scholarly journals Design of an Optimally-Diagnostic Skin Test With Fewer Samples for Diagnosis of Sensitivity to Eight Allergens: a First-In-Human Study of Dose Escalation and Simultaneous Administration in Chinese Subjects

2020 ◽  
Author(s):  
Xiaoyi Ning ◽  
Yun Kuang ◽  
Shuwei Zhao ◽  
Guoping Yang ◽  
Wenjing Hou ◽  
...  
Keyword(s):  
Skin Test ◽  
Human Study ◽  
Allergic Diseases ◽  
Significance Test ◽  
Simultaneous Administration ◽  
Open Label ◽  
Prick Test ◽  
Wheal Diameter ◽  
The Difference ◽  
Allergen Extracts

Abstract Background: Skin prick test is usually the preferred test in the diagnostic workup for allergic diseases, while there are few types of standardized allergen extracts available. Besides, standardization and composition give no assurance that the allergen extracts are within the concentration range that give the best chance of a true diagnosis. We designed a first-in-human diagnostic skin test with fewer samples to identify the optimally diagnostic concentration for eight standardized extracts from frequent native allergens, and to assess the safety of the eight allergens extracts’ simultaneous administration for supporting clinical allergen screening.Methods: Patients aged 18-45 years who had a history of allergic diseases were enrolled in this two-part open-label, parallel study: Study 1, each patient was given three concentrations of one allergen extract in turn. Study 2, each patient was given two concentrations of eight allergens extracts. Negative and positive controls were given each time the allergen was given. Both safety and sensitivity were evaluated to determine the optimally diagnostic concentration. Related-Samples Friedman's Two-Way Analysis was used to evaluate the difference of wheal diameter between different concentrations of each allergen. SPSS Statistics 26 was used for statistical analysis, and the significance test level was 0.05.Results: The sensitivity of allergens increased with the increasing of concentration. The eight investigated allergens showed good safety and did not reach the dose limit toxicity whether used alone or in combination. The optimally diagnostic concentration for eight aeroallergens were respectively determined as 33333 DU/mL, 12000 DU/mL, 8667 DU/mL, 50000 DU/mL, 40000 DU/mL, 3333 DU/mL, 7000 DU/mL, and 5000 DU/mL.Conclusions: This study designed a solution to determine the optimally diagnostic concentration with fewer subjects for further clinical trials of the eight investigated allergens and the results of this phase I clinical trial support further clinical research of investigated allergens. Trial registration: The trial was registered on www.chictr.org.cn (ChiCTR1900023952, 06/19/2019, retrospectively registered).

Prevalence of aeroallergens and food allergens in allergic patients in Tehran, Iran

2018 ◽  
Author(s):  
Nasrin Pazoki ◽  
Ali Ahmadi ◽  
Fatemeh Onsori ◽  
Mohsen Mosavi Khorshidi ◽  
Mahboubeh Mansori ◽  
...  
Keyword(s):  
Skin Prick Test ◽  
Egg Yolk ◽  
Allergic Diseases ◽  
Cross Sectional Study ◽  
Food Allergens ◽  
Sectional Study ◽  
Cross Sectional ◽  
Prick Test ◽  
Allergy And Immunology ◽  
Allergen Extracts

Background and Aims: Identification of different allergens is a major challenge in allergic diseases. Avoiding these allergens is known as one of the best types of treatment. The aim of this study is to determine the prevalence of aeroallergens and food allergens in patients with allergy by Skin Prick Test. Materials and Methods: A cross-sectional study was conducted on 255 patients with allergic diseases who had referred to the Khorshid Allergy and Immunology Clinic. Skin Prick Test was performed using 82 allergen extracts to determine the patients' sensitivity to food and aeroallergens. Results: One hundred percent of the patients were sensitive to at least one allergen. Allergy to food allergens and aeroallergens was 49% and 51 %, respectively. Most sensitivity to food allergens included hazelnut (26.27%), bananas (21.96%), egg yolk (21.56%) and wheat (20.39%). Among the aeroallergens, grass with a frequency of 87% and fungi with a frequency of 34% had the highest and lowest frequencies. Conclusion: Depending on the nutrition, cultural habits, environmental conditions, and life style, prevalence of the allergens in each area may be different. Therefore, early identification and avoidance from these allergens can be suggested.

