scholarly journals Safety and Efficacy of CR6261 in an Influenza A H1N1 Healthy Human Challenge Model

2020 ◽  
Author(s):  
Alison Han ◽  
Lindsay Czajkowski ◽  
Luz Angela Rosas ◽  
Adriana Cervantes-Medina ◽  
Yongli Xiao ◽  
...  
Keyword(s):  
Influenza A ◽  
Controlled Trial ◽  
Influenza Infection ◽  
Area Under The Curve ◽  
Surface Protein ◽  
Healthy Human ◽  
Double Blind ◽  
Duration Of Symptoms ◽  
Influenza A H1n1 ◽  
Clinically Significant

Abstract Background It is imperative to identify new targets for improved vaccines and therapeutics against influenza and one such target is the relatively conserved stalk region of the influenza A hemagglutinin (HA) surface protein. Methods We conducted a randomized, double-blind, Phase II placebo-controlled trial of a monoclonal antibody that targets the HA stalk (CR6261) in a H1N1pdm09 healthy volunteer human challenge model. A single 50mg/kg dose of CR6261 was infused 24 hours after challenge and the primary efficacy outcome was area under the curve of viral RNA detection over time. Results Ninety-one healthy volunteers were randomized and underwent influenza challenge; 49 received CR6261 and 42 placebo. CR6261 had no statistically significant effect on AUC (AUC 48.56 log (copies/mL) x days, IQR 202 vs. AUC 25.53 log (copies/mL) x days, IQR 155), P=0.315), and no clinically significant effect on influenza disease measures including number of symptoms, duration of symptoms, or FLU-PRO scores. Preexisting anti-NA antibody titers were most predictive of reduced influenza disease. CR6261 reached a mean peak serum concentration of 1x10 6 ng/ml 15 minutes after infusion, and a mean peak of 5.97x10 2 ng/ml in the nasal mucosa 2-3 days after infusion. Conclusions The results of this study suggest that a monoclonal anti-stalk approach to prevent or treat influenza infection may be limited in efficacy. Future approaches should consider including and evaluating anti-stalk antibodies as part of a multi-faceted strategy rather than as a standalone therapeutic.

scholarly journals 1522. Safety and Efficacy of CR6261 in an Influenza A H1N1 Healthy Human Challenge Model

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S763-S763
Author(s):  
Alison Han ◽  
Lindsay Czajkowski ◽  
Luz Angela Rosas ◽  
Adriana Cervantes-Medina ◽  
Yongli Xiao ◽  
...  
Keyword(s):  
Pharmaceutical Company ◽  
Influenza A ◽  
Controlled Trial ◽  
Influenza Infection ◽  
Healthy Human ◽  
Double Blind ◽  
Duration Of Symptoms ◽  
Viral Shedding ◽  
Influenza A H1n1 ◽  
Significant Difference

Abstract Background Influenza virus infections cause significant morbidity and mortality during yearly seasonal epidemics and during sporadic pandemics. It is imperative to identify new targets for vaccines and therapeutics. One such target is the relatively conserved stalk region of the influenza A hemagglutinin (HA) surface protein. Methods We conducted a randomized, double-blind, Phase II placebo-controlled trial of a monoclonal antibody that targets the HA stalk (CR6261) in a H1N1pdm09 healthy volunteer human challenge model. CR6261 was infused 24 hours after challenge with H1N1pdm09 and the primary efficacy outcome was area under the curve (AUC) of viral shedding. Results Between March 2015-May 2018, 104 healthy volunteers were enrolled and randomized with 91 undergoing influenza challenge, of which 49 participants (54%) received treatment with CR6261 and 42 participants (46%) received placebo. A mean of 1x106 ng/mL of serum CR6261 was detected by 24 hours after infusion. Nasal CR6261 levels reached a peak mean of 5.97x102 ng/ml 2 days after infusion. There was no statistically significant difference in the primary outcome measure between the CR6261 group and placebo (median AUC 48.56 and 25.53 respectively, P=0.31). The severity of illness was compared between the two groups, and no significant difference was observed in number of symptoms, duration of symptoms, or FLU-PRO scores. Conclusion CR6261 had no statistically significant effect on AUC of viral shedding, and no clinically significant effect on overall influenza disease. Preexisting anti-neuraminidase (NA) antibody titers were most predictive of reduced influenza disease. Nasal CR6261 levels were much lower compared to serum, which may be a factor in the limited effect of CR6261 on this upper respiratory infection. These results suggest that a monoclonal anti-stalk approach to prevent or treat influenza infection may have limited efficacy. Future approaches should consider including and evaluating anti-stalk antibodies as part of a multi-faceted strategy rather than as a standalone therapeutic or vaccine strategy. Funding This study was funded in part by the intramural program of NIAID, NIH, by the NCI Contract No. 75N910D00024, Task Order No. 75N91019F00130, and through a CRADA with Janssen Infectious Diseases and Vaccines. Disclosures Amy Lwin, RN, BSN, Janssen Pharmaceutical Company of J&J (Employee) Jerald Sadoff, MD, Janssen Pharmaceutical Company of J&J (Employee)

