Project description:COVID-19 has rapidly developed into a worldwide pandemic with a significant health and economic burden. There are currently no approved treatments or preventative therapeutic strategies. Hundreds of clinical studies have been registered with the intention of discovering effective treatments. Here, we review currently registered interventional clinical trials for the treatment and prevention of COVID-19 to provide an overall summary and insight into the global response.
Project description:Coronavirus disease 2019 (COVID-19) has developed as a pandemic, and it created an outrageous effect on the current healthcare and economic system throughout the globe. To date, there is no appropriate therapeutics or vaccines against the disease. The entire human race is eagerly waiting for the development of new therapeutics or vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Efforts are being taken to develop vaccines at a rapid rate for fighting against the ongoing pandemic situation. Amongst the various vaccines under consideration, some are either in the preclinical stage or in the clinical stages of development (phase-I, -II, and -III). Even, phase-III trials are being conducted for some repurposed vaccines like Bacillus Calmette-Guérin, polio vaccine, and measles-mumps-rubella. We have highlighted the ongoing clinical trial landscape of the COVID-19 as well as repurposed vaccines. An insight into the current status of the available antigenic epitopes for SARS-CoV-2 and different types of vaccine platforms of COVID-19 vaccines has been discussed. These vaccines are highlighted throughout the world by different news agencies. Moreover, ongoing clinical trials for repurposed vaccines for COVID-19 and critical factors associated with the development of COVID-19 vaccines have also been described.
Project description:Large-scale deployment of COVID-19 vaccines will seriously affect the ongoing phases 2 and 3 randomised placebo-controlled trials assessing SARS-CoV-2 vaccine candidates. The effect will be particularly acute in high-income countries where the entire adult or older population could be vaccinated by late 2021. Regrettably, only a small proportion of the population in many low-income and middle-income countries will have access to available vaccines. Sponsors of COVID-19 vaccine candidates currently in phase 2 or initiating phase 3 trials in 2021 should consider continuing the research in countries with limited affordability and availability of COVID-19 vaccines. Several ethical principles must be implemented to ensure the equitable, non-exploitative, and respectful conduct of trials in resource-poor settings. Once sufficient knowledge on the immunogenicity response to COVID-19 vaccines is acquired, non-inferiority immunogenicity trials-comparing the immune response of a vaccine candidate to that of an authorised vaccine-would probably be the most common trial design. Until then, placebo-controlled, double-blind, crossover trials will continue to play a role in the development of new vaccine candidates. WHO or the Council for International Organizations of Medical Sciences should define an ethical framework for the requirements and benefits for trial participants and host communities in resource-poor settings that should require commitment from all vaccine candidate sponsors from high-income countries.
Project description:Ulcerative colitis (UC) is a chronic and progressive inflammatory disorder that affects the colon. The advent of advanced therapies such as biologic agents and small molecules has revolutionized the management of UC. Despite the expanding therapeutic armamentarium of advanced therapies to treat UC, the overall net remission rates and durability of currently available agents are relatively low. This highlights the need for further drug development and more innovative clinical trial design. There are currently multiple emerging agents in the pipeline for the management of UC. This includes agents with alternative routes of administration such as oral or subcutaneous tumor necrosis factor inhibitors or novel mechanisms of action such as toll-like receptor 9 (TLR9) agonist cobitolimod and phosphodiesterase 4 inhibitor apremilast. In this review, we will highlight novel and emerging advanced therapies currently in the pipeline for the management of UC.
Project description:The coronavirus disease-19 (COVID-19) is caused due to the infection by a unique single stranded enveloped RNA virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The COVID-19 has claimed many lives around the globe, and a promising solution to end this pandemic is still awaited. Till date neither an exact antiviral drug nor a vaccine is available in the market for public use to cure or control this pandemic. Repurposed drugs and supportive measures are the only available treatment options. This systematic review focuses on different treatment strategies based on various clinical studies. The review discusses all the current treatment plans and probable future strategies obtained as a result of a systematic search in PubMed and Science Direct database. All the possible options for the treatment as well as prophylaxis of COVID-19 are discussed. Apart from this, the article provides details on the clinical trials related to COVID-19, which are registered under ClinicalTrials.gov. Potential of drugs based on the previous researches on SARS-CoV, MERS-CoV, Ebola, influenza, etc. which fall under the same category of coronavirus are also emphasized. Information on cell-based and immunology-based approaches is also provided. In addition, miscellaneous therapeutic approaches and adjunctive therapies are discussed. The drug repurposing options, as evidenced from various in vitro and in silico models, are also covered including the possible future solutions to this pandemic.
