Decitabine for COVID-19

(DART Trial)

Overseen By Katrina Bazemore

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Immunosuppressants, Immunomodulating biologics

Disqualifiers: Active malignancy, HIV, Sepsis, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 1 week

33 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if the drug decitabine can safely and effectively treat severe lung issues in critically ill COVID-19 patients. Patients will receive either decitabine or standard care. The goal is to see if decitabine helps improve their condition by reducing lung damage.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using certain immunosuppressants or are in another clinical trial for COVID-19 treatments.

What data supports the effectiveness of the drug Decitabine for COVID-19?

Decitabine has shown effectiveness in treating certain blood disorders like acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) by improving survival rates and remission rates in patients. While this doesn't directly relate to COVID-19, it suggests that Decitabine can be effective in managing conditions involving abnormal cell growth. ^{1 2 3 4 5}

Is Decitabine safe for human use?

Decitabine has been used in older patients with acute myeloid leukemia and is generally well tolerated, with common side effects including fever, low platelet counts, and anemia. In combination with other drugs, it has shown similar safety profiles, though some studies in mice indicated potential severe toxicity at high doses, especially in females. ^{1 2 6 7 8}

What makes the drug Decitabine unique for treating COVID-19?

Decitabine is unique because it is primarily known as a DNA methyltransferase inhibitor used in cancer treatment, particularly for blood-related cancers like leukemia. Its potential use for COVID-19 is novel, as it may work by altering DNA methylation patterns, which is different from typical antiviral drugs that directly target the virus. ^{1 2 6 9 10}

Research Team

Pali Shah, MD

Principal Investigator

Johns Hopkins UIniversity

Eligibility Criteria

This trial is for adults over 18 with severe COVID-19 and ARDS, using mechanical ventilation or high-flow oxygen. They must have a lab-confirmed SARS-CoV-2 infection and agree to use birth control if of childbearing age. Excluded are those with certain organ failures, active cancers, blood disorders, other experimental treatments for COVID-19, uncontrolled infections like HIV, pregnant or breastfeeding women.

Inclusion Criteria

I use a machine to help with my breathing.

My lung function is severely impaired, as shown by a specific oxygen test.

I have tested positive for COVID-19 through a lab test.

Exclusion Criteria

My liver enzymes or bilirubin levels are very high, or my kidneys are not working well.

Any Condition, per opinion of PI that would affect subject safety and/or compliance

I am not currently taking any immune system modifying drugs or specific medications like Palifermin, Dipyrone, or Deferiprone.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive decitabine 10 mg/m2 daily for 5 days, 1 cycle only

1 week

Daily visits for 5 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Weekly visits (in-person or virtual)

Treatment Details

Interventions

• Decitabine
• Placebo Saline

Trial Overview The DART Trial is testing the safety and effectiveness of Decitabine in treating critically ill COVID-ARDS patients. It's a Phase 2 study where participants get either Decitabine plus standard care or a saline placebo plus standard care. The main goal is to see if they improve on a clinical scale.

Participant Groups

Group I: Decitabine + Standard of Care (SOC) Active Control 1 Intervention

Study drug Decitabine will be administered via Intravenous injection. Dosage Regimen: 10mg/m\^2/day IV day x 5 days (1 cycle only)

Group II: Standard of Care (SOC) + Placebo Placebo Group 1 Intervention

Saline based placebo will be administered via Intravenous injection. Dosage Regimen: 10mg/m\^2/day IV day x 5 days (1 cycle only)

Decitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dacogen for:

• Acute myeloid leukemia
• Myelodysplastic syndromes

Approved in United States as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Canada as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Findings from Research

Decitabine, administered at a dose of 20 mg/m² for 5 consecutive days, has been approved for older patients (≥65 years) with acute myeloid leukaemia (AML) who cannot undergo standard treatment, showing clinically meaningful improvements in overall survival after extended follow-up.

In a pivotal phase III trial, decitabine demonstrated significantly higher complete remission rates compared to standard treatment options like cytarabine, with a safety profile similar to cytarabine, including common side effects like fever and low blood cell counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine: a review of its use in older patients with acute myeloid leukaemia. Curran, MP.[2021]

Decitabine is a DNA methyltransferase inhibitor with a long history of antileukemic efficacy, particularly effective in treating acute myeloid leukemia in older patients or those unable to undergo intensive therapy.

The current dosing regimen of decitabine (20 mg/m² for 5 days) has been refined to minimize nonhematologic toxicity, making it a promising option for patients who may not tolerate more aggressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine for acute myeloid leukemia. Marks, PW.[2018]

The combination of tetrahydrouridine (THU) with decitabine (DAC) enhances the effectiveness of DAC by inhibiting cytidine deaminase, which normally breaks down DAC, thus increasing its absorption and exposure time in the body.

In nonhuman primates, this combination therapy was shown to be safe, not causing myelosuppression, while effectively increasing fetal hemoglobin levels, suggesting a potential treatment for hemoglobinopathies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of tetrahydrouridine on pharmacokinetics and pharmacodynamics of oral decitabine. Lavelle, D., Vaitkus, K., Ling, Y., et al.[2022]

The phase 2 study found that oral cedazuridine/decitabine (100 mg/35 mg) provided similar systemic exposure and DNA demethylation compared to standard IV decitabine (20 mg/m2) in patients with myelodysplastic syndromes or chronic myelomonocytic leukemia, indicating comparable efficacy.

Clinical responses were observed in 60% of patients, with 21% achieving a complete response, while the most common serious side effects included neutropenia (46%) and thrombocytopenia (38%), highlighting the treatment's safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Garcia-Manero, G., Griffiths, EA., Steensma, DP., et al.[2021]

The combination of decitabine (DAC) and tetrahydrouridine (THU) showed increased oral bioavailability of DAC, with THU enhancing DAC plasma concentration by approximately 10-fold, indicating a potential for improved therapeutic efficacy in treating sickle cell disease and β-thalassemia.

However, the therapy also revealed significant safety concerns, particularly in female mice, where high doses of DAC combined with THU led to severe toxicity, including bone marrow suppression and other harmful effects, necessitating careful monitoring and dose adjustments in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subchronic oral toxicity study of decitabine in combination with tetrahydrouridine in CD-1 mice. Terse, P., Engelke, K., Chan, K., et al.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Decitabine: a review of its use in older patients with acute myeloid leukaemia. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Decitabine for acute myeloid leukemia. [2018]

3. China pubmed.ncbi.nlm.nih.gov

[The efficacy and safety of the patients of myelodysplastic syndromes-refractory anemia with excess blasts treated with decitabine alone or CAG/HAG regimen]. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Effects of tetrahydrouridine on pharmacokinetics and pharmacodynamics of oral decitabine. [2022]

5. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin in MDS-EB and AML-MRC]. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Subchronic oral toxicity study of decitabine in combination with tetrahydrouridine in CD-1 mice. [2021]

8. China pubmed.ncbi.nlm.nih.gov

[Clinical Efficacy of Decitabine Combined with CAG Regimen for Myelodysplastic Syndrome-RAEB and Refractory Acute Myeloid Leukemia]. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Epigenetic therapy with decitabine for myelodysplasia and leukemia. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

Decitabine. [2018]