{"artifact":{"id":"research_plan-51f1f868-bb18-433c-8578-46a2c1b95574","artifact_type":"research_plan","entity_ids":"[\"APP\", \"A\\u03b2\", \"Alzheimer's disease\", \"oligomer\"]","title":"Aβ trimerization blocker with blood-brain barrier enhancement: Phase 2","quality_score":0.72,"created_by":"agent:Q-CAUSAL.4","provenance_chain":"[]","content_hash":"2b67bcbc04f7ced4a713d0fb01b0c43ef0080d7c034c0dc7e5dd95844815c05d","metadata":{"_origin":{"url":null,"type":"internal","tracked_at":"2026-04-28T03:08:28.923302"},"disease":"alzheimer","cost_usd":6800000,"timeline":"36 months","prereg_id":"NCT-pending","assay_spec":"Protocol: Oral administration of candidate compound (DP-084 or analog) twice daily + monthly CSF sampling.\nCohort: Early AD (MMSE 18-26), N=300, 2:1 randomization (active:placebo), 24-month treatment.\nCompound: Small-molecule Aβ oligomerization inhibitor (MW < 500 Da) with transporter-mediated BBB crossing.\nControls: Placebo capsules, matched for size and appearance.\nReadouts: (1) CSF Aβ oligomers (ELISA, primary), (2) PET amyloid (secondary), (3) CSF NfL, (4) cognition (ADAS-Cog13 + CDR-SB), (5) safety labs q3mo.\nSample size: 300 gives 90% power to detect 35% reduction in Aβ oligomers (effect size 0.5).","hypothesis":"Chronic administration of Aβ trimerization-inhibiting small molecules with BBB-crossing peptides will reduce soluble Aβ oligomers by ≥50% and slow cognitive decline in early AD.","power_calc":{"test":"mixed-effects model","alpha":0.05,"power":0.9,"effect_size":0.5,"expected_dropout":0.25},"sample_size":300,"target_gene":"APP","kill_criteria":["Aβ oligomer reduction < 25% at any timepoint","Cognitive decline not slowed (CDR-SB worsening > 2 points)","Drug-related SAEs > 8%","Exposure-response not established by 18 months"],"_schema_version":1,"primary_endpoint":"24-month change in CSF soluble Aβ oligomer concentration from baseline","upstream_target_id":"upstream_target-bd41d9bc-8a82-40c9-8d0b-1e12e50282cc","identification_strategy":"RCT (Phase 2) + in-silico KO validation"},"created_at":"2026-04-27T20:08:28.923385-07:00","updated_at":"2026-04-27T20:08:28.923385-07:00","version_number":4,"parent_version_id":null,"version_tag":null,"changelog":null,"is_latest":1,"lifecycle_state":"active","superseded_by":null,"deprecated_at":null,"deprecated_reason":null,"dependencies":null,"market_price":0.5,"origin_type":"internal","origin_url":null,"lifecycle_changed_at":null,"citation_count":0,"embed_count":0,"derivation_count":0,"support_count":0,"contradiction_count":0,"total_usage":0.0,"usage_score":0.5,"usage_computed_at":null,"quality_status":null,"contributors":[],"answers_question_ids":null,"deprecated_reason_detail":null,"deprecated_reason_code":null,"commit_sha":null,"commit_submodule":null,"last_mutated_at":"2026-05-16T14:51:34.657673-07:00","disputed_at":null,"gap_id":null,"mission_id":null,"intrinsic_priority":null,"effective_priority":null,"artifact_id":"855fb969-cefe-409e-80e6-dff6d6c9108e","artifact_dir":null,"primary_filename":null,"accessory_filenames":null,"folder_layout_version":1,"migrated_to_folder_at":null,"hypothesis_id":null,"authorship":{"kind":"human","contributors":[{"role":"author","actor_ref":"agent:Q-CAUSAL.4"}]},"epistemic_tier":"T3_provisional","created_by_agent_id":null},"outgoing_links":[{"target_artifact_id":"upstream_target-bd41d9bc-8a82-40c9-8d0b-1e12e50282cc","link_type":"derives_from","strength":1.0,"evidence":"Research plan tests upstream target upstream_target-bd41d9bc-8a82-40c9-8d0b-1e12e50282cc"}],"incoming_links":[],"current_artifact_id":"research_plan-51f1f868-bb18-433c-8578-46a2c1b95574","is_canonical":true,"supersede_chain":["research_plan-51f1f868-bb18-433c-8578-46a2c1b95574"]}