Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Efficacy and Safety of DV890 in Patients With COVID-19 Pneumonia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04382053
Recruitment Status : Completed
First Posted : May 11, 2020
Last Update Posted : May 4, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE May 8, 2020
First Posted Date  ICMJE May 11, 2020
Last Update Posted Date May 4, 2021
Actual Study Start Date  ICMJE May 27, 2020
Actual Primary Completion Date December 10, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2020)
APACHE II severity of disease score on Day 15 or on the day of discharge (whichever is earlier) [ Time Frame: up to Day 15 ]
The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. Worst case imputation for death will be applied.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2020)
  • Serum C-reactive protein (CRP) levels [ Time Frame: up to Day 29 ]
    C-reactive protein (CRP) is a blood test marker for inflammation in the body. For a standard CRP test, a normal reading is less than 10 milligram per liter (mg/L). It will be analyzed on a log-scale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline CRP as a covariate.
  • Clinical status over time [ Time Frame: up to Day 29 ]
    Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.
  • Proportion of participants not requiring mechanical ventilation for survival. [ Time Frame: Day 15, Day 29 ]
    Proportion of participants not requiring mechanical ventilation for survival.
  • Proportion of participants with at least one-point improvement from baseline in clinical status [ Time Frame: Baseline, Day 15, Day 29 ]
    Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Efficacy and Safety of DV890 in Patients With COVID-19 Pneumonia
Official Title  ICMJE Phase 2, Randomized, Controlled, Open Label Multi-center Study to Assess Efficacy and Safety of DFV890 for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infected Patients With Coronavirus Disease 2019 (COVID-19) Pneumonia and Impaired Respiratory Function
Brief Summary The study will assess the efficacy and safety of DFV890 for the treatment of SARS-Cov-2 infected patients with COVID-19 pneumonia and impaired respiratory function.
Detailed Description

This is a Phase 2, randomized, controlled, open label multi-center study to assess the efficacy and safety of DFV890 for the treatment of SARS-CoV-2 infected patients with COVID-19 pneumonia and impaired respiratory function.

The study consists of four parts:

Screening / Baseline visit (Day -1 to 1): lasts up to a maximum of 24 hours and comprises a screening / baseline assessment. This visit will be used to confirm that the study inclusion and exclusion criteria are met and serves as baseline assessment prior to randomization.

Treatment period (Day 1-15): Participants in the investigational treatment arm will receive DFV890 orally or via a nasogastric feeding tube administered for a total of 14 days in addition to SoC. Study drug will be supplied in tablet form which can be crushed, allowing for both oral and nasogastric administration. Participants in the control arm will receive SoC alone.

Participants will be randomized as soon as possible, but within a maximum of 24 hours after screening in a 1:1 ratio to receive either DFV890 in addition to SoC or SoC alone. Study assessments will be conducted every 2 days for hospitalized participants.

The End of Treatment (EOT) visit will take place on Day 15. If participants are discharged from the hospital prior to Day 15, assessments on the day of discharge should be performed according to the schedule listed under Day 15; participants will continue to take the investigational treatment at home to complete the 14-day treatment period and the participants should return to the site for the Day 15/EOT assessment (all other visits between discharge and Day 15 can be omitted). If a hospital visit is not possible at Day 15, then home nursing services may be used to support this last visit where these are available in accordance with local guidelines and should include all possible assessments (e.g., oxygen saturation with portable monitors).

Follow-up (Day 16-29): After completion of the 14 day- treatment period, participants will be observed until Day 29 or discharged from hospital, whichever is sooner. Study assessments to be conducted every 2 days for hospitalized participants.

If participants are discharged from hospital prior to Day 29, a study visit conducted by telephone will occur on Day 29 (all other visits between discharge and Day 29 can be omitted).

