scholarly journals Phase I/II Clinical Trial of the Anti-Podoplanin Monoclonal Antibody Therapy in Dogs with Malignant Melanoma

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2529
Author(s):  
Satoshi Kamoto ◽  
Masahiro Shinada ◽  
Daiki Kato ◽  
Sho Yoshimoto ◽  
Namiko Ikeda ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Malignant Melanoma ◽  
Adverse Effects ◽  
Phase I ◽  
Tumor Cells ◽  
Antibody Therapy ◽  
Human Tumor ◽  
Preclinical Trial ◽  
Canine Tumor

Podoplanin (PDPN), a small transmembrane mucin-like glycoprotein, is ectopically expressed on tumor cells. PDPN is known to be linked with several aspects of tumor malignancies in certain types of human and canine tumors. Therefore, it is considered to be a novel therapeutic target. Monoclonal antibodies targeting PDPN expressed in human tumor cells showed obvious anti-tumor effects in preclinical studies using mouse models. Previously, we generated a cancer-specific mouse–dog chimeric anti-PDPN antibody, P38Bf, which specifically recognizes PDPN expressed in canine tumor cells. In this study, we investigated the safety and anti-tumor effects of P38Bf in preclinical and clinical trials. P38Bf showed dose-dependent antibody-dependent cellular cytotoxicity against canine malignant melanoma cells. In a preclinical trial with one healthy dog, P38Bf administration did not induce adverse effects over approximately 2 months. In phase I/II clinical trials of three dogs with malignant melanoma, one dog vomited, and all dogs had increased serum levels of C-reactive protein, although all adverse effects were grade 1 or 2. Severe adverse effects leading to withdrawal of the clinical trial were not observed. Furthermore, one dog had stable disease with P38Bf injections. This is the first reported clinical trial of anti-PDPN antibody therapy using spontaneously occurring canine tumor models.

scholarly journals Immunogenicity and Safety of Inactivated Sabin-Strain Polio Vaccine “PoliovacSin”: Clinical Trials Phase I and II

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 565
Author(s):  
Anastasia Piniaeva ◽  
Georgy Ignatyev ◽  
Liubov Kozlovskaya ◽  
Yury Ivin ◽  
Anastasia Kovpak ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Phase I ◽  
Safety Profile ◽  
Neutralizing Antibody ◽  
Polio Eradication ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Good Tolerability ◽  
Poliomyelitis Vaccine

Global polio eradication requires both safe and effective vaccines, and safe production processes. Sabin oral poliomyelitis vaccine (OPV) strains can evolve to virulent viruses and result in poliomyelitis outbreaks, and conventional inactivated poliomyelitis vaccine (Salk-IPV) production includes accumulation of large stocks of neurovirulent wild polioviruses. Therefore, IPV based on attenuated OPV strains seems a viable option. To increase the global supply of affordable inactivated vaccine in the still not-polio free world we developed an IPV made from the Sabin strains–PoliovacSin. Clinical trials included participants 18–60 years of age. A phase I single-center, randomized, double-blind placebo-controlled clinical trial included 60 participants, who received one dose of PoliovacSin or Placebo. A phase II multicenter, randomized, double-blind, comparative clinical trial included 200 participants, who received one dose of PoliovacSin or Imovax Polio. All vaccinations were well tolerated, and PoliovacSin had a comparable safety profile to the Placebo or the reference Imovax Polio preparations. A significant increase in neutralizing antibody levels to polioviruses types 1–3 (Sabin and wild) was observed in PoliovacSin and Imovax Polio vaccinated groups. Therefore, clinical trials confirmed good tolerability, low reactogenicity, and high safety profile of the PoliovacSin and its pronounced immunogenic properties. The preparation was approved for clinical trials involving infants.

scholarly journals Self-Replicating RNA Viruses for RNA Therapeutics

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3310 ◽  
Author(s):  
Kenneth Lundstrom
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Tumor Cells ◽  
Neutralizing Antibodies ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Rna Viruses ◽  
Antibody Responses ◽  
Phase Iii ◽  
Phase I Clinical Trials

