Reconvalescent Plasma/Camostat Mesylate Early in SARS-CoV-2 Q-PCR (COVID-19) Positive High-risk Individuals

Heinrich-Heine University, Duesseldorf22 enrolled

Overview

This study is a 4-arm, multicenter, randomized, partly double- blind, controlled trial to evaluate the safety and efficacy of convalescent serum (CP) or camostat mesylate with control or placebo in adult patients diagnosed with SARS-CoV-2 and high risk for moderate/severe COVID-19. The working hypothesis to be tested in the RES-Q-HR study is that the early use of convalescent plasma (CP) or camostat mesylate (Foipan®) reduces the likelihood of disease progression to modified WHO stages 4b-8 in SARS-CoV-2 positive adult patients at high risk of moderate or severe COVID-19 progression. The primary endpoint of the study is the cumulative number of individuals who progressed to or beyond category 4b on the modified WHO (World Health Organization) COVID-19 ordinal scale within 28 days after randomization.

The novel coronavirus designated SARS CoV-2, and the disease caused by this virus designated COVID-19. No treatment is available for early disease stages and non-hospitalized patients to date. This trial focusses on SARS-CoV-2 positive patients with pre-existing risk factors for a moderate or severe COVID-19 disease course. This study is a 4-arm, multicenter, randomized, partly double-blind, controlled trial to evaluate the safety and efficacy of convalescent serum (CP) or camostat mesylate with control or placebo in adult patients diagnosed with SARS-CoV-2 and high risk for moderate/severe COVID-19. Camostat mesylate acts as an inhibitor of the host cell serine protease TMPRSS2 and prevents the virus from entering the cell. Convalescent plasma (CP) represents another antiviral strategy in terms of passive immunization. The working hypothesis to be tested in the RES-Q HR study is that the early use of convalescent plasma (CP) or camostat mesylate (Foipan®) reduces the likelihood of disease progression to modified WHO stages 4b-8 in SARS-CoV-2 positive adult patients at high risk of moderate or severe COVID-19 progression.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Interventions

Convalescent plasmaBIOLOGICAL

transfusion of convalescent plasma (CP) with neutralizing antibodies against anti-SARS-CoV-2 ((titer of at least 1:160)

Camostat MesilateDRUG

Tablets over 7 days, daily dose of 600 mg split into 3 doses

Placebo for Camostat MesilateDRUG

Placebo Tablets over 7 days, split into 3 doses

Standard of Care (SoC)OTHER

Control Arm for convalescent plasma (CP)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Individuals (female, male, diverse) ≥ 18 years with SARS-CoV-2 infection, confirmed by PCR before study enrollment 2. SARS-CoV-2 positive PCR ≤ 3 days old (date of NP swab) 3. Presence of ≥ 1 SARS-CoV-2 typical symptom (fever, cough, shortness of breath, sore throat, headache, fatigue, smell/and or taste disorder, diarrhea, abdominal symptoms, exanthema) and symptom duration \<= 3 days. 4. Ability to provide written informed consent 5. Presence of at least one of the following criteria: * Patients \> 75 years * Patients \> 65 years with at least one other risk factor (BMI \>35 kg/m2, coronary artery disease, chronic kidney disease (CKD) with glomerular filtration rate (GFR) \<60 ml/min but \>= 30 ml/min, diabetes mellitus, active tumor disease) * Patients with a BMI \>35 kg/m2 with at least one other risk factor (CAD, CKD with GFR \<60 ml/min but \>= 30 ml/min, diabetes mellitus, active tumor disease) * Patients with a BMI \>40 kg/m2 * Patients with chronic obstructive pulmonary disease (COPD) and/or pulmonary fibrosis Exclusion Criteria: 1. Age \<18 years 2. Unable to give informed consent 3. Pregnant women or breast-feeding mothers 4. Previous transfusion reaction or other contraindication to a plasma transfusion 5. Known hypersensitivity to camostat mesylate and/or severe pancreatitis 6. Volume stress due to CP administration would be intolerable 7. Known IgA deficiency 8. Life expectancy \< 6 months 9. Duration SARS-CoV-2 typical symptoms \> 3 days 10. SARS-CoV-2 PCR detection older than 3 days 11. SARS-CoV-2 associated clinical condition \>= WHO stage 3 (patients hospitalized for other reasons than COVID-19 may be included if they fulfill all inclusion and none of the exclusion criteria). 12. Previously or currently hospitalized due to SARS-CoV-2 13. Previous antiviral therapy for SARS-CoV-2 14. alanine aminotransferase (ALT) or aspartate transferase (AST) \> 5 times upper limit of normal (ULN) at screening 15. Liver cirrhosis \> Child A (patients with Child B/C cirrhosis are excluded from the trial) 16. Chronic kidney disease with GFR \< 30 ml/min 17. Concurrent or planned anticancer treatment during trial period 18. Accommodation in an institution due to legal orders (§40(4) AMG). 19. Any psycho-social condition hampering compliance with the study protocol. 20. Evidence of current drug or alcohol abuse. 21. Use of other investigational treatment within 5 half-lives of enrollment is prohibited 22. Previous use of convalescent plasma for COVID-19 23. Concomitant proven influenza A infection 24. Patients with organ or bone marrow transplant in the three months prior to Screening Visit