scholarly journals The effectiveness of oral immunotherapy in patients with Sesame anaphylaxis using Omalizumab

2021 ◽  
Author(s):  
Fereshteh Salari ◽  
Mohammad Hassan Bemanian ◽  
Morteza Fallahpour ◽  
Seyed Alireza Mahdaviani ◽  
Sima Shokri ◽  
...  
Keyword(s):  
Treatment Effectiveness ◽  
Sesame Seed ◽  
Food Challenge ◽  
Maintenance Phase ◽  
Specific Ige ◽  
Oral Immunotherapy ◽  
Open Label ◽  
Prick Test ◽  
Wheal Diameter ◽  
History Of

Abstract Objective Sesame allergy is the most prevalent allergy to seeds. Oral immunotherapy (OIT) is defined as continuous consumption of an allergen at special doses and time. Omalizumab (Anti-IgE) increases tolerance to allergens used in OIT. This study evaluated the effectiveness of a new sesame OIT protocol in patients with sesame anaphylaxis in combination with omalizumab. Methods In this prospective open-label interventional trial study, 11 patients with a history of sesame anaphylaxis were enrolled after approval by Oral Food Challenge (OFC) test. At baseline, skin prick test (SPT) and skin prick to prick (SPP) test were performed. Serum sesame-specific IgE (sIgE) levels were measured. The maintenance phase was continued at home with daily sesame intake for 4 months. At the end of month 4, the OFC and above-mentioned tests were repeated to evaluate the treatment effectiveness. Results All 11 patients who underwent sesame OIT after 4 months could tolerate a dietary challenge of 22 ml tahini (natural sesame seed, equal to 5,000 mg of sesame protein and higher) and the average of wheal diameter in the SPT and SPP tests significantly decreased after desensitization. Conclusion This OIT protocol may be a promising desensitization strategy for patients with sesame anaphylaxis. Also, omalizumab obviously reduced the severity of reactions.

scholarly journals A comparative study to assess the efficacy of fluticasone and mometasone in allergic rhinitis

2020 ◽  
Vol 6 (9) ◽  
pp. 1587
Author(s):  
Waqar Ul Hamid ◽  
Deepshikha Sumbria ◽  
Ihsan Ali ◽  
Rauf Ahmad
Keyword(s):  
Allergic Rhinitis ◽  
Comparative Study ◽  
Nasal Spray ◽  
Allergic Diseases ◽  
Therapeutic Benefit ◽  
Nasal Symptom ◽  
Open Label ◽  
Nasal Sprays ◽  
Parallel Group ◽  
The Difference

<p class="abstract"><strong>Background:</strong> Allergic rhinitis is the most prevalent of allergic diseases in the world. Pharmacotherapy remains the mainstay of treatment.  Nasal corticosteroids being the most applicable drugs for its treatment. The objective of this study was to compare the efficacy of fluticasone propionate (FP) and mometasone furoate (MF) nasal sprays in the treatment of allergic rhinitis based on total nasal symptom score (TNSS) questionnaire.</p><p class="abstract"><strong>Methods:</strong> A prospective, randomized, open-label, parallel-group, comparative study was conducted among 80 allergic rhinitis patients fulfilling the inclusion and exclusion criteria. They were randomly assigned to two groups: FP and MF groups. FP group received 200 µg dose of FP nasal spray (1 spray/nostril) daily and the MF group received 100 µg dose of MF nasal spray (1 spray/nostril) daily for 8 weeks. The effects of the two agents were compared based on TNSS questionnaire in 0, 4 and 8 weeks after the beginning of the treatment.  </p><p class="abstract"><strong>Results:</strong> At the end of eight weeks of treatment, both groups showed statistically significant (p&lt;0.005) improvements from their baseline TNSS. Mean TNSS was reduced from to 9.46 to 2.716 in FP group and from 10.18 to 2.504 in MF group.</p><p class="abstract"><strong>Conclusions:</strong> Both the groups showed a significant therapeutic benefit in patients with allergic rhinitis. Even though, the difference between the two is not significant for 8 weeks therapy.   </p>

scholarly journals COMPARATIVE STUDY ON THE EFFICACY OF MOMETASONE AND FLUTICASONE NASAL SPRAYS FOR TREATMENT OF ALLERGIC RHINITIS

