scholarly journals A Multi‑Center, Open‑Label, Single‑Arm Trial to Evaluate the Efficacy, Pharmacokinetics, and Safety and Tolerability of IGSC 20% in Subjects with Primary Immunodeficiency

2022 ◽  
Author(s):  
Manuel Santamaria ◽  
Olaf Neth ◽  
Jo A. Douglass ◽  
Gergely Krivan ◽  
Robin Kobbe ◽  
...  
Keyword(s):  
Primary Immunodeficiency ◽  
Bacterial Infections ◽  
Alternative Hypothesis ◽  
Open Label ◽  
Upper Confidence Limit ◽  
Specific Pathogen ◽  
Previous Regimen ◽  
Immunoglobulin Treatment ◽  
The Individual ◽  
Antibody Levels

Abstract Purpose The purpose of this phase 3 study was to evaluate the efficacy, pharmacokinetics (PK), and safety of Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (IGSC 20%) in patients with primary immunodeficiency (PI). Methods Immunoglobulin treatment-experienced subjects with PI received 52 weeks of IGSC 20% given weekly at the same dose as the subject’s previous IgG regimen (DAF 1:1); the minimum dose was 100 mg/kg/week. The primary endpoint was serious bacterial infections (SBIs [null vs alternative hypothesis: SBI rate per person per year ≥ 1 vs < 1]). IgG subclasses and specific pathogen antibody levels were also measured. Results Sixty-one subjects (19 children [≤ 12 years], 10 adolescents [> 12–16 years], and 32 adults) were enrolled. The rate of SBIs per person per year was 0.017. The 1-sided 99% upper confidence limit was 0.036 (< 1), and the null hypothesis was rejected. The rate of hospitalization due to infection per person per year was 0.017 (2-sided 95% confidence interval: 0.008–0.033) overall. The mean trough total IgG concentrations were comparable to the previous IgG replacement regimen. The average of the individual mean trough ratios (IGSC 20%:previous regimen) was 1.078 (range: 0.83–1.54). The average steady-state mean trough IgG concentrations were 947.64 and 891.37 mg/dL, respectively. Seven subjects had serious treatment-emergent adverse events (TEAEs); none was drug-related. The rate of all TEAEs, including local infusion site reactions, during 3045 IGSC 20% infusions was 0.135. Most TEAEs were mild or moderate. Conclusions IGSC 20% demonstrated efficacy and good safety and tolerability in subjects with PI.

scholarly journals Efficacy, safety, and tolerability of Kedrion 10% IVIG in primary immunodeficiency

2016 ◽  
Vol 3 (3) ◽  
pp. 99-109 ◽  
Author(s):  
Mark Stein ◽  
Agnes Nemet ◽  
Santhosh Kumar ◽  
William Lumry ◽  
Hartwig Gajek ◽  
...  
Keyword(s):  
Primary Immunodeficiency ◽  
Confidence Limit ◽  
Bacterial Infections ◽  
Phase Iii ◽  
Open Label ◽  
Safety Endpoint ◽  
Ivig Preparation ◽  
Phase Iii Study ◽  
Serious Bacterial Infections ◽  
Primary Safety Endpoint

Background: Primary immunodeficiency involving defective antibody formation requires antibody replacement therapy with immunoglobulin products to prevent and reduce infections. Immunoglobulin for intravenous use (IVIG) is a processed blood product with limited availability, and the various marketed IVIG products may have different tolerability among patients. New IVIG products are therefore necessary to offer options to patients and to reduce the risk of a product shortage. Methods: Forty-five adult and pediatric patients with primary immunodeficiency, documented agammaglobulinemia or hypogammaglobulinemia, and antibody deficiency were enrolled in a prospective, multi-centre, open-label, single-arm historically controlled Phase III study to evaluate the safety, efficacy, and pharmacokinetics of a new 10% IVIG produced by Kedrion. Results: Forty-four patients completed the study while one withdrew consent. Over the 12-month study period, only 2 episodes of acute serious bacterial infections (both bacterial pneumonias) were recorded, for a mean annual event rate of 0.04 per subject, with an upper one-sided 99% confidence limit of 0.11. Values for all secondary efficacy endpoints were comparable with those in similar studies. The primary safety endpoint was met as the rate of infusions temporally associated (i.e., within 72 hours) with ≥1 adverse event was 16% (upper 95% confidence limit 20.4%). Pharmacokinetics were assessed in 31 patients and found to be comparable with those published for other IVIG products. Conclusion: Kedrion IVIG 10% is safe, efficacious, and well tolerated by patients with primary immunodeficiency. Statement of novelty: This report describes the safety, efficacy, and pharmacokinetics of a new IVIG preparation.

