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

NCT05027815 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: UCSF-cePolyTregs-013UM1AI109565-08S3
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

  28 days post infusion

Study Arms (3)

cePolyTregs 100 x10^6 cells Open Label

EXPERIMENTAL

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

Biological: Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory Cells

cePolyTregs 200 x10^6 cells Open Label

EXPERIMENTAL

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

Biological: Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory Cells

cePolyTregs 400 x10^6 cells Open Label

EXPERIMENTAL

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

Biological: Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory Cells

Interventions

Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory Cells BIOLOGICAL

cryopreserved cellular therapy product in cryostor CS5, for IV infusion

Also known as: cePolyTregs

cePolyTregs 100 x10^6 cells Open Label; cePolyTregs 200 x10^6 cells Open Label; cePolyTregs 400 x10^6 cells Open Label

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jeffrey Bluestone: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Immune Tolerance Network (ITN): collaborator

Study Sites (2)

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Limitations and Caveats

The trial was terminated early due to a decline in the available participants, which prevent the analysis of some secondary and exploratory endpoints from completion as initially planned. The safety and tolerability, and recommended phase 2 dose can not be determined based on the limited data.

Results Point of Contact

• Title: Jonathan Esensten MD, PhD
• Organization: University of California, San Francisco

Jonathan.Esensten@ucsf.edu

415-502-3785

Study Officials

• Maor Sauler, MD

  Yale University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 26, 2021
• First Posted: August 30, 2021
• Study Start: September 23, 2021
• Primary Completion: March 2, 2022
• Study Completion: March 2, 2022
• Last Updated: June 5, 2023
• Results First Posted: June 5, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)