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

NCT04382053 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CDFV890D122012020-001870-32
• Study Type: interventional
• Target: 143
• Locations: 12 countries
• Sites: 29

Brief Summary

This clinical study was designed to assess the 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.

Conditions

COVID-19 Pneumonia, Impaired Respiratory Function

Keywords

COVID-19 pneumonia; SARS-CoV-2; APACHE II; DFV890; inflammasome

Outcome Measures

Primary Outcomes (1)

• APACHE II Severity of Disease Score on Day 15 or on the Day of Discharge (Whichever is Earlier)

  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. In practice, it is rare for any participant to accumulate more than 55 points. APACHE II score was measured on Day 15 or on the day of discharge (whichever was earlier). Participants who died on Day 15 or earlier were assigned the highest observed APACHE II score of any of the participants at any time during the trial (worst case imputation for deaths). Missing data values of the parameters required for the derivation of the APACHE II score were replaced by the last available assessment.

  up to Day 15

Secondary Outcomes (4)

• Serum C-reactive Protein (CRP) Levels

  Days 2, 4, 6, 8, 10, 12, 14 and 15

• Clinical Status Over Time

  Baseline, days 2, 4, 6, 8, 10, 12, 14, 15, 17, 19, 21, 23, 25, 27 and 29

• Number of Participants Not Requiring Mechanical Ventilation for Survival

  Until Day 15 (Assessments on Days 2, 4, 6, 8, 10, 12, 14 and 15) and until Day 29 (Assessments on Days 17, 19, 21, 23, 25, 27 and 29)

• Number of Participants With at Least One-point Improvement From Baseline in Clinical Status

  Baseline, Day 15 and Day 29

Study Arms (2)

DFV890 + SoC

EXPERIMENTAL

DFV890 50 mg was administered orally or nasogastrically twice per day (b.i.d) approximately 12 hours apart (morning and evening) for 14 days in addition to SoC.

Drug: DFV890; Drug: Standard of Care (SoC)

Standard of Care (SoC)

ACTIVE COMPARATOR

SoC was used as an active comparator arm.

Drug: Standard of Care (SoC)

Interventions

DFV890 DRUG

DFV890 25 mg tablets orally/nasogastrically administered 50 mg b.i.d for 14 days in addition to SoC.

DFV890 + SoC

Standard of Care (SoC) DRUG

SoC included a variety of supportive therapies that ranged from the administration of supplementary oxygen to full intensive care support, alongside the use of antiviral treatment, convalescent plasma, corticosteroids, antibiotics or other agents.

DFV890 + SoC; Standard of Care (SoC)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (29)

Novartis Investigative Site

CABA, Buenos Aires, C1180AAX, Argentina

Location

Novartis Investigative Site

Buenos Aires, B1846BMF, Argentina

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 04029-000, Brazil

Location

Novartis Investigative Site

Hvidovre, 2650, Denmark

Location

Novartis Investigative Site

Regensburg, Bavaria, 93053, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Budapest, 1121, Hungary

Location

Novartis Investigative Site

Coimbatore, Tamil Nadu, 641028, India

Location

Novartis Investigative Site

Kolkata, West Bengal, 700099, India

Location

Novartis Investigative Site

New Delhi, 110029, India

Location

Novartis Investigative Site

New Delhi, 110075, India

Location

Novartis Investigative Site

Mexico City, Mexico CP, 14080, Mexico

Location

Novartis Investigative Site

Monterrey, Nuevo León, 64460, Mexico

Location

Novartis Investigative Site

Harderwijk, 3840 AC, Netherlands

Location

Novartis Investigative Site

San Martín de Porres, Lima region, 31, Peru

Location

Novartis Investigative Site

San Miguel, Lima region, 32, Peru

Location

Novartis Investigative Site

Barnaul, 656045, Russia

Location

Novartis Investigative Site

Chelyabinsk, 454021, Russia

Location

Novartis Investigative Site

Krasnoyarsk, 660049, Russia

Location

Novartis Investigative Site

Moscow, 119991, Russia

Location

Novartis Investigative Site

Ryazan, 390039, Russia

Location

Novartis Investigative Site

Saint Petersburg, 193079, Russia

Location

Novartis Investigative Site

Saint Petersburg, 199106, Russia

Location

Novartis Investigative Site

Yekaterinburg, 620035, Russia

Location

Novartis Investigative Site

George, Western Cape, 6529, South Africa

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Madrid, 28006, Spain

Location

Related Publications (1)

• Madurka I, Vishnevsky A, Soriano JB, Gans SJ, Ore DJS, Rendon A, Ulrik CS, Bhatnagar S, Krishnamurthy S, Mc Harry K, Welte T, Fernandez AA, Mehes B, Meiser K, Gatlik E, Sommer U, Junge G, Rezende E; Study group. DFV890: a new oral NLRP3 inhibitor-tested in an early phase 2a randomised clinical trial in patients with COVID-19 pneumonia and impaired respiratory function. Infection. 2023 Jun;51(3):641-654. doi: 10.1007/s15010-022-01904-w. Epub 2022 Sep 14.

  PMID: 36104613 DERIVED

MeSH Terms

Conditions

Respiratory Insufficiency

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862 778 8300

Study Officials

• Novartis pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2020
• First Posted: May 11, 2020
• Study Start: May 27, 2020
• Primary Completion: December 10, 2020
• Study Completion: December 24, 2020
• Last Updated: July 26, 2022
• Results First Posted: November 30, 2021

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share

Locations

AR (2); NL (1); PE (2); ME (2); IN (4); DE (3); HU (1); RU (8); DK (1); ZA (1); ES (2); BR (2)