S1143 The Anti-TL1A Antibody PRA023 Demonstrated Proof-of-Concept in Crohn’s Disease: Phase 2a APOLLO-CD Study Results
Bibliographic record
Abstract
Introduction: Tumor necrosis factor–like cytokine 1A (TL1A) is regulator of inflammation and fibrosis. PRA023 is an anti-TL1A monoclonal antibody in development for inflammatory/fibrotic diseases with a companion genetic-based diagnostic test (Dx). This phase 2a, multicenter, open-label study aimed to assess the efficacy and safety of PRA023 as induction treatment in adults with moderately to severely active Crohn’s Disease (CD). Methods: Key eligibility criteria included Crohn’s Disease Activity Index (CDAI) ≥220 and ≤450 with centrally read Simple Endoscopic Score (SES)-CD of ≥6 (≥4 isolated ileal disease) and a history of insufficient/loss of response and/or intolerance to conventional and/or approved biologic therapies. Eligible patients received intravenous PRA023 1000 mg on Day 1, 500 mg at weeks 2, 6, and 10. The primary endpoint was endoscopic response (reduction in SES-CD of ≥50%) at week 12. Historical placebo control rates were used as a reference for the null hypothesis. An exploratory efficacy assessment in a subpopulation identified by the Dx was included. Results: Of the 55 patients enrolled, 53 (96.4%) completed the 12-week induction period. Patients had a high rate of prior biologic exposure (70.9%) and a mean (SD) disease duration of 10.3 (9.3) years (Table 1). A significantly greater proportion of patients receiving PRA023 achieved endoscopic response (26% PRA023 vs 12% historical placebo estimate, P=0.002) and clinical remission (CDAI < 150 points; 49% PRA023 vs 16% historical placebo estimate, P< 0.001). Efficacy was observed in biologic-exposed patients (33% endoscopic response and 38.5% clinical remission), while concurrent steroid or immunosuppressant use did not impact efficacy. Significant reductions from baseline in C-reactive protein and fecal calprotectin were observed at all time points (Figure 1). Although the pre-specified Dx algorithm provided only limited additional benefit in clinical responses, an alternative CD-specific algorithm demonstrated enhanced performance across both clinical (12/21 [57%] remission) and endoscopic (9/20 [45%] response) outcomes. No serious/severe adverse events were deemed as study drug–related. Conclusion: This phase 2a study demonstrated robust proof-of-concept for PRA023’s efficacy in moderately to severely active CD with favorable tolerability. Patient selection using prespecified genetic markers showed promising results. Placebo-controlled clinical trials will be conducted to confirm these findings. Table 1. - Demographics and Baseline Characteristics PRA023 (N=55) Age, y 39.1±15.7 Female, No. (%) 21 (38.2) Weight, kg 77.6±20.6 Geographic region, No. (%) North America 33 (60) Eastern Europe 13 (23.6) Western Europe 7 (12.7) Rest of world (Australia) 2 (3.6) Duration of disease, y 10.3±9.3 Extent of disease, No. (%) Ileal 8 (14.5) Colonic 15 (27.3) Ileocolonic 32 (58.2) Baseline CDAI Score 317.9±67.2 Baseline SES-CD 13.4±6.7 Concomitant immunosuppressant use, No. (%) 8 (14.5) Concomitant corticosteroid use, No. (%) 22 (40) Prior biologics exposure, No. (%) 0 16 (29.1) 1 10 (18.2) 2 10 (18.2) ≥3 19 (34.5) Plus-minus values are means ±SD.Abbreviations: CDAI, Crohn’s Disease Activity Index; SES-CD, Simple Endoscopic Score for Crohn's Disease. Figure 1.: Change Over Time in Geometric Mean Values ± SE for (A) High-Sensitivity C-Reactive Protein (hsCRP) and (B) Fecal Calprotectin Nominal p values, *P<0.05, **P<0.01, ***P<0.001.
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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 | 0.003 | 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 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 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".