Efficacy and safety of treatment with an anti-m2e monoclonal antibody in experimental human influenza.

BACKGROUND: The efficacy of TCN-032, a human monoclonal antibody targeting a conserved epitope on M2e, was explored in experimental human influenza. METHODS: Healthy volunteers were inoculated with influenza A/Wisconsin/67/2005 (H3N2) and received a single dose of the study drug, TCN-032, or placebo 24 hours later. Subjects were monitored for symptoms, viral shedding, and safety, including cytokine measurements. Oseltamivir was administered 7 days after inoculation. RESULTS: Although the primary objective of reducing the proportion of subjects developing any grade ≥2 influenza symptom or pyrexia, was not achieved, TCN-032-treated subjects showed 35% reduction (P = .047) in median total symptom area under the curve (days 1-7) and 2.2 log reduction in median viral load area under the curve (days 2-7) by quantitative polymerase chain reaction (P = .09) compared with placebo-treated subjects. TCN-032 was safe and well tolerated with no additional safety signals after administration of oseltamivir. Serum cytokine levels (interferon γ, tumor necrosis factor α, and interleukin 8 and 10) were similar in both groups. Genotypic and phenotypic analyses showed no difference between virus derived from subjects after TCN-032 treatment and parental strain. CONCLUSIONS: These data indicate that TCN-032 may provide immediate immunity and therapeutic benefit in influenza A infection, with no apparent emergence of resistant virus. TCN-032 was safe with no evidence of immune exacerbation based on serum cytokine expression. Clinicaltrials.gov registry number. NCT01719874.

Peginterferon Lambda-1a Is Associated with a Low Incidence of Autoimmune Thyroid Disease in Chronic Hepatitis C.

Peginterferon alfa (alfa) increases the risk of autoimmune disease. Peginterferon lambda-1a (Lambda) acts through a receptor with a more liver-specific distribution compared to the alfa receptor. In a phase-2b study, 525 treatment-naive patients with chronic hepatitis C virus (HCV) infection received ribavirin and Lambda interferon (120, 180, or 240 µg) or alfa interferon (180 µg) for 24 (genotypes 2 and 3) or 48 (genotypes 1 and 4) weeks. Retrospective analysis found that adverse events of MedDRA-coded thyroid dysfunction and abnormal levels of thyroid-stimulating hormone (TSH) were significantly more frequent with alfa versus Lambda (12% versus 2.6% and 15.2% versus 3.4%, respectively, both P<0.0001). Most Lambda recipients with abnormal TSH had levels below the lower limit of normal; the frequency of low and high TSH was similar in alfa recipients with abnormal TSH. Blinded review by an endocrinologist found that new-onset primary hypothyroidism or painless thyroiditis was less frequent with Lambda versus alfa (0.5% and 1.8% versus 5.3% and 7.5%, respectively, P<0.0001). Most TSH elevations reflected new-onset hypothyroidism requiring treatment, while most markedly suppressed TSH values reflected probable painless thyroiditis and resolved without sequelae. In conclusion, HCV-infected patients treated with Lambda/ribavirin experienced fewer adverse events of thyroid dysfunction compared with patients treated with alfa/ribavirin.

Recombinant human thrombin: safety and immunogenicity in pediatric burn wound excision.

BACKGROUND: Previous studies of recombinant human thrombin (rThrombin) enrolled adult and adolescent patients. This phase 4, open-label, single-group study was conducted in pediatric patients undergoing synchronous burn wound excision and skin grafting to provide information regarding the safety and immunogenicity of rThrombin (primary and secondary endpoints) in this population. METHODS: Topical rThrombin was applied as a hemostatic aid during a surgical procedure (day 1). Adverse events and clinical laboratory abnormalities were recorded during the study. Immunogenicity samples were collected on days 1 and 29 (study end). Study results were summarized with descriptive statistics. RESULTS: Thirty patients enrolled and 28 completed the study. Mean age was 6.9 years (range, 0.9-17.8 years); 40.0% of patients were girls. Flame and scald were the most common burn types (33.3% each, n = 10/30). Mean graft size was 3.6% total body surface area. Procedural pain (50.0% patients), pruritus (43.3%), and anemia (30.0%) were the most commonly reported adverse events. All adverse events and clinical laboratory abnormalities were considered unrelated to treatment. No patients developed anti-rThrombin product antibodies at day 29. CONCLUSIONS: In pediatric patients undergoing burn wound excision and skin grafting, rThrombin was well tolerated and did not lead to the formation of anti-rThrombin product antibodies.

Efficacy, safety, and treatment satisfaction of tadalafil versus placebo in patients with erectile dysfunction evaluated at tertiary-care academic centers.

OBJECTIVES: To determine the efficacy, safety, and treatment satisfaction of tadalafil 20 mg for erectile dysfunction (ED) in patients evaluated at tertiary-care academic centers. METHODS: In this randomized, double-blind, placebo-controlled trial, patients were randomly allocated to receive fixed-dose tadalafil 20 mg (n = 146) or placebo (n = 49) for 12 weeks. Efficacy was assessed by the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and Global Assessment Question (GAQ); patient and partner treatment satisfaction by the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) and SEP; and safety by adverse events, laboratory values, and vital signs. RESULTS: Mean baseline IIEF erectile function (EF) domain was 12.98. Fifty-one percent of enrolled patients had severe baseline ED, and 82% had organic ED. Pre-existing, ED-associated comorbid conditions were common. When compared with patients treated with placebo, those receiving tadalafil reported significant improvement from baseline in the IIEF EF domain (P <0.001), successful penetration attempts (SEP question 2; P <0.001), successful intercourse (SEP question 3; P <0.001), and all secondary efficacy outcomes (P <0.001). Patients and their sexual partners were also significantly more satisfied with tadalafil treatment (P <0.001), including overall satisfaction (P <0.001) and length of time the treatment worked (P <0.001). Mild or moderate headache, dyspepsia, and myalgia were the most frequent treatment-emergent adverse events reported. CONCLUSIONS: Tadalafil significantly improved erectile function and patient and partner satisfaction and was well tolerated. These results were observed in a tertiary-care, academic center population with a high incidence of severe, organic ED, and comorbid medical conditions, factors known to compromise erectile function and treatment outcome.