Locations (6)

Abteilung Infektiologie Klinik für Innere Medizin II Department Innere Medizin Universitätsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Klinik und Poliklinik für Innere Medizin II Klinikum rechts der Isar Technische Universität München

München, Bavaria, Germany

Universitätsklinikum Frankfurt Medizinische Klinik 2: Hämatologie, Onkologie, Hämostaseologie, Rheumatologie, Infektiologie/HIV

Frankfurt am Main, Hesse, Germany

Klinikum Dortmund

Dortmund, North Rhine-Westphalia, Germany

Universitätsklinikum Düsseldorf Klinik für Hepatologie und Infektiologie

Düsseldorf, North Rhine-Westphalia, Germany

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, Germany

Outcomes

Primary Outcomes

WHO ordinal Covid-19 scale up to day 28

The primary endpoint of the study is the number of individuals whose clinical status is on the COVID-19 modified WHO ordinal scale ≥ 4b up to and including day 28

Time frame: up to and including day 28

Secondary Outcomes

Cumulative number WHO categories 4b-8

Cumulative number of persons in the respective treatment arms versus SoC/placebo in WHO categories 4b-8

Time frame: day 8, day 14, day 56 and day 90

Cumulative number WHO categories 3-4a

Cumulative number of persons in the respective treatment arms versus SoC/placebo in WHO categories 3-4a

Time frame: day 8, day 14, day 28, day 56 and day 90

Not hospitalized

Cumulative number of participants not hospitalized at day 90

Time frame: at day 90

All-cause mortality

All-cause mortality at day 90

Time frame: at day 90

Reinfection

Number of patient with SARS-CoV-2 reinfection up to day 90

Time frame: up to day 90

Secondary sclerosing cholangitis (SSC)

Number of patient with secondary sclerosis cholangitis at day 90

Time frame: at day 90

chronic pulmonary disease as sequelae from COVID-19

Number of patient with COVID-19 associated chronic pulmonary disease

Time frame: at day 90

patients with remdesivir treatment

The proportion of patients with remdesivir therapy

Time frame: up to day 90

COVID-19 WHO status of patients at start of remdesivir treatment

The clinical status on the WHO COVID-19 ordinal scale of at the start of remdesivir treatment WHO ordinal scale ranges from 0 to 8; whereas 0 = no COVID-19 infection and 8 = death

Time frame: up to day 90

patients with dexamethasone treatment

The proportion of patients on dexamethasone therapy

Time frame: up to day 90

COVID-19 WHO status of patients at start of dexamethasone treatment

The clinical status on the WHO COVID-19 ordinal scale of at the start of dexamethasone treatment WHO ordinal scale ranges from 0 to 8; whereas 0 = no COVID-19 infection and 8 = death

Time frame: up to day 90

resolution of COVID-19 symptoms

Time to resolution of COVID-19 related symptoms (e.g. fever)

Time frame: until day of resolution up to day 90

negative SARS-CoV-2-PCR test

Time to first negative SARS-CoV-2-PCR (polymerase chain reaction)

Time frame: until day of first negative test up to day 90

Oxygen therapy

Duration of oxygen therapy (in days)

Time frame: number of days with oxygen therapy up to day 90

COVID-19 pneumonia

Frequency of occurrence of COVID-19 pneumonia

Time frame: up to day 90

Percentage of participants requiring mechanical ventilation

Percentage of participants in each group with need for mechanical ventilation

Time frame: up to day 90

Number of ventilation days per participant up to day 90

Time frame: up to day 90

hospital stay and intensive care

Duration of hospital stay (in days), duration in intensive care/intermediate care (IMC) (in days)

Time frame: up to day 90

Mortality

All-cause mortality at day 28

Time frame: at day 28

SAEs

Cumulative incidence of Serious Adverse Events (SAE) per group within 90 days follow up

Time frame: up to day 90

Grade 3/4 AEs

Cumulative incidence of grade 3/4 Adverse Events (AE) per group

Time frame: up to day 90

SARS-CoV-2 antibody IgA concentrations

SARS-CoV-2 antibody concentrations (IgA in g/l) in serum on day 8, day 14, day 90

Time frame: on day 8, day 14, day 90

SARS-CoV-2 antibody IgG concentrations

SARS-CoV-2 antibody concentrations (IgG in g/l) in serum on day 8, day 14, day 90

Time frame: on day 8, day 14, day 90

SARS-CoV-2 neutralizing antibody titers

SARS-CoV-2 neutralizing antibody titers in serum on day 8, day 14, day 90

Time frame: on day 8, day 14, day 90

Plasma treatment screening failures

Number of screening failures due to the lack of a suitable plasma preparation

Time frame: up to day 8 (End of treatment)

Reconvalescent Plasma/Camostat Mesylate Early in SARS-CoV-2 Q-PCR (COVID-19) Positive High-risk Individuals

Overview

Conditions

Interventions

Eligibility

Locations (6)

Outcomes

Primary Outcomes

Secondary Outcomes