Self-replicating single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses, and rhabdoviruses provide efficient delivery and high-level expression of therapeutic genes due to their high capacity of RNA replication. This has contributed to novel approaches for therapeutic applications including vaccine development and gene therapy-based immunotherapy. Numerous studies in animal tumor models have demonstrated that self-replicating RNA viral vectors can generate antibody responses against infectious agents and tumor cells. Moreover, protection against challenges with pathogenic Ebola virus was obtained in primates immunized with alphaviruses and flaviviruses. Similarly, vaccinated animals have been demonstrated to withstand challenges with lethal doses of tumor cells. Furthermore, clinical trials have been conducted for several indications with self-amplifying RNA viruses. In this context, alphaviruses have been subjected to phase I clinical trials for a cytomegalovirus vaccine generating neutralizing antibodies in healthy volunteers, and for antigen delivery to dendritic cells providing clinically relevant antibody responses in cancer patients, respectively. Likewise, rhabdovirus particles have been subjected to phase I/II clinical trials showing good safety and immunogenicity against Ebola virus. Rhabdoviruses have generated promising results in phase III trials against Ebola virus. The purpose of this review is to summarize the achievements of using self-replicating RNA viruses for RNA therapy based on preclinical animal studies and clinical trials in humans.

Ethics in Clinical Studies: The Dilemma of very Young and Old

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Avisek Dutta ◽  
Avisek Dutta ◽  
Avisek Dutta
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Human Physiology ◽  
Informed Consent ◽  
Adverse Effects ◽  
Age Groups ◽  
The Elderly ◽  
Infantile Spasms ◽  
Care Givers ◽  
Improve Health

The objectives of the research are to percolate knowledge which can improve health and improve understanding of human physiology. Pervasive exclusion of children and elderly in clinical trials as is happening today is not justified. Children have different physiology and pharmacology from adults; often adverse effects are also different and specific. Diseases like neonatal hyperbilirubinemia, infantile spasms are very age specific. Elderly too, have age specific issues like dementias, malignancies, weakened systems and polypharmacy that make them a special cohort. Clinical trials in these age groups are essential so as to gather comprehensive data about a medication across all age groups. Informed consent is a challenge in both these groups. It can be remedied by obtaining consent from parents, or legally acceptable representative in case of children and care givers and/or LARs in case of the elderly. Oral assent from 7 to 11 years, and written assent from 12 to 18 years and in the elderly, along with consent from the LAR, parents, care givers as the case may be, forms the bedrock of good clinical trial ethics.

A Study on the Characteristics of Healthy Volunteers who Participate in Phase I Clinical Trials in Korea

2021 ◽  
pp. 155626462110342
Author(s):  
Ji-Hye Seo ◽  
Ock-Joo Kim ◽  
Sang-Ho Yoo ◽  
Eun Kyung Choi ◽  
Ji-Eun Park
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Phase I ◽  
Healthy Volunteers ◽  
Health Science ◽  
Trial Participation ◽  
Phase I Clinical Trials ◽  
Financial Reward ◽  
Therapeutic Purpose ◽  
The Republic

The phase I trial is the first step in administering a drug to humans, but it has no therapeutic purpose. Under the absence of therapeutic purpose, healthy volunteers demonstrated different motivations, unlike the actual patients participating in trials. There were many reported motivations, such as financial motivation, contributing to the health science, accessing ancillary health care benefits, scientific interest or interest in the goals of the study, meeting people, and general curiosity. The aim of this study was to identify the motivation and characteristics of healthy volunteers participating in phase I trials in the Republic of Korea. We gave surveys to 121 healthy volunteers to study their demographic characteristics and the reasons of participation. We identified whether the decision to participate in the research was influenced by demographic factors and whether the perception and attitudes toward the research were influenced by the characteristics of the healthy volunteers. After completion of the first survey, 12 healthy volunteers who had participated in a phase I clinical trial were selected to answer the second interview. According to our survey, most healthy volunteers were unmarried men and economically dependent. Most of them participated in the study because of financial reward. The most important factor to measure financial reward was the research period. Also, 43% of the volunteers were university students, 42% answered “university graduation” and 55% were residing in family-owned houses. Many healthy volunteers were found to be living in family homes and to have a student status or lack of economic independence. Results of the survey showed that 64% of respondents indicated having more than one clinical trial participation. In-depth interviews showed that healthy volunteers had diverse motivation to participate in research and that healthy volunteer perceive the clinical trial positively. The main motivation for healthy volunteers’ participation in research was “financial reward.” Healthy volunteers also considered research schedules, processes, and safety, and had a positive perception of clinical trials, but they thought that the public has a negative perception.

