121 Clinical Trials for Various Conditions
Novel coronavirus pneumonia (NCP) and acute respiratory distress syndrome (ARDS) are both associated with the prevailing upper respiratory tract infections caused by the RNA-containing SARS-CoV2 virus of the genius Betacoronavirus of the Coronaviridae family. As both the viral infiltration and infection progress, the host immune system response can be one of a rapidly developing fatal cytokine storm. In the ARDS or NCP ensuing progression, the patient often succumbs to the effects of the hyper pro-inflammatory response, hence contributing to the associated increased mortality as a result of the cytokine storm and associated pathogenesis.
The first-in-human Phase 1 study component will evaluate two dose levels of RAPA-501-ALLO off the shelf cells in patients with COVID-19-related ARDS, with key endpoints of safety, biologic and potential disease-modifying effects. The randomized, double-blind, placebo-controlled Phase 2b study component will evaluate infusion of RAPA-501 ALLO off the shelf cells or a control infusion, with the primary endpoint assessing whether RAPA-501 cells reduce 30-day mortality. The COVID-19 pandemic is a disaster playing out with progressive morbidity and mortality. As of April 6th, 2021, an estimated 132.1 million people have contracted the virus and 2,866,000 deaths have resulted globally. The United States has the highest totals with an estimated 30.8 million people diagnosed and 556,000 deaths. In stages 1 and 2 of COVID-19, viral propagation within the patient is predominant. As such, therapeutic interventions focus on immune molecules (convalescent serum, monoclonal antibodies) and anti-viral medications (remdesivir). In marked contrast, the most severe and deadly form of COVID-19, stage 3, is driven not by viral propagation, but by an out-of-control immune response (hyperinflammation) caused by increases in immune molecules known as cytokines and chemokines. As such, therapeutic interventions for stage 3 disease focus on anti-inflammatory medications such as anti-cytokine therapy (anti-IL-6 drugs) or corticosteroid therapy. Unfortunately, such interventions do not address the full pathogenesis of stage 3 COVID-19, which includes hyperinflammation due to "cytokine storm" and "chemokine storm," tissue damage, hypercoagulation, and multi-organ failure (including lung, heart, kidney and brain). The pulmonary component of stage 3 disease includes acute respiratory distress syndrome (ARDS), which is a final-common-pathway of patient death due to a myriad of conditions, including pneumonia, sepsis, and trauma. There is a dire need for novel cellular treatments that can deliver both a broad-based immune modulation effect and a tissue regenerative effect, such as RAPA-501-ALLO off-the-shelf allogeneic hybrid TREG/Th2 Cells. Stage 3 COVID-19 carries an estimated 30-day mortality of over 50% in spite of ICU utilization, mechanical ventilation, and supportive care therapies to manage ARDS and multiorgan failure. Narrowly acting targeted anti-inflammatory approaches such as anti-IL-6 therapeutics have not been particularly effective in stage 3 COVID-19 and the broad anti-inflammatory pharmaceutical approach of corticosteroid therapy, has only modestly tempered stage 3 disease in some studies. Cell therapy is also being evaluated in stage 3 COVID-19, in particular, mesenchymal stromal cells (MSC) and now, with the current RAPA-501-ALLO protocol, regulatory T (TREG) cells. TREG therapy has a mechanism of action that includes a multi-faceted anti-inflammatory effect, which puts TREG therapy at the forefront of future curative therapy of a wide range of autoimmune and neurodegenerative diseases, plus transplant complications, such as graft-versus-host disease (GVHD) and graft rejection. In addition, TREG therapy can provide a tissue regenerative effect, which places TREG cell therapy at the lead of novel regenerative medicine efforts to repair a myriad of tissue-based diseases, such as diseases of the skin, muscle, lung, liver, intestine, heart (myocardial infarction) and brain (stroke). RAPA-501-ALLO off-the-shelf cell therapy offers this potential dual threat mechanism of action that incorporates both anti-inflammatory and tissue repair effects for effective treatment of COVID-19 and multiple lethal conditions. RAPA-501-ALLO cells are generated from healthy volunteers, cryopreserved, banked, and are then available for off-the-shelf therapy anytime. During manufacturing, T cells are "reprogrammed" ex vivo using a novel, patented 7-day two-step process that involves T cell de-differentiation and subsequent re-differentiation towards the two key anti-inflammatory programs, the TREG and Th2 pathways, thus creating a "hybrid" product. The hybrid phenotype inhibits inflammatory pathways operational in COVID-19, including modulation of multiple cytokines and chemokines, which attract inflammatory cells into tissue for initiation of multi-organ damage. The hybrid TREG and Th2 phenotype of RAPA-501-ALLO cells cross-regulates Th1 and Th17 populations that initiate hyperinflammation of COVID-19. RAPA-501 immune modulation occurs in a T cell receptor independent manner, thus permitting off-the-shelf cell therapy. Finally, in experimental models of viral pneumonia and ARDS, TREG cells mediate a protective effect on the lung alveolar tissue. Because of this unique mechanism of action that involves both anti-inflammatory and tissue protective effects, the allogeneic RAPA-501 T cell product is particularly suited for evaluation in the setting of COVID-19-related ARDS.
