scholarly journals Safety and immunogenicity of a high-dose quadrivalent influenza vaccine administered concomitantly with a third dose of the mRNA-1273 SARS-CoV-2 vaccine in adults ≥ 65 years of age: a Phase II, open-label study

2021 ◽  
Author(s):  
Ruvim Izikson ◽  
Daniel Brune ◽  
Jean-Sébastien Bolduc ◽  
Pierre Bourron ◽  
Marion Fournier ◽  
...  
Keyword(s):  
Seasonal Influenza ◽  
Geometric Mean ◽  
Concomitant Administration ◽  
High Dose ◽  
Open Label ◽  
Open Label Study ◽  
Systemic Reactions ◽  
Vaccine Booster ◽  
Binding Antibody ◽  
Quadrivalent Influenza Vaccine

Background Concomitant seasonal influenza vaccination with a COVID-19 vaccine booster could help to minimise potential disruption to the seasonal influenza vaccination campaign and maximise protection against both diseases among individuals at risk of severe disease and hospitalisation. This study assesses the safety and immunogenicity of concomitant administration of high-dose quadrivalent influenza vaccine (QIV-HD) and a mRNA-1273 vaccine booster dose in older adults. Methods This is an ongoing Phase II, multi-centre, open-label study (NCT04969276). We describe interim results up to 21 days after vaccination (July 2021–August 2021). Adults aged ≥ 65 years living in the community, who were to have received a second mRNA-1273 dose at least five months previously, were randomised (1:1:1) to concomitant QIV-HD and mRNA-1273 vaccination (Coad), QIV-HD alone, or mRNA-1273 vaccine alone. Unsolicited adverse events (AEs) occurring immediately, solicited local and systemic reactions up to day (D)8, and unsolicited AEs, serious AEs (SAEs), AEs of special interest (AESIs) and medically attended AEs (MAAEs) up to D22 were reported. Haemagglutination inhibition (HAI) antibody responses to influenza A/H1N1, A/H3N2, B/Yamagata and B/Victoria strains and SARS CoV-2 binding antibody responses (SARS-CoV-2 Pre-Spike IgG ELISA) were assessed at D1 and D22. Findings Of 306 participants randomised, 296 were included for analysis (Coad, n=100; QIV-HD, n=92; mRNA-1273, n=104). Reactogenicity profiles were similar between the Coad and mRNA-1273 groups, with lower reactogenicity rates in the QIV-HD group (frequency [95% CIs] of solicited injection site reactions: 86·0% [77·6–92·1], 91·3% [84·2–96·0] and 61·8% [50·9–71·9] ; solicited systemic reactions: 80·0% [70·8–87·3], 83·7% [75·1–90·2] and 49·4% [38·7–60·2], respectively). Up to D22, unsolicited AEs were reported for 17·0% and 14·4% participants in the Coad and mRNA-1273 groups, respectively, with a lower rate (10·9%) in the QIV-HD group. Seven MAAEs were reported (Coad, n=3; QIV-HD, n=1; mRNA-1273, n=3). There were no SAEs, AESIs or deaths. HAI antibody geometric mean titres (GMTs) increased from D1 to D22 to similar levels for each influenza strain in the Coad and QIV-HD groups (GMTs [95% confidence interval], range across strains: Coad, 286 [233–352] to 429 [350–525] ; QIV-HD, 315 [257–386] to 471 [378–588]). SARS-CoV-2 binding antibody geometric mean concentrations (GMCs) also increased to similar levels in the Coad and mRNA-1273 groups (D22 GMCs [95% confidence interval]: 7634 [6445–9042] and 7904 [6883–9077], respectively). Interpretation No safety concerns or immune interference were observed for concomitant administration of QIV-HD with mRNA-1273 booster in adults aged ≥ 65 years, supporting co-administration recommendations.

scholarly journals High-dose oral and intravenous rifampicin for the treatment of tuberculous meningitis in predominantly HIV-positive Ugandan adults: a phase II open-label randomised controlled trial

2021 ◽  
Author(s):  
Fiona V Cresswell ◽  
David B Meya ◽  
Enock Kagimu ◽  
Daniel Grint ◽  
Lindsey te Brake ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Tuberculous Meningitis ◽  
Geometric Mean ◽  
Standard Of Care ◽  
Hiv Positive ◽  
High Dose ◽  
Open Label ◽  
Dose Oral ◽  
Csf Levels

Abstract Background High-dose rifampicin may improve outcomes of tuberculous meningitis (TBM). Little safety or pharmacokinetic (PK) data exist on high-dose rifampicin in HIV co-infection, and no cerebrospinal fluid (CSF) PK data exist from Africa. We hypothesized that high-dose rifampicin would increase serum and CSF concentrations without excess toxicity. Methods In this phase II open-label trial, Ugandan adults with suspected TBM were randomised to standard-of-care control (PO-10, rifampicin 10mg/kg/day), intravenous rifampicin (IV-20, 20mg/kg/day), or high-dose oral rifampicin (PO-35, 35mg/kg/day). We performed PK sampling on day 2 and 14. The primary outcomes were total exposure (AUC0-24), maximum concentration (Cmax), CSF concentration and grade 3-5 adverse events. Results We enrolled 61 adults, 92% were HIV-positive, median CD4 count was 50cells/µL (IQR 46–56). On day 2, geometric mean plasma AUC0-24hr was 42.9h.mg/L with standard-of-care 10mg/kg dosing, 249h.mg/L for IV-20 and 327h.mg/L for PO-35 (P<0.001). In CSF, standard-of-care achieved undetectable rifampicin concentration in 56% of participants and geometric mean AUC0-24hr 0.27mg/L, compared with 1.74mg/L (95%CI 1.2–2.5) for IV-20 and 2.17mg/L (1.6–2.9) for PO-35 regimens (p<0.001). Achieving CSF concentrations above rifampicin minimal inhibitory concentration (MIC) occurred in 11% (2/18) of standard-of-care, 93% (14/15) of IV-20, and 95% (18/19) of PO-35 participants. Higher serum and CSF levels were sustained at day 14. Adverse events did not differ by dose (p=0.34) Conclusion Current international guidelines result in sub-therapeutic CSF rifampicin concentration for 89% of Ugandan TBM patients. High-dose intravenous and oral rifampicin were safe, and respectively resulted in exposures ~6- and ~8-fold higher than standard-of-care, and CSF levels above the MIC

Testing G-CSF responsiveness predicts the individual susceptibility to infection and consecutive treatment in recipients of high-dose chemotherapy

Blood ◽  
2011 ◽  
Vol 117 (7) ◽  
pp. 2121-2128 ◽  
Author(s):  
Christian Straka ◽  
Michael Sandherr ◽  
Hans Salwender ◽  
Hannes Wandt ◽  
Bernd Metzner ◽  
...  
Keyword(s):  
Unknown Origin ◽  
High Dose Chemotherapy ◽  
Individual Risk ◽  
High Dose ◽  
Open Label ◽  
Open Label Study ◽  
Susceptibility To Infection ◽  
Intravenous Antibiotics ◽  
Grade 3 ◽  
The Individual

Abstract The individual risk of infection and requirements for medical treatment after high-dose chemotherapy have been unpredictable. In this prospective, multicenter, open-label study we investigated the potential of granulocyte colony-stimulating factor (G-CSF) responsiveness as a predictor. A total of 168 patients with multiple myeloma or lymphoma received a single dose of subcutaneous G-CSF (lenograstim, 263 μg) after high-dose chemotherapy. Highly variable leukocyte peaks were measured and grouped as low (quartile 1; leukocytes 100-10 100/μL), medium (quartile 2; leukocytes > 10 100-18 300/μL), and high (quartiles 3/4; leukocytes > 18 300-44 800/μL). G-CSF responsiveness (low vs medium vs high) was inversely correlated with febrile neutropenia (77% vs 60% vs 48%; P = .0037); the rate of infection, including fever of unknown origin (91% vs 67% vs 54%; P < .0001); days with intravenous antibiotics (9 vs 6 vs 5; P < .0001); and antifungal therapy (P = .042). In multivariate analysis, G-CSF responsiveness remained the only factor significantly associated with infection (P = .016). In addition, G-CSF responsiveness was inversely correlated with grade 3/4 oral mucositis (67% vs 33% vs 23%; P < .0001). G-CSF responsiveness appears as a signature of the myeloid marrow reserve predicting defense against neutropenic infection after intensive chemotherapy. This study is registered at http://www.clinicaltrials.gov as NCT01085058.

Safety of AT-1015, a novel 5-HT2A antagonist, in combination with high-dose aspirin: an open-label study

2004 ◽  
Vol 42 (02) ◽  
pp. 98-102 ◽  
Author(s):  
D. Anderson ◽  
N. Kato ◽  
K. Onomichi ◽  
H. Uchida ◽  
S. Shelley ◽  
...  
Keyword(s):  
High Dose ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Dose Aspirin ◽  
High Dose Aspirin

Pharmacokinetic (PK) interactions between capecitabine (X), oxaliplatin (O) and bevacizumab (A) when used in combination for first-line treatment of metastatic colorectal cancer (MCRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2554-2554 ◽  
Author(s):  
B. Brennan ◽  
L. Siu ◽  
B. Dhesy-Thind ◽  
C. Cripps ◽  
A. Gandhi ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Dosing Regimen ◽  
Open Label ◽  
Open Label Study ◽  
Free Survival ◽  
Primary Parameter ◽  
Baseline Characteristics ◽  
Potential Improvement

2554 Background: X + O in combination (XELOX) has similar efficacy to FOLFOX-4 in untreated MCRC patients (pts) [1]. The addition of A to irinotecan/5-FU/LV improves progression-free survival (PFS) and overall survival [2], and the potential improvement of adding A to XELOX in MCRC is currently being investigated. Here we present the first PK evaluation of the effects of X on O, O on X, X+A on O, and O+A on X in a multicenter open-label study of pts with untreated MCRC. Methods: Pts received treatment for up to 16 cycles with blood samples for PK analysis taken during cycles 1–3. Treatment: cycle 1: X 1000 mg/m2 orally on morning of d1, O 130 mg/m2 i.v. infusion d2, X 1000 mg/m2 bid orally d5–14, rest d15–21; cycle 2: O 130 mg/m2 i.v. infusion d1 + X 1000 mg/m2 bid orally d1–14, rest d15–21; cycle 3 (XOA): A 7.5 mg/kg i.v. infusion d1 + O 130 mg/m2 i.v. infusion d1 + X 1000 mg/m2 bid orally d1–14, q3w. Treatment with the XOA regimen continued for a further 13 cycles. Safety was evaluated throughout. Results: 36 pts were enrolled; 26 pts completed cycles 1–3 and were evaluable for PK analysis; all pts were evaluable for safety. Baseline characteristics were: M/F 42%/58%; median age 60 years (range 22–74). The primary parameter for PK analysis of X, AUC0-8 of 5’-DFUR, was slightly lower in cycle 2 d1 (XO) and cycle 3 d1 (XOA) vs. cycle 1 d1 (X) (10% and 13% lower, respectively, with CV 27–33%); a decrease in the Cmax of 5’-DFUR was also observed (26% and 36% lower, respectively, with CV 48–54%). However these differences were not considered clinically important. The primary parameter for PK analysis of O, AUC0-8 of free platinum, was very similar among cycle 2 d1 (XO), cycle 3 d1(XOA), and cycle 1 d2 (O), with geometric mean ratios very close to 1. Treatment with X, O and A in combination was generally well tolerated. Conclusions: No large differences in exposure of X or its metabolites, free platinum or total platinum occur when X, O and A are administered in combination. This provides further support for the development of the above dosing regimen in MCRC. References: 1. Cassidy J et al. J Clin Oncol 2004;22:2084–91. 2. Hurwitz H et al. N Eng J Med 2004;350:2335–42. No significant financial relationships to disclose.

scholarly journals Results from a Randomized Clinical Trial of Coadministration of RotaTeq, a Pentavalent Rotavirus Vaccine, and NeisVac-C, a Meningococcal Serogroup C Conjugate Vaccine

2011 ◽  
Vol 18 (5) ◽  
pp. 878-884 ◽  
Author(s):  
Timo Vesikari ◽  
Aino Karvonen ◽  
Ray Borrow ◽  
Nick Kitchin ◽  
Martine Baudin ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Geometric Mean ◽  
Fold Increase ◽  
Concomitant Administration ◽  
Rotavirus Vaccine ◽  
Open Label ◽  
Seroprotection Rate ◽  
Content Type ◽  
Healthy Infants ◽  
Sequential Administration

