Trial of Imatinib for Hospitalized Adults With COVID-19

NCT04394416 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: 2038GCCC
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized Double-Blind Placebo-Controlled Trial on the Safety and Efficacy of Imatinib for Hospitalized Adults with COVID-19

Conditions

COVID-19

Outcome Measures

Primary Outcomes (1)

• To Evaluate the Efficacy and Safety of Oral Administration of Imatinib Combined With BCC vs. Placebo Plus BCC in Hospitalized Patients With COVID-19

  The primary endpoint is all-cause mortality at Day 28 after the start of imatinib/placebo.

  Day 28 after the start of imatinib/placebo.

Secondary Outcomes (10)

• All-Cause Mortality

  Day 29 to Day 60 after the start of imatinib/placebo

• Time to a 2-point Clinical Change Using the 8-category Ordinal Scale.

  Day 14 from baseline

• Hospitalization

  Up to 60 days post baseline

• Duration of ECMO or Invasive Mechanical Ventilation

  Up to 60 days post baseline

• Duration of ICU Stay

  Up to 60 days post baseline

Study Arms (2)

Imatinib

EXPERIMENTAL

Imatinib oral 400 mg daily for 14 days.

Drug: Imatinib

Placebo

ACTIVE COMPARATOR

Placebo oral for 14 days

Drug: Placebo oral tablet

Interventions

Imatinib DRUG

Therapeutic

Imatinib

Placebo oral tablet DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients may be included in the study only if they meet all of the following criteria:
• Ability to understand and willingness to sign a written informed consent document. Informed consent must be obtained prior to participation in the study. For patients who are too unwell to provide consent such as patients on invasive ventilator or ECMO, Legally Authorized Representative (LAR) can sign the informed consent.
• Hospitalized patients ≥ 18 years of age
• Positive RT-PCR assay for SARS-CoV-2 in the respiratory tract sample (oropharyngeal, nasopharyngeal or BAL) by Center for Disease Control or local laboratory within 7 days of randomization.

You may not qualify if:

• Patients meeting any of the following criteria are not eligible for the study:
• Pregnant or breastfeeding women.
• Patients with significant liver or renal dysfunction function at screen as defined as:
• Direct bilirubin \> 2.5 mg/dL
• AST, ALT, or alkaline phosphatase \> 5 x upper limit of normal
• eGFR ≤ 30 mL/min or requiring renal replacement therapy
• Patients with significant hematologic disorder at screen as defined as:
• Absolute neutrophil count (ANC) \< 500/μL
• Platelet \< 20,000/μL
• Hemoglobin \< 7 g/dL
• Uncontrolled undercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled active seizure disorder, or psychiatric illness/social situations that per site Principal Investigator's judgment would limit compliance with study requirements.
• Known allergy to imatinib or its component products.
• Any other clinical conditions that in the opinion of the investigator would make the subject unsuitable for the study.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Related Publications (39)

• Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.

  PMID: 32007143 BACKGROUND

• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.

  PMID: 31986264 BACKGROUND

• Liu K, Fang YY, Deng Y, Liu W, Wang MF, Ma JP, Xiao W, Wang YN, Zhong MH, Li CH, Li GC, Liu HG. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl). 2020 May 5;133(9):1025-1031. doi: 10.1097/CM9.0000000000000744.

  PMID: 32044814 BACKGROUND

• Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.

  PMID: 32031570 BACKGROUND

• Al-Bari MA. Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases. J Antimicrob Chemother. 2015;70(6):1608-21. doi: 10.1093/jac/dkv018. Epub 2015 Feb 17.

  PMID: 25693996 BACKGROUND

• Daniel WA, Bickel MH, Honegger UE. The contribution of lysosomal trapping in the uptake of desipramine and chloroquine by different tissues. Pharmacol Toxicol. 1995 Dec;77(6):402-6. doi: 10.1111/j.1600-0773.1995.tb01050.x.

  PMID: 8835367 BACKGROUND

• Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis. 2003 Nov;3(11):722-7. doi: 10.1016/s1473-3099(03)00806-5.

