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"TRIAL-GD-001": {
"disease": "Gaucher Disease Type 1",
"disease_group": "Rare metabolic",
"phase": "Phase 3",
"intervention": "Imiglucerase ERT vs Eliglustat SRT",
"n_target": 120,
"duration_months": 24,
"primary_endpoint": "Enzyme activity normalization at 12 months",
"secondary_endpoints": [
"Spleen volume reduction",
"Hemoglobin normalization",
"Platelet count normalization"
],
"inclusion": {
"min_age": 2,
"max_age": 70,
"required_acmg": [
"Pathogenic",
"Likely pathogenic"
],
"required_gene": "GBA1",
"max_functional_status": 3,
"min_eligibility_score": 0.55
},
"exclusion": {
"ae_grade_cutoff": 4,
"required_prior_treatment": false
},
"arm_allocation": {
"Imiglucerase": 0.5,
"Eliglustat": 0.5
},
"biomarker_response_threshold": 0.4
},
"TRIAL-SMA-001": {
"disease": "Spinal Muscular Atrophy",
"disease_group": "Rare neurological",
"phase": "Phase 3",
"intervention": "Nusinersen ASO vs Onasemnogene gene therapy",
"n_target": 80,
"duration_months": 24,
"primary_endpoint": "Motor milestone achievement at 14 months",
"secondary_endpoints": [
"Ventilator-free survival",
"HINE-2 motor score",
"Caregiver burden reduction"
],
"inclusion": {
"min_age": 0,
"max_age": 18,
"required_acmg": [
"Pathogenic"
],
"required_gene": "SMN1",
"max_functional_status": 3,
"min_eligibility_score": 0.6
},
"exclusion": {
"ae_grade_cutoff": 3,
"required_prior_treatment": false
},
"arm_allocation": {
"Nusinersen": 0.5,
"Onasemnogene": 0.5
},
"biomarker_response_threshold": 0.35
},
"TRIAL-CF-001": {
"disease": "Cystic Fibrosis",
"disease_group": "Rare pulmonary",
"phase": "Phase 3",
"intervention": "Elexacaftor/Tezacaftor/Ivacaftor triple therapy",
"n_target": 200,
"duration_months": 24,
"primary_endpoint": "ppFEV1 change from baseline at 24 weeks",
"secondary_endpoints": [
"Sweat chloride reduction",
"CFQ-R score improvement",
"Pulmonary exacerbation rate"
],
"inclusion": {
"min_age": 6,
"max_age": 65,
"required_acmg": [
"Pathogenic",
"Likely pathogenic"
],
"required_gene": "CFTR",
"max_functional_status": 2,
"min_eligibility_score": 0.6
},
"exclusion": {
"ae_grade_cutoff": 3,
"required_prior_treatment": true
},
"arm_allocation": {
"ETI-triple": 0.67,
"Placebo": 0.33
},
"biomarker_response_threshold": 0.45
},
"TRIAL-DMD-001": {
"disease": "Duchenne Muscular Dystrophy",
"disease_group": "Rare muscular",
"phase": "Phase 2/3",
"intervention": "Exon 51 skipping ASO therapy",
"n_target": 60,
"duration_months": 18,
"primary_endpoint": "6MWT distance change at 48 weeks",
"secondary_endpoints": [
"NSAA score",
"EK score",
"Respiratory function (FVC)",
"Dystrophin expression"
],
"inclusion": {
"min_age": 5,
"max_age": 18,
"required_acmg": [
"Pathogenic"
],
"required_gene": "DMD",
"max_functional_status": 3,
"min_eligibility_score": 0.55
},
"exclusion": {
"ae_grade_cutoff": 3,
"required_prior_treatment": false
},
"arm_allocation": {
"ASO-active": 0.67,
"Placebo": 0.33
},
"biomarker_response_threshold": 0.3
},
"TRIAL-HD-001": {
"disease": "Huntington Disease",
"disease_group": "Rare neurological",
"phase": "Phase 2/3",
"intervention": "HTT-lowering ASO intrathecal therapy",
"n_target": 100,
"duration_months": 24,
"primary_endpoint": "mHTT concentration reduction in CSF at 13 months",
"secondary_endpoints": [
"UHDRS motor score",
"Cognitive composite",
"Brain volume preservation"
],
"inclusion": {
"min_age": 25,
"max_age": 65,
"required_acmg": [
"Pathogenic"
],
"required_gene": "HTT",
"max_functional_status": 2,
"min_eligibility_score": 0.6
},
"exclusion": {
"ae_grade_cutoff": 3,
"required_prior_treatment": false
},
"arm_allocation": {
"HTT-ASO": 0.67,
