Evaluation of safety and efficacy as an adjuvant for the chitosan-based vaccine delivery vehicle ViscoGel in a single-blind randomised Phase I/IIa clinical trial

Vaccine ◽  
2014 ◽  
Vol 32 (45) ◽  
pp. 5967-5974 ◽  
Author(s):  
Theresa Neimert-Andersson ◽  
Jonas Binnmyr ◽  
Mattias Enoksson ◽  
Joakim Langebäck ◽  
Louise Zettergren ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Vaccine Delivery ◽  
Delivery Vehicle ◽  
Safety And Efficacy ◽  
Vaccine Delivery Vehicle ◽  
Single Blind

Mesoporous ZnO nanocapsules for the induction of enhanced antigen-specific immunological responses

Nanoscale ◽  
2017 ◽  
Vol 9 (38) ◽  
pp. 14641-14653 ◽  
Author(s):  
Sumbul Afroz ◽  
Himadri Medhi ◽  
Somedutta Maity ◽  
Gillipsie Minhas ◽  
Srikanth Battu ◽  
...  
Keyword(s):  
Vaccine Delivery ◽  
Delivery Vehicle ◽  
Immunological Responses ◽  
Mesoporous Zno ◽  
Vaccine Delivery Vehicle

Herein, we have designed novel mesoporous ZnO (mZnO) nanocapsules with a size of ∼12 nm and loaded them with Ova protein. In vivo studies in mice highlight the potency of the antigen loaded mZnO nanocapsules as an efficient adjuvant and vaccine delivery vehicle.

Cell-Based Regenerative Endodontics for Treatment of Periapical Lesions: A Randomized, Controlled Phase I/II Clinical Trial

2020 ◽  
Vol 99 (5) ◽  
pp. 523-529 ◽  
Author(s):  
C. Brizuela ◽  
G. Meza ◽  
D. Urrejola ◽  
M.A. Quezada ◽  
G. Concha ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Phase I ◽  
Umbilical Cord ◽  
Root Canal ◽  
Categorical Variables ◽  
Safety And Efficacy ◽  
Randomized Controlled

A randomized controlled phase I/II clinical trial was designed to evaluate the safety and efficacy of encapsulated human umbilical cord mesenchymal stem cells in a plasma-derived biomaterial for regenerative endodontic procedures (REPs) in mature permanent teeth with apical lesions. The trial included 36 patients with mature incisors, canines, or mandibular premolars showing pulp necrosis and apical periodontitis. Patients were randomly and equally allocated between experimental (REP) or conventional root canal treatment (ENDO) groups. On the first visit, cavity access and mechanical preparation of the root canal were performed. Calcium hydroxide medication was used, and the cavity was sealed. Three weeks later, patients were treated following their assigned protocol of ENDO or REP. Clinical follow-up examinations were performed at 6 and 12 mo. Categorical variables were evaluated by Fisher’s exact test. Quantitative variables were compared using the Mann-Whitney test. The evolution over time of the percentage of perfusion units and the dimensions of lesion and cortical compromise were explored. After the 12-mo follow-up, no adverse events were reported, and the patients showed 100% clinical efficacy in both groups. Interestingly, in the REP group, the perfusion unit percentage measured by laser Doppler flowmetry revealed an increase from 60.6% to 78.1% between baseline and 12-mo follow-up. Sensitivity tests revealed an increase of the positive pulp response in the REP group at 12-mo follow-up (from 6% to 56% on the cold test, from 0% to 28% on the hot test, and from 17% to 50% on the electrical test). We present the first clinical safety and efficacy evidence of the endodontic use of allogenic umbilical cord mesenchymal stem cells encapsulated in a plasma-derived biomaterial. The innovative approach, based on biological principles that promote dentin-pulp regeneration, presents a promising alternative for the treatment of periapical pathology (ClinicalTrials.gov NCT03102879).

