Clinical Pharmacology in Drug Development最新文献

{"title":"Pharmacokinetics, Immunogenicity, and Safety of a Modified YTE Antibody in Healthy Adults","authors":"Maria Rosario,&nbsp;Jan de Hoon,&nbsp;Flonza Isa,&nbsp;Kenneth Turner,&nbsp;Jing Li,&nbsp;Joel Kantrowitz,&nbsp;Samit Ganguly,&nbsp;Sasha Fraser,&nbsp;Zhongqing Will He,&nbsp;Hong Yan,&nbsp;Ana Gonzalez Ortiz,&nbsp;Lori Faria,&nbsp;Ingeborg Heirman,&nbsp;Alina Baum,&nbsp;Thomas D Norton,&nbsp;Yogesh Patel,&nbsp;Veronica Mas Casullo,&nbsp;John D Davis","doi":"10.1002/cpdd.70107","DOIUrl":"https://doi.org/10.1002/cpdd.70107","url":null,"abstract":"<p>REGN17092, a fully human immunoglobulin (Ig) G1 antibody with M252Y/S254T/T256E (YTE) modification in the Fc portion, was assessed in a first-in-human study (ClinicalTrials.gov, NCT05923424). REGN17092 was designed to target the severe acute respiratory coronavirus 2 (SARS-CoV-2) S protein. However, due to the emergence of new SARS-CoV-2 variants, the program was discontinued. In this single-center, randomized, placebo-controlled, single-ascending-dose study, participants received a single IV dose of REGN17092 (300, 1200, or 2400 mg) or placebo, or a single SC dose of REGN17092 (300 or 1200) or placebo. Endpoints assessed included pharmacokinetics (PK), safety, and immunogenicity. Allometric scaling was used to predict the terminal half-life of REGN17092 and to ensure adequate exposure multiples relative to the exposure at the NOAEL. Forty participants were included. Mean concentrations of REGN17092 in serum increased in a dose-proportional manner and were consistent with linear PK for a single dose administered IV or SC. PK analysis of a single dose of REGN17092 administered IV or SC suggests that REGN17092 has a half-life of 80–90 days and showed detectable penetration into nasal fluid. No anti-drug antibody responses were noted. In this Phase 1 study, REGN17092 was tolerable with a long half-life, highlighting the value of YTE modification.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 10","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2026 ACCP Abstract Booklet","authors":"","doi":"10.1002/cpdd.70089","DOIUrl":"https://doi.org/10.1002/cpdd.70089","url":null,"abstract":"<p><b>DATE: September 27, 2026</b></p><p><b>TIME: 5:00 – 7:00 PM</b></p><p><b>DATE: September 28, 2026</b></p><p><b>TIME: 5:00 – 7:00 PM</b></p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 S1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Dose-Escalation Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of HP501 in Male Chinese Gout Patients with Hyperuricemia","authors":"Longxia Chen,&nbsp;Ruilin Ding,&nbsp;Yuanwei Chen,&nbsp;Xinghai Li,&nbsp;Tengqiong Xiong,&nbsp;Hong Chen,&nbsp;Xiaojing Hu,&nbsp;Yi Zhou,&nbsp;Feng Jiang,&nbsp;Qing Peng","doi":"10.1002/cpdd.70101","DOIUrl":"10.1002/cpdd.70101","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>HP501, a novel highly selective renal urate transporter 1 (URAT1) inhibitor, represents a promising therapeutic option for hyperuricemia. This Phase I study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of HP501 in Chinese gout patients. 37 patients with gout and hyperuricemia were enrolled in this single-center, open-label, dose-escalation study. Participants were sequentially assigned to receive HP501 at 60, 80, and 100 mg twice daily (BID) following single- and multiple-dose regimens. Safety assessments, PK parameters, and PD reductions were systematically evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p>HP501 demonstrated an acceptable safety and tolerability profile across all dose cohorts. The most common adverse events (≥10% of patients) included gout flare (36.1%), prostatic hypertrophy (36.1%), elevated ALT (16.7%), and kidney stones (11.1%), all of which were mild to moderate in severity. PK analysis revealed dose-proportional increases in Cmax and AUC (60 to 100 mg BID), with corresponding dose-dependent reductions in serum UA levels. All patients achieved therapeutic UA targets (&lt;360 µmol/L).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p>These findings support the clinical advancement of HP501, with 60 to 100 mg BID identified as the recommended dose range for further investigation in subsequent trials. However, these findings are preliminary and limited by the single-center design, small sample size, and exclusion of female patients, warranting confirmation in larger, more diverse populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 9","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A First-in-Japanese Phase 1, Double-Blind, Placebo-Controlled, Parallel-Cohort Study of Sefaxersen, an Antisense Oligonucleotide Targeting Complement Factor B, in Healthy Participants","authors":"Takakazu Sato,&nbsp;Hiroyuki Fukase,&nbsp;Takaaki Ishida,&nbsp;Arisa