2017 ◽  
Vol 9 (3) ◽  
pp. 211
Author(s):  
Mahshid Sadat Mirmoezzi ◽  
Mohammad Shurideh Yazdi ◽  
Omid Gholami
Keyword(s):  
Allergic Rhinitis ◽  
Nasal Spray ◽  
Allergic Diseases ◽  
Nasal Symptom ◽  
P Value ◽  
Inclusion Criteria ◽  
Prick Test ◽  
Nasal Sprays ◽  
Total Nasal Symptom Score ◽  
The Difference

Objective: Allergic rhinitis is the most prevalent of allergic diseases in the world. Nasal corticosteroids are the most applicable drugs for the treatment of allergic rhinitis. In this study, we compared the efficacy of fluticasone propionate (FP) and mometasone furoate (MF) nasal sprays in the treatment of allergic rhinitis based on total nasal symptom score (TNSS) questionnaire.Methods: For this study, 75 allergic rhinitis patients based on skin prick test and inclusion criteria were randomly assigned to two groups: FP and MF groups. FP group received 200 µg dose of FP nasal spray (1 spray/nostril) daily and the MF group received 100 mg dose of MF nasal spray (1 spray/nostril) daily for 8 w. The effects of the two agents were compared based on TNSS questionnaire in 0, 4 and 8 w after the beginning of the treatment.Results: Results showed that patients in both groups exhibited significant improvement in their TNSS (P Value<0.001). A detailed TNSS analysis showed MF to be more effective for relieving all symptoms than FP. The most difference is in decreasing postnasal discharge (PND) symptom. However, the difference for relieving all symptoms is not significant (P value>0.05).Conclusion: In conclusion, FP and MF are significantly effective in relieving of allergic rhinitis symptoms. Even though, the difference between the two is not significant for 8 w therapy. 

scholarly journals Force Generation on the Hallux Is More Affected by the Ankle Joint Angle than the Lesser Toes: An In Vivo Human Study

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 48
Author(s):  
Junya Saeki ◽  
Soichiro Iwanuma ◽  
Suguru Torii
Keyword(s):  
Repeated Measures ◽  
Joint Angle ◽  
Plantar Flexion ◽  
Human Study ◽  
Force Generation ◽  
Functional Difference ◽  
Multiple Comparison Test ◽  
The Difference ◽  
Metatarsophalangeal Joints

The structure of the first toe is independent of that of the other toes, while the functional difference remains unclear. The purpose of this study was to investigate the difference in the force generation characteristics between the plantar-flexion of the first and second–fifth metatarsophalangeal joints (MTPJs) by comparing the maximal voluntary plantar-flexion torques (MVC torque) at different MTPJs and ankle positions. The MVC torques of the first and second–fifth MTPJs were measured at 0°, 15°, 30°, and 45° dorsiflexed positions of the MTPJs, and at 20° plantar-flexed, neutral, and 20° dorsiflexed positions of the ankle. Two-way repeated measures analyses of variance with Holm’s multiple comparison test (MTPJ position × ankle position) were performed. When the MTPJ was dorsiflexed at 0°, 15°, and 30°, the MVC torque of the first MTPJ when the ankle was dorsiflexed at 20° was higher than that when the ankle was plantar-flexed at 20°. However, the ankle position had no significant effect on the MVC torque of the second–fifth MTPJ. Thus, the MVC torque of the first MTPJ was more affected by the ankle position than the second–fifth MTPJs.

scholarly journals Phase I first-in-human study of HLX07, a novel and improved recombinant anti-EGFR humanized monoclonal antibody, in patients with advanced solid cancers

2021 ◽  
Author(s):  
Ming-Mo Hou ◽  
Ching-Liang Ho ◽  
Hsuan-Yu Lin ◽  
Yunting Zhu ◽  
Xiaodi Zhang
Keyword(s):  
Phase I ◽  
Standard Therapy ◽  
Human Study ◽  
Growth Factor Receptor ◽  
Systemic Exposure ◽  
Open Label ◽  
Dose Escalation Study ◽  
Clinical Trial Registration ◽  
Humanized Monoclonal Antibody ◽  
Open Label Phase