A phase I/II study to assess the safety and efficacy of pazopanib (PAZ) and pembrolizumab (PEM) in patients (pts) with advanced renal cell carcinoma (aRCC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4506-4506 ◽  
Author(s):  
Simon Chowdhury ◽  
David F. McDermott ◽  
Martin Henner Voss ◽  
Robert E. Hawkins ◽  
Paola Aimone ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Cell Carcinoma ◽  
Phase I ◽  
Liver Toxicity ◽  
Maximum Tolerated Dose ◽  
Limited Information ◽  
Safety And Efficacy ◽  
Sequential Schedule ◽  
Anti Tumor Activity ◽  
Clinical Trial Information

4506 Background: PAZ is indicated for the treatment of aRCC. The combination of an anti-angiogenic agent and immunotherapy may improve anti-tumor activity. We report preliminary safety and efficacy results of the phase I part of the study. Methods: Twenty pts were originally enrolled in cohorts A and B assessing PAZ 800 mg and 600 mg, respectively, both with 2mg/kg (Q2W and then Q3W) PEM to determine the maximum tolerated dose. Due to dose limiting liver toxicity, cohort C was opened to assess if the sequential schedule of 9 weeks PAZ run-in followed by PAZ+PEM would improve safety. Strict safety criteria for initiating PAZ+PEM were set. The data from this ongoing study are presented given the limited information available on the combination of TKI + PD-1 inhibitors in RCC. Results: Overall, 35 pts were treated; 5 out of 15 pts in cohort C received PAZ+PEM at the data cut-off. Three dose-limiting toxicities (DLT) occurred in cohort C in pts receiving PAZ+PEM; updated DLTs in all cohorts are reported in Table. G3/4 AEs were observed in 90% of pts in cohorts A and B and in 80% of pts in cohort C receiving PAZ+PEM. No G3/4 ALT/AST elevation was reported in cohort C PAZ+PEM while they were observed in 70% and 60% in cohorts A and B, respectively. Best overall response (CR+PR) was reported in 6, 2 and 1 pts receiving PAZ+PEM in cohorts A, B and C, respectively. Conclusions: Results from cohorts A and B showed significant hepatotoxicity. The sequential schedule PAZ → PAZ+PEM has shown reduced hepatotoxicity and preliminary signs of efficacy but overall limited tolerability. PAZ+PEM is not suitable to test in a larger cohort. Clinical trial information: 2013-003785-14. [Table: see text]

TACTICAL: A phase I/II trial to assess the safety and efficacy of MSCTRAIL in the treatment of metastatic lung adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS9116-TPS9116 ◽  
Author(s):  
Alice Davies ◽  
Beth Sage ◽  
Krishna Kolluri ◽  
Doraid Alrifai ◽  
Rebecca Graham ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Lung Adenocarcinoma ◽  
Phase Ii ◽  
Metastatic Cancer ◽  
Cancer Therapies ◽  
Synergistic Activity ◽  
Safety And Efficacy ◽  
Anti Cancer ◽  
Metastatic Lung

TPS9116 Background: Mesenchymal stromal cells (MSCs) migrate to and incorporate into tumour stroma allowing them to act as vehicles for delivering anti-cancer therapies. TNF-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in malignant cells however short biological half-life has its limited therapeutic efficacy. We have transduced umbilical cord MSCs with a lentiviral vector to express TRAIL (MSCTRAIL). These cells trigger apoptosis selectively in cancer cells with evidence of synergistic activity with other systemic anti-cancer therapies. Given their immune-privileged nature we are delivering ex vivo pooled MSCTRAIL from third party donors without tissue matching or immunosuppression. Efficacy has been demonstrated using in vitro co-culture assays and in vivo in orthotopic lung metastasis murine model, showing regression of metastases following treatment with intravenous MSCTRAIL [1]. Methods: TACTICAL is a phase I/II trial assessing safety and efficacy of MSCTRAIL in combination with first line standard of care (SOC); pemetrexed (500mg/m2) and cisplatin (75mg/m2) and/or pembrolizumab (200mg), in treatment naïve patients with stage IIIB/IV metastatic lung adenocarcinoma. Patients have no actionable driver mutations and ECOG performance status 0-1. Phase I is a dose de-escalation study, patients receive SOC on day 1 and 4x108 MSCTRAIL cells on day 2 of a 21 day cycle for 3 cycles. A Bayesian adaptive design will recommend dose reductions if excessive toxicities occur. Primary outcomes are to determine recommended phase II dose along with safety and tolerability of MSCTRAIL. 46 patients will then be randomised into a multi-centre phase II double blind, placebo-controlled trial to receive SOC and either MSCTRAIL or placebo (1:1). Primary outcome is tumour response rate by RECIST (v 1.1) criteria at 12 weeks. Secondary outcomes include, best overall response, duration of response, progression free survival and overall survival. TACTICAL is the first clinical trial of this novel cell and gene therapy and if successful will pave the way for future allogeneic MSC therapy in cancer. 1. Loebinger, M.R., et al., Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer. Cancer Res, 2009. 69(10): p. 4134-42. Clinical trial information: NCT03298763.