A phase I randomized, double-blind, controlled trial of 2009 influenza A (H1N1) inactivated monovalent vaccines with different adjuvant systems

Vaccine ◽  
2011 ◽  
Vol 29 (48) ◽  
pp. 8974-8981 ◽  
Author(s):  
Alexander R. Precioso ◽  
João L. Miraglia ◽  
Lúcia Maria A. Campos ◽  
Alessandra C. Goulart ◽  
Maria do Carmo S.T. Timenetsky ◽  
...  
Keyword(s):  
Phase I ◽  
Influenza A ◽  
Controlled Trial ◽  
Double Blind ◽  
Influenza A H1n1

scholarly journals A Rapid Immune Response to 2009 Influenza A(H1N1) Vaccines in Adults: A Randomized, Double‐Blind, Controlled Trial

2010 ◽  
Vol 202 (5) ◽  
pp. 675-680 ◽  
Author(s):  
Jiang Wu ◽  
Wei Li ◽  
Hua‐Qing Wang ◽  
Jiang‐Ting Chen ◽  
Min Lv ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza A ◽  
Controlled Trial ◽  
Double Blind ◽  
Influenza A H1n1

scholarly journals Long-Acting Neuraminidase Inhibitor Laninamivir Octanoate (CS-8958) versus Oseltamivir as Treatment for Children with Influenza Virus Infection

2010 ◽  
Vol 54 (6) ◽  
pp. 2575-2582 ◽  
Author(s):  
Norio Sugaya ◽  
Yasuo Ohashi
Keyword(s):  
Virus Infection ◽  
Influenza A ◽  
H1n1 Virus ◽  
Controlled Trial ◽  
Influenza Virus Infection ◽  
Neuraminidase Inhibitor ◽  
Double Blind ◽  
Influenza A H1n1 ◽  
B Virus ◽  
Long Acting

ABSTRACT We conducted a double-blind, randomized controlled trial to compare a long-acting neuraminidase inhibitor, laninamivir octanoate, with oseltamivir. Eligible patients were children 9 years of age and under who had febrile influenza symptoms of no more than 36-h duration. Patients were randomized to 1 of 3 treatment groups: a group given 40 mg laninamivir (40-mg group), a group given 20 mg laninamivir (20-mg group), and an oseltamivir group. Laninamivir octanoate was administered as a single inhalation. Oseltamivir (2 mg/kg of body weight) was administered orally twice daily for 5 days. The primary end point was the time to alleviation of influenza illness. The primary analysis included 184 patients (61, 61, and 62 in the 40-mg group, 20-mg group, and oseltamivir group, respectively). Laninamivir octanoate markedly reduced the median time to illness alleviation in comparison with oseltamivir in patients infected with oseltamivir-resistant influenza A (H1N1) virus, and the reductions were 60.9 h for the 40-mg group and 66.2 h for the 20-mg group. On the other hand, there were no significant differences in the times to alleviation of illness between the laninamivir groups and oseltamivir group for patients with influenza A (H3N2) or B virus infection. Laninamivir octanoate was well tolerated. The most common adverse events were gastrointestinal events. Laninamivir octanoate was an effective and well-tolerated treatment for children with oseltamivir-resistant influenza A (H1N1) virus infection. Further study will be needed to confirm clinical efficacy against influenza A (H3N2) or B virus infection. Its ease of administration is noteworthy, because a single inhalation is required during the course of illness.

Safety and immunogenicity of 2009 pandemic influenza A H1N1 vaccines in China: a multicentre, double-blind, randomised, placebo-controlled trial

The Lancet ◽  
2010 ◽  
Vol 375 (9708) ◽  
pp. 56-66 ◽  
Author(s):  
Xiao-Feng Liang ◽  
Hua-Qing Wang ◽  
Jun-Zhi Wang ◽  
Han-Hua Fang ◽  
Jiang Wu ◽  
...  
Keyword(s):  
Pandemic Influenza ◽  
Influenza A ◽  
Controlled Trial ◽  
Double Blind ◽  
Influenza A H1n1

Influenza A (H1N1) 2009 two-dose immunization of US children: An observer-blinded, randomized, placebo-controlled trial

Vaccine ◽  
2011 ◽  
Vol 29 (8) ◽  
pp. 1569-1575 ◽  
Author(s):  
Eric Plennevaux ◽  
Mark Blatter ◽  
Matthew J. Cornish ◽  
Kerry Go ◽  
Daniel Kirby ◽  
...  
Keyword(s):  
Influenza A ◽  
Controlled Trial ◽  
Influenza A H1n1 ◽  
Us Children

scholarly journals Influence of Cinnamon on Glycemic Control in Individuals With Prediabetes: A Randomized Controlled Trial

2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Giulio R Romeo ◽  
Junhee Lee ◽  
Christopher M Mulla ◽  
Youngmin Noh ◽  
Casey Holden ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Controlled Trial ◽  
Area Under The Curve ◽  
Cost Effective ◽  
Tolerance Test ◽  
Controlled Clinical Trial ◽  
Oral Glucose ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Favorable Safety

Abstract Context The identification of adjunct safe, durable, and cost-effective approaches to reduce the progression from prediabetes to type 2 diabetes (T2D) is a clinically relevant, unmet goal. It is unknown whether cinnamon’s glucose-lowering properties can be leveraged in individuals with prediabetes. Objective The objective of this work is to investigate the effects of cinnamon on measures of glucose homeostasis in prediabetes. Design, Setting, Participants, and Intervention This double-blind, placebo-controlled, clinical trial randomly assigned adult individuals meeting any criteria for prediabetes to receive cinnamon 500 mg or placebo thrice daily (n = 27/group). Participants were enrolled and followed at 2 academic centers for 12 weeks. Main Outcome Measures Primary outcome was the between-group difference in fasting plasma glucose (FPG) at 12 weeks from baseline. Secondary end points included the change in 2-hour PG of the oral glucose tolerance test (OGTT), and the change in the PG area under the curve (AUC) derived from the OGTT. Results From a similar baseline, FPG rose after 12 weeks with placebo but remained stable with cinnamon, leading to a mean between-group difference of 5 mg/dL (P < .05). When compared to the respective baseline, cinnamon, but not placebo, resulted in a significant decrease of the AUC PG (P < .001) and of the 2-hour PG of the OGTT (P < .05). There were no serious adverse events in either study group. Conclusions In individuals with prediabetes, 12 weeks of cinnamon supplementation improved FPG and glucose tolerance, with a favorable safety profile. Longer and larger studies should address cinnamon’s effects on the rate of progression from prediabetes to T2D.

scholarly journals Long-Lasting Mucosal and Systemic Immunity against Influenza A Virus Is Significantly Prolonged and Protective by Nasal Whole Influenza Immunization with Mucosal Adjuvant N3 and DNA-Plasmid Expressing Flagellin in Aging In- and Outbred Mice

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 64 ◽  
Author(s):  
Jorma Hinkula ◽  
Sanna Nyström ◽  
Claudia Devito ◽  
Andreas Bråve ◽  
Steven E. Applequist
Keyword(s):  
Immune Responses ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Infection ◽  
Inbred Mouse ◽  
Herd Immunity ◽  
Serum Antibody ◽  
Mouse Strains ◽  
Virus Challenge ◽  
Influenza A H1n1

