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.
Biological: Convalescent plasma
transfusion of convalescent plasma (CP) with neutralizing antibodies against anti-SARS-CoV-2 ((titer of at least 1:160)
Drug: Camostat Mesilate
Tablets over 7 days, daily dose of 600 mg split into 3 doses
Drug: Placebo for Camostat Mesilate
Placebo Tablets over 7 days, split into 3 doses
Other: Standard of Care (SoC)
Control Arm for convalescent plasma (CP)
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
Abteilung Infektiologie Klinik für Innere Medizin II Department Innere Medizin Universitätsklinikum Freiburg
Freiburg im Breisgau, Baden-Württemberg, 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, Hessen, Germany
Universitätsklinikum Düsseldorf Klinik für Hepatologie und Infektiologie
Duesseldorf, North Rhine Westphalia, Germany
Klinikum Dortmund
Dortmund, North Rhine-Westphalia, Germany
Universitätsklinikum Essen
Essen, North Rhine-Westphalia, Germany
Verena Keitel-Anselmino, Prof.Dr.med., Principal Investigator
Klinik für Gastroenterologie, Hepatologie und Infektiologie Universitätsklinikum Düsseldorf