[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT06692712":3,"trial-entities:NCT06692712":105,"trial-summary:NCT06692712":113},{"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":25,"primary_purpose":26,"phases":27,"enrollment_info":29,"interventions":32,"primary_outcomes":39,"secondary_outcomes":44,"sex":63,"minimum_age":64,"maximum_age":65,"healthy_volunteers":66,"eligibility_criteria":67,"std_ages":71,"locations":73,"central_contacts":92,"overall_officials":98,"references":99,"see_also_links":104},"NCT06692712","MELPIDA -Pivotal Trial","Phase 3 Efficacy Study With Concurrent Control of IT MELPIDA in SPG50.Concurrent Controls.","Intrathecal Administration of MELPIDA (AAV9\u002FAP4M1) For Hereditary Spastic Paraplegia Type 50 (SPG50): A Phase 3, Open-Label Trial With Matched Prospective Concurrent Control Arm","RECRUITING","2032-06-01","2026-04","2026-04-20","2026-04-01","Elpida Therapeutics SPC","INDUSTRY",true,"Phase 3, open-label study to assess the efficacy and safety of a single lumbar intrathecal administration of MELPIDA in individuals with Hereditary Spastic Paraplegia Type 50 (SPG50).","MELPIDA is an AAV9-based gene therapy vector that expresses the fully functional form of AP4M1 under the control of a synthetic promoter. MELPIDA will be delivered intrathecally and is designed to achieve stable, potentially life-long expression of AP4M1 in non-dividing cells. This clinical study is a pivotal open-label phase 3 study designed to assess safety and efficacy of MELPIDA in individuals with SPG50.",[19],"Hereditary Spastic Paraplegia Type 50",[21,22,23,24],"SPG50","Spastic Paraplegia","Gene Therapy","Phase 3","INTERVENTIONAL","TREATMENT",[28],"PHASE3",{"count":30,"type":31},24,"ESTIMATED",[33],{"type":34,"name":35,"description":36,"armGroupLabels":37},"GENETIC","MELPIDA","Gene Therapy agent",[38],"MELPIDA Treatment",[40],{"measure":41,"description":42,"timeFrame":43},"Gross Motor Function Measure (GMFM-88) Defined Major Milestones","Change in total percent score of the 8 Major Motor Milestone Scores from baseline in treated group compared to change in total percent score of the 8 Major Motor Milestone Scores from baseline in untreated controls\n\n1. #24: Sit on mat: Maintain, arms free, 3 seconds\n2. #38: Prone: Creeps forward 1.8m (6')\n3. #52: On the floor: Pulls to stand at large bench\n4. #67: Standing: 2 hands held: walks forward 10 steps\n5. #69: Standing: Walks forward 10 steps\n6. #84: Standing: Holding 1 rail: walks up 4 steps, holding 1 rail, alternating feet\n7. #85: Standing: Holding 1 rail: walks down 4 steps, holding 1 rail, alternating feet\n8. #88: Standing on 15cm (6\") step: Jumps off, both feet simultaneously","156 weeks",[45,48,51,54,57,60],{"measure":46,"description":47,"timeFrame":43},"Composite Endpoint Defined by the Win Ratio","Composite Endpoint Defined by the Win Ratio using matching criteria after 156 Weeks of Follow-up of the 8 selected items and the raw scores of the Cognitive domain of the Bayley Scale of Infant and Toddler Development 4th Edition (Bayley-4).",{"measure":49,"description":50,"timeFrame":43},"Developmental Milestones- Bayley-4 Cognitive Domain","Developmental Milestones- Bayley-4 Cognitive Domain-Change in Total Raw Score from Baseline",{"measure":52,"description":53,"timeFrame":43},"Gross and Fine Motor Function (GMFM-88 full scale)","Gross and Fine Motor Function (GMFM-88 full scale) - Change in Total Score from Baseline.",{"measure":55,"description":56,"timeFrame":43},"Disease Severity (Spastic Paraplegia Rating Scale )","Disease Severity (Spastic Paraplegia Rating Scale ). Change in Total Score from Baseline.",{"measure":58,"description":59,"timeFrame":43},"Disease Severity (Clinical Global Impression)","Disease Severity (Clinical Global Impression) Change in Physician-assessed Clinical Global Impression) from Baseline.",{"measure":61,"description":62,"timeFrame":43},"Muscle Spasticity (Modified Ashworth Scale)","Change from Baseline in Muscle Spasticity (Modified Ashworth Scale) Score","ALL","4 Months","72 Months",false,{"inclusion":68,"exclusion":69,"raw_text":70},[],[],"Inclusion:\n\nFor the treatment group\n\n* Male and females between the ages of 4 months to 72 months at the time of screening.