Acute Respiratory Distress Syndrome Due to Disease Caused by 2019-nCoVPhase 1regARDSNCT05027815
Tregs for the Treatment of Acute Respiratory Distress Syndrome (ARDS) Associated With COVID-19 (regARDS)
A Phase 1 study testing Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory Cells in people with Acute Respiratory Distress Syndrome Due to Disease Caused by 2019-nCoV, run by Jeffrey Bluestone at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute Respiratory Distress Syndrome Due to Disease Caused by 2019-nCoV
- What is being tested?
- Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 2 sitesUnited States
- Study dates
- 23 Sep 2021to 2 Mar 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of North Carolina
Chapel Hill, North Carolina, 27514
The Ohio State University
Columbus, Ohio, 43210
About this study
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)
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.
Read the 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.
- Being tested
- Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory Cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory CellsBiological
Also called cePolyTregs
cryopreserved cellular therapy product in cryostor CS5, for IV infusion
| Study group | Role | What they receive |
|---|---|---|
| cePolyTregs 100 x10^6 cells Open Label | Experimental | single dose of 100 x 10^6 cells by IV infusion Receives: 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 Receives: 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 Receives: Biological: Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 28 days post infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2021
- Study start23 Sep 2021
- Primary completion2 Mar 2022
- Study completion2 Mar 2022
Why it stopped: Decrease in COVID-19 cases made further enrollment infeasible.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Respiratory Distress Syndrome Due to Disease Caused by 2019-nCoVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jeffrey Bluestone
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Immune Tolerance Network (ITN)
- Responsible party
- Sponsor-investigator, Jeffrey Bluestone, University of California, San Francisco
- Investigators
- Maor Sauler, MD, Study chair, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05027815
- Sponsor's protocol ID
- UCSF-cePolyTregs-01
- Other IDs
- 3UM1AI109565-08S3
- Acronym
- regARDS
- Status last verified
- May 2023
- First submitted
- 26 Aug 2021
- Last updated
- 5 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05027815
- Acronym / sponsor ID
- regARDS / UCSF-cePolyTregs-01
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Decrease in COVID-19 cases made further enrollment infeasible.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Jeffrey BluestoneUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Immune Tolerance Network (ITN)
- Study start
- 23 Sep 2021 (actual)
- Primary completion
- 2 Mar 2022 (actual)
- Study completion
- 2 Mar 2022 (actual)
- First posted
- 30 Aug 2021 (actual)
- Results
- Posted 5 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| cePolyTregs 100 x10^6 cells Open Label | Experimental | Biological: Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory Cellssingle dose of 100 x 10^6 cells by IV infusion |
| cePolyTregs 200 x10^6 cells Open Label | Experimental | Biological: Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory Cellssingle dose of 200 x 10^6 cells by IV infusion |
| cePolyTregs 400 x10^6 cells Open Label | Experimental | Biological: Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory Cellssingle dose of 400 x 10^6 cells by IV infusion |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory CellsAlso: cePolyTregscryopreserved cellular therapy product in cryostor CS5, for IV infusion | Biological | cePolyTregs 100 x10^6 cells Open Label, cePolyTregs 200 x10^6 cells Open Label, cePolyTregs 400 x10^6 cells Open Label |
Primary outcome
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Time frame: 28 days post infusion
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maor Sauler, MD study chair
Yale University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory Cells in people with Acute Respiratory Distress Syndrome Due to Disease Caused by 2019-nCoV, run by Jeffrey Bluestone at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) (time frame: 28 days post infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2023.