scholarly journals Low Immunogenicity of Intravesical Phage Therapy for Urogenitary Tract Infections

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 627
Author(s):  
Sławomir Letkiewicz ◽  
Marzanna Łusiak-Szelachowska ◽  
Ryszard Międzybrodzki ◽  
Maciej Żaczek ◽  
Beata Weber-Dąbrowska ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Serum Antibody ◽  
Multidrug Resistant ◽  
Antibody Responses ◽  
Urogenital Infections ◽  
Reliable Model ◽  
Tract Infections ◽  
Antibody Levels

Patients with chronic urinary and urogenital multidrug resistant bacterial infections received phage therapy (PT) using intravesical or intravesical and intravaginal phage administration. A single course of PT did not induce significant serum antibody responses against administered phage. Whilst the second cycle of PT caused a significant increase in antibody levels, they nevertheless remained quite low. These data combined with good therapy results achieved in some patients suggest that this mode of PT may be an efficient means of therapy for urogenital infections and a reliable model for a clinical trial of PT.

An individualized treatment rule to optimize probability of remission by continuation, switching, or combining antidepressant medications after failing a first-line antidepressant in a two-stage randomized trial

2021 ◽  
pp. 1-10
Author(s):  
Ronald C. Kessler ◽  
Toshi A. Furukawa ◽  
Tadashi Kato ◽  
Alex Luedtke ◽  
Maria Petukhova ◽  
...  
Keyword(s):  
Pragmatic Trial ◽  
Secondary Analysis ◽  
Individualized Treatment ◽  
Second Line ◽  
Open Label ◽  
Individual Level ◽  
Ensemble Machine Learning ◽  
Medication Selection ◽  
The Individual ◽  
Optimized Treatment

Abstract Background There is growing interest in using composite individualized treatment rules (ITRs) to guide depression treatment selection, but best approaches for doing this are not widely known. We develop an ITR for depression remission based on secondary analysis of a recently published trial for second-line antidepression medication selection using a cutting-edge ensemble machine learning method. Methods Data come from the SUN(^_^)D trial, an open-label, assessor blinded pragmatic trial of previously-untreated patients with major depressive disorder from 48 clinics in Japan. Initial clinic-level randomization assigned patients to 50 or 100 mg/day sertraline. We focus on the 1549 patients who failed to remit within 3 weeks and were then rerandomized at the individual-level to continuation with sertraline, switching to mirtazapine, or combining mirtazapine with sertraline. The outcome was remission 9 weeks post-baseline. Predictors included socio-demographics, clinical characteristics, baseline symptoms, changes in symptoms between baseline and week 3, and week 3 side effects. Results Optimized treatment was associated with significantly increased cross-validated week 9 remission rates in both samples [5.3% (2.4%), p = 0.016 50 mg/day sample; 5.1% (2.7%), p = 0.031 100 mg/day sample] compared to randomization (30.1–30.8%). Optimization was also associated with significantly increased remission in both samples compared to continuation [24.7% in both: 11.2% (3.8%), p = 0.002 50 mg/day sample; 11.7% (3.9%), p = 0.001 100 mg/day sample]. Non-significant gains were found for optimization compared to switching or combining. Conclusions An ITR can be developed to improve second-line antidepressant selection, but replication in a larger study with more comprehensive baseline predictors might produce stronger and more stable results.

scholarly journals Serological Evaluation of Specific-Antibody Levels in Patients Treated for Chronic Chagas' Disease