Dexamethasone has been approved for the treatment of severe COVID-19, but higher doses of steroids may be more effective. The purpose of this research study is to compare the current standard dose of dexamethasone 6 mg to a higher, weight-based dosing (0.2 mg/kg with maximum dose of 20 mg) to determine if it would be more effective against COVID-19 pneumonia.
The study is designed as a multicenter, randomized, double-blind, placebo-controlled, parallel group study of the safety and efficacy of tofacitinib in hospitalized adult participants with COVID-19 pneumonia who are receiving SoC therapy and who are not on HFNC, noninvasive ventilation, invasive mechanical ventilation, or ECMO on Day 1 at the time of randomization. Participants with laboratory confirmed SARS-CoV-2 infection as determined by a positive PCR or other commercially available or public health assay, who have agreed to participate will be screened within 48 hours after hospitalization to determine eligibility. This should be completed within 48 hours prior to Day 1. Eligible participants will be randomized on Day 1 in a 1:1 ratio to the tofacitinib treatment group or the placebo treatment group and will receive treatment for up to 14 days, or until discharge from the hospital, whichever is earlier. If a participant requires intubation prior to the end of the 14-day treatment period, they will continue to receive tofacitinib or matching placebo until Day 14 (or until discharge from the hospital, if earlier than Day 14), if clinically appropriate. Participants will be assessed daily (up to Day 28) while hospitalized for clinical, safety, and laboratory parameters. Follow-up visits will occur on Day 28, 28 to 35 days after the ET/ED/EOT visit, and on Day 60. An independent, external DSMB will be convened to oversee the safety of participants and make recommendations regarding the conduct of the trial in accordance with the Charter.
Up to 240 patients with confirmed COVID-19 pneumonia with a baseline imputed PaO2/FiO2 ≤200 receiving oxygen therapy via a high flow nasal cannula (HFNC) or non-invasive ventilation (NIV) will be enrolled at up to 40 sites. All patients will receive three doses of Auxora. Patients who continue to have severe hypoxemic respiratory failure at 48 hours will be randomized to receive three additional doses of Auxora or three doses of placebo. All patients will be followed for 60 days after enrollment into the study.
This is a single-blind study consisting of up to 3 cohorts Patients will be randomized 3:1 to Auxora or Placebo. The first 4 patients will be enrolled in Cohort 1. If dose escalation occurs, the next 4 patients will be enrolled in Cohort 2 If dose escalation occurs, the next 8 patients will be enrolled in Cohort 3. The decision to escalate dosing will be made by CalciMedica in consultation with the PI and after the review of safety events in Cohorts 1 and 2.
This is a a randomized double blind placebo controlled Phase 2 trial with a 12 patient lead-in to evaluate safety, prior to full enrollment to an additional 28 patients (for a total of 40 patients) to assess efficacy of decitabine in the treatment of critically ill patients with COVID-ARDS. The patients will be randomized in a 1:1 ratio to receive standard of care plus Decitabine or standard of care plus saline based placebo. The primary objective is to determine safety and efficacy of decitabine for COVID-19 ARDS based on clinical improvement on a 6-point clinical scale.
The study will evaluate the safety and efficacy of orally-administered M5049 in Coronavirus disease 2019 (COVID-19) pneumonia participants who are hospitalized but not on mechanical ventilation.
The purpose of the COVIDNOCHE trial (HFNO versus CPAP Helmet Evaluation in COVID-19 Pneumonia) is to evaluate the comparative effectiveness of standard care non-invasive respiratory support (helmet CPAP versus HFNO) for acute hypoxemic respiratory failure from COVID-19 pneumonia on ventilator-free days (primary outcome) and other clinical outcomes measured up to 90 days.