Karasawa","doi":"10.1002/cpdd.70097","DOIUrl":"10.1002/cpdd.70097","url":null,"abstract":"<p>Increased activity in the complement alternative pathway (AP) plays a key role in diseases such as IgA nephropathy (IgAN). This first-in-Japanese double-blind Phase 1 study investigated the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of sefaxersen (RO7434656), an antisense oligonucleotide targeting complement factor B messenger RNA. Healthy participants were randomized equally into four cohorts: placebo or sefaxersen 20, 40, or 70 mg. The PK, PD, and safety endpoints were monitored throughout the study and during the 90-day follow-up period. All 24 participants completed the study, with no new safety signals or clinically meaningful changes in blood chemistry, electrocardiogram, or vital signs observed. Plasma sefaxersen concentration demonstrated a biphasic PK profile, characterized by an initial rapid decline followed by a slow elimination. Sefaxersen decreased PD markers related to the complement AP selectively, without affecting the classical pathway, in a dose-dependent manner, and the PD effects persisted over 2 to 3 months. Sefaxersen was well tolerated by healthy Japanese participants, with a manageable safety profile. These findings support the inclusion of Japanese patients with IgAN in the global Phase 3 study (IMAGINATION, NCT05797610).</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 9","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic and Pharmacodynamic Bio-Similarity of ADL-018 to Innovator Omalizumab: A Randomized Study in Healthy Adults","authors":"Sunil Soitawala,&nbsp;Hiren Prajapati,&nbsp;Hiren Mehta,&nbsp;Pawan Kumar Singh","doi":"10.1002/cpdd.70098","DOIUrl":"10.1002/cpdd.70098","url":null,"abstract":"<p>Bioequivalence and safety of ADL-018, an omalizumab biosimilar, were compared with United States-licensed omalizumab (US-OMA) and European Union-approved omalizumab (EU-OMA), both approved for allergies. Healthy adults were randomized (1:1:1) to receive a dose of ADL-018, US-OMA, or EU-OMA (150 mg/mL). Pharmacokinetic (PK) parameters, including AUC_(0–last), AUC_(0–∞), and C_max, were considered equivalent if 90% CIs of geometric mean ratios (GMRs) were within predefined equivalence margin (0.80–1.25) using ANCOVA model. Other PK parameters, pharmacodynamics (PD) (free/total immunoglobulin E [IgE]), immunogenicity, and safety were compared. Overall, 306 participants (n = 102 per arm) were dosed; 287 completed the study. Equivalence of primary PK parameters was confirmed for pairwise comparisons, with 90% CIs within the predefined margin (GMRs of ADL-018 vs US-OMA: AUC_(0–last)—1.08, AUC_(0–∞)—1.07, C_max—1.05; GMRs of ADL-018 vs EU-OMA: AUC_(0–last)—1.06, AUC_(0–∞)—1.06, C_max – 1.05; and GMRs of US-OMA vs EU-OMA: AUC_(0–last)—0.99, AUC_(0–∞)—0.99, C_max—1.00). PK/PD parameters were comparable across arms. Increase in total IgE (AUEC ∼30,000 to 35,000 h IU/mL) and decrease in free IgE (AUEC ∼29,000 to 35,000 h IU/mL) were comparable across arms. Similar incidence of adverse events across arms (treatment-emergent adverse events: ADL-018, n = 6; US-OMA, n = 5; EU-OMA, n = 4) was observed. ADL-018 demonstrated PK/PD equivalence and comparable safety profile to reference omalizumab.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 9","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Open-Label Study Investigating the 5-HT2A Receptor Occupancy of Remlifanserin (ACP-204) With the PET Radioligand [18F]Altanserin in Healthy Male Participants","authors":"Ethan S. Burstein,&nbsp;Christine Sandiego,&nbsp;Brian Raether,&nbsp;Xiaoshu Feng,&nbsp;Bryan Dirks,&nbsp;Mona Darwish,&nbsp;Peter Zhang,&nbsp;David S. Russell,&nbsp;Eugenii A. Rabiner,&nbsp;Sanjeev Pathak","doi":"10.1002/cpdd.70096","DOIUrl":"https://doi.org/10.1002/cpdd.70096","url":null,"abstract":"<p>Remlifanserin (ACP-204) is a selective 5-HT_2A receptor inverse agonist that builds upon scientific findings of its structural analog, pimavanserin. This Phase 1, open-label study in healthy adults (N = 16) describes the central 5-HT_2A receptor occupancy of remlifanserin at different doses and plasma concentrations using positron emission tomography imaging and radioligand [¹⁸F]altanserin, with pimavanserin as a reference molecule. Receptor occupancy measurements taken at time to maximum plasma concentration (T_max) and various intervals up to five half-lives after T_max were correlated with study drug plasma concentrations and estimated from a Lassen plot. Administration of remlifanserin or pimavanserin resulted in plasma-concentration-dependent occupancy of 5-HT_2A receptors (ranges, 53%–100% and 41%–100%, respectively) and was adequately predicted by an E_max model with a fixed Hill slope of 1. The half maximal effective plasma concentration (EC₅₀) values for remlifanserin and pimavanserin were estimated to be 0.37 and 0.55 ng/mL, respectively, suggesting that remlifanserin occupies 5-HT_2A receptors with comparable to slightly greater potency than pimavanserin. Single doses of remlifanserin were safe and well tolerated. Study findings will inform the development and dosing of remlifanserin in future Phase 2/3 trials.