<< Go Back

Metadata

Name
RAPA-501-Allo Therapy of COVID-19-ARDS
Repository
ClinicalTrials.gov
Identifier
clinicaltrials:NCT04482699
Description
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.
Data or Study Types
clinical trial
Keywords
Off-the-shelf, Acute Respiratory Distress Syndrome, Corona Virus Infection, COVID-19 Pneumonia, 2019 Novel Coronavirus Pneumonia, Lung Diseases, SARS, SARS Coronavirus 2, Respiratory Distress Syndrome, ARDS, Lung Injury, Reprogram, Allogeneic Hybrid TReg/Th2Cells, RAPA-501-ALLO, COVID-19, Cytokine Storm, SARS-CoV-2, Pneumonia, Severe Acute Respiratory Syndrome Coronavirus 2, Acute Lung Injury
Source Organization
Unknown
Access Conditions
available
Year
2020
Access Hyperlink
https://clinicaltrials.gov/ct2/show/NCT04482699

Distributions