SARS-CoV-2 infected patients MedDRA version: 23.0 Level: LLT Classification code 10084270 Term: SARS-CoV-2 acute respiratory disease System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Fevarin 50mg filmtabletta
Product Name: Fevarin 50mg filmtabletta
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: FLUVOXAMINE MALEATE
CAS Number: 61718-82-9
Concentration unit
Sponsors
SigmaDrugs Research Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Males and females 18-80 years of age at screening • Hospitalized patients with confirmed SARS-CoV-2 by PCR or known contact of confirmed case with syndrome consistent with coronavirus disease (COVID-19) with PCR pending (positive PCR result should be available prior to randomisation) • Moderate cases (at least one of the following criteria is met): - dyspnoea/tachypnoe, respiratory rate 22-29 / min; - with the need for oxygen supplementation; - pulmonary infiltrates on medical imaging • Subjects who are able to communicate with the Investigator and research staff, who understand the study, are able to comply with all study procedures, and willing to provide written informed consent prior to the screening examinations NB. Women of childbearing potential should agree to use a highly effective method of contraception throughout the study and up to 3 months afterwards. Male subjects shall agree to effective contraception during the study and for 14 days following the last drug administration. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: • Mild COVID-19 at randomisation (each of the followings met): no dyspnoe, respiratory rate 50%; arterial partial O2 tension (PaO2)/ inhaling O2-fraction (FiO2)=300 Hgmm; multilobular involvement showing on CT or progression of pulmonary infiltrates with 50% within 24-48 hours • Critical COVID-19 at randomization (at least one of the following criteria is met): SpO2 = 90%, need for oxygen supplementation: with FiO2>100%; PaO2/FiO2=200Hgmm, acute respiratory distress, requiring mechanical ventilation; radiomorphology of ARDS; shock, including septic shock; other organ dysfunction necessitating ICU admission • High-risk patient for progression of COVID-19, as defined by having a calculated pneumonia PORT-score of > 90 • Concomitant or previous administration of any experimental, non-established COVID-19 therapy, either in off-label indication (of a registered medicinal product) or as a non-registered drug candidate in a clinical trial setting or compassionate use program (or equivalents thereof), EXCEPT therapies recommended by the “Magyar Koronavírus Kézikönyv” (Hungarian Coronavirus Manual), and as such, are considered as standard-of-care. Concomittant use of LMWHs can be considered as emerging standard-of-care, and therefore their application is not prohibited • Standard of care treatment planned with chloroquine or hydroxychloroquine • Any clinically significant abnormality identified during pre-study full physical examination, vital signs, laboratory tests and ECG which is deemed by the Investigator to be incompatible / inappropriate for study participation • Known hepatitis B, C, or HIV infection • A current or recent history of drug or substance abuse, including alcohol (> 14 units per week), within 3 months prior to screening (one unit of alcohol equals ½ pint [285 mL] of beer or lager, one glass [125 mL] of wine, or one shot [25 mL] of spirits) • Patients who regularly consume more than 4 cups daily of beverage containing caffeine • Current strong smoker as defined by smoking over 10 cigarettes a day, or its equivalent (for one month prior to screening) • Positive pregnancy test result for women with childbearing potential at screening • Women who are pregnant or nursing, or who are planning to get pregnant within 3 months after the last dose of study drug • A history of allergy, intolerance or sensitivity to fluvoxamine or any component of the study drug formulation • Closed-angle glaucoma • Patients who are assessed as at risk for suicidal intent during screening by psychiatric evaluation (including C-SSRS questionnaire). A score of 15 or higher on the PHQ-9 depression scale at screening. • Have undergone surgery or have donated blood within 12 weeks prior to the start of the study • A history of bleeding diathesis or other bleeding disorders • Participated in any clinical trial involving an investigational drug or investigational device within 1 month preceding study entry, or within 5 terminal half-life of the investigational drug of this previous study • A history of (within 5 years from screening visit) or present malignancy, with the exception of resected basal cell ca
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess efficacy of fluvoxamine administration in moderate SARS-CoV-2 infected patients on short term healing.;Secondary Objective: • Assessment of efficacy of fluvoxamine administration in moderate SARS-CoV-2 infected patients on healing course. • Assessment of efficacy of fluvoxamine administration in moderate SARS-CoV-2 infected patients on prevention of long-term complications of COVID-19, in particular, development of pulmonary fibrosis. • Assessment of safety of fluvoxamine administration in moderate SARS-CoV-2 infected patients.;Primary end point(s): • Time to clinical recovery after treatment, defined as days from randomization (Day 1) to ANY THREE items of the following four: 1.) resolution from fever: oral or tympanic (core body) temperature = 37.5 °C, axillary, forehead or wrist (surface body) temperature = 37.0 °C for at least 48 hours without antipyretics 2.) return of respiratory rate to normal (= 20 / min) 3.) normalization of SpO2 ( =95% on room air ) 4.) cough remission (any reduction in cough-burden Visual Analogue Scale, compared to Day 1 baseline) ;Timepoint(s) of evaluation of this end point: Time to endpoint, up to Day 75 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •[SEC 01] Time to achieve a score of 0-2 (ambulatory state) on the WHO Ordinal Scale for Clinical Improvement • [SEC 02] Characterization of time course of select cytokine levels (TNF-alfa, IL-1 beta, IL-6, IL-8), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), D-dimer - in subjects randomized to either fluvoxamine or PBO • [SEC 03] Dynamic changes in oxygenation index (SpO2) • [SEC 04] Time course of cough burden • [SEC 05] Time to negative COVID-19 nucleic acid results • [SEC 06] Rate of patients with native chest CT recovery from the acute stage of COVID-19 by Day 30 visit • [SEC 07] Rate of patients requiring oxygen supplementation (WHO Ordinal Scale for Clinical Improvement score = 4, any time during the course of the disease) • [SEC 08] Rate of patients requiring mechanical ventilation (WHO Ordinal Scale for Clinical Improvement score = 5-7, any time during the course of the disease) • [SEC 09] Rate of ICU admission • [SEC 10] 30-day mortality and overall mortality (WHO Ordinal Scale for Clinical Improvement score = 8, at or any time before Day 30; by Month 6 final visit, respectively) • [SEC 11] Long-term efficacy of fluvoxamine in preventing pulmonary pathology (fibrosis), as monitored by native chest CT - Presence / quantification (e.g. percentage) / absence of: 1.) Reticular abnormality, 2.) Traction bronchiectasis and bronchiolectasias, 3.) Honeycombing. • [SEC 12] Rate of patients requiring treatment with antiviral and immunmodulant therapy or reconvalscent plasma against COVID-19 disease Safety Endpoints: • [SAF 01] Change in the total score of PHQ-9 questionnaire from baseline. • [SAF 02] Number and frequency of Adverse Events, descriptive statistical parameters of safety laboratory and other safety parameter values. ;Timepoint(s) of evaluation of this end point: During hospital stay: SEC 01, SEC 03, SEC 11 Up to day 75: SEC 02, SEC 04, SEC 05, SEC 06, | — |
Countries
Hungary
Contacts
Public ContactCEO
SigmaDrugs Research Ltd.
Outcome results
None listed