Background: Vaccination is commonly used to prevent and control influenza infection in humans. However, improvements in the ease of delivery and strength of immunogenicity could markedly improve herd immunity. The aim of this pre-clinical study is to test the potential improvements to existing intranasal delivery of formalin-inactivated whole Influenza A vaccines (WIV) by formulation with a cationic lipid-based adjuvant (N3). Additionally, we combined WIV and N3 with a DNA-encoded TLR5 agonist secreted flagellin (pFliC(-gly)) as an adjuvant, as this adjuvant has previously been shown to improve the effectiveness of plasmid-encoded DNA antigens. Methods: Outbred and inbred mouse strains were intranasally immunized with unadjuvanted WIV A/H1N1/SI 2006 or WIV that was formulated with N3 alone. Additional groups were immunized with WIV and N3 adjuvant combined with pFliC(-gly). Homo and heterotypic humoral anti-WIV immune responses were assayed from serum and lung by ELISA and hemagglutination inhibition assay. Homo and heterotypic cellular immune responses to WIV and Influenza A NP were also determined. Results: WIV combined with N3 lipid adjuvant the pFliC(-gly) significantly increased homotypic influenza specific serum antibody responses (>200-fold), increased the IgG2 responses, indicating a mixed Th1/Th2-type immunity, and increased the HAI-titer (>100-fold). Enhanced cell-mediated IFNγ secreting influenza directed CD4+ and CD8+ T cell responses (>40-fold) to homotypic and heterosubtypic influenza A virus and peptides. Long-term and protective immunity was obtained. Conclusions: These results indicate that inactivated influenza virus that was formulated with N3 cationic adjuvant significantly enhanced broad systemic and mucosal influenza specific immune responses. These responses were broadened and further increased by incorporating DNA plasmids encoding FliC from S. typhimurum as an adjuvant providing long lasting protection against heterologous Influenza A/H1N1/CA09pdm virus challenge.

Modafinil for fatigue associated with docetaxel-based chemotherapy: A randomized controlled trial.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 211-211
Author(s):  
Elizabeth J. Hovey ◽  
Paul L. De Souza ◽  
Gavin M. Marx ◽  
Phillip Parente ◽  
Tal Rapke ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Controlled Trial ◽  
Area Under The Curve ◽  
Study Medication ◽  
Double Blind ◽  
Patients With Cancer ◽  
Parallel Group ◽  
Grade 3 ◽  
Chemotherapy Patients ◽  
Md Anderson

211 Background: Chemotherapy-induced fatigue is a common complaint for patients with cancer. We investigated whether modafinil, a psychostimulant, could reduce fatigue in patients on chemotherapy. Methods: A multicenter, randomized, double-blind, placebo-controlled, parallel group study was conducted in patients with metastatic prostate or breast cancer suffering significant chemotherapy-related fatigue whilst undergoing docetaxel-based chemotherapy. Patients were enrolled at the start of their 3rdor subsequent cycles of docetaxel which was continued for up to four further cycles (defined here as ‘treatment periods’). Patients were randomized 2:1 to receive modafinil 200mg daily or placebo for 15 days during each treatment period. Fatigue was evaluated by the MD Anderson Symptom Inventory (MDASI). The primary endpoint was MDASI area under the curve (AUC) during the first 7 days of study medication for the first two treatment periods (possible range 0-70). Other validated tools were used to record disturbances in sleep, mood and functional status. Results: Eighty-three patients (65 with prostate cancer) were randomized and received at least one dose of study medication. The number of grade 3 or 4 adverse events (AEs) was 16/55 (29.1%) in the modafinil group and 5/28 (17.9%) in the placebo group. The toxicity profile was largely consistent with docetaxel-based chemotherapy and with previously reported AEs associated with modafinil use in the community; 11 AEs were possibly related to docetaxel; 1 to modafinil and 9 to neither treatment. Conclusions: Managing chemotherapy-related fatigue remains a major challenge. Despite not reaching the primary endpoint, there was a consistent trend towards improvement of chemotherapy-related fatigue in the modafinil arm. Further studies are needed to better understand the clinical implications of these findings. Funding sanofi-aventis; Study ID NCT00917748 . [Table: see text]

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