|drug3973||not applicable (observational study) Wiki||1.00|
There is one clinical trial.
The first-in-human Phase 1 study component will evaluate two dose levels of RAPA-501-ALLO off the shelf cells in patients with post-intubation, stage 3 COVID-19 disease, 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 December 15, 2020, an estimated 73.3 million people have contracted the virus and 1,630,000 deaths have resulted globally. The United States has the highest totals with an estimated 16.6 million people diagnosed and 302,000 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 post-intubation, Stage 3 COVID-19.
Description: On the phase 1 study component, determine the safety of allogeneic RAPA-501 cells when administered at dose level 1 (Cohort 1, 40 x 106 cells) and dose level 2 (Cohort 2, 160 x 106 cells).Measure: Dose-Limiting Toxicity (DLT) Time: 30 days after the first infusion of allogeneic RAPA-501 cells.
Description: On the phase II study component, determine whether allogeneic RAPA-501 cells result in a mortality rate that is reduced relative to the randomized placebo-control cohort.Measure: Mortality Rate Time: 30 days after the first infusion of allogeneic RAPA-501 cells.
Description: Number of days requiring ventilation support.Measure: Ventilation Support Time: 90 days after the infusion of allogeneic RAPA-501 cells.
Description: Number of days of hospitalization among survivors.Measure: Days of Hospitalization Time: 90 days after the infusion of allogeneic RAPA-501 cells.
Description: Number of deaths due to any cause.Measure: Number of Deaths Time: 90 days after the infusion of allogeneic RAPA-501 cells.
Description: Incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infection.Measure: Incidence of Infection Time: 90 days after the infusion of allogeneic RAPA-501 cells.
Description: GVHD incidence and severity.Measure: GVHD Incidence Time: 90 days after the infusion of allogeneic RAPA-501 cells.
Description: COVID-19 viral load, as determined by standard reverse transcriptase polymerase chain reaction (RT-PCR) assay or equivalent test on nasopharyngeal and/or endotracheal tube swab samples.Measure: Viral Load Time: Six months after treatment initiation.
Description: Development of potentially protective host immunity to COVID-19, as determined by serologic studies.Measure: Host Immunity Time: Six months after treatment initiation.
Description: Peripheral blood immune counts, including CD4+ and CD8+ T cells, NK cells, and B cells.Measure: Peripheral Blood Immune Counts Time: Six months after treatment initiation.
Description: T cell expression of co-stimulation molecules (including CD28) and checkpoint receptor molecules (including PD-1).Measure: T Cell Expression Time: Six months after treatment initiation.
Description: Peripheral blood micro-chimerism, as determined by PCR amplification of donor and host STR loci.Measure: Peripheral Blood Micro-chimerism Time: Six months after treatment initiation.
Data processed on January 01, 2021.
An HTML report was created for each of the unique drugs, MeSH, and HPO terms associated with COVID-19 clinical trials. Each report contains a list of either the drug, the MeSH terms, or the HPO terms. All of the terms in a category are displayed on the left-hand side of the report to enable easy navigation, and the reports contain a list of correlated drugs, MeSH, and HPO terms. Further, all reports contain the details of the clinical trials in which the term is referenced. Every clinical trial report shows the mapped HPO and MeSH terms, which are also hyperlinked. Related HPO terms, with their associated genes, protein mutations, and SNPs are also referenced in the report.Drug Reports MeSH Reports HPO Reports