Part 1 of this trial enrolled 30 patients to receive Auxora (formerly CM4620) in a 2:1 randomized, open label trial of patients with severe and critical COVID-19 pneumonia. Part 2 will consist of a randomized, double blind, placebo-controlled (RCT) study that will evaluate efficacy, safety, and the pharmacokinetic profile of Auxora in patients with severe COVID-19 pneumonia. The number of patients with an imputed PaO2/FiO2 \>200 randomized into the study will be capped at 26. 320 patients with a PaO2/FiO2 ≤200 will be enrolled. Patients with an estimated PaO2/FiO2 of 75-200 will be stratified to ensure balanced randomization between the Auxora and placebo arms. Subgroup analyses will be performed to explore how time to recovery is influenced by baseline variables and to evaluate the treatment effect at different levels of each of these variables. The dose of Auxora will be 2.0 mg/kg (1.25 mL/kg) administered at 0 hour, and then 1.6 mg/kg (1 mL/kg) at 24 hours and 1.6 mg/kg (1 mL/kg) at 48 hours from the SFISD. The dose of placebo will be 1.25 mL/kg administered at 0 hour and then 1 mL/kg at 24 hours and 1 mL/kg at 48 hours from the SFISD. Remdesivir, corticosteroids and convalescent plasma will be allowed. The infusion of Auxora will start within 12 hours from the time the patient or LAR provides informed consent. Efficacy analyses will be presented by treatment group (Auxora vs Placebo) based on the Efficacy Analysis Set of the imputed PaO2/FiO2 ≤200 subgroup, except where it is specified otherwise. The statistical analysis approach will be designed to assess the significance of the primary and first secondary endpoint using the Benjamini and Hochberg method to control the overall trial level alpha level.
The study hypothesis is that cromolyn, when combined with standard COVID-19 treatment, will improve patient symptoms and reduce the number of days to improved quality of life. Investigators will study the effects of adding cromolyn to the standard treatment of hospitalized patients with COVID-19 pneumonia and who require supplemental oxygen. Cromolyn will be administered as a nebulized treatment four times a day for four days followed by intranasal administration for two weeks. Investigators may also screen for biomarkers that could indicate inflammatory responses and treatment-induced improvement. Participants will receive either study drug or placebo which will be administered by nebulization for 4 days followed by 14 days of intranasal administration. Participants will be followed while in the hospital and then as outpatients up to day 21 following randomization.
The purpose of this study is to find out whether the drug uproleselan can help patients with severe COVID-19 pneumonia. Investigators will study both the side effects of the drug and assess if the drug will help patients recover more quickly and slow down the progression of acute respiratory failure.
The primary purpose of this study is to determine whether the drug sirolimus reduces the likelihood of developing of pulmonary fibrosis in patients who are hospitalized with COVID-19 pneumonia.
The aim of the current clinical study is to evaluate the efficacy and safety of inhibition of Interleukin-1 receptor associated kinase 4 (IRAK4) in ameliorating the proinflammatory state and improving outcomes in severe COVID-19.
The study objective is to assess Efficacy and safety of Reparixin treatment as compared to placebo (both on top of standard treatment) in adult patients with severe COVID-19 pneumonia.
The aim of this study will test the safety, tolerability, and efficacy of RLS-0071 for approximately 28 days in comparison to a placebo control in patients with acute lung injury due to COVID-19 pneumonia in early respiratory failure. Patients will be randomized and double-blinded for two parts, a single-ascending dose (SAD) part and a multiple-ascending dose (MAD) part. The name of the study drug involved in this study is: RLS-0071.
This study is an open-label, single-arm study to evaluate the safety and efficacy of Astrostem-V, allogenic adipose tissue derived mesenchymal stem cells (AdMSC), in patients with COVID-19 pneumonia. After each subject completes 12-Weeks visit (Visit 12) and the data management team confirms all individual data have no issue, the individual database will be locked and the blinding will be open for the statistical analysis.
The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.
To assess the safety and efficacy of CK0802 in treatment of patients with COVID-19 induced moderate-to-severe PNA-ARDS.
A phase 2/3 multi-center randomized, double-blind, parallel arm, placebo- controlled study in Adult Subjects Hospitalized with Severe SARS-CoV-2 Positive Pneumonia to determine the potential of opaganib to improve and/or stabilize the clinical status of the patient.
