The purpose of this study is to evaluate the efficacy and safety of DFV890 in addition to current standard of care (SoC) compared with SoC alone in controlling the inflammatory syndrome and resultant acute respiratory distress syndrome (ARDS) in…
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
APACHE II severity of disease score on Day 15 or on day of discharge (whichever
is earlier)
Secondary outcome
Serum C-reactive protein (CRP) levels
Background summary
As of 22-Apr-2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection has been confirmed in over 2.5 million people worldwide, with over
179,000 deaths to date due to coronavirus disease 2019 (COVID-19). The
mortality rate of approximately 4-5% is significantly higher than that seen
with seasonal influenza (less than 1%).
Between 5-10% of COVID-19 patients develop lung injury, respiratory distress
progressing to acute respiratory distress syndrome (ARDS) requiring prolonged
ventilator support over weeks that results in intensive care units, hospitals
and health care systems becoming overwhelmed.
ARDS is characterized by pro-inflammatory cytokine release, inflammatory
cellular infiltrate and cell death resulting in severe pulmonary damage and the
development of respiratory failure that requires mechanical ventilation with
high positive end-expiratory pressures (PEEP) to maintain life.
There is at present no health authority (HA) approved treatments for COVID-19
or its sequelae, including the cytokine storm which develops in those most
severely affected. Current SoC in the European Union (EU) and United States of
America (US) includes a variety of supportive therapies, ranging from the
administration of supplementary oxygen to full intensive care support,
alongside the use of antiviral agents and intravenous corticosteroids, though
there is considerable inter-center variability regarding the use of these.
Local SoC is permitted in all participants of the study, though every effort
will be made by investigators to standardize this within individual centers.
Study objective
The purpose of this study is to evaluate the efficacy and safety of DFV890 in
addition to current standard of care (SoC) compared with SoC alone in
controlling the inflammatory syndrome and resultant acute respiratory distress
syndrome (ARDS) in hospitalized patients presenting with COVID-19 pneumonia and
impaired respiratory function
Study design
A Phase 2, randomized, controlled, open label multi-center study
The study consists of four parts:
Screening / Baseline visit (Day -1 to 1): lasts up to a maximum of 24 hours 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 50 mg b.i.d. orally or via a nasogastric feeding tube
administered for a total of 14 days (28 doses) in addition to SoC. Study
assessments will be conducted every 2 days for hospitalized participants. The
End of Treatment (EOT) visit will take place on Day 15.
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.
30-day safety follow-up assessment (Day 45): A follow-up visit for safety will
be conducted by telephone.
Intervention
DFV890 50 mg: administered orally twice per day approximately 12 hours apart
(morning and evening) 14 days
Study burden and risks
Known side effects of the investigational drug DFV890
Very common side effects
- Skin rash (more common in women) -
- Infections
- Headache
Common side effects
- Vomiting
Uncommon side effects
- Changes in kidney function
Risks and inconveniences related to assessments
- Blooddraw (vene or artery)
- COVID-19 testing by using via a nasal swab
- Imaging (X-Ray and CT-scan)
- Urine collection
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
* Clinically diagnosed with the SARS-CoV-2 virus
* Hospitalized with COVID-19-induced pneumonia evidenced by chest Xray, CT
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)
* APACHE II score of *10 at time of randomization
* C-reactive protein (CRP) *20 mg/L and/or ferritin level *600 *g/L
* Body weight mass index of *18 to <40kg/m2
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
* Have received either oral anti-rejection, or immunomodulatory drugs within
the past 2 weeks, or immunomodulatory therapeutic antibodies within the 5
half-lives or 30 days from randomization (whichever is longer), with the
exception of hydroxychloroquine, chloroquine or corticosteroids at doses up to
and including prednisolone 10mg daily or equivalent. In patients in the
Netherlands only, the use of hydroxychloroquine and/or chloroquine in the past
2 weeks are exclusionary
*ALT or AST >5 x ULN (upper limit of normal) detected within 24 hours at
screening or at baseline or other evidence of severe hepatic impairment
(Child-Pugh Class C)
* Absolute peripheral blood neutrophil count of *1000/mm3
* Estimated glomerular filtration rate (eGFR) *30 mL/min/1.73m2
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-001870-32-NL |
| CCMO | NL73972.056.20 |