"Placebo": 0.33
},
"biomarker_response_threshold": 0.4
},
"TRIAL-FAB-001": {
"disease": "Fabry Disease",
"disease_group": "Rare metabolic",
"phase": "Phase 3",
"intervention": "Agalsidase beta ERT vs Migalastat chaperone",
"n_target": 90,
"duration_months": 24,
"primary_endpoint": "GFR stabilization and lyso-Gb3 reduction at 24 months",
"secondary_endpoints": [
"Neuropathic pain (BPI)",
"Cardiac mass reduction",
"Quality of life"
],
"inclusion": {
"min_age": 18,
"max_age": 65,
"required_acmg": [
"Pathogenic",
"Likely pathogenic"
],
"required_gene": "GLA",
"max_functional_status": 3,
"min_eligibility_score": 0.55
},
"exclusion": {
"ae_grade_cutoff": 4,
"required_prior_treatment": false
},
"arm_allocation": {
"Agalsidase-beta": 0.5,
"Migalastat": 0.5
},
"biomarker_response_threshold": 0.35
},
"TRIAL-MFS-001": {
"disease": "Marfan Syndrome",
"disease_group": "Rare cardiac",
"phase": "Phase 3",
"intervention": "Losartan vs Atenolol for aortic root dilation",
"n_target": 150,
"duration_months": 36,
"primary_endpoint": "Aortic root z-score change at 36 months",
"secondary_endpoints": [
"Aortic dissection rate",
"Systolic/diastolic function",
"QoL"
],
"inclusion": {
"min_age": 6,
"max_age": 60,
"required_acmg": [
"Pathogenic",
"Likely pathogenic"
],
"required_gene": "FBN1",
"max_functional_status": 2,
"min_eligibility_score": 0.55
},
"exclusion": {
"ae_grade_cutoff": 3,
"required_prior_treatment": true
},
"arm_allocation": {
"Losartan": 0.5,
"Atenolol": 0.5
},
"biomarker_response_threshold": 0.3
},
"TRIAL-HEM-001": {
"disease": "Hemophilia A",
"disease_group": "Rare hematological",
"phase": "Phase 3",
"intervention": "Gene therapy (AAV5-F8) vs Factor VIII prophylaxis",
"n_target": 70,
"duration_months": 36,
"primary_endpoint": "ABR reduction \u226580% from baseline at 12 months",
"secondary_endpoints": [
"Factor VIII activity",
"Joint health score",
"Treatment burden"
],
"inclusion": {
"min_age": 18,
"max_age": 70,
"required_acmg": [
"Pathogenic"
],
"required_gene": "F8",
"max_functional_status": 2,
"min_eligibility_score": 0.6
},
"exclusion": {
"ae_grade_cutoff": 3,
"required_prior_treatment": true
},
"arm_allocation": {
"AAV5-F8": 0.67,
"Factor-VIII-prophylaxis": 0.33
},
"biomarker_response_threshold": 0.5
},
"TRIAL-PKD-001": {
"disease": "ADPKD",
"disease_group": "Rare renal",
"phase": "Phase 3",
"intervention": "Tolvaptan vs placebo for TKV reduction",
"n_target": 180,
"duration_months": 36,
"primary_endpoint": "TKV change from baseline at 36 months",
"secondary_endpoints": [
"eGFR decline rate",
"Kidney pain events",
"Osmolality"
],
"inclusion": {
"min_age": 18,
"max_age": 55,
"required_acmg": [
"Pathogenic",
"Likely pathogenic"
],
"required_gene": "PKD1",
"max_functional_status": 2,
"min_eligibility_score": 0.55
},
"exclusion": {
"ae_grade_cutoff": 3,
"required_prior_treatment": false
},
"arm_allocation": {
"Tolvaptan": 0.67,
"Placebo": 0.33
},
"biomarker_response_threshold": 0.35
},
"TRIAL-OI-001": {
"disease": "Osteogenesis Imperfecta",
"disease_group": "Rare skeletal",
"phase": "Phase 2/3",
"intervention": "Setrusumab anti-sclerostin vs bisphosphonate",
"n_target": 100,
"duration_months": 24,
"primary_endpoint": "Lumbar spine BMD change at 24 months",
"secondary_endpoints": [
"Fracture rate",
"Height velocity",
"Pain score"
],
"inclusion": {
"min_age": 5,
"max_age": 50,
"required_acmg": [
"Pathogenic",
"Likely pathogenic"
],
"required_gene": "COL1A1",
"max_functional_status": 3,
"min_eligibility_score": 0.5
},
"exclusion": {
"ae_grade_cutoff": 3,
"required_prior_treatment": true
},
"arm_allocation": {
"Setrusumab": 0.67,
"Bisphosphonate": 0.33
},
"biomarker_response_threshold": 0.3
