contacts":205,"overall_officials":206,"references":210,"see_also_links":218},"NCT05898620","RTT-200","A Novel, Regulated Gene Therapy (NGN-401) Study for Females With Rett Syndrome","A Baseline-Controlled, Open-Label, Multicenter, Single-Arm, Pivotal Study to Evaluate the Efficacy, Safety, and Tolerability of NGN-401 in Subjects With Rett Syndrome (Embolden)","ACTIVE_NOT_RECRUITING","2029-12","2026-06","2026-06-10","2023-06-13","Neurogene Inc.","INDUSTRY",true,"This study will evaluate the efficacy and safety profiles of the investigational gene therapy, NGN-401, in females with typical Rett syndrome.","The pivotal study, Embolden (TM), is a conversion of the phase 1\u002F2 study and is an open-label, baseline-controlled, multicenter, single-arm study designed to assess the efficacy, safety, and tolerability of administration of NGN401, an adeno-associated viral vector serotype 9 (AAV9) using Neurogene's proprietary transgene regulation technology. NGN-401 contains a full-length human MECP2 gene and is designed to express therapeutic levels of the MeCP2 protein while avoiding overexpression.\n\nThe study treatment will be given as a single administration under general anesthesia via intracerebroventricular (ICV) delivery. Each participant will be followed for efficacy and safety for 3 years after treatment, and is expected to enroll in a long-term follow-up study for 12 years.",[19],"Rett Syndrome",[21,22,23,24,25,26,27,28,29,30,31,32],"Typical Rett Syndrome","MECP2","Rett Disorder","Genetic Diseases, Inborn","Genetic Diseases, X-Linked","Neurodevelopmental Disorders","Neurobehavioral Manifestations","Neurologic Manifestations","Intellectual Disability","Nervous System Diseases","Pathologic Processes","RTT","INTERVENTIONAL","TREATMENT",[36],"PHASE3",{"count":38,"type":39},33,"ESTIMATED",[41],{"type":42,"name":43,"description":44,"armGroupLabels":45},"GENETIC","NGN-401","NGN-401 is a non-replicating, recombinant AAV9 carrying a full length human MECP2 transgene.",[46,47,48,49],"Adolescent\u002FAdult 1e15 vg Dose (fully enrolled)","Pediatric 1e15 vg dose (fully enrolled)","Pediatric 3e15 vg dose (discontinued)","Pivotal Cohort",[51],{"measure":52,"description":53,"timeFrame":54},"Efficacy of NGN-401","Responders will be defined as participants who:\n\n* Attain a CGI-I score of ≤ 3 (\"minimally improved\");\n* and gain any one developmental milestone\u002Fskill from a list of 28, as captured through standardized video recordings and independently verified by blinded central raters.","52 Weeks",[],"FEMALE","3 Years",null,false,{"inclusion":61,"exclusion":68,"raw_text":72},[62,63,64,65,66,67],"Females who are between the ages of ≥4 and ≤10 years for Arms 1 and 2 (Arms closed). Females who are ≥11 years of age or older for Arm 3 (Arm closed). Females who are ≥3 for Arm 4, the pivotal cohort.","Diagnosis of typical Rett syndrome with a documented disease-causing mutation in the methyl-CpG-binding protein 2 (MECP2) gene","Current anti-epileptic drug regimen has been stable for at least 12 weeks","Participant must be in the post-regression stage","Participant and caregiver should reside within a 2-hour drive of the study center for at least 3 months following treatment","Participant must have never taken trofinetide or have taken trofinetide and discontinued due to tolerability, lack of efficacy, or other reasons. Following NGN-401 dosing, trofinetide may be initiated after a specified time period and with the support of the treating clinician.",[69,70,71],"Normal or near normal hand function","Has a current clinically significant condition other than Rett syndrome","Presence of a concomitant medical condition that precludes intracerebroventricular administration, or use of anesthetics or immune suppression needed for study related procedures","Inclusion Criteria:\n\n* Females who are between the ages of ≥4 and ≤10 years for Arms 1 and 2 (Arms closed). Females who are ≥11 years of age or older for Arm 3 (Arm closed). Females who are ≥3 for Arm 4, the pivotal cohort.\n* Diagnosis of typical Rett syndrome with a documented disease-causing mutation in the methyl-CpG-binding protein 2 (MECP2) gene\n* Current anti-epileptic drug regimen has been stable for at least 12 weeks\n* Participant must be in the post-regression stage\n* Participant and caregiver should reside within a 2-hour drive of the study center for at least 3 months following treatment\n* Participant must have never taken trofinetide or have taken trofinetide and discontinued due to tolerability, lack of efficacy, or other reasons. Following NGN-401 dosing, trofinetide may be initiated after a specified time period and with the support of the treating clinician.