SummaryPurpose This study aimed to evaluate the safety and pharmacokinetic (PK) profiles of HLX07, a novel, recombinant, humanized anti-epidermal growth factor receptor (EGFR) antibody, in patients with advanced solid cancers who had failed standard therapy or for whom no standard therapy was available. Methods In this prospective, open-label, Phase I dose escalation study, patients aged ≥18 years (≥20 years for patients in Taiwan) with histologically-confirmed metastatic or recurrent epithelial carcinoma that had no K-RAS or B-RAF mutations were enrolled in a ‘3 + 3’ escalation design. HLX07 was administered weekly by 2-h intravenous infusion at doses ranging from 50 to 800 mg. The primary endpoint was summary listing of participants reporting treatment-emergent adverse events (TEAEs). Secondary endpoints included PK analysis, serum anti-HLX07 antibody assessments and efficacy. Results In total, 19 patients were enrolled between 1 October 2016 and 16 July 2019 to receive HLX07 at doses of 50 (n = 3), 100 (n = 3), 200 (n = 3), 400 (n = 3), 600 (n = 3) and 800 (n = 4) mg per week. All patients experienced at least one TEAE, most commonly fatigue (68.4%), nausea (47.4%), paronychia (31.6%) and vomiting (31.6%). Serious TEAEs were reported in 11 patients but only one serious TEAE (dyspnea in 600 mg cohort) was regarded as possibly related to study treatment. No dose limiting toxicity (DLT) was reported. Systemic exposure to HLX07 increased proportionally with dose. Anti-HLX07 antibodies were not detected in any patients. Conclusion HLX07 was well tolerated (at dose levels up to 800 mg/week) and promising in patients with advanced solid cancers.Clinical Trial Registration: The study was registered at ClinicalTrials.gov: NCT02648490 (Jan 7, 2016).

Early safety and efficacy from a phase I open-label clinical trial of CD137(4-1BB) agonistic antibody LVGN6051 as monotherapy and in combination with pembrolizumab.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2521-2521
Author(s):  
Siqing Fu ◽  
Wael A. Harb ◽  
Sapna Pradyuman Patel ◽  
Charles Lu ◽  
Daniel M. Halperin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Antitumor Activity ◽  
Safety Profile ◽  
Single Agent ◽  
Human Study ◽  
Hepatic Metastases ◽  
Preliminary Evidence ◽  
Open Label ◽  
Grade 3 ◽  
Favorable Safety

2521 Background: LVGN6051, a monoclonal antibody against CD137 (also known as 4-1BB or TNFRSF9) with an engineered Fc capable of selectively binding to the Fcγ receptor IIB, acts as a conditional CD137 agonist, resulting in immune activation optimally in tumor microenvironment ( Qi, Nat. Commun. 2019 ). In preclinical models, LVGN6051 demonstrated robust anti-tumor efficacy and safety as a single agent and in combination with anti-PD-1 antibodies. Therefore, we have initiated this first-in-human study of LVGN6051 alone or in combination with pembrolizumab for the treatment of advanced or metastatic malignancy. Methods: This study includes accelerated dose escalation monotherapy up to 2 mg/kg of LVGN6051, and traditional 3 + 3 design for higher doses of LVGN6051 alone or in combination with pembrolizumab. Then, this study will enroll patients with specific types of malignancies following Simon’s two-stage design. Both agents are administered once every 3 weeks. Primary objectives of this study were to define the safety profile and to establish the recommended phase 2 dose (RP2D) of LVGN6051 alone or in combination with pembrolizumab. Pharmacokinetics, immunogenicity, pharmacodynamics and clinical efficacy will be also evaluated. Results: At the cut-off date on January 18, 2021, 16 subjects have been enrolled into the monotherapy cohorts (n=12, no DLT observed up to 7 mg/kg), and the combination cohort (n=4, ongoing at LVGN6051 2 mg/kg and pembrolizumab 200 mg, one DLT observed). No treatment-related adverse event (TRAE) was observed in monotherapy. Treatment-emergent adverse events (TEAE) in combination included increased ALT/AST, thrombocytopenia, and fatigue. In the combination cohort, one patient with predominant hepatic metastases and history of intermittent grade 2 hepatic impairment experienced grade 3 increased ALT/AST (DLT) on cycle 1 day 15 that were resolved to her baseline without corticosteroids on cycle 1 day 18. TRAE included increased ALT/AST, thrombocytopenia, neutropenia, nausea and fatigue. Seven of 10 evaluable patients in the monotherapy cohorts demonstrated stable disease with the longest treatment being 8+ months. Tumor reductions by >10% were observed in melanoma and neuroendocrine tumor on monotherapy. One patient with metastatic head and neck squamous cell carcinoma who had progressed on an anti-PD-L1 based therapy showed an immune partial response (iPR) for 6+ months to the combination therapy. Conclusions: Preliminary evidence showed that LVGN6051 was well tolerated and tumor shrinkages were observed. While we continue assessing its safety profile, antitumor activity was observed in the LVGN6051 and pembrolizumab cohort. The favorable safety profile and preliminary antitumor activity warrant further evaluation in patients with advanced malignancies. Clinical trial information: NCT04130542.

