PRECISE‐AD, A Phase 1b, Double‐Blind, Placebo‐Controlled, Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PMN310 in Patients with Early Alzheimer's Disease
Bibliographic record
Abstract
BACKGROUND: Toxic Aβ oligomers (AβO) are implicated in the progression of Alzheimer's disease (AD). PMN310 is a humanized IgG1 monoclonal antibody that binds to a computationally derived three-dimensional epitope specific to misfolded Aβ in AβO. Because PMN310 inhibits toxicity of AβO and does not bind to plaque, thereby potentially limiting risk of ARIA, it is being developed as a therapy for early AD. Results from a single ascending dose study of PMN310 (A Phase 1a Study of PMN310 In Healthy Volunteers NCT06105528) indicate that PK parameters and CSF concentrations of PMN310 were linearly dose-dependent and CSF concentrations were 100-600 times the estimated AβO molar concentration. The plasma half-life (t ½) was approximately 17.5 days and the CSF t ½ was approximately 27 days. METHODS: PRECISE-AD, NCT06750432, is a placebo-controlled, multiple-ascending dose study of PMN310 to evaluate safety, tolerability, PK, PD, and preliminary efficacy of multiple intravenous infusions of PMN310 in patients with early Alzheimer's disease. The study consists of three staggered dosing arms of 350 mg, 700 mg, 1400 mg. Patients will be randomized 3:1, PMN310: placebo and will receive either PMN310 or placebo once every 28 days for a total of 12 infusions. The study will enroll 128 patients with either Stage 3 or 4 AD. Diagnosis will be determined by clinical criteria, CSF and plasma biomarkers, and Aβ PET. MRI scans will be done at months 2, 4, 6, 9, 12 to detect potential ARIA. Plasma biomarkers (pTau217, pTau 243, GFAP, SNAP25, neurogranin, Aβ42/Aβ40, NfL) will be measured at baseline and at 3-month intervals. Biomarkers in CSF will be measured at baseline, 6, 12 months. Cognitive outcomes (CDR-SB, ADAS-cog, ADAS-ADL IADRS Clinical Impression of Change) will be assessed at baseline, month 6 and month 12. RESULTS: The proposed study has sufficient power to detect at least one ARIA event. The proposed sample size has sufficient power to provide statistically meaningful insight into effects of PMN310 on biomarkers and clinical outcomes. CONCLUSIONS: PRECISE-AD will be the first study to examine the effects of a monoclonal antibody directed solely against AβO on biomarkers associated with AD pathology and clinical outcomes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".