2007 ◽  
Vol 15 (2) ◽  
pp. 297-302 ◽  
Author(s):  
Olga Sánchez Negrette ◽  
Fernando J. Sánchez Valdéz ◽  
Carlos D. Lacunza ◽  
María Fernanda García Bustos ◽  
María Celia Mora ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Treatment Effectiveness ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Serological Tests ◽  
Recombinant Antigens ◽  
Antibody Titers ◽  
Laboratory Procedures ◽  
The Individual ◽  
Antibody Levels

ABSTRACT Serological tests are the main laboratory procedures used for diagnosis during the indeterminate and chronic stages of Chagas' disease. A serological regression to negativity is the main criterion used to define parasitological cure in treated patients. The aim of this work was to monitor the individual specificities of antibody levels for 3 years posttreatment in 18 adult patients. Conventional serological techniques (hemagglutination assays and enzyme-linked immunosorbent assay [ELISA]) were modified by using recombinant antigens to detect early markers of treatment effectiveness. For this purpose, serum samples were taken before and during treatment and every 6 months after treatment for at least 3 years. When hemagglutination assays were used, a decrease in antibody levels was observed in only one patient. When ELISA with serum dilutions was used, antibody clearance became much more apparent: in 77.7% (14/18) of the patients, antibody titers became negative with time. This was observed at serum dilutions of 1/320 and occurred between the 6th and the 30th months posttreatment. The immune response and the interval for a serological regression to negativity were different for each patient. For some of the recombinant antigens, only 50% (9/18) of the patients reached the serological regression to negativity. Recombinant antigen 13 might be a good marker of treatment effectiveness, since 66.6% (six of nine) of the patients presented with an early regression to negativity for specific antibodies to this antigen (P = 0.002).

scholarly journals Application of Immunosignatures for Diagnosis of Valley Fever

2014 ◽  
Vol 21 (8) ◽  
pp. 1169-1177 ◽  
Author(s):  
Krupa Arun Navalkar ◽  
Stephen Albert Johnston ◽  
Neal Woodbury ◽  
John N. Galgiani ◽  
D. Mitchell Magee ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Random Sequence ◽  
False Negative ◽  
False Negative Rate ◽  
Peptide Array ◽  
Igg Antibodies ◽  
False Negatives ◽  
Peptide Microarray ◽  
Valley Fever ◽  
Antibody Levels

ABSTRACTValley fever (VF) is difficult to diagnose, partly because the symptoms of VF are confounded with those of other community-acquired pneumonias. Confirmatory diagnostics detect IgM and IgG antibodies against coccidioidal antigens via immunodiffusion (ID). The false-negative rate can be as high as 50% to 70%, with 5% of symptomatic patients never showing detectable antibody levels. In this study, we tested whether the immunosignature diagnostic can resolve VF false negatives. An immunosignature is the pattern of antibody binding to random-sequence peptides on a peptide microarray. A 10,000-peptide microarray was first used to determine whether valley fever patients can be distinguished from 3 other cohorts with similar infections. After determining the VF-specific peptides, a small 96-peptide diagnostic array was created and tested. The performances of the 10,000-peptide array and the 96-peptide diagnostic array were compared to that of the ID diagnostic standard. The 10,000-peptide microarray classified the VF samples from the other 3 infections with 98% accuracy. It also classified VF false-negative patients with 100% sensitivity in a blinded test set versus 28% sensitivity for ID. The immunosignature microarray has potential for simultaneously distinguishing valley fever patients from those with other fungal or bacterial infections. The same 10,000-peptide array can diagnose VF false-negative patients with 100% sensitivity. The smaller 96-peptide diagnostic array was less specific for diagnosing false negatives. We conclude that the performance of the immunosignature diagnostic exceeds that of the existing standard, and the immunosignature can distinguish related infections and might be used in lieu of existing diagnostics.