Low doses of radiation in the form of chest x-rays has been in the past to treat people with pneumonia. This treatment was thought to reduce inflammation and was found to be effective without side effects. However, it was an expensive treatment and was eventually replaced with less expensive treatment options like penicillin. The COVID-19 virus has emerged recently, causing high rates of pneumonia in people. The authors believe that giving a small dose of radiation to the lungs may reduce inflammation and neutralize the pneumonia caused by COVID-19. For this study, the x-ray given is called radiation therapy. Radiation therapy uses high-energy X-ray beams from a large machine to target the lungs and reduce inflammation. Usually, it is given at much higher doses to treat cancers. The purpose of this study is to find out if adding a single treatment of low-dose x-rays to the lungs might reduce the amount of inflammation in the lungs from COVID-19 infection, which could reduce the need for a ventilator or breathing tube.
The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.
Interventional, randomized, double-blind, placebo-controlled study encompassing 2 development phases (Phase 2 and Phase 3).
A pilot study to investigate the effects of the prone positioning (PP) on hospital patients diagnosed with COVID-19 pneumonia. Investigators that early self-proning may prevent intubation and improve mortality in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2). Up to 100 participants with a primary diagnosis of confirmed COVID-19 pneumonia will be enrolled to the study. All participants will be screened and those that meet inclusion and exclusion criteria will be enrolled to one of two groups: one with prone positioning (on the belly) and the other with standard supine positioning (on the back). The patient and nursing staff will monitor times spent in various positions. Outcome measures include incidence of intubation, max oxygen requirements, length of hospital stay, ventilator-free days, worsening of oxygenation saturation, and mortality.
The study is a prospective, randomized, placebo-controlled, double-blind phase 2 clinical study of the efficacy and safety of CERC-002, a potent inhibitor of LIGHT (Lymphotoxin-like, exhibits Inducible expression, and competes with Herpes Virus Glycoprotein D for Herpesvirus Entry Mediator, a receptor expressed by T lymphocytes), for the treatment of patients with 2019 novel coronavirus disease (COVID-19) pneumonia who have mild to moderate Acute Respiratory Distress Syndrome (ARDS). LIGHT is a cytokine in the tumor necrosis factor super family (TNFSF14) which drives inflammation and induces many other cytokines including IL-1, IL-6 and GM-CSF. LIGHT levels have been shown to be elevated in COVID-19 infected patients and inhibiting LIGHT is hypothesized to ameliorate the cytokine storm which has shown to be a major factor in progression of ARDS. The study will assess the efficacy and safety of CERC-002 in patients with severe COVID-19 over a 28 day period as single dose on top of standard of care.
This study will evaluate the efficacy and safety of combination therapy with remdesivir plus tocilizumab compared with remdesivir plus placebo in hospitalized patients with COVID-19 pneumonia.
The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.
In this research study the investigators want to learn more about the potential benefit of radiation to the lung to improve the health of patients who are hospitalized with Coronavirus-19 (COVID-19) due to infection with a virus called SARS-CoV-2. This infection causes inflammation of the lung, which can make it difficult to breathe. As a result, patients may need supplemental oxygen or be placed on a ventilator. The investigators believe that low dose radiation therapy to the lung may reduce this inflammation and increase the likelihood that patients will need less oxygen support such as ventilation or supplemental oxygen, or be discharged from the hospital in fewer days, compared to without radiation therapy. The amount of radiation is much lower than what is typically used to treat other conditions such as cancer, although it is higher than the dose used for routine medical imaging.
This is a Phase II, randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of MSTT1041A (astegolimab) compared with placebo and of UTTR1147A compared with placebo, in combination with standard of care (SOC), in patients hospitalized with severe coronavirus disease 2019 (COVID-19) pneumonia.
Novel coronavirus SARS(Severe Acute Respiratory Syndrome)-CoV-2 was first identified during the outbreak in Wuhan, China in December 2019 with the now resulting pandemic. Aggressive supportive care is the mainstay of treatment currently and rescue with lung protective mechanical ventilation is essential for survival in patients with severe acute respiratory distress syndrome. Despite supportive care, mortality is significant in hospitalized patients in the U.S., especially among patients \> 65 years of age. Pharmacologic treatments to decrease disease severity are urgently needed. Hydroxychloroquine is currently widely used for treatment of autoimmune disease including systemic lupus erythematosus and rheumatoid arthritis, and it has been used to prevent and treat malaria. In vitro and in vivo antiviral activity towards SARS-CoV-2 has been reported. Since hydroxychloroquine has been used for decades its properties as a drug are well known. The investigators propose a pragmatic trial of hydroxychloroquine in moderately ill hospitalized adults with SARS-CoV-2 pneumonia with the hypothesis that hydroxychloroquine reduces severity of acute lung injury caused by SARS-CoV-2 infection.