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Record W4405035165 · doi:10.1182/blood-2024-200797

Renew Trial in Progress: A Phase 3, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Elritercept (KER-050) for the Treatment of Transfusion-Dependent Anemia in Adult Participants with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Neoplasms (MDS)

2024· article· en· W4405035165 on OpenAlexaff
Rami S. Komrokji, María Diez‐Campelo, Lynette Chee, Thomas Cluzeau, Amy E. DeZern, Pierre Fenaux, Guillermo Garcia‐Manero, Aristoteles Giagounidis, Uwe Platzbecker, Matteo Giovanni Della Porta, Valeria Santini, Mikkael A. Sekeres, Amer M. Zeidan, Rena Buckstein, Miranda Ross, Ying Jiang, Suresh Bobba, Montagu Hankin, Chris Materna, Christine Graham, Sanjay Thamake, Christopher Rovaldi, Dena Grayson, Jen L. Salstrom

Bibliographic record

VenueBlood · 2024
Typearticle
Languageen
FieldMedicine
TopicAcute Myeloid Leukemia Research
Canadian institutionsHealth Sciences CentreSunnybrook Health Science Centre
Fundersnot available
KeywordsPlaceboMedicineAnemiaClinical trialDouble blindInternal medicineAlternative medicinePathology

Abstract

fetched live from OpenAlex

Background and Significance: In MDS, defects occur at multiple stages of hematopoiesis. Available Erythropoiesis Stimulating or Erythroid Maturation Agents (ES/EMAs) target early or late stages of erythropoiesis, respectively, and are only effective in subsets of patients. For patients with high transfusion burden (HTB) who have diminished erythropoietic capacity and a worse prognosis, ES/EMAs show limited efficacy and durability of response (DOR). Elritercept is an investigational, modified activin receptor type IIA ligand trap designed to inhibit activin A and other select TGF-β superfamily ligands (activin B, GDFs 8, & 11) that is being evaluated in diseases with ineffective hematopoiesis (IH), including MDS (NCT04419649) and myelofibrosis (NCT05037760). In preclinical studies, elritercept increased erythropoiesis and thrombopoiesis and acted on early- and late-stage erythropoietic and megakaryocyte progenitors, indicating a differentiated mechanism of action, potentially due to inhibition of activin A. By eliciting effects on hematopoiesis across multiple differentiation stages and cell lineages, elritercept has the potential to address the complex nature of IH and to provide robust and sustained hematological improvement in patients with MDS who have limited treatment options, including those with HTB and/or non-ring sideroblast (RS) MDS. Study Design and Methods: RENEW (NCT06499285) is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study to evaluate the efficacy and safety of elritercept in adults with transfusion-dependent, very low-, low-, and intermediate-risk MDS per IPSS-R (lower-risk [LR] MDS). Eligible participants are aged ≥18 years and have MDS with or without RS and low transfusion burden (LTB, 4 to 7 RBC units per 16 weeks) or HTB (≥8 RBC units per 16 weeks). Approximately 225 participants will be randomized 2:1 to receive either elritercept, administered SC Q4W starting at 3.75mg/kg with up-titration to 5mg/kg after at least 8 weeks of treatment, or placebo. Participants will be stratified by RS status (RS-positive vs non-RS) and baseline transfusion burden (LTB vs HTB). Participants will be enrolled into a double-blind treatment period consisting of a primary phase (24 weeks), secondary phase (24 weeks), and extension phase (until the end of treatment [EOT]). Following EOT, participants will undergo an 8-week safety follow-up period and a long-term follow-up period as per protocol. Every quarter during the long-term follow-up, data will be collected on survival, first dose of the next MDS treatment line, and progression to AML, if applicable. The primary endpoint is the proportion of participants with achievement of transfusion independence (TI) ≥8 weeks from baseline through week 24. Secondary endpoints are the proportion of participants with achievement of TI ≥24 weeks from baseline through week 48, the proportion of participants with HTB achieving TI for ≥8 weeks from baseline through week 24, and the incidence and severity of adverse events (AEs) and serious AEs. The RENEW trial is expected to support the registration of elritercept for the treatment of anemia in adults with LR-MDS.

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 score0.014
Threshold uncertainty score0.046

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0040.002
Bibliometrics0.0000.000
Science and technology studies0.0010.002
Scholarly communication0.0020.002
Open science0.0010.000
Research integrity0.0030.005
Insufficient payload (model declined to judge)0.0140.003

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 head0.036
GPT teacher head0.362
Teacher spread0.327 · 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

Citations2
Published2024
Admission routes1
Has abstractyes

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