Tregs for the Treatment of Acute Respiratory Distress Syndrome (ARDS) Associated With COVID-19 (regARDS)

A Phase 1/2a Study of Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory Cells (cePolyTregs) for the Treatment of Acute Respiratory Distress Syndrome (ARDS) Associated With SARS-CoV-2 Infection (regARDS)

In patients with Acute Respiratory Distress Syndrome (ARDS) associated with COVID-19 inflammatory syndrome, the administration of Treg cells is a novel treatment complementary to other pharmacologic interventions that potentially can reduce lung inflammation, promote lung tissue repair, and significantly improve clinical outcomes. This trial is to evaluate the impact of a single IV dose of cePolyTregs given to ARDS patients with COVID-19 inflammatory syndrome.

Tregs are a subset of CD4+ T cells that function to maintain immune system balance. The function of Tregs in maintaining immune tolerance can be harnessed through Treg cell therapy for treating various immunological diseases. Adoptive Tregs therapies have been shown to be effective in dozens of animal models, including models of virus-induced ARDS. This is a Phase 1 study to evaluate the safety and tolerability of cePolyTregs in subjects with ARDS associated with SARS-CoV-2 infection. The study is an open-label Phase 1 study to assess escalating doses of cePolyTregs administered as a single IV dose. The study will include up to 3 cohorts of 3 to 6 subjects/cohort followed for a total of 12 weeks. All subjects will receive standard of care treatment for COVID-19, including dexamethasone per institutional guidelines and other approved therapies for ARDS associated with SARS-CoV-2 infection per institutional guidelines.

Inclusion Criteria:

• Diagnosis of ARDS and respiratory failure requiring mechanical ventilation for less than 72 hours at the time of enrollment
• PaO2/FiO2 < 300 and PEEP > 5
• Male or female, age 18 to 70 years at Screening
• Weight > 40 kg
• Documented diagnosis of infection with SARS-CoV-2 virus by PCR
• Chest imaging (radiograph or CT scan) with abnormalities consistent with COVID-19 pneumonia that could not be explained by effusions, pulmonary collapse, or nodules; and respiratory failure that could not be explained by cardiac failure or fluid overload
• Females of childbearing potential and males must use effective contraception practices from Screening until 28 days after the EOS visit
• Females of childbearing potential must have a negative pregnancy test at Screening and within 24 hours prior to dosing of study drug
• Able to provide Informed Consent, either by self or by medical proxy
• Willing and able to comply with this protocol for the entire duration of the study

Exclusion Criteria:

• Any history or sign of significant chronic active or recurrent infection or screening laboratory evidence consistent with a significant chronic active or recurrent infection requiring treatment with antibiotics, antivirals or antifungals (other than SARS-CoV-2); ongoing antimicrobial treatments will not be exclusionary if, in the opinion of the investigator, no active infection is present (other than SARS-CoV-2)

• Receiving extracorporeal membrane oxygenation therapy

• Moribund patients not expected to survive 24 hours after enrollment based on clinical assessment

• History of significant underlying pulmonary disease (requiring home oxygen), renal disease (requiring dialysis for chronic kidney disease), hepatic disease (Child-Pugh score ≥ 7), or known history of cirrhosis.

• Known or suspected immunodeficiency disease

• Positive serology for HBV, HCV, or HIV at Screening

• Abnormal CBC defined by:

  • Platelet count < 75,000/mm3
  • White blood cell count < 2500/mm3
  • Absolute neutrophil count < 500/mm3

• History of bone marrow or stem cell transplantation

• Received any type of live attenuated vaccine < 1 month prior to Screening or is planning to receive any such live attenuated vaccine over the course of the study

• History of lung cancer or any other malignancy requiring active treatment, except adequately treated basal cell carcinoma or in situ carcinoma of the uterine cervix

• Any female who is pregnant or breastfeeding, or any female who is planning to become pregnant during the study and follow-up period

• Any condition that, in the investigator's opinion, may compromise study participation, present a safety risk to the subject, or may confound the interpretation of the study results

• A QT duration corrected for heart rate by Fridericia's formula (QTcF) > 450 millisecond (msec) for males or > 470 msec for females, based on either single or averaged QTcF values of triplicate ECGs obtained over a 3-minute interval

• Currently enrolled in another investigational device or drug study