30-day safety follow-up assessment (Day 45): A follow-up visit for safety will be conducted by telephone.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE COVID 19 Pneumonia, Impaired Respiratory Function
Intervention  ICMJE
  • Drug: DFV890
    DFV890 administerated in addition to the SoC for 14 days
  • Drug: Standard of Care (SoC)
    SoC includes a variety of supportive therapies that ranges from the administration of supplementary oxygen to full intensive care support, alongside the use of antiviral agents and intravenous corticosteroids.
Study Arms  ICMJE
  • Experimental: DFV890 + SoC
    DFV890 will be administered for 14 days in addition to Standard of Care (SoC). SoC will be used as an active comparator.
    Interventions:
    • Drug: DFV890
    • Drug: Standard of Care (SoC)
  • Active Comparator: Standard of Care (SoC)
    Standard of Care will be used as a comparator arm.
    Intervention: Drug: Standard of Care (SoC)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 14, 2021)
143
Original Estimated Enrollment  ICMJE
 (submitted: May 8, 2020)
120
Actual Study Completion Date  ICMJE December 24, 2020
Actual Primary Completion Date December 10, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • Male and female patients aged 18-80 years inclusive at screening
  • Clinically diagnosed with the SARS-CoV-2 virus by polymerase chain reaction (PCR) or by other approved diagnostic methodology within 7 days prior to randomization
  • Hospitalized with COVID-19-induced pneumonia evidenced by chest X-ray, computed tomography scan (CT scan) or magnetic resonance scan (MR scan), taken within 5 days prior to randomization (within 24 hours in patients in the Netherlands)
  • Impaired respiratory function, defined as peripheral oxygen saturation (SpO2) ≤93% on room air or partial pressure of oxygen (PaO2) / fraction of inspired oxygen (FiO2) <300 millimeter of mercury (mmHg) at screening. For cities located at altitudes greater than 2500 m above sea level, these will be substituted with SpO2 <90% and PaO2/FiO2 <250 mmHg.
  • APACHE II score of ≥10 at screening
  • C-reactive protein (CRP) ≥20 mg/L and/or ferritin level ≥600 μg/L at screening
  • Body mass index of ≥18 to <40kg/m2 at screening

Exclusion Criteria

  • Suspected active or chronic bacterial (including Mycobacterium tuberculosis), fungal, viral, or other infection (besides SARS-CoV-2)
  • In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatment
  • Intubated prior to randomization
  • Previous treatment with anti-rejection and immunomodulatory drugs within the past 2 weeks, or within the past 30 days or 5 half-lives (whichever is the longer) for immunomodulatory therapeutic antibodies or prohibited drugs, with the exception of hydroxychloroquine, chloroquine or corticosteroids:

For COVID-19 infection, ongoing corticosteroid treatment is permitted at doses as per local SoC For non-COVID-19 disorders, ongoing corticosteroid treatment is permitted at doses up to and including prednisolone 10 mg daily or equivalent In patients in the Netherlands only, the use of hydroxychloroquine and/or chloroquine in the past 2 weeks are exclusionary

  • Serum alanine transaminase (ALT) or aspartate transaminase (AST) >5 times upper limit of normal detected within 24 hours at screening or at baseline (according to local laboratory reference ranges) or other evidence if severe hepatic impairment (Child-Pugh Class C)
  • Absolute peripheral blood neutrophil count of ≤1000/mm3
  • Estimated GFR (eGFR) ≤30 mL/min/1.73m2 (based on CKD-EPI formula)
  • Patients currently being treated with drugs known to be strong or moderate inducers of isoenzyme CYP2C9 and/or strong inhibitors of CYP2C9 and/or strong inducers of cytochrome P450, family 3, subfamily A (CYP3A) and the treatment cannot be discontinued or switched to a different medication prior to starting study treatment
  • Patients with innate or acquired immunodeficiencies
  • Patients who have undergone solid organ or stem cell transplantation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Denmark,   Germany,   Hungary,   India,   Mexico,   Netherlands,   Peru,   Russian Federation,   South Africa,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04382053
Other Study ID Numbers  ICMJE CDFV890D12201
2020-001870-32 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP