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

Primary Purpose

Acute Respiratory Distress Syndrome Due to Disease Caused by 2019-nCoV

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory Cells
Sponsored by
Jeffrey Bluestone
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Respiratory Distress Syndrome Due to Disease Caused by 2019-nCoV

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of North Carolina
  • The Ohio State University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

cePolyTregs 100 x10^6 cells Open Label

cePolyTregs 200 x10^6 cells Open Label

cePolyTregs 400 x10^6 cells Open Label

Arm Description

single dose of 100 x 10^6 cells by IV infusion

single dose of 200 x 10^6 cells by IV infusion

single dose of 400 x 10^6 cells by IV infusion

Outcomes

Primary Outcome Measures

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
DLT is defined as any related treatment-emergent adverse event (TEAE) with a National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE 5.0) grade ≥ 3 which also represents a shift from baseline clinical status of ≥ 1 NCI CTCAE grade

Secondary Outcome Measures

Full Information

First Posted
August 26, 2021
Last Updated
May 8, 2023
Sponsor
Jeffrey Bluestone
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Immune Tolerance Network (ITN)
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1. Study Identification

Unique Protocol Identification Number
NCT05027815
Brief Title
Tregs for the Treatment of Acute Respiratory Distress Syndrome (ARDS) Associated With COVID-19 (regARDS)
Acronym
regARDS
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Terminated
Why Stopped
Decrease in COVID-19 cases made further enrollment infeasible.
Study Start Date
September 23, 2021 (Actual)
Primary Completion Date
March 2, 2022 (Actual)
Study Completion Date
March 2, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jeffrey Bluestone
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Immune Tolerance Network (ITN)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Distress Syndrome Due to Disease Caused by 2019-nCoV

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
cePolyTregs 100 x10^6 cells Open Label
Arm Type
Experimental
Arm Description
single dose of 100 x 10^6 cells by IV infusion
Arm Title
cePolyTregs 200 x10^6 cells Open Label
Arm Type
Experimental
Arm Description
single dose of 200 x 10^6 cells by IV infusion
Arm Title
cePolyTregs 400 x10^6 cells Open Label
Arm Type
Experimental
Arm Description
single dose of 400 x 10^6 cells by IV infusion
Intervention Type
Biological
Intervention Name(s)
Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory Cells
Other Intervention Name(s)
cePolyTregs
Intervention Description
cryopreserved cellular therapy product in cryostor CS5, for IV infusion
Primary Outcome Measure Information:
Title
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Description
DLT is defined as any related treatment-emergent adverse event (TEAE) with a National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE 5.0) grade ≥ 3 which also represents a shift from baseline clinical status of ≥ 1 NCI CTCAE grade
Time Frame
28 days post infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maor Sauler, MD
Organizational Affiliation
Yale University
Official's Role
Study Chair
Facility Information:
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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