\n\nExclusion Criteria:\n\n* Normal or near normal hand function\n* Has a current clinically significant condition other than Rett syndrome\n* Presence of a concomitant medical condition that precludes intracerebroventricular administration, or use of anesthetics or immune suppression needed for study related procedures\n\nOther inclusion and exclusion criteria apply.",[74,75,76],"CHILD","ADULT","OLDER_ADULT",[78,87,95,103,111,119,127,135,142,150,158,166,174,182,190,198],{"facility":79,"city":80,"state":81,"zip":82,"country":83,"geoPoint":84},"University of Alabama at Birmingham","Birmingham","Alabama","35233","United States",{"lat":85,"lon":86},33.52066,-86.80249,{"facility":88,"city":89,"state":90,"zip":91,"country":83,"geoPoint":92},"UCSF Benioff Children's Hospital Oakland","Oakland","California","94609",{"lat":93,"lon":94},37.80437,-122.2708,{"facility":96,"city":97,"state":98,"zip":99,"country":83,"geoPoint":100},"Children's Hospital Colorado","Aurora","Colorado","80045",{"lat":101,"lon":102},39.72943,-104.83192,{"facility":104,"city":105,"state":106,"zip":107,"country":83,"geoPoint":108},"Nicklaus Children's Hospital Research Institute","Miami","Florida","33155",{"lat":109,"lon":110},25.77427,-80.19366,{"facility":112,"city":113,"state":114,"zip":115,"country":83,"geoPoint":116},"Rush University Medical Center","Chicago","Illinois","60612",{"lat":117,"lon":118},41.85003,-87.65005,{"facility":120,"city":121,"state":122,"zip":123,"country":83,"geoPoint":124},"Kennedy Krieger Institute","Baltimore","Maryland","21205",{"lat":125,"lon":126},39.29038,-76.61219,{"facility":128,"city":129,"state":130,"zip":131,"country":83,"geoPoint":132},"Boston Children's Hospital","Boston","Massachusetts","02115",{"lat":133,"lon":134},42.35843,-71.05977,{"facility":136,"city":137,"state":137,"zip":138,"country":83,"geoPoint":139},"Montefiore Medical Center","New York","10467",{"lat":140,"lon":141},40.71427,-74.00597,{"facility":143,"city":144,"state":145,"zip":146,"country":83,"geoPoint":147},"UNC at Chapel Hill","Chapel Hill","North Carolina","27514",{"lat":148,"lon":149},35.9132,-79.05584,{"facility":151,"city":152,"state":153,"zip":154,"country":83,"geoPoint":155},"Nationwide Children's Hospital","Columbus","Ohio","43205",{"lat":156,"lon":157},39.96118,-82.99879,{"facility":159,"city":160,"state":161,"zip":162,"country":83,"geoPoint":163},"Children's Hospital of Philadelphia","Philadelphia","Pennsylvania","19104",{"lat":164,"lon":165},39.95238,-75.16362,{"facility":167,"city":168,"state":169,"zip":170,"country":83,"geoPoint":171},"Vanderbilt University Medical Center","Nashville","Tennessee","37232",{"lat":172,"lon":173},36.16589,-86.78444,{"facility":175,"city":176,"state":177,"zip":178,"country":83,"geoPoint":179},"Texas Children's Hospital","Houston","Texas","77030",{"lat":180,"lon":181},29.76328,-95.36327,{"facility":183,"city":184,"state":185,"country":186,"geoPoint":187},"The Children's Hospital at Westmead","Sydney","New South Wales","Australia",{"lat":188,"lon":189},-33.86785,151.20732,{"facility":191,"city":192,"zip":193,"country":194,"geoPoint":195},"Royal Hospital for Children and Young People","Edinburgh","EH16 4TJ","United Kingdom",{"lat":196,"lon":197},55.95206,-3.19648,{"facility":199,"city":200,"zip":201,"country":194,"geoPoint":202},"Manchester University NHS Foundation Trust","Manchester","M13 9WL",{"lat":203,"lon":204},53.48095,-2.23743,[],[207],{"name":208,"affiliation":13,"role":209},"Julie Jordan, MD","STUDY_DIRECTOR",[211,215],{"pmid":212,"type":213,"citation":214},"40173263","DERIVED","Ross PD, Gadalla KKE, Thomson SR, Selfridge J, Bahey NG, Benito J, Burstein SR, McMinn R, Bolon B, Hector RD, Cobb SR. Self-regulating gene therapy ameliorates phenotypes and overcomes gene dosage sensitivity in a mouse model of Rett syndrome. Sci Transl Med. 2025 Apr 2;17(792):eadq3614. doi: 10.1126\u002Fscitranslmed.adq3614. Epub 2025 Apr 2.",{"pmid":216,"type":213,"citation":217},"38723617","Jagadeeswaran I, Oh J, Sinnett SE. Preclinical Milestones in MECP2 Gene Transfer for Treating Rett Syndrome. Dev Neurosci. 2025;47(2):147-156. doi: 10.1159\u002F000539267. Epub 2024 May 9.",[],{"nct_id":4,"conditions":220,"biomarkers":221},[19],[222],"MECP2 Gene",{"nct_id":4,"found":15,"summary":224,"prompt_version":234},{"design":225,"status":226,"heading":227,"summary":228,"follow_up":229,"word_count":230,"commitments":231,"compensation":232,"drugs_mentioned":233},"This is an open-label (meaning everyone knows what treatment is given), single-arm study, which means all participants receive the same treatment. It plans to enroll 33 participants.","completed","NGN-401 Gene Therapy for Rett Syndrome","This study is testing a new gene therapy called NGN-401 for females with Rett syndrome. NGN-401 is designed to deliver a working copy of the MECP2 gene, which is faulty in Rett syndrome, to help the body produce the necessary protein. The study aims to see how well NGN-401 works and if it is safe. To join, you must be a female with a confirmed diagnosis of typical Rett syndrome due to a MECP2 gene mutation, and be at least 3 years old. The study is currently recruiting participants for Arm 4. Success will be measured by how well NGN-401 works after 52 weeks.","Participants will be followed for 3 years after treatment to check for effectiveness and safety, and are expected to join a long-term follow-up study for 12 years.",104,"The study treatment, NGN-401, is given once as a single injection into the fluid surrounding the brain and spinal cord (intracerebroventricular or ICV delivery) while under general anesthesia.","Not stated in the trial record.",[43],"v2"]