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225.3: Randomized phase 2 trial of felzartamab in humoral transplant rejection.

2024· article· en· W4402801236 on OpenAlexaff
Katharina A. Mayer, Eva Schrezenmeier, Matthias Diebold, Philip F. Halloran, Martina Schatzl, Alexander Kainz, Farsad Eskandary, Konstantin Doberer, Uptdal D Patel, Jaideep S. Dudani, Heinz Regele, Nicolas Kozakowski, Johannes Kläger, Kerstin Amann, Elisabeth Puchhammer-Stöckl, Hannes Vietzen, Julia Beck, Ekkehard Schütz, Aylin Akifova, Bilgin Osmanodja, Fabian Halleck, Bernd Jilma, Klemens Budde, Georg A. Böhmig

Bibliographic record

VenueTransplantation · 2024
Typearticle
Languageen
FieldMedicine
TopicHematopoietic Stem Cell Transplantation
Canadian institutionsThe Metabolomics Innovation CentreUniversity of Alberta
Fundersnot available
KeywordsMedicineRandomized controlled trialImmunologyInternal medicine

Abstract

fetched live from OpenAlex

Felzartamab Study Group. Background: Antibody-mediated rejection (ABMR) is a leading cause of renal allograft failure. Targeting CD38 to inhibit alloantibody- and natural killer (NK) cell−driven injury may be a therapeutic option. Methods: In a double-blind, placebo-controlled phase 2 trial, patients with ABMR ≥180 days post-transplant were randomized 1:1 to receive nine infusions of the CD38 monoclonal antibody felzartamab (16 mg/kg) or placebo over 6 months, followed by a 6-month observational period. The primary outcome was felzartamab safety and tolerability. Secondary outcomes included 24- and 52-week renal biopsies, donor-specific antibody (DSA) levels, peripheral NK cell counts, and donor-derived cell-free DNA (dd-cfDNA). Results: Of 22 patients randomized (felzartamab, n=11; placebo, n=11), eight had mild to moderate infusion reactions (felzartamab, n=8; placebo, n=0) and five had serious adverse events (felzartamab, n=1; placebo, n=4). One patient who received placebo had graft loss. After week 24, resolution of morphologic ABMR activity was more frequent with felzartamab (9 of 11 [81.8%]) versus placebo (2 of 10 [20%]; P=0.009). Felzartamab decreased median (interquartile range) microvascular inflammation scores (0 [0−1] versus 2.5 [2−3]; P=0.001), molecular ABMR activity (ABMRProb: 0.17 [0.09−0.51] versus 0.77 [0.37−0.86]; P=0.007), CD16bright NK cell counts (16 [8−41] versus 54 [38-170] cells/ml; P=0.004), and dd-cfDNA (0.31 [0.21−0.49] versus 0.82 [0.34−2.90)%]; P=0.036). DSA changed minimally. At week 52, ABMR activity recurrence was observed in 3 of 9 felzartamab responders, with molecular activity and biomarker levels increasing towards baseline. Conclusion: Felzartamab exhibited favorable safety and efficacy, underscoring its potential as a novel therapeutic option in ABMR.

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)0.002
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.010
Threshold uncertainty score0.033

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0100.002

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.

Opus teacher head0.023
GPT teacher head0.326
Teacher spread0.303 · 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 designRandomized 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
Published2024
Admission routes1
Has abstractyes

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