British journal of clinical pharmacology · 2026
A phase 1 study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of PF-07261271 in healthy participants.
СтатьяКлиническое исследование I фазыРандомизированное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Neelakantan Srividya, Banfield Christopher, Hung Kenneth, Sapone Anna, Pradhan Vivek, Zhao Yuxi, Parsons-Rich Dana, Lee Grace, Johnson Bryce G, Peeva Elena, Vincent Michael S, Clerin Valerie M
Аннотация
AIM: There is an unmet need for more effective therapies in inflammatory bowel disease (IBD). A single drug that blocks multiple distinct pathogenic pathways may offer therapeutic benefit superior to current monotherapies. PF-07261271, a bispecific antibody targeting both the p40 subunit of interleukin-12/23 and tumour necrosis factor-like cytokine 1A (TL1A), is being investigated as a potential new IBD therapy. This study evaluates the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of PF-07261271 in healthy participants.
METHODS: This phase 1, randomized, double-blind, placebo-controlled study assessed single ascending doses (SAD; intravenous 30-1000 mg) and multiple doses (MD; subcutaneous 300 mg once every 4 weeks) of PF-07261271 in healthy adults. Safety, PK, immunogenicity and exploratory PD serum biomarkers (total soluble TL1A [sTL1A] and p40) were evaluated.
RESULTS: Thirty-five participants were enrolled (Part A: SAD, N = 27; Part B: MD, N = 8). PF-07261271 was generally safe and well tolerated; all treatment-emergent adverse events were mild/moderate. Following peak serum concentration, there was a multi-phase decline with a trend towards increased terminal half-life at the higher doses. For the MD cohort, the estimated bioavailability of PF-07261271 administered subcutaneously was 48%. Dose-dependent increases from baseline in serum total sTL1A and p40 levels were observed in participants receiving PF-07261271, demonstrating target engagement. There was no apparent impact of anti-drug antibodies on safety, PK or PD parameters.
CONCLUSION: PF-07261271 demonstrated p40 and TL1A target engagement and a favourable safety profile. Further studies are warranted to evaluate its safety and efficacy in patients with IBD.
CLINICALTRIALS: gov: NCT05536440.
METHODS: This phase 1, randomized, double-blind, placebo-controlled study assessed single ascending doses (SAD; intravenous 30-1000 mg) and multiple doses (MD; subcutaneous 300 mg once every 4 weeks) of PF-07261271 in healthy adults. Safety, PK, immunogenicity and exploratory PD serum biomarkers (total soluble TL1A [sTL1A] and p40) were evaluated.
RESULTS: Thirty-five participants were enrolled (Part A: SAD, N = 27; Part B: MD, N = 8). PF-07261271 was generally safe and well tolerated; all treatment-emergent adverse events were mild/moderate. Following peak serum concentration, there was a multi-phase decline with a trend towards increased terminal half-life at the higher doses. For the MD cohort, the estimated bioavailability of PF-07261271 administered subcutaneously was 48%. Dose-dependent increases from baseline in serum total sTL1A and p40 levels were observed in participants receiving PF-07261271, demonstrating target engagement. There was no apparent impact of anti-drug antibodies on safety, PK or PD parameters.
CONCLUSION: PF-07261271 demonstrated p40 and TL1A target engagement and a favourable safety profile. Further studies are warranted to evaluate its safety and efficacy in patients with IBD.
CLINICALTRIALS: gov: NCT05536440.