},
"TRIAL-TS-001": {
"disease": "Tuberous Sclerosis",
"disease_group": "Rare neurological",
"phase": "Phase 3",
"intervention": "Everolimus mTOR inhibitor",
"n_target": 80,
"duration_months": 18,
"primary_endpoint": "SEGA volume reduction \u226550% at 9 months",
"secondary_endpoints": [
"Angiomyolipoma response",
"Seizure frequency",
"Skin lesion response"
],
"inclusion": {
"min_age": 3,
"max_age": 65,
"required_acmg": [
"Pathogenic",
"Likely pathogenic"
],
"required_gene": "TSC1",
"max_functional_status": 3,
"min_eligibility_score": 0.55
},
"exclusion": {
"ae_grade_cutoff": 3,
"required_prior_treatment": true
},
"arm_allocation": {
"Everolimus": 0.67,
"Placebo": 0.33
},
"biomarker_response_threshold": 0.4
},
"TRIAL-SCD-001": {
"disease": "Sickle Cell Disease",
"disease_group": "Rare hematological",
"phase": "Phase 3",
"intervention": "Betibeglogene gene therapy vs Voxelotor",
"n_target": 75,
"duration_months": 24,
"primary_endpoint": "VOC rate reduction \u226550% at 24 months",
"secondary_endpoints": [
"Hemoglobin level",
"Transfusion independence",
"Quality of life"
],
"inclusion": {
"min_age": 12,
"max_age": 50,
"required_acmg": [
"Pathogenic"
],
"required_gene": "HBB",
"max_functional_status": 3,
"min_eligibility_score": 0.55
},
"exclusion": {
"ae_grade_cutoff": 4,
"required_prior_treatment": true
},
"arm_allocation": {
"Betibeglogene": 0.67,
"Voxelotor": 0.33
},
"biomarker_response_threshold": 0.45
},
"TRIAL-NPC-001": {
"disease": "Niemann-Pick Type C",
"disease_group": "Rare metabolic",
"phase": "Phase 2/3",
"intervention": "Arimoclomol HSP inducer",
"n_target": 50,
"duration_months": 18,
"primary_endpoint": "NPC-CSS score stabilization at 12 months",
"secondary_endpoints": [
"Oculomotor function",
"Cerebellar ataxia",
"Swallowing function"
],
"inclusion": {
"min_age": 4,
"max_age": 45,
"required_acmg": [
"Pathogenic",
"Likely pathogenic"
],
"required_gene": "NPC1",
"max_functional_status": 3,
"min_eligibility_score": 0.5
},
"exclusion": {
"ae_grade_cutoff": 3,
"required_prior_treatment": true
},
"arm_allocation": {
"Arimoclomol": 0.67,
"Placebo": 0.33
},
"biomarker_response_threshold": 0.25
},
"TRIAL-LCA-001": {
"disease": "Leber Congenital Amaurosis",
"disease_group": "Rare ophthalmic",
"phase": "Phase 3",
"intervention": "Voretigene neparvovec gene therapy",
"n_target": 40,
"duration_months": 12,
"primary_endpoint": "MLMT performance score improvement at 1 year",
"secondary_endpoints": [
"Full-field light sensitivity",
"Visual acuity",
"Visual field"
],
"inclusion": {
"min_age": 3,
"max_age": 65,
"required_acmg": [
"Pathogenic",
"Likely pathogenic"
],
"required_gene": "CEP290",
"max_functional_status": 2,
"min_eligibility_score": 0.6
},
"exclusion": {
"ae_grade_cutoff": 3,
"required_prior_treatment": false
},
"arm_allocation": {
"Voretigene": 0.67,
"Sham-control": 0.33
},
"biomarker_response_threshold": 0.5
},
"TRIAL-CAH-001": {
"disease": "Congenital Adrenal Hyperplasia",
"disease_group": "Rare endocrine",
"phase": "Phase 3",
"intervention": "Crinecerfont (CRF1 receptor antagonist)",
"n_target": 110,
"duration_months": 24,
"primary_endpoint": "Androstenedione normalization at 24 weeks",
"secondary_endpoints": [
"Cortisol sufficiency",
"Corticosteroid dose reduction",
"Growth velocity"
],
"inclusion": {
"min_age": 4,
"max_age": 50,
"required_acmg": [
"Pathogenic",
"Likely pathogenic"
],
"required_gene": "CYP21A2",
"max_functional_status": 2,
"min_eligibility_score": 0.55
},
"exclusion": {
"ae_grade_cutoff": 3,
"required_prior_treatment": true
},
"arm_allocation": {
"Crinecerfont": 0.67,
"Placebo": 0.33
},
"biomarker_response_threshold": 0.4
}
} |