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 9","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148859947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Originality, Authorship, and Accountability in AI-Enabled Pharmaceutical Design","authors":"Mark F. Hubbard,&nbsp;Amalia M. Issa,&nbsp;Michael J. Fossler","doi":"10.1002/cpdd.70093","DOIUrl":"https://doi.org/10.1002/cpdd.70093","url":null,"abstract":"&lt;p&gt;The pharmaceutical sector is entering a period in which artificial intelligence (AI) no longer merely accelerates familiar workstreams; it may increasingly participate in the generation of hypotheses, the identification of targets, the prioritization of candidate compounds, the design of clinical trial strategies, the preparation of regulatory narratives, and the construction of patent portfolios. These uses promise extraordinary gains in speed and scale. The use of AI may also upset a basic legal premise: protected and trusted work in pharmaceutical innovation has historically been attributed to identifiable human judgment, skill, and knowledge.&lt;/p&gt;&lt;p&gt;In this editorial, we argue that pharmaceutical patent law, as well as inventors, should treat AI as a powerful instrument of assistance rather than as an independent author, inventor, or source of regulatory truth. In drug development, the question is not simply whether an output is new. The more important question is whether the output can be connected to a traceable human contribution, a reliable evidentiary record, and a governance system capable of explaining why the result deserves legal protection or regulatory approval, and ultimately clinical use.&lt;/p&gt;&lt;p&gt;In ordinary conversation, an AI-generated molecule, formulation strategy, protocol summary, or safety narrative may appear “original” if it did not previously exist in that precise form. Patent law is more demanding regarding originality and novelty. Patent law asks who conceived the claimed invention and whether the claim satisfies novelty, non-obviousness, enablement, and written-description requirements.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Copyright law&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; asks whether protectable expression reflects human authorship. Trade-secret law asks whether information derives value from secrecy and has been reasonably protected.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Regulatory law asks whether data and analysis are credible for the intended use of the therapeutic under examination.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Those doctrines differ, but they share a common concern in pharmaceutical applications: accountability cannot be assigned to a machine or search engine. A model may propose structures, rank candidates, draft text, or identify correlations, but legal and scientific responsibility must remain with qualified people and institutions that can justify decisions, disclose limitations, preserve records, be held ethically and legally accountable, and correct errors.&lt;/p&gt;&lt;p&gt;The leading US inventorship decision remains &lt;i&gt;Thaler v. Vidal&lt;/i&gt;,&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; in which the 4th Federal Circuit Court held that the Patent Act requires an inventor to be a natural person. The decision did not foreclose patent protection for inventions developed with AI assistance; rather, it rejected the proposition that an AI system itself may be named as the inventor. That distinction is central for pharmaceutical design. A medicinal chemist, computational bi","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 9","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.70093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148859925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioequivalence of two rabeprazole formulations and pharmacokinetic variability by CYP2C19 genotype and sex in healthy Korean participants: A four-period replicated crossover study","authors":"Nakyong Lee,&nbsp;Joo-Youn Cho,&nbsp;Byungwook Kim","doi":"10.1002/cpdd.70099","DOIUrl":"10.1002/cpdd.70099","url":null,"abstract":"<p>Rabeprazole is a highly variable drug for which demonstration of bioequivalence is often challenging, and CYP2C19 genotype and sex have been suggested as potential contributors to pharmacokinetic variability. We evaluated the pharmacokinetics, bioequivalence (BE), and tolerability of a generic rabeprazole formulation compared with the reference product in healthy Korean participants