\n* Molecularly-confirmed diagnosis of SPG50 (confirmed by a CLIA certified, CE-marked, or equivalent lab): Genomic DNA mutation analysis demonstrating bi-allelic pathogenic or likely pathogenic variants in the AP4M1 gene.\n* Subjects must have features of neurologic dysfunction by clinical history and physical examination.\n* Stable doses of concomitant medications such as anti-spasticity medications, anti-seizure medications, behavioral management medications, sleep medications, and special diets, supplements, or nutritional support for at least 3 months prior to Screening. If recent changes (\\\u003C 3 months) in medications, the subject may be allowed per Investigator judgement.\n* Parent\u002Flegal guardian willing to provide written informed consent for their child prior to participation in the study,\n* Subjects and caregivers must demonstrate the ability to travel to the study center. For the 30 days post treatment subjects must reside within 100 miles (approximately 160 km) of the clinical site.\n\nFor the control group\n\n* Male and females between the ages of 4 to 72 months at the time of screening.\n* A molecularly confirmed diagnosis of SPG47, SPG50 or SPG52 (confirmed by a CLIA certified, CE-marked, or equivalent lab). Genomic DNA mutation analysis demonstrating bi-allelic pathogenic variants in the AP4B1, AP4M1, or AP4S1 gene,\n* Subjects must have features of neurologic dysfunction by clinical history and physical examination.\n* Parent\u002Flegal guardian willing to provide written informed consent for their child prior to participation in the study.\n* Subject able to comply with all protocol requirements and procedures.\n* Subjects and caregivers must demonstrate the ability to travel to the study center.\n\nExclusion\n\nFor the treatment group\n\n* Loss of one of the 8 major motor milestones within the last 12 months. Milestones defined as:\n\n  * #24: Sit on mat: Maintain, arms free, 3 seconds\n  * #44: 4 Point: Crawls or hitches forward 1.8m (6')\n  * #53: Standing: Maintains, arms free, 3 seconds\n  * #67: Standing: 2 hands held: walks forward 10 steps\n  * #69: Standing: Walks forward 10 steps\n  * #84: Standing: Holding 1 rail: walks up 4 steps, holding 1 rail, alternating feet\n  * #85: Standing: Holding 1 rail: walks down 4 steps, holding 1 rail, alternating feet\n  * #88: Standing on 15cm (6\") step: Jumps off, both feet simultaneously\n* Inability to participate in the clinical evaluation as determined by the principal investigators.\n* Clinically significant abnormal laboratory values (hemoglobin \\\u003C 6 or \\> 20 g\u002FdL; white blood cell \\> 20,000 per cmm, platelets count \\\u003C 100,000 per cmm; INR \\> ULN; GGT, ALT, and AST or total bilirubin \\> 1.5 × ULN, creatinine ≥ 1.5 mg\u002FdL) prior to gene replacement therapy.\n* Presence of a concomitant medical condition (eg, scoliosis or bleeding disorder) that precludes a lumbar puncture or use of anesthetics for sedated procedures.\n* Documented cardiomyopathy or significant congenital heart abnormalities.\n* History of severe\u002Flife-threatening allergic reaction to sirolimus, tacrolimus, corticosteroids, or gadolinium.\n* Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer, or interactions with the immunosuppressive agents.\n* Any item which would exclude the subject from being able to undergo MRI according to local institutional policy, or any other procedure.\n* The presence of significant AP-4 related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study.\n* Recent or planned elective surgical procedures (within 6 months) that would confound the scientific rigor or interpretation of results of the study.\n* Failure to obtain appropriate informed consent.\n* Reason to believe that the subject or parents of the subject will not comply with the study procedures outlined in the study protocol.\n* Have received an investigational drug within 30 days prior to screening or plan to receive an investigational drug (other than gene therapy) during the study.