Lambda display phage as a mucosal vaccine delivery vehicle for peptide antigens

Vaccine ◽  
2017 ◽  
Vol 35 (52) ◽  
pp. 7256-7263 ◽  
Author(s):  
Patricia González-Cano ◽  
Lakshman N.A. Gamage ◽  
Kristen Marciniuk ◽  
Connie Hayes ◽  
Scott Napper ◽  
...  
Keyword(s):  
Vaccine Delivery ◽  
Mucosal Vaccine ◽  
Delivery Vehicle ◽  
Peptide Antigens ◽  
Vaccine Delivery Vehicle

scholarly journals Evaluation of Safety and Efficacy of Cell Therapy Based on Osteoblast Derived from Umbilical Cord Mesenchymal Stem Cell for Osteonecrosis of the Femoral Head: Study Protocol for a Single-Center, Open-Label, Phase I Clinical Trial

2021 ◽  
Author(s):  
Heejae Won ◽  
Shin-Yoon Kim ◽  
Sunray Lee ◽  
Hyun Sook Park ◽  
Seung-Hoon Baek
Keyword(s):  
Clinical Trial ◽  
Femoral Head ◽  
Phase I ◽  
Umbilical Cord ◽  
Early Stage ◽  
Phase 1 ◽  
High Dose ◽  
Human Umbilical Cord ◽  
Single Center ◽  
Safety And Efficacy

Abstract BackgroundVarious techniques for joint preservation have been attempted in early stage of osteonecrosis of femoral head (ONFH), but the effects are still controversial. Recently, a combination therapy of core decompression (CD) and MSCs collected from bone marrow, adipocytes or human umbilical cord has been introduced, and satisfactory results have been reported. However, there is no study in which human umbilical cord-derived osteoblasts (hUC-O) were administered directly to the lesion in early ONFH. We have classified the location and size of lesions in early-stage ONFH, and will evaluate the hypothesis that the application of hUC-O is a safe and effective treatment.MethodsThis is a prospective, single-center, phase I and open-labeled clinical trial. Nine patients with Association Research Circulation Osseous (ARCO) stage 1 or 2 ONFH will be assigned to a low-dose (n = 3, 1 ´ 107 hUC-O cells), medium-dose (n = 3, 2 ´ 107 cells), and high-dose group (n = 3, 4 ´ 107 cells) in the order of their arrival at the facility, and up to 18 patients will be enrolled depending on whether dose limiting toxicity occurs. We will perform CD on the participants, administer hUC-O according to the assigned group, and followed up for 12 weeks, including a total of 5 visits. This study will have 3 aims; first, to evaluate the safety of hUC-O through adverse events assessment, laboratory tests, vital sign assessment, physical examination, and electrocardiogram (ECG) test.; and second, to assess the clinical outcomes after hUC-O application by comparing pain visual analog scale (VAS), Harris Hip scores (HHS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) before and after surgery; and third, to evaluate the radiographic results after hUC-O application by comparing extent of necrotic lesions according to the ARCO and Japanese Investigation Committee (JIC) classification on magnetic resonance imaging.DiscussionThis clinical trial is a pilot phase 1 study evaluating the safety and efficacy of hUC-O local application combined with CD in early-stage ONFH patients. This study will provide the useful information on the treatment with hUC-O for those suffering from ONFH.Trial registration: Clinical Research Information Center (CRIS) established at the Korea Centers for Disease Control and Prevention (KDCA), KCT0006627. Registered 30 September 2021, https://cris.nih.go.kr/cris/search/detailSearch.do/20332

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