using an open-label, randomized, single-dose, two-sequence, four-period replicated crossover design with a scaled average BE (SABE) approach. Exploratory subgroup analyses according to CYP2C19 genotype and sex were also performed. Fifty-two participants received single 20 mg doses under fasting conditions, and 46 completed the trial. BE was evaluated using SABE and conventional average BE (ABE), with subgroup analyses by genotype and sex. Geometric mean ratios (GMRs) of the test to reference formulations were within the BE acceptance range under ABE and SABE approaches. The reference formulation showed high intra-CV in maximum plasma concentration (<i>C</i>_max; 67.9%), consistent with the classification of rabeprazole as a highly variable drug. These results demonstrated bioequivalence between the test and reference formulations under both conventional average bioequivalence and scaled bioequivalence approaches.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 8","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Bioavailability of a Fixed-Dose Combination of Etoricoxib and Betamethasone in Healthy Volunteers","authors":"Lourdes Garza-Ocañas,&nbsp;Christian T. Badillo-Castañeda,&nbsp;Sandra L. Montoya-Eguía,&nbsp;María T. Zanatta-Calderón,&nbsp;Julia D. Torres-Garza,&nbsp;Pedro Lennon Sáenz- Chávez,&nbsp;Kevin F. Rios-Brito,&nbsp;Pablo E. Morales-Hernandez,&nbsp;Seydhel C. Reyes-Granados,&nbsp;Jorge González-Canudas","doi":"10.1002/cpdd.70100","DOIUrl":"10.1002/cpdd.70100","url":null,"abstract":"<p>This study evaluated the pharmacokinetic profiles and comparative bioavailability of etoricoxib 90 mg tablets and betamethasone 0.25 mg/0.5 mL solution, administered individually (reference drugs), versus a fixed-dose combination (FDC) tablet containing etoricoxib 90 mg and betamethasone 0.25 mg (test drug) under fasting conditions in healthy Mexican volunteers. A randomized, open-label, three-period, crossover, single-dose study with a 14-day washout period was conducted. Study drugs were administered orally following a 10-h overnight fast with 250 mL of water and fasting continued for at least 4 h post-dose. Serial blood samples were collected pre- and post-dose, and the drug concentrations were quantified using Liquid Chromatography coupled to Tandem Mass Spectrometry (LC-MS/MS). Forty-two subjects (22 women, 20 men; mean age 22.7 years; mean weight 64.7 kg) were enrolled, and 39 completed the study. Comparative bioavailability was established if the 90% confidence intervals of log-transformed C_max and AUC_{0–72 h} fell within the predefined range of 80%–125%. Two non-serious adverse events were reported. Results demonstrated that the pharmacokinetic profile and bioavailability of the etoricoxib/betamethasone FDC were comparable to those of reference formulations, with no evidence of pharmacokinetic interactions.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 8","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 1, Single-Center, Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Escalation Study for the Evaluation of the Safety, Tolerability, and Pharmacokinetics of Recombinant Human Plasma Gelsolin (rhu-pGSN) Following Intravenous Administration to Healthy Volunteers","authors":"Yao Liu,&nbsp;Susan L. Levinson,&nbsp;Edward Kowalik,&nbsp;Jeremy Pronchik,&nbsp;Lester Kobzik,&nbsp;Mark J. DiNubile","doi":"10.1002/cpdd.70094","DOIUrl":"10.1002/cpdd.70094","url":null,"abstract":"<p>Plasma gelsolin (pGSN) is a non-immunosuppressive anti-inflammatory immunomodulator with demonstrated efficacy in animal models of acute lung injury. Its therapeutic potential for moderate-to-severe acute respiratory distress syndrome is currently under investigation. This randomized, double-blind, placebo-controlled study assessed the safety, pharmacokinetics, and immunogenicity of multiple ascending doses of recombinant human pGSN (rhu-pGSN) in healthy volunteers. Thirty-two participants were enrolled across four dose cohorts (6, 12, 18, and 24 mg/kg of body weight), randomized 3:1 to receive five daily intravenous (IV) infusions of rhu-pGSN or placebo. Plasma pGSN concentrations increased as dose increased after single and multiple IV administrations. Following the final dose, geometric mean C_max ranged from 218.9 to 970.9 µg/mL, and geometric mean AUC_0–inf ranged from 6634.8 to 17,779.1 h µg/mL across four dose levels. Ten subjects (41.7%) who received rhu-pGSN reported a total of 13 adverse events (AEs), and one subject (12.5%) who received placebo reported an AE. All AEs were mild or moderate. No anti-rhu-pGSN antibodies were detected pre-dose or at Day 28 post first dose. Overall, five IV rhu-pGSN doses (up to 24 mg/kg daily) appeared safe and well tolerated.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 8","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}