{
  "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
  }
}