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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called decitabine to determine its effectiveness for critically ill COVID-19 patients experiencing severe lung issues, known as ARDS (Acute Respiratory Distress Syndrome). Participants will receive either decitabine with standard care or a placebo with the same standard care to compare results. The main goal is to assess the safety and effectiveness of decitabine in improving patients' conditions. Suitable candidates for this trial are those requiring mechanical breathing support due to severe COVID-19 lung issues. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that decitabine is likely to be safe for humans?

Research has shown that decitabine has been studied in patients with certain blood disorders. In one study, 208 patients with conditions like myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) took decitabine tablets. The treatment was generally well-tolerated.

While some side effects occurred, they were mostly manageable. Common issues included low blood cell counts, which could lead to infections or bruising. However, these side effects are typical for treatments of blood disorders.

The FDA has approved decitabine for these other conditions, indicating some known level of safety. However, its use for COVID-19 ARDS (acute respiratory distress syndrome) remains under study. The researchers aim to confirm if it's safe and effective for this new purpose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for COVID-19?

Most treatments for COVID-19 focus on reducing symptoms and supporting the immune system. But Decitabine works differently, targeting the body's genetic machinery to potentially alter immune responses. This unique mechanism could help manage the inflammatory response associated with severe COVID-19 cases. Researchers are excited because this approach might offer a new way to reduce complications and improve outcomes in patients who don't respond well to existing therapies.

What evidence suggests that Decitabine might be an effective treatment for COVID-19 ARDS?

Research is exploring the use of decitabine to treat severe lung problems in critically ill COVID-19 patients. In this trial, some participants will receive decitabine alongside Standard of Care (SOC) to determine if it can improve lung function in severe COVID pneumonia. Although decitabine is typically used for certain blood cancers, researchers are now investigating its potential benefits for COVID-19. While solid proof of its effectiveness for COVID-19-related severe lung issues is lacking, there is hope it might reduce inflammation and aid recovery. Early studies suggest it could be safe, but its actual effect on COVID-19 remains under investigation. More research is needed to confirm these potential benefits. ^{2 3 6 7 8}

Who Is on the Research Team?

Pali Shah, MD

Principal Investigator

Johns Hopkins UIniversity

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04482621

Decitabine for Coronavirus (COVID-19) Pneumonia- Acute ... 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. Detailed ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8330207/

Outcomes of COVID-19 Infection in Patients Receiving ... High mortality rates were observed for both ruxolitinib and HMA in this high-risk group of patients with hematologic malignancy regardless of whether therapy ...

3. withpower.com withpower.com/trial/phase-3-pneumonia-8-2020-5c3e5

Decitabine for COVID-19 (DART Trial) This trial tests if the drug decitabine can safely and effectively treat severe lung issues in critically ill COVID-19 patients.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10528038/

Decitabine/Cedazuridine in the Management of ... Subgroup analyses based on treatment duration revealed that a significantly greater proportion of patients who received <4 cycles stopped ...

5. reaganudall.org reaganudall.org/clinical-trial/decitabine-coronavirus-covid-19-pneumonia-acute-respiratory-distress-syndrome-ards

Decitabine for Coronavirus (COVID-19) Pneumonia- Acute Theprimary objective is to determine safety and efficacy of decitabine for COVID-19 ARDSbased on clinical improvement on a 6-point clinical scale. Detailed ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9378483/

FDA approval summary: decitabine and cedazuridine ... Safety was assessed in 208 patients (78 from ASTX727-01-B, 130 from ASTX727-02) with MDS or CMML treated with at least 1 dose of DEC-C tablets. Safety data was ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-10810

Testing the Addition of an Anti-cancer Drug, ASTX727 ... This phase I trial tests the safety, side effects, and best dose of ASTX727 when given in combination with a usual approach of treatment with paclitaxel and ...

8. vicc.org vicc.org/sites/default/files/drupalfiles/2023-10/Oral_decitabine_cedazuridine_vs_intravenous_decitabine_protocol.pdf

Astex Pharmaceuticals, Inc. ASTX727 Clinical Protocol Data from study ASTX727-01 showed that similar daily dose exposure profiles between the IV and orally administered drug resulted in similar clinical activity ...