ABSTRACTRotaTeq (Merck & Co. Inc./Sanofi Pasteur MSD) is a three-dose, oral pentavalent rotavirus vaccine for the immunization of infants from 6 weeks of age for the prevention of rotavirus gastroenteritis. The primary objective of the present trial was to demonstrate that RotaTeq can be coadministered with meningococcal serogroup C conjugate vaccine (MenCC; NeisVac-C; Baxter Healthcare) to healthy infants without impairing the protective immune responses to MenCC. This was an open-label, randomized, comparative study conducted in Finland. The study was designed to assess concomitant versus sequential administration of RotaTeq and MenCC on the immune response to both vaccines. Healthy infants (n= 247), aged 6 to 7 weeks, were recruited. Coadministration of MenCC with RotaTeq was noninferior to sequential administration for the seroprotection rate against meningococcal serogroup C (the proportion of infants with a serum bactericidal antibody titer using baby rabbit complement of ≥8 was 100% in both groups). The other responses to MenCC (titer of ≥1:128, ≥4-fold increase in titer, and geometric mean titers [GMTs]) and the responses to RotaTeq (IgA and SNA response to G1 to G4 and P1A[8], GMTs, and ≥3-fold increase in titer) were comparable between groups, including a ≥3-fold IgA increase in >96% of the infants in both groups. Concomitant administration of the first doses of MenCC, diphtheria and tetanus toxoids and acellular pertussis vaccine, inactivated poliovirus vaccine, andHaemophilus influenzaetype b conjugate vaccine (DTaP-IPV-Hib), and RotaTeq was associated with a higher rate of vomiting and diarrhea than concomitant administration of MenCC and DTaP-IPV-Hib, but that was not observed after the second concomitant administration. The convenience of concomitant administration of RotaTeq and MenCC may, however, outweigh the additive effect of mostly mild adverse events reported after the individual administration of each vaccine. These results support the coadministration of RotaTeq and MenCC.

scholarly journals Immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine: a Phase III, open-label study of adults in Brazil

2017 ◽  
Vol 21 (1) ◽  
pp. 63-70 ◽  
Author(s):  
Cristiano A.F. Zerbini ◽  
Rodrigo Ribeiro dos Santos ◽  
Maria Jose Nunes ◽  
Jyoti Soni ◽  
Ping Li ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Southern Hemisphere ◽  
Phase Iii ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Quadrivalent Influenza Vaccine

Effect of Bosentan on Systemic Sclerosis-associated Interstitial Lung Disease Ineligible for Cyclophosphamide Therapy: A Prospective Open-label Study

2011 ◽  
Vol 38 (10) ◽  
pp. 2186-2192 ◽  
Author(s):  
YOSHIAKI FURUYA ◽  
MASATAKA KUWANA
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Pulmonary Function ◽  
Lung Disease ◽  
Pulmonary Function Tests ◽  
High Dose ◽  
Open Label ◽  
High Resolution Computed Tomography ◽  
Open Label Study ◽  
Label Study

Objective.To evaluate the clinical benefits of the endothelin receptor antagonist bosentan on interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) who are ineligible for cyclophosphamide (CYC) therapy.Methods.In this prospective open-label study, 9 patients with SSc and ILD received bosentan for 24 months. The main reasons for avoiding CYC included severely impaired lung function, long disease duration, and relapse after CYC treatment. Pulmonary function tests and Doppler echocardiograms were evaluated every 6 months, and high-resolution computed tomography (HRCT) was performed every 12 months. For an extended survival analysis, 17 historical controls who met the inclusion criteria at referral and had not used any immunosuppressive or antifibrotic agents thereafter were selected from the SSc database.Results.Two patients did not finish the study; one developed vasculitis requiring high-dose corticosteroids and another died of bacterial pneumonia. The remaining 7 patients tolerated bosentan and completed the study period. There were trends toward mildly reduced forced vital capacity, total lung capacity, and diffusing capacity for carbon monoxide over time. Two patients developed pulmonary hypertension during the 24-month period. HRCT scores for ground-glass opacity, pulmonary fibrosis, and honeycomb cysts gradually increased. In the extended study, there was no difference in cumulative survival rate between the bosentan-treated and historical control groups.Conclusion.The gradual worsening of pulmonary function and HRCT findings in patients treated with bosentan was consistent with the natural course of SSc-associated ILD. This study does not support the use of bosentan for SSc-associated ILD even when CYC treatment is inadvisable.

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