Clinical trial NCT04681430: Reconvalescent Plasