Model-Based Characterization of the Pharmacokinetics, Target Engagement Biomarkers, and Immunomodulatory Activity of PF-06342674, a Humanized mAb Against IL-7 Receptor-α, in Adults with Type 1 Diabetes.

IL-7 receptor-α (IL-7Rα) blockade has been shown to reverse autoimmune diabetes in the non-obese diabetic mouse by promoting inhibition of effector T cells and consequently altering the balance of regulatory T (T) and effector memory (T) cells. PF-06342674 is a humanized monoclonal antibody that binds to and inhibits the function of IL-7Rα. In the current phase 1b study, subjects with type 1 diabetes (T1D) received subcutaneous doses of either placebo or PF-06342674 (1, 3, 8 mg/kg/q2w or 6 mg/kg/q1w) for 10 weeks and were followed up to 18 weeks.

Immunomodulatory activity of humanized anti-IL-7R monoclonal antibody RN168 in subjects with type 1 diabetes.

Background: The cytokine IL-7 is critical for T cell development and function. We performed a Phase Ib study in patients with type 1 diabetes (T1D) to evaluate how blockade of IL-7 would affect immune cells and relevant clinical responses.

Methods: Thirty-seven subjects with T1D received s.

The effects of single- and multiple-dose administration of bococizumab (RN316/PF-04950615), a humanized IgG2Δa monoclonal antibody binding proprotein convertase subtilisin/kexin type 9, in hypercholesterolemic subjects treated with and without atorvastatin: Results from four phase I studies.

Aims: Three single-dose and one multiple-dose phase I studies were conducted in subjects with primary hypercholesterolemia to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of bococizumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor.

Methods: The dosing schedules for hypercholesterolemic subjects randomized in the four phase I studies were (1) ascending, single, intravenous (IV) bococizumab (0.3, 1, 3, 6, 12, or 18 mg/kg), or placebo (N = 48; baseline low-density lipoprotein cholesterol [LDL-C] ≥130 mg/dL); (2) single, IV bococizumab (0.

Bosutinib versus Placebo for Autosomal Dominant Polycystic Kidney Disease.

Overactivation of Src has been linked to the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). This phase 2, multisite study assessed the efficacy and safety of bosutinib, an oral dual Src/Bcr-Abl tyrosine kinase inhibitor, in patients with ADPKD. Patients with ADPKD, eGFR≥60 ml/min per 1.

A Phase I Randomized Study of a Specifically Engineered, pH-Sensitive PCSK9 Inhibitor RN317 (PF-05335810) in Hypercholesterolemic Subjects on Statin Therapy.

This phase I study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of RN317 (PF-05335810), a specifically engineered, pH-sensitive, humanized proprotein convertase subtilisin kexin type 9 (PCSK9) monoclonal antibody, in hypercholesterolemic subjects (low-density lipoprotein cholesterol (LDL-C) ≥ 80 mg/dl) 18-70 years old receiving statin therapy. Subjects were randomized to: single-dose placebo, RN317 (subcutaneous (s.c.