  PMID: 14592603 BACKGROUND

• Yan Y, Zou Z, Sun Y, Li X, Xu KF, Wei Y, Jin N, Jiang C. Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model. Cell Res. 2013 Feb;23(2):300-2. doi: 10.1038/cr.2012.165. Epub 2012 Dec 4. No abstract available.

  PMID: 23208422 BACKGROUND

• Keyaerts E, Vijgen L, Maes P, Neyts J, Van Ranst M. In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem Biophys Res Commun. 2004 Oct 8;323(1):264-8. doi: 10.1016/j.bbrc.2004.08.085.

  PMID: 15351731 BACKGROUND

• Devaux CA, Rolain JM, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents. 2020 May;55(5):105938. doi: 10.1016/j.ijantimicag.2020.105938. Epub 2020 Mar 12.

  PMID: 32171740 BACKGROUND

• Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271. doi: 10.1038/s41422-020-0282-0. Epub 2020 Feb 4. No abstract available.

  PMID: 32020029 BACKGROUND

• Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16;14(1):72-73. doi: 10.5582/bst.2020.01047. Epub 2020 Feb 19.

  PMID: 32074550 BACKGROUND

• Biot C, Daher W, Chavain N, Fandeur T, Khalife J, Dive D, De Clercq E. Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities. J Med Chem. 2006 May 4;49(9):2845-9. doi: 10.1021/jm0601856.

  PMID: 16640347 BACKGROUND

• Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Jul 28;71(15):732-739. doi: 10.1093/cid/ciaa237.

  PMID: 32150618 BACKGROUND

• Chapuy B, Panse M, Radunski U, Koch R, Wenzel D, Inagaki N, Haase D, Truemper L, Wulf GG. ABC transporter A3 facilitates lysosomal sequestration of imatinib and modulates susceptibility of chronic myeloid leukemia cell lines to this drug. Haematologica. 2009 Nov;94(11):1528-36. doi: 10.3324/haematol.2009.008631.

  PMID: 19880777 BACKGROUND

• Gotink KJ, Broxterman HJ, Labots M, de Haas RR, Dekker H, Honeywell RJ, Rudek MA, Beerepoot LV, Musters RJ, Jansen G, Griffioen AW, Assaraf YG, Pili R, Peters GJ, Verheul HM. Lysosomal sequestration of sunitinib: a novel mechanism of drug resistance. Clin Cancer Res. 2011 Dec 1;17(23):7337-46. doi: 10.1158/1078-0432.CCR-11-1667. Epub 2011 Oct 6.

  PMID: 21980135 BACKGROUND

• Gotink KJ, Rovithi M, de Haas RR, Honeywell RJ, Dekker H, Poel D, Azijli K, Peters GJ, Broxterman HJ, Verheul HM. Cross-resistance to clinically used tyrosine kinase inhibitors sunitinib, sorafenib and pazopanib. Cell Oncol (Dordr). 2015 Apr;38(2):119-29. doi: 10.1007/s13402-015-0218-8. Epub 2015 Feb 11.

  PMID: 25665527 BACKGROUND

• Colombo F, Trombetta E, Cetrangolo P, Maggioni M, Razini P, De Santis F, Torrente Y, Prati D, Torresani E, Porretti L. Giant Lysosomes as a Chemotherapy Resistance Mechanism in Hepatocellular Carcinoma Cells. PLoS One. 2014 Dec 10;9(12):e114787. doi: 10.1371/journal.pone.0114787. eCollection 2014.

  PMID: 25493932 BACKGROUND

• Ruzickova E, Skoupa N, Dolezel P, Smith DA, Mlejnek P. The Lysosomal Sequestration of Tyrosine Kinase Inhibitors and Drug Resistance. Biomolecules. 2019 Oct 31;9(11):675. doi: 10.3390/biom9110675.