\n* Enrollment and participation in another interventional clinical trial 90 days before first visit (screening).\n\nFor the control group\n\n* Loss of one of the 8 major motor milestones within the last 12 months. Milestones defined as:\n\n  * #24: Sit on mat: Maintain, arms free, 3 seconds\n  * #44: 4 Point: Crawls or hitches forward 1.8m (6')\n  * #53: Standing: Maintains, arms free, 3 seconds\n  * #67: Standing: 2 hands held: walks forward 10 steps\n  * #69: Standing: Walks forward 10 steps\n  * #84: Standing: Holding 1 rail: walks up 4 steps, holding 1 rail, alternating feet\n  * #85: Standing: Holding 1 rail: walks down 4 steps, holding 1 rail, alternating feet\n  * #88: Standing on 15cm (6\") step: Jumps off, both feet simultaneously\n* Inability to participate in the clinical evaluation as determined by the principal investigators.\n* Any other situation that would exclude the subject from undergoing any other procedure required in this study.\n* The presence of significant AP-4 related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study.\n* Recent or planned elective surgical procedures that would confound the scientific rigor or interpretation of results of the study.\n* Failure to obtain appropriate informed consent.\n* Reason to believe that the subject or parents of the subject will not comply with the study procedures outlined in the study protocol.\n* Have received an investigational drug within 30 days prior to screening or plans to receive an investigational drug (other than gene therapy) during the study.\n* Enrollment and participation in another interventional clinical trial 90 days before first visit (screening).",[72],"CHILD",[74,83],{"facility":75,"status":8,"city":76,"state":77,"zip":78,"country":79,"geoPoint":80},"University of Texas Southwestern Medical Center","Dallas","Texas","75025","United States",{"lat":81,"lon":82},32.78306,-96.80667,{"facility":84,"status":85,"city":86,"zip":87,"country":88,"geoPoint":89},"Sant Joan de Deu","ACTIVE_NOT_RECRUITING","Barcelona","08950","Spain",{"lat":90,"lon":91},41.38879,2.15899,[93],{"name":94,"role":95,"phone":96,"email":97},"Rachel Thomas","CONTACT","+1-833-335-7432","studyinfo@elpidatx.com",[],[100],{"pmid":101,"type":102,"citation":103},"41491634","DERIVED","Agianda HAP, Kim HM, Battaglia N, Rong J, Tam A, Gonzalez Saez-Diez E, Boerkoel CF, Saffari A, Quiroz V, Schierbaum L, Zaman Z, Bernardi K, Ebrahimi-Fakhari D. Diagnostic Utility of the ATG9A Ratio in AP-4-Associated Hereditary Spastic Paraplegia. Ann Clin Transl Neurol. 2026 Apr;13(4):834-839. doi: 10.1002\u002Facn3.70308. Epub 2026 Jan 5.",[],{"nct_id":4,"conditions":106,"biomarkers":109},[107,108],"Autosomal recessive spastic paraplegia type 15","Hereditary Spastic Paraplegia",[110,111,112],"ADAPTOR-RELATED PROTEIN COMPLEX 4, SIGMA-1 SUBUNIT","AP4B1 Gene","AP4M1 Gene",{"nct_id":4,"found":15,"summary":114,"prompt_version":124},{"design":115,"status":116,"heading":117,"summary":118,"follow_up":119,"word_count":120,"commitments":121,"compensation":122,"drugs_mentioned":123},"This is an open-label Phase 3 study, meaning both you and the study team will know you are receiving MELPIDA. It plans to enroll 24 participants.","completed","Phase 3 Study of MELPIDA for Hereditary Spastic Paraplegia Type 50 (SPG50)","This study is testing a gene therapy called MELPIDA for children with Hereditary Spastic Paraplegia Type 50 (SPG50). SPG50 is a genetic condition that affects movement. MELPIDA is designed to deliver a working copy of the AP4M1 gene, which is faulty in people with SPG50. The study will give MELPIDA as a single injection into the fluid around the spinal cord. Researchers will look at how well MELPIDA helps with motor skills, like sitting, standing, and walking, over 156 weeks (about 3 years). To join, you must be between 4 months and 72 months old and have a confirmed diagnosis of SPG50 through genetic testing. This study is currently unclear about its recruitment status.","Participants will be followed for 156 weeks (about 3 years) to assess motor function.",114,"Not specified in the trial record.","Not stated in the trial record.",[35],"v2"]