Comparison of efficacy and tolerability of oral desloratadine, rupatadine and ketotifen in seasonal allergic rhinitis

2021 ◽  
Vol 4 (3) ◽  
pp. 106-114
Author(s):  
Syed Khadeer ◽  
B Jagannath
Keyword(s):  
Allergic Rhinitis ◽  
Adverse Events ◽  
Nasal Congestion ◽  
Primary Outcome Measure ◽  
Nasal Symptom ◽  
Secondary Outcome ◽  
Open Label ◽  
Non Allergic Rhinitis ◽  
The Individual ◽  
Change In Mean

Rhinitis is inflammation of nasal mucosa which characteristically presents as running nose, blocked nose, itching on nose or sneezing. Allergic rhinitis is more common than non-allergic rhinitis. Anti-histamines are the mainstay of SAR treatment. Desloratadine, rupatadine and ketotifen are the commonly prescribed anti histamines in our region. In this study, we have compared efficacy and tolerability of desloratadine, rupatadine and ketotifen in SAR. This was a prospective, randomized, three arm, open label comparative study of desloratadine, rupatadine and ketotifen in SAR, conducted at Department of ENT, Kempegowda Institute of Medical Sciences, Bangalore; between January 2014 and December 2014. Patients’ severity of SAR symptoms were assessed by TNSS, QoL was measured using Medical Outcomes Study questionnaire (SF-12). SF-12 was administered at the start of study and then at the end of study. Adverse effects were monitored during clinical examination at each visit. Study subjects were systemically randomized into three groups – desloratadine (DES), rupatadine (RUP) and ketotifen (KET). Based on the assigned group; desloratadine was given orally in dose of 10mg OD, rupatadine orally 10 mg OD and ketotifen orally 1mg BD. All medications were given for 4 weeks. Follow up was done for all patients every week during treatment period of 4 weeks. The primary outcome measure was change in mean TNSS from baseline; secondary outcome measures were changes in the individual nasal symptom scores, change in the quality of life and tolerability to the study medications. Total 150 patients were recruited for this study, divided into 3 groups. DES and RUP were equally effective but significantly better than KET in improving rhinorrhea, nasal congestion, TNSS and AEC. (p=0.05). All the drugs were equally effective with no statistically significant intergroup difference in improving sneezing, nasal itching and QoL. RUP appeared to have better tolerability as the total number of adverse events were marginally less. DES and RUP are comparatively more effective and faster acting than KET. All the study medications were well tolerated with few mild, self-limiting, transient adverse events requiring no intervention.

Antibodies to Rotaviruses in Chickens' Eggs: A Potential Source of Antiviral Immunoglobulins Suitable for Human Consumption

PEDIATRICS ◽  
1988 ◽  
Vol 81 (2) ◽  
pp. 291-295
Author(s):  
Robert H. Yolken ◽  
Flora Leister ◽  
Siok-Bi Wee ◽  
Robin Miskuff ◽  
Steven Vonderfecht
Keyword(s):  
Binding Activity ◽  
Human Consumption ◽  
Antigen Binding ◽  
Rotavirus Gastroenteritis ◽  
Potential Source ◽  
Egg Products ◽  
Egg Yolks ◽  
The Individual ◽  
Antibody Levels ◽  
Infants And Young Children

The prevalence of antibodies to human rotaviruses in commercially available eggs and egg products that are suitable for human consumption was investigated. The yolks of virtually all of the individual eggs and pasteurized pooled egg preparations contain antirotavirus antibodies detectable by means of enzyme immunoassay systems. Also, the eggs and egg preparations are capable of inhibiting the growth of two strains of rotaviruses in tissue culture. Chromatographic studies indicated that the antigen-binding activity is limited largely to the immunoglobulin fractions of the egg yolks. The antibody levels in eggs can be increased by the immunization of hens with purified rotavirus preparations, and the immunoglobulins isolated from the eggs of immunized hens can prevent the development of rotavirus gastroenteritis in experimentally infected animals. Egg preparations might serve as a practical source of antiviral antibodies suitable for consumption by infants and young children.

