Update on the TOGETHER study: a patient‐ and investigator‐blind, randomized, placebo‐controlled study evaluating the efficacy, safety and tolerability of bepranemab, UCB0107, in prodromal‐to‐mild Alzheimer’s disease
Bibliographic record
Abstract
Abstract Background Bepranemab is a recombinant, humanized, full‐length IgG4 monoclonal antibody that binds to a central tau epitope (amino acids 235‐250). Here, we update on the progress of the TOGETHER study (AH0003; NCT04867616) with bepranemab in early Alzheimer’s disease (AD). Method TOGETHER is a global, multicenter, double‐blind, placebo‐controlled, parallel‐group study investigating the efficacy, safety and tolerability of bepranemab versus placebo. Patients with prodromal (National Institute on Aging‐Alzheimer’s Association [NIA‐AA] Stage 3) or mild (NIA‐AA Stage 4) AD (target N = 450) will be randomized (1:1:1) to receive one of two doses of bepranemab or placebo (intravenous, every 4 weeks), over an 80‐week treatment period, followed by an optional 48‐week open‐label‐extension period. Participants will have a global Clinical Dementia Rating (CDR) score of 0.5 (prodromal AD) or 0.5–1.0 (mild AD) and a CDR‐Memory Box score ≥0.5 at screening and baseline, a score of ≤85 for the delayed recall domain of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), mini‐mental state examination (MMSE) ≥20 at screening and must meet the NIA‐AA 2018 definition of cerebral beta‐amyloid (Aβ) accumulation, by either a positive centrally read positron emission tomography (PET) scan or a positive cerebrospinal fluid (CSF) pTau181/Aβ1‐42 ratio. The primary endpoint is change from baseline to Week 80 in CDR scale Sum of Boxes total score. Secondary endpoints include: pharmacokinetics; safety and tolerability; tau PET imaging and change from baseline in AD Assessment Scale‐Cognitive Subscale 14, Amsterdam Instrumental Activities of Daily Living questionnaire and MMSE at Weeks 56 and 80. Result As of March 1, 2022, 56/125 planned centers have enrolled participants across 8 countries: Belgium, Canada, France, Netherlands, Poland, Spain, UK and USA. Of the 538 participants who entered screening, 62 have been randomized so far and 334 failed screening. Predominant reasons for screen failure include not meeting RBANS, MMSE or Aβ positivity (CSF or PET) criteria. Conclusion This proof‐of‐concept study employs clinical outcome measures, imaging, pharmacokinetics, and biomarkers to assess the ability of bepranemab to slow progression of AD when administered in the early stages of disease. Enrollment and randomization are underway with nearly half of the study centers active.
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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 | 0.013 | 0.009 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.004 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.004 | 0.005 |
| Insufficient payload (model declined to judge) | 0.007 | 0.002 |
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".