Pamrevlumab did not meet its primary endpoint for non-ambulatory patients with Duchenne Muscular Dystrophy: the LELANTOS-1 trial
Bibliographic record
Abstract
ABSTRACT Background In Duchenne muscular dystrophy (DMD), fibrosis is linked to connective tissue growth factor (CTGF) overexpression. Pamrevlumab, a fully human monoclonal antibody, inhibits CTGF activity and showed promise as a DMD treatment in a phase 2 trial. Objective LELANTOS-1 ( NCT04371666 ) was a global phase 3 study of the safety and efficacy of pamrevlumab for non-ambulatory males ≥12 years old with DMD. Methods Patients were randomized 1:1 to pamrevlumab 35 mg/kg every 2 weeks for 52 weeks or placebo. All received a stable corticosteroid regimen (deflazacort or prednisone/prednisolone). Primary endpoint was total Performance of Upper Limb (PUL) v2.0 score change from baseline to Week 52 in the modified intent-to-treat (mITT) set (baseline PUL score ≥2). Treatment-emergent adverse events (TEAEs) were noted. Patients who completed the main study period were eligible to enroll in the open-label extension (OLE). Results Ninety-eight patients (mean [SD] age, 15.5 [2.57] years) enrolled; 48 received pamrevlumab and 49 received placebo. Between-group baseline characteristics were similar. In the mITT set (mean [SD] age, 15.5 [2.64] years; pamrevlumab, n=41; placebo, n=42), the total PUL v2.0 score change was not significantly different ( p =0.8802). The pamrevlumab group had more grip strength deterioration than placebo in dominant ( p =0.0161) and nondominant hands ( p =0.0052). Most patients (pamrevlumab, n=45/48 [93.8%]; placebo, n=48/49 [98.0%]) experienced TEAEs (most mild/moderate). One death occurred in the pamrevlumab group (unrelated to study drug). The OLE mITT set included 72 patients. OLE efficacy and safety were consistent with the main study period. No deaths occurred during the OLE. Conclusions Pamrevlumab failed to meet the primary endpoint. Its future as a DMD treatment is uncertain. Trial Registration ClinicalTrials.gov Identifier: NCT04371666
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".