Project description:The improvement of imaging techniques over the years has contributed to the understanding of the natural history of autosomal dominant polycystic kidney disease, and facilitated the observation of its structural progression. Advances in molecular biology and genetics have made possible a greater understanding of the genetics, molecular, and cellular pathophysiologic mechanisms responsible for its development and have laid the foundation for the development of potential new therapies. Therapies targeting genetic mechanisms in ADPKD have inherent limitations. As a result, most experimental therapies at the present time are aimed at delaying the growth of the cysts and associated interstitial inflammation and fibrosis by targeting tubular epithelial cell proliferation and fluid secretion by the cystic epithelium. Several interventions affecting many of the signaling pathways disrupted in ADPKD have been effective in animal models and some are currently being tested in clinical trials.
Project description:INTRODUCTION:The authors describe the medications for treatment-resistant depression (TRD) in phase II/III of clinical development in the EU and USA and provide an opinion on how current treatment can be improved in the near future. Areas covered: Sixty-two trials were identified in US and EU clinical trial registries that included six investigational compounds in recent phase III development and 12 others in recent phase II clinical trials. Glutamatergic agents have been the focus of many studies. A single intravenous dose of the glutamatergic modulator ketamine produces a robust and rapid antidepressant effect in persons with TRD; this effect continues to remain significant for 1 week. This observation was a turning point that opened the way for other, more selective glutamatergic modulators (intranasal esketamine, AVP-786, AVP-923, AV-101, and rapastinel). Of the remaining compounds, monoclonal antibodies open highly innovative therapeutic options, based on new pathophysiological approaches to depression. Expert commentary: Promising new agents are emerging for TRD treatment. Glutamatergic modulators likely represent a very promising alternative to monoaminergic antidepressant monotherapy. We could see the arrival of the first robust and rapid acting antidepressant drug in the near future, which would strongly facilitate the ultimate goal of recovery in persons with TRD.
Project description:The COVID-19 pandemic has driven an unprecedented level of global activity in drug discovery and clinical development for effective therapeutics targeting the coronavirus disease. There are currently 744 therapeutics being tested in 2879 clinical trials globally. Almost 90% of these clinical trials are focused on monotherapies. Combination therapies are the mainstay of antiviral therapeutics to increase the potency of the individual compounds and to combat the rapid evolution of resistance, although combination therapies have inherently complex clinical and regulatory development challenges. Increased understanding of the SARS-CoV-2 lifecycle and COVID-19 pathology provides a scientific rationale for evaluating the effectiveness of different combinations. In this paper, we provide an overview of the current clinical trial landscape for combination therapeutics targeting COVID-19 through weekly scanning of national and international clinical trial registries. Our analysis delves specifically into dual combination therapies in what can be defined as "pivotal clinical trials" (active, randomised, controlled and at least phase II), with a focus on new and repurposed therapeutic candidates that have shown positive signals and/or been granted authorisation for emergency use based on positive efficacy and safety data.
Project description:In recent years, we have seen rapid expansion of chimeric antigen receptor T-cell (CAR-T) therapies in multiple malignancies. CAR-T therapy has profoundly altered the treatment landscape of non-Hodgkin lymphoma, B-cell acute lymphoblastic leukemia, and multiple myeloma. Currently available CD19 and B-cell maturation antigen-directed CAR-T therapies have shown high overall response rate and durable remissions in patients who have failed standard therapies. Multiple studies are underway exploring the role of CAR-T-cell therapy as earlier line of treatment. In high-grade B-cell lymphoma, CD19 CAR-T therapy may replace autologous hematopoietic cell transplantation as second line therapy in near future. CAR-T-cell therapy targeting novel tumor-associated antigens will help expand utility of this treatment modality in other hematological malignancies. It may also help overcome limitations of currently approved CAR-T-cell therapies. In this review, we have provided an overview of currently approved CAR-T therapies and upcoming clinical trials which may potentially impact the clinical practice.