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

NCT ID: NCT04382053

Last Updated: 2022-07-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 143 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-27
• Study Completion Date: 2020-12-24

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.

Detailed Description

This was a Phase II, 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 consisted of four distinct study periods:

Screening / Baseline visit (Day -1 to 1): lasted up to a maximum of 24 hours and comprised a screening / baseline assessment. This visit was used to confirm that the study inclusion and exclusion criteria were met and served as baseline assessment prior to randomization.

Treatment period (Day 1-15): Participants were randomized as soon as possible, but within a maximum of 24 hours after screening in a 1:1 ratio receiving either DFV890 in addition to standard of care (SoC) or SoC alone. Participants in the investigational treatment arm received DFV890 administered for a total of 14 days in addition to SoC. Participants in the control arm received SoC alone. Study assessments were conducted every 2 days for hospitalized participants.

The End of Treatment (EOT) visit took place on Day 15. If participants were discharged from the hospital prior to Day 15, assessments on the day of discharge were performed according to the schedule listed under Day 15; participants continued to take the investigational treatment at home to complete the 14-day treatment period and the participants returned to the site for the Day 15/EOT assessment. If a hospital visit was not possible at Day 15, then home nursing services were used to support the last visit.

Follow-up (Day 16-29): After completion of the treatment period, participants were observed until Day 29 or discharged from hospital, whichever was sooner. Study assessments were conducted every 2 days for hospitalized participants. If participants were discharged from hospital prior to Day 29, a study visit conducted by telephone was performed on Day 29.

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

Conditions

COVID-19 Pneumonia, Impaired Respiratory Function

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DFV890 + SoC

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.

Group Type: EXPERIMENTAL

DFV890

Intervention Type: DRUG

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

Standard of Care (SoC)

Intervention Type: 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.

Standard of Care (SoC)

SoC was used as an active comparator arm.

Group Type: ACTIVE_COMPARATOR

Standard of Care (SoC)

Intervention Type: 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.

Interventions

DFV890

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

Intervention Type: DRUG

Standard of Care (SoC)

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, Brazil

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Novartis Investigative Site

Hvidovre, , Denmark

Novartis Investigative Site

Regensburg, Bavaria, Germany

Novartis Investigative Site

Hanover, , Germany

Novartis Investigative Site

Würzburg, , Germany

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Coimbatore, Tamil Nadu, India

Novartis Investigative Site

Kolkata, West Bengal, India

Novartis Investigative Site

New Delhi, , India

Novartis Investigative Site

New Delhi, , India

Novartis Investigative Site

Mexico City, Mexico CP, Mexico

Novartis Investigative Site

Monterrey, Nuevo León, Mexico

Novartis Investigative Site

Harderwijk, , Netherlands

Novartis Investigative Site

San Martín de Porres, Lima region, Peru

Novartis Investigative Site

San Miguel, Lima region, Peru

Novartis Investigative Site

Barnaul, , Russia

Novartis Investigative Site

Chelyabinsk, , Russia

Novartis Investigative Site

Krasnoyarsk, , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Ryazan, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Yekaterinburg, , Russia

Novartis Investigative Site

George, Western Cape, South Africa

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Madrid, , Spain

Countries

Argentina; Brazil; Denmark; Germany; Hungary; India; Mexico; Netherlands; Peru; Russia; South Africa; Spain

References

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.

Reference Type: DERIVED

PMID: 36104613 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-001870-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CDFV890D12201

Identifier Type: -

Identifier Source: org_study_id