scholarly journals Disease activity in acromegaly may be assessed 6 weeks after discontinuation of pegvisomant

2005 ◽  
Vol 152 (1) ◽  
pp. 47-51 ◽  
Author(s):  
W M Drake ◽  
R A Loureiro ◽  
C Parkinson ◽  
J P Monson ◽  
G M Besser ◽  
...  
Keyword(s):  
Disease Activity ◽  
Cross Reactivity ◽  
Systematic Change ◽  
Open Label ◽  
Igf I ◽  
Gh Receptor Antagonist ◽  
The Difference ◽  
Design And Methods ◽  
Change In Mean ◽  
Serum Gh

Objective: Pegvisomant, a modified growth hormone (GH) molecule, is a novel medical therapy for acromegaly that functions as a GH receptor antagonist. Serum GH cannot be used as a marker of disease activity in patients taking this form of therapy, partly because GH levels rise on pegvisomant and partly because the drug cross-reacts with many routine GH assays. The purpose of this study was to assess the time for which it is necessary to discontinue pegvisomant prior to biochemical reassessment of acromegaly. Design and methods: This was a retrospective study of 13 patients (seven male, median age 61 years, range 43–77) enrolled in two separate, open-label studies of the efficacy and tolerability of pegvisomant in the treatment of acromegaly. All had been taking a stable dose of pegvisomant (median dose 15 mg daily, range 10–30) as monotherapy for at least 3 months before discontinuing the drug. After discontinuation of pegvisomant, serum IGF-I was measured at 0, 2, 4, 6 and 8 weeks in all patients. Serum GH (single sample) was measured in nine patients at 2, 4, 6 and 8 weeks, but not at baseline on account of the cross-reactivity of pegvisomant with the GH assay. Results: Mean serum IGF-I rose from 210±105 ng/ml (s.d.) at baseline to 392±175 ng/ml at 2 weeks after discontinuation of pegvisomant (P < 0.0001). Although there was no statistically significant change in mean serum IGF-I beyond 2 weeks (412±181, 392±152 and 399±150 ng/ml at 4, 6 and 8 weeks respectively; P = 0.13 (2 vs 4 weeks), 0.31 (4 vs 6 weeks) and 0.46 (6 vs 8 weeks), serum IGF-I rose by more than twice the interassay coefficient of variation (CV) in two of the 13 patients between weeks 2 and 4. The standard deviation of the difference in serum IGF-I between time points was calculated. The values declined from 118% (weeks 0–2) 17%, 19.7% and 10% (weeks 2–4, 4–6 and 6–8 respectively). The expected measure if there was no systematic change in base would be 15% (1.4 ×interassay CV). Mean serum GH was virtually unchanged at 2–8 weeks after cessation of pegvisomant therapy. Conclusions: These results suggest that the activity of acromegaly may be assessed by serum IGF-I levels 6 weeks after the discontinuation of pegvisomant.

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