Clinical Trial to Evaluate Efficacy of 3 Types of Treatment in Patients With Pneumonia by COVID-19 (Covid19COVINIB)

Prospective, Phase II, Randomized, Open-label, Parallel Group Study to Evaluate the Efficacy of Baricitinib, Imatinib or Supportive Treatment in Patients With SARS Cov2 Pneumonia

In absence of vaccine and medications specifically designed to treat SARS-CoV-2 disease, identifying treatment options is critical at this time to control the disease outbreak.

For this, we have designed a phase II trial of efficacy and safety with 3 branches of different combinations of treatment to identify which is the best early treatment option for patients with pneumonia due to SARS-CoV-2 (Covid-19) Identifying treatment options as early as possible is critical to the SARS-CoV-2 outbreak response. Currently, there is no approved vaccine for the disease and the treatments being used are not specifically designed for the SARS-CoV-2 virus, but are different groups of drugs used for other pathologies with mechanisms of action that justify their use because they inhibit entry of the virus into virus cells or proteases.

The study aims to compare Imatinib 400mg, Baricitinib 4mg or supportive treatment, administered for 7 days in the setting of SARS-CoV-2 pneumonia treatment.

Patients who meet inclusion criteria and do not have any exclusion criteria will be randomized to receive open treatment 1:1:1

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19 Pneumonia
• Intervention / Treatment: Drug: Imatinib tablets; Drug: Baricitinib Oral Tablet; Other: Supportive tratment

Detailed Description

Identifying treatment options is critical to the SARS-CoV-2 outbreak response. Currently there is no vaccine and treatments used are not specifically designed for this virus; They are drugs used for other pathologies. We have identified possible drugs with a known safety profile, selected the most promising ones and designed 3 combinations to select the one with the best results in clinical improvement of pneumonia due to Covid-19.

-Virus entry inhibitors: broad spectrum antivirals (antimalarials). They block viral infection by increasing endosomal pH necessary for virus / cell fusion, as well as interfering with glycosylation of cellular SARS-CoV receptors. It also has immunomodulatory activity, which can enhance antiviral effect. Latest evidence from the UK RECOVERY and WHO SOLIDARITY trials suggest that antimalarials do not provide clinical benefit in hospitalized patients with COVID-19.

Baricitinib, Janus kinase inhibitor, showing high affinity for AAK1. Disruption of AAK1 (one of the known regulators of viral endocytosis) could block passage of SARS-CoV-2 to cells and also the intracellular assembly of virus particles. Furthermore, it has the capacity to bind cyclin G-associated kinase, another regulator of endocytosis. You can limit systemic inflammatory response and cytokine production by inhibiting the JAK-STAT32 pathway.

Imatinib; Antitumor agent inhibitory activity of some tirsin kinases (TK), especially fusion oncoprotein BCR-ABL1, c-kit and native kinase ABL1. It has shown antiviral properties in early stages of infection against SARS-CoV and MERS-CoV, phylogenetically related to SARS-CoV2. In addition, it has been linked to reduced inflammation and improved endothelial barrier and pulmonary edema.

-Protease inhibitors: lopinavir / ritonavir (HIV treatment); expected interactions with SARS-CoV-2 proteases; The therapeutic effect of ritonavir and lopinavir could be mainly due to its inhibitory effect on coronavirus endopeptidase C30. The RECOVERY clinical trial investigators have also reviewed the data concluding that LPV / r does not provide clinical benefit in hospitalized patients with COVID-19.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Madrid
    • Fuenlabrada, Madrid, Spain, 28942
      • Hospital Universitario de Fuenlabrada

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent form
• ≥18 years
• Confirmed diagnosis Pneumonia Covid19 + (Pneumonia confirmed radiologically and positive test for detection of SARS-CoV-2 RNA in respiratory samples)
• ECOG functional state 0 or 1
• Less than 10 days from onset of symptoms saw.
• NO contraindication for medication
• ECG QT < < 440 ms males and < 460 ms females

• Adequate liver, kidney and hematological function (or within the safety range to use these drugs):

  1. Absolute granulocyte count> 1.5 x 109 / L
  2. Absolute platelet count> 100 x 109 / L
  3. Hb> 10 g / dL
  4. Cr <1.5 mg / dL or Clearance> 50mL / min
  5. Bilirubin <3 ULN
  6. AST / ALT ≤ 2.5 times ULN

Exclusion Criteria:

• No Covid confirmation
• No pneumonia
• Previous treatment with any of the study drugs

• Concomitant serious medical condition:

  1. Congestive Heart failure
  2. Acute myocardial infarction 6 months prior
  3. Unstable Angina
  4. Cardiomyopathy
  5. Unstable Ventricular Arrhythmia
  6. Uncontrolled Hypertension
  7. Uncontrolled psychotic disorders
  8. Serious active infections
  9. HIV infections
  10. Active hepatitis
  11. Neoplasia in active cancer treatment
• Inability to take oral medication or malabsorption syndrome saw.
• Inability to comply with study and follow-up procedures
• History of only relevant thromboembolic or hemorrhagic episodes in the last 6 months
• Contraindication to any study medication
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Imatinib 400 mg; Imatinib 400 mg 1 tablet 24 hours	Drug: Imatinib tablets; Imatinib 400 mg QD oral; Other Names: Arm A
Experimental: Baricitinib 4 mg; Baricitinib 4 mg 1 tablet 24 hours	Drug: Baricitinib Oral Tablet; Baricitinib 4 mg QD oral; Other Names: Arm B
Experimental: Supportive treatment; Any therapeutic intervention aimed at the control of clinical deterioration is contemplated without initiating or having previously initiated any drug with potential beneficial effect previously described in vitro or in pre-clinical / clinical models against SARS-CoV-2 prior to patient recruitment.	Other: Supportive tratment; Any therapeutic intervention aimed at the control of clinical deterioration is contemplated without initiating or having previously initiated any drug with potential beneficial effect previously described in vitro or in pre-clinical / clinical models against SARS-CoV-2 prior to patient recruitment.; Other Names: Best care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to clinical improvement	time from inclusion to improvement by 2 points on the "seven-category ordinal scale" or high, whichever comes first	baseline to day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of treatments	number of serious adverse effects and premature discontinuation of treatment	through study completion, an average of 1 month
Tolerability of treatments	Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0	during treatment and up to 30 days after the last treatment dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers and genetic markers of susceptibility to SARS-CoV-2	Possible biomarkers and genetic markers of susceptibility to SARS-CoV-2 using high-performance techniques with serum DNA from the participants	baseline

Collaborators and Investigators

• Sponsor: Hospital Universitario de Fuenlabrada
• Collaborators: Centro Nacional de Investigaciones Oncologicas CARLOS III
• Investigators: Principal Investigator: David Bernal, Ph MD, Hospital Universitario de Fuenlabrada

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2020
• Primary Completion (Actual): June 2, 2021
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: April 7, 2020
• First Submitted That Met QC Criteria: April 11, 2020
• First Posted (Actual): April 15, 2020

Study Record Updates

• Last Update Posted (Actual): August 3, 2021
• Last Update Submitted That Met QC Criteria: August 2, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: 24032020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No