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Record W4397047970 · doi:10.1681/asn.20223311s1967c

A Phase 1b, Multicenter, Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Tegoprubart (AT-1501) in Patients Undergoing Kidney Transplant

2022· article· en· W4397047970 on OpenAlexaff
Jean Tchervenkov, Patrick T. Coates, Matthew Kadatz, Jeffrey D. Bornstein, John S. Gill

Bibliographic record

VenueJournal of the American Society of Nephrology · 2022
Typearticle
Languageen
FieldMedicine
TopicPharmacological Effects and Toxicity Studies
Canadian institutionsSt. Paul's HospitalVancouver General HospitalMcGill University Health Centre
Fundersnot available
KeywordsPharmacokineticsMedicineOpen labelMulticenter studyKidney transplantationKidney transplantInternal medicineKidneyIntensive care medicineAdverse effectUrologyPharmacologyRandomized controlled trial

Abstract

fetched live from OpenAlex

Background: Calcineurin inhibitors (CNIs) are the backbone of kidney transplant anti-rejection therapy, and they substantially reduce the risk of acute rejection, providing excellent one-year patient and graft survival. However, only ˜50% of the grafts survive 10 years, with these graft failures often being due to either late onset antibody mediated rejection or the direct nephrotoxicity of the CNIs themselves. CNIs are also associated with an increased risk of new onset diabetes after transplant, tremor, cognitive impairment, and other adverse events. As such, an agent that could produce comparable one-year results while improving long term outcomes and reducing CNI toxicities would address a significant unmet medical need. Tegoprubart (AT-1501) is a monoclonal antibody directed against the CD40 ligand (CD40L), a key mediator of co-stimulation. Inhibition of CD40L should result in a decrease in both cell and antibody mediated immunity and create a more tolerogenic immune environment. Tegoprubart has been shown to be effective in animal models and is currently being studied in kidney transplant recipients. Methods: This pilot study will investigate the use of tegoprubart to prevent rejection in human kidney transplant recipients. Up to 12 participants will be enrolled in this open label study, and enrollment will be staggered such that the second subject cannot be screened until the first subject completes 28-days post-transplant and the DMC completes a review of the data. Adult recipients of their first allograft are eligible if they meet inclusion / exclusion criteria and if the donor kidney does not meet extended criteria, have a prolonged cold ischemia time, or come from a donor with cardiac death. All study participants will receive rATG induction therapy and a maintenance regimen of tegoprubart dosed at 20mg/kg IV every 3 weeks after a loading dose, MMF and corticosteroids. The safety of the regimen, PK of tegoprubart, and the ability of this regimen to prevent rejection will be assessed. Results: The results will be presented when available. Conclusions: Tegoprubart is a potential alternative to CNI in maintenance therapy for the prevention of allograft rejection in kidney transplant recipients. A Phase 1b trial to assess its safety, PK and efficacy is ongoing. Funding: Commercial Support - Eledon Pharmaceuticals

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.004
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.007
Threshold uncertainty score0.024

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0040.002
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0000.000
Science and technology studies0.0010.001
Scholarly communication0.0010.002
Open science0.0010.001
Research integrity0.0020.003
Insufficient payload (model declined to judge)0.0070.001

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.

Opus teacher head0.039
GPT teacher head0.374
Teacher spread0.334 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNon-randomized trial
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2022
Admission routes1
Has abstractyes

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