  PMID: 31683643 BACKGROUND

• Burger H, den Dekker AT, Segeletz S, Boersma AW, de Bruijn P, Debiec-Rychter M, Taguchi T, Sleijfer S, Sparreboom A, Mathijssen RH, Wiemer EA. Lysosomal Sequestration Determines Intracellular Imatinib Levels. Mol Pharmacol. 2015 Sep;88(3):477-87. doi: 10.1124/mol.114.097451. Epub 2015 Jun 24.

  PMID: 26108972 BACKGROUND

• Fu D, Zhou J, Zhu WS, Manley PW, Wang YK, Hood T, Wylie A, Xie XS. Imaging the intracellular distribution of tyrosine kinase inhibitors in living cells with quantitative hyperspectral stimulated Raman scattering. Nat Chem. 2014 Jul;6(7):614-22. doi: 10.1038/nchem.1961. Epub 2014 May 25.

  PMID: 24950332 BACKGROUND

• Chilakapati SR, Serasanambati M, Vissavajjhala P, Kanala JR, Chilakapati DR. Amelioration of bleomycin-induced pulmonary fibrosis in a mouse model by a combination therapy of bosentan and imatinib. Exp Lung Res. 2015 May;41(4):173-88. doi: 10.3109/01902148.2014.939312. Epub 2015 Apr 6.

  PMID: 25844688 BACKGROUND

• Li M, Abdollahi A, Grone HJ, Lipson KE, Belka C, Huber PE. Late treatment with imatinib mesylate ameliorates radiation-induced lung fibrosis in a mouse model. Radiat Oncol. 2009 Dec 21;4:66. doi: 10.1186/1748-717X-4-66.

  PMID: 20025728 BACKGROUND

• Wolf AM, Wolf D, Rumpold H, Ludwiczek S, Enrich B, Gastl G, Weiss G, Tilg H. The kinase inhibitor imatinib mesylate inhibits TNF-alpha production in vitro and prevents TNF-dependent acute hepatic inflammation. Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13622-7. doi: 10.1073/pnas.0501758102. Epub 2005 Sep 8.

  PMID: 16174751 BACKGROUND

• Rizzo AN, Sammani S, Esquinca AE, Jacobson JR, Garcia JG, Letsiou E, Dudek SM. Imatinib attenuates inflammation and vascular leak in a clinically relevant two-hit model of acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2015 Dec 1;309(11):L1294-304. doi: 10.1152/ajplung.00031.2015. Epub 2015 Oct 2.

  PMID: 26432864 BACKGROUND

• Schrezenmeier E, Dorner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020 Mar;16(3):155-166. doi: 10.1038/s41584-020-0372-x. Epub 2020 Feb 7.

  PMID: 32034323 BACKGROUND

• Horne GA, Stobo J, Kelly C, Mukhopadhyay A, Latif AL, Dixon-Hughes J, McMahon L, Cony-Makhoul P, Byrne J, Smith G, Koschmieder S, BrUmmendorf TH, Schafhausen P, Gallipoli P, Thomson F, Cong W, Clark RE, Milojkovic D, Helgason GV, Foroni L, Nicolini FE, Holyoake TL, Copland M. A randomised phase II trial of hydroxychloroquine and imatinib versus imatinib alone for patients with chronic myeloid leukaemia in major cytogenetic response with residual disease. Leukemia. 2020 Jul;34(7):1775-1786. doi: 10.1038/s41375-019-0700-9. Epub 2020 Jan 10.

  PMID: 31925317 BACKGROUND

• Wang Y, Fan G, Salam A, Horby P, Hayden FG, Chen C, Pan J, Zheng J, Lu B, Guo L, Wang C, Cao B. Comparative Effectiveness of Combined Favipiravir and Oseltamivir Therapy Versus Oseltamivir Monotherapy in Critically Ill Patients With Influenza Virus Infection. J Infect Dis. 2020 Apr 27;221(10):1688-1698. doi: 10.1093/infdis/jiz656.

  PMID: 31822885 BACKGROUND

• Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 May 7;382(19):1787-1799. doi: 10.1056/NEJMoa2001282. Epub 2020 Mar 18.