scholarly journals Provider Recommendations for Phase I Clinical Trials Within a Shared Decision-Making Model in Phase I Cancer Clinical Trial Discussions

2020 ◽  
Vol 16 (9) ◽  
pp. e859-e867
Author(s):  
Rachel S. Hianik ◽  
Gavin P. Campbell ◽  
Eli Abernethy ◽  
Colleen Lewis ◽  
Christina S. Wu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Clinical Trials ◽  
Phase I ◽  
Shared Decision Making ◽  
Phase I Trial ◽  
Performance Status ◽  
Shared Decision ◽  
Phase I Clinical Trials ◽  
Decision Making Model

PURPOSE: Debate continues over whether explicit recommendations for a clinical trial should be included as an element of shared decision making within oncology. We aimed to determine if and how providers make explicit recommendations in the setting of phase I cancer clinical trials. METHODS: Twenty-three patient/provider conversations about phase I trials were analyzed to determine how recommendations are made and how the conversations align with a shared decision-making framework. In addition, 19 providers (9 of whose patient encounters were observed) were interviewed about the factors they consider when deciding whether to recommend a phase I trial. RESULTS: We found that providers are comprehensive in the factors they consider when recommending clinical trials. The two most frequently stated factors were performance status (89%) and patient preferences (84%). Providers made explicit recommendations in 19 conversations (83%), with 12 of those being for a phase I trial (12 [63%] of 19). They made these recommendations in a manner consistent with a shared decision-making model; 18 (95%) of the 19 conversations during which a recommendation was made included all steps, or all but 1 step, of shared decision making, as did 11 of the 12 conversations during which a phase I trial was recommended. In 7 (58%) of these later conversations, providers also emphasized the importance of the patient’s opinion. CONCLUSION: We suggest that providers not hesitate to make explicit recommendations for phase I clinical trials, because they are able to do so in a manner consistent with shared decision making. With further research, these results can be applied to other clinical trial settings.

A phase I clinical trial of recombinant human tumor necrosis factor given daily for five days

1989 ◽  
Vol 23 (3) ◽  
Author(s):  
PatrickJ. Creaven ◽  
DeanE. Brenner ◽  
J.Wayne Cowens ◽  
RobertP. Huben ◽  
RichardM. Wolf ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Tumor Necrosis Factor ◽  
Phase I ◽  
Tumor Necrosis ◽  
Human Tumor ◽  
Phase I Clinical Trial ◽  
Human Tumor Necrosis Factor ◽  
Necrosis Factor

scholarly journals Integrated deep learned transcriptomic and structure-based predictor of clinical trials outcomes

2016 ◽  
Author(s):  
Artem V. Artemov ◽  
Evgeny Putin ◽  
Quentin Vanhaelen ◽  
Alexander Aliper ◽  
Ivan V. Ozerov ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Systems Biology ◽  
Phase I ◽  
Biological Data ◽  
Drug Induced ◽  
Multi Stage ◽  
Pathway Activation ◽  
Trial Outcomes ◽  
Analytical Tools

AbstractDespite many recent advances in systems biology and a marked increase in the availability of high-throughput biological data, the productivity of research and development in the pharmaceutical industry is on the decline. This is primarily due to clinical trial failure rates reaching up to 95% in oncology and other disease areas. We have developed a comprehensive analytical and computational pipeline utilizing deep learning techniques and novel systems biology analytical tools to predict the outcomes of phase I/II clinical trials. The pipeline predicts the side effects of a drug using deep neural networks and estimates drug-induced pathway activation. It then uses the predicted side effect probabilities and pathway activation scores as an input to train a classifier which predicts clinical trial outcomes. This classifier was trained on 577 transcriptomic datasets and has achieved a cross-validated accuracy of 0.83. When compared to a direct gene-based classifier, our multi-stage approach dramatically improves the accuracy of the predictions. The classifier was applied to a set of compounds currently present in the pipelines of several major pharmaceutical companies to highlight potential risks in their portfolios and estimate the fraction of clinical trials that were likely to fail in phase I and II.

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