A randomized phase 2 study of efmarodocokin alfa, an IL-22 agonist, versus vedolizumab in patients with ulcerative colitis.

Background And Aims: Efmarodocokin alfa is an interleukin (IL)-22 agonist, with favorable pharmacokinetic (PK) properties and an acceptable safety profile. This study further explored the therapeutic potential of efmarodocokin alfa compared to vedolizumab in patients with ulcerative colitis (UC).

Methods: This randomized phase 2 trial evaluated the efficacy, safety, PK, and pharmacodynamics of 3 doses of efmarodocokin alfa administered intravenously every 4 weeks (30 μg/kg [n=43], 60 μg/kg [n=44], and 90 μg/kg [n=43]) compared with placebo (n=22) and with vedolizumab (n=43) in the treatment of moderate to severe UC.

Comparative Pharmacokinetics and Safety Assessment of 1st- and 2nd-Generation Zinpentraxin Alfa Drug Products in Healthy Volunteers: A Randomized Crossover Study.

Zinpentraxin alfa is a recombinant form of the human pentraxin-2 that was studied in idiopathic pulmonary fibrosis (IPF). To improve the purity and yield of the drug material, a 2nd-generation drug product was developed. To characterize and compare the pharmacokinetic (PK) properties of the 1st- and 2nd-generation zinpentraxin alfa, PK studies were conducted in healthy volunteers (HVs).

Population pharmacokinetics and pharmacodynamics of efmarodocokin alfa (IL-22Fc).

Efmarodocokin alfa (IL-22Fc) is a fusion protein of human IL-22 linked to the crystallizable fragment (Fc) of human IgG4. It has been tested in multiple indications including inflammatory bowel disease (IBD). The purposes of the present analyses were to describe the population pharmacokinetics (PK) of efmarodocokin alfa and perform pharmacodynamic (PD) analysis on the longitudinal changes of the PD biomarker REG3A after efmarodocokin alfa treatment as well as identify covariates that affect efmarodocokin alfa PK and REG3A PD.

Archway Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration 2-Year Results.

Purpose: To report 2-year results from the Archway clinical trial of the Port Delivery System with ranibizumab (PDS) for treatment of neovascular age-related macular degeneration (nAMD).

Design: Phase 3, randomized, multicenter, open-label, active-comparator-controlled trial.

Participants: Patients with previously treated nAMD diagnosed within 9 months of screening and responsive to anti-vascular endothelial growth factor therapy.

Pharmacokinetics of the Port Delivery System with Ranibizumab in the Ladder Phase 2 Trial for Neovascular Age-Related Macular Degeneration.

Introduction: Ladder was a phase 2 trial that evaluated the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration. Serum and aqueous humor samples were collected to characterize the pharmacokinetics (PK) of ranibizumab delivered through the PDS.

Methods: Ladder was a multicenter, randomized, active treatment-controlled, phase 2 clinical trial.

A phase 1, randomized study to evaluate safety, tolerability, and pharmacokinetics of GDC-3280, a potential novel anti-fibrotic small molecule, in healthy subjects.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. Although anti-fibrotic treatments, such as pirfenidone, are available that reduce the rate of disease progression, these medications have limitations in tolerability, and IPF patients still have poor prognoses. GDC-3280, an orally available small molecule that was designed to improve upon pirfenidone's activity, has anti-fibrotic activity in animal models.

Translational and pharmacokinetic-pharmacodynamic application for the clinical development of GDC-0334, a novel TRPA1 inhibitor.

GDC-0334 is a novel small molecule inhibitor of transient receptor potential cation channel member A1 (TRPA1), a promising therapeutic target for many nervous system and respiratory diseases. The pharmacokinetic (PK) profile and pharmacodynamic (PD) effects of GDC-0334 were evaluated in this first-in-human (FIH) study. A starting single dose of 25 mg was selected based on integrated preclinical PK, PD, and toxicology data following oral administration of GDC-0334 in guinea pigs, rats, dogs, and monkeys.

Comparable Pharmacokinetics, Safety, and Tolerability of Etrolizumab Administered by Prefilled Syringe or Autoinjector in a Randomized Trial in Healthy Volunteers.

Introduction: Etrolizumab is a novel, dual-action anti-β7 integrin antibody studied in phase 3 trials in patients with inflammatory bowel disease. An autoinjector (AI) is being developed in parallel to complement the prefilled syringe with needle safety device (PFS-NSD) for subcutaneous (SC) administration in these trials. Here we demonstrate the comparable pharmacokinetics, tolerability, and safety of both devices.

A TRPA1 inhibitor suppresses neurogenic inflammation and airway contraction for asthma treatment.

Despite the development of effective therapies, a substantial proportion of asthmatics continue to have uncontrolled symptoms, airflow limitation, and exacerbations. Transient receptor potential cation channel member A1 (TRPA1) agonists are elevated in human asthmatic airways, and in rodents, TRPA1 is involved in the induction of airway inflammation and hyperreactivity. Here, the discovery and early clinical development of GDC-0334, a highly potent, selective, and orally bioavailable TRPA1 antagonist, is described.

Phase I Study of Enavatuzumab, a First-in-Class Humanized Monoclonal Antibody Targeting the TWEAK Receptor, in Patients with Advanced Solid Tumors.

This phase I study evaluates the safety, MTD, pharmacokinetics (PK), pharmacodynamics, and preliminary anticancer activity of enavatuzumab, a humanized IgG1 antibody to the TWEAK receptor, in patients with advanced solid malignancies. Patients received escalating doses of enavatuzumab given intravenously over 60 minutes every 2 weeks. Blood was obtained for PK and biomarker assessment.

A Pharmacokinetic Bioequivalence Study Comparing Pirfenidone Tablet and Capsule Dosage Forms in Healthy Adult Volunteers.

Introduction: Pirfenidone film-coated tablets were developed to offer an alternative to the marketed capsule formulation. This study assessed the bioequivalence of the tablet and capsule formulations under fed and fasted states.

Methods: A Phase I, open-label, randomized, four-treatment-period, four-sequence, crossover pharmacokinetics study (NCT02525484) was conducted.