  PMID: 32187464 BACKGROUND

• Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honore S, Colson P, Chabriere E, La Scola B, Rolain JM, Brouqui P, Raoult D. RETRACTED: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Jul;56(1):105949. doi: 10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20.

  PMID: 32205204 BACKGROUND

• Rainsford KD, Parke AL, Clifford-Rashotte M, Kean WF. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology. 2015 Oct;23(5):231-69. doi: 10.1007/s10787-015-0239-y. Epub 2015 Aug 6.

  PMID: 26246395 BACKGROUND

• Cutler DJ, MacIntyre AC, Tett SE. Pharmacokinetics and cellular uptake of 4-aminoquinoline antimalarials. Agents Actions Suppl. 1988;24:142-57. doi: 10.1007/978-3-0348-9160-8_13. No abstract available.

  PMID: 3263755 BACKGROUND

• Tett SE. Clinical pharmacokinetics of slow-acting antirheumatic drugs. Clin Pharmacokinet. 1993 Nov;25(5):392-407. doi: 10.2165/00003088-199325050-00005.

  PMID: 7904547 BACKGROUND

• Carmichael SJ, Charles B, Tett SE. Population pharmacokinetics of hydroxychloroquine in patients with rheumatoid arthritis. Ther Drug Monit. 2003 Dec;25(6):671-81. doi: 10.1097/00007691-200312000-00005.

  PMID: 14639053 BACKGROUND

• Yusuf IH, Foot B, Galloway J, Ardern-Jones MR, Watson SL, Yelf C, Burdon MA, Bishop PN, Lotery AJ. The Royal College of Ophthalmologists recommendations on screening for hydroxychloroquine and chloroquine users in the United Kingdom: executive summary. Eye (Lond). 2018 Jul;32(7):1168-1173. doi: 10.1038/s41433-018-0136-x. Epub 2018 Jun 11. No abstract available.

  PMID: 29887605 BACKGROUND

• Chatre C, Roubille F, Vernhet H, Jorgensen C, Pers YM. Cardiac Complications Attributed to Chloroquine and Hydroxychloroquine: A Systematic Review of the Literature. Drug Saf. 2018 Oct;41(10):919-931. doi: 10.1007/s40264-018-0689-4.

  PMID: 29858838 BACKGROUND

• McHenry AR, Wempe MF, Rice PJ. Stability of Extemporaneously Prepared Hydroxychloroquine Sulfate 25-mg/mL Suspensions in Plastic Bottles and Syringes. Int J Pharm Compd. 2017 May-Jun;21(3):251-254.

  PMID: 28557788 BACKGROUND

• Emadi A, Chua JV, Talwani R, Bentzen SM, Baddley J. Safety and Efficacy of Imatinib for Hospitalized Adults with COVID-19: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Oct 28;21(1):897. doi: 10.1186/s13063-020-04819-9.

  PMID: 33115543 DERIVED

• Zhao H, Mendenhall M, Deininger MW. Imatinib is not a potent anti-SARS-CoV-2 drug. Leukemia. 2020 Nov;34(11):3085-3087. doi: 10.1038/s41375-020-01045-9. Epub 2020 Sep 30. No abstract available.

  PMID: 32999432 DERIVED

Related Links

• FDA. Imatinib Label. Food and Drug Administration 2018
• WHO. Coronavirus disease (COVID-2019) R\&D Blueprint. World Health Organization 2020

MeSH Terms

Conditions

COVID-19

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Andrea Levine, MD
• Organization: University of Maryland Greenebaum Comprehensive Cancer Center

Andrea.Levine@som.umaryland.edu

410-328-7394

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Arm A: Imatinib Arm B: Placebo

Study Record Dates

• First Submitted: May 8, 2020
• First Posted: May 19, 2020
• Study Start: June 2, 2020
• Primary Completion: June 30, 2024
• Study Completion: July 17, 2025
• Last Updated: March 25, 2026
• Results First Posted: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)