Journal of Crohn's & colitis
October 1, 2026 · via Europe PMC
Safety and tolerability of anti-toll-like receptor 3, monoclonal antibody PRV-300 in patients with moderate-to-severe ulcerative colitis: a randomized phase 1B clinical trial (PULSE).
Pokryszka J, Comer GM, Richmond CA, Leon F, Reinisch W.
AI summary — for doctors, generated from the abstract only
Anti-TLR3 antibody PRV-300 was acceptably tolerated in ulcerative colitis but showed no clinical or endoscopic benefit.
What was studied
Randomized phase 1B trial (PULSE) in 38 patients with moderate-to-severe UC given 7 IV doses of PRV-300 (28) or placebo (9) over 12 weeks.
Key findings
- Adverse events were numerically higher with PRV-300 (50.0% vs 11.1%; serious 39.3% vs 0%), but only 2 of 28 stopped for adverse events
- TLR3 expression in biopsies fell more with PRV-300 but not significantly, with no change in the UC gene signature
- No difference in Mayo score or endoscopic severity
Clinical relevance
Blocking TLR3 does not appear to be a useful mechanism in UC.
Who should care
Limitations
Tiny trial with an unbalanced 28 vs 9 allocation, not powered for efficacy, and industry funded.
Nothing to change in practice; this target seems not worth pursuing in UC.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Background & aims
PRV-300 is a fully human IgG4κ monoclonal antibody that binds the extracellular domain of human toll-like receptor 3, which is overexpressed in the inflamed colonic epithelium in patients with inflammatory bowel disease. This study aimed at proving its safety and efficacy in patients with ulcerative colitis (UC).
Methods
Patients with moderate-to-severe UC (Mayo Clinical Score [MCS] 6-12) were randomized to receive 7 doses of PRV-300 intravenously or matched placebo (PBO). After a 12-week treatment period, participants underwent an 8-week follow-up. The primary endpoint was to assess the safety and tolerability of PRV-300. Secondary endpoints included assessment of pharmacodynamics, pharmacokinetics, immunogenicity, and endoscopic disease activity.
Results
In total, 38 patients were randomized (28 in PRV-300 arm, 9 in placebo arm), of whom 32 completed the trial (24 and 8, respectively). Although TEAEs and TE-SAEs were numerically higher with PRV-300 than placebo (50.0% vs 11.1% and 39.3% vs 0.0%, respectively), the drug was well-tolerated, with only 7.1% (2/28) discontinuing therapy due to AEs and most events being mild, non-specific, or related to underlying disease. In colonic biopsies, PRV-300 had a greater, albeit not statistically significant, effect on the downregulation of TLR3 expression, but not on a UC gene expression signature. No differences in MCS and endoscopic severity were observed.
Conclusions
While PRV-300 demonstrated an acceptable safety profile, TLR3 blockade did not translate into clinical benefit despite exploratory evidence of target engagement. Our results are challenging a pivotal role of the mode-of-action for the pathogenesis of UC (funded by Provention Bio).
Clinical trial registration number
ClinicalTrials.gov (NCT03849599).
DOI
10.1093/ecco-jcc/jjag154
PMID
42896861
PMCID
PMC13680009
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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