| { |
| "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 |
| } |
| } |