Letters to the Editor

PEDIATRICS ◽  
1957 ◽  
Vol 20 (5) ◽  
pp. 918-919
Author(s):  
AIMS C. MCGUINNESS
Keyword(s):  
United States ◽  
Bacterial Infections ◽  
The United States ◽  
The State ◽  
Letters To The Editor ◽  
Mild Disease ◽  
The Individual

I certainly agree with Dr. Dietrich that Asian influenza thus far has been a mild disease and not too serious a problem for the individual. Dr. Burney has pointed this out on a number of occasions, as, for example, in his remarks before the State and Territorial Health Officers on August 27. I agree, too, that the availability of antibiotics to deal with secondary bacterial infections should, to a great extent, minimize the severity of any epidemic in the United States.

scholarly journals Serum and Lung Pharmacokinetics of ASN100, a Monoclonal Antibody Combination for the Prevention and Treatment of Staphylococcus aureus Pneumonia

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S310-S310 ◽  
Author(s):  
Zoltan Magyarics ◽  
Fraser Leslie ◽  
Steven A Luperchio ◽  
Johann Bartko ◽  
Christian Schörgenhofer ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Phase 1 ◽  
Fixed Dose ◽  
Open Label ◽  
Post Dose ◽  
Double Blind ◽  
Dose Time ◽  
Prevention And Treatment ◽  
Acute Bacterial Infections

Abstract Background Monoclonal antibodies (mAbs) are well-suited for the prevention and treatment of acute bacterial infections. ASN100 is a combination of two fully human IgG1 mAbs, ASN-1 and ASN-2 that together neutralize six Staphylococcus aureus cytotoxins, alpha-hemolysin (Hla) and five leukocidins (HlgAB, HlgCB, LukED, LukSF [PVL] and LukGH) that are important in the pathogenesis of S. Aureus pneumonia. We aimed to characterize the pharmacokinetics (PK) of ASN100 in both serum and lung epithelial lining fluid (ELF) in male and female healthy volunteers. Methods The safety, tolerability, and serum and lung PK of single intravenous infusion of ASN100 was evaluated in a Phase 1 study. Eight subjects (3:1 randomization) in two double-blind cohorts received ASN100 (doses of 3600 mg or 8000 mg) or placebo. ASN-1 and ASN-2 were administered in a fixed dose 1:1 ratio. Twelve subjects received ASN100 open-label at doses of 3600 mg or 8000 mg and each underwent two bronchoalveolar lavage (BAL) fluid collections either on days 1 and 30 or on days 2 and 8 post-dosing. ASN-1 and ASN-2 concentrations were determined by ELISA. The ELF concentrations were normalized based on urea concentrations in serum and BAL fluid. Results No dose limiting toxicity was observed. Adverse events (AEs) showed no association of increased incidence with higher dose. All AEs were mild or moderate in severity, with 83.3% of subjects receiving ASN100 reporting at least one AE vs. 100% of placebo subjects. A dose proportional increase in serum peak and exposure (AUC) of ASN-1 and ASN-2 was observed and the serum PK of ASN-1 and ASN-2 were comparable (approximate half-life of each antibody was 3 weeks). Penetration of ASN-1 and ASN-2 into the ELF of the lung was observed at the first post-dose time point of 24 hours, peak concentrations were observed after day 2 and the mAbs remained detectable at day 30. Conclusion ASN100 was safe and well tolerated at doses up to 8000 mg (4000 mg ASN-1 and 4000 mg ASN-2). The PK profiles of ASN-1 and ASN-2 were comparable following simultaneous administration. Significant lung concentrations of each mAb were demonstrated between day 1 and 30 post-dosing. These data support continued clinical development of ASN100 for the prevention and treatment of S. Aureus pneumonia. Disclosures Z. Magyarics, Arsanis Biosciences GmbH: Employee, Salary. Arsanis, Inc.: Shareholder, Share options. F. Leslie, Arsanis., Inc.: Employee and Shareholder, Salary. S. A. Luperchio, Arsanis Inc.: Employee and Shareholder, Salary. B. Jilma, Arsanis Biosciences GmbH: Investigator, Investigator fee. C. Stevens, Arsanis Inc.: Employee and Shareholder, Salary.E. Nagy, Arsanis: Employee and Shareholder, Salary.

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.

Sign in / Sign up

Export Citation Format

Share Document