This is a a randomized double blind placebo controlled Phase 2 trial with a 12 patientlead-in to evaluate safety, prior to full enrollment to an additional 28 patients (for atotal of 40 patients) to assess efficacy of decitabine in the treatment of critically illpatients with COVID-ARDS. The patients will be randomized in a 1:1 ratio to receivestandard of care plus Decitabine or standard of care plus saline based placebo. Theprimary objective is to determine safety and efficacy of decitabine for COVID-19 ARDSbased on clinical improvement on a 6-point clinical scale.
This is a randomized double blind placebo controlled Phase 2 trial with a 12 patient
lead-in to evaluate safety, prior to full enrollment to an additional 28 patients (for a
total of 40 patients) to assess efficacy of decitabine in the treatment of critically ill
patients with COVID-ARDS. The patients will be randomized in a 1:1 ratio to receive
standard of care plus Decitabine or standard of care plus saline based placebo.
Eligible patients will receive decitabine 10 mg/m2 daily for 5 days, 1 cycle only. This
is a dose that is half the FDA approved dose for myelodysplastic syndrome (MDS), and
using a single cycle.
If less than 2 of the first 6 (treatment arm) patients experience an unacceptable
toxicity, defined as any treatment related grade III or higher adverse events, as per
section 5.7, within 15 days of initiation of treatment, the drug is safe to continue. If
the investigators observe more than 33% patients with unacceptable toxicity, the
investigators will pause the accrual pending safety evaluation. After validating safety,
the investigators will enroll additional 28 patients towards the primary efficacy
endpoint. The investigators will monitor safety throughout the trial by monitoring
clinical hematologic, chemistry, vital signs, respiratory parameters, medications, and
clinical changes daily as per the schedule of procedures.
Bio samples from peripheral blood mononuclear cell (PBMC) and Mini Bronchoalveolar lavage
(BAL) will be collected and stored for secondary analysis and mini BAL will only be
collected as an optional sub-study for patient consented to a separate study protocol
either at time-point of for-cause clinically indicated bronchoscopy, or for subjects
consented to a separate Bronchoalveolar lavage (BAL) interventional study, under the
auspices of that protocol. For research bio specimens required after study drug
initiation, a window period of +/-24 hours while inpatient, and +/- 4 days for outpatient
monitoring will be permitted.
These objectives will allow for the planning of subsequent phase 3 studies, and
strengthen implementation of a multi-center randomized trial should this study confirm
safety, and suggest efficacy of therapy.
Drug: Decitabine
Study duration is 6 weeks after the last dose of study drug. Number of study visits is
dependent on Length of hospitalization of study participant. Study visits are scheduled
on days 0-7, 11, 15, 29, and may occur via telemedicine or inpatient assessment or
outpatient assessment in COVID recovered participants.
Decitabine will be administered via Intravenous Administration 10/mg/m^2/day Dosage:
10mg/m^2/day IV day x 5 days (1 cycle only)
Other Name: 5-aza-2'- deoxycytidine,DACOGEN
Other: Placebo Saline
Saline based placebo will be administered via Intravenous injection. Dosage Regimen:
10mg/m^2/day IV day x 5 days (1 cycle only)
Inclusion Criteria:
1. ≥18 years
2. Use of Intermittent Mechanical Ventilation, non-invasive mechanical ventilation
(NIMV) or High Flow Nasal Cannula.
3. Have ARDS or Acute Lung Injury physiology confirmed by Pao2/Fio2 ratio of < 300
4. Severe Acute Respiratory Distress Syndrome (SARS) - Coronavirus (CoV-2) determined
by lab polymerase chain reaction assay in either upper or lower respiratory tract
sampling (e.g. bronchoalveolar lavage or nasopharyngeal swab)
5. If childbearing age: agree to practice effective birth control from screening until
at least 180 days after last dose
Exclusion Criteria:
1. Hematologic cytopenias: Absolute Neutrophil Count (ANC) <1500/mm3, Hgb<7.0 and/or
platelets <100,000/mm3
2. Subjects receiving or enrolled in clinical trial for other investigational treatment
for SARS- 2-CoV.
3. Active malignancy, solid tumors, and current or recent chemotherapy
4. Concomitant use of nonbiologic immunosuppressants (e.g. Janus Kinase (JAK)
inhibitors, Bruton's Tyrosine Kinase (BTK) inhibitors)
5. Active HIV viremia, or any other uncontrolled secondary infection.
6. Concurrent immunomodulating biologics or use of Palifermin, Dipyrone, Deferiprone
7. Subjects with severe sepsis with vasopressors or extrapulmonary organ failure:
8. Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) /alkaline
phosphatase (ALK) Phos ≥3x upper limit of normal (ULN) and Total Bilirubin (TBILI)
≥2x ULN; or Creatinine clearance <30 mL/min
9. Pregnant women or women who are breastfeeding
10. Any Condition, per opinion of PI that would affect subject safety and/or compliance
11. Prior hypersensitivity to decitabine
Johns Hopkins University
Baltimore, Maryland, United States
Pali Shah, M.D, Principal Investigator
Johns Hopkins UIniversity