This is a 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. The primary objective is to determine safety and efficacy of decitabine for COVID-19 ARDS based 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: Array
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
Franco D'Alessio, M.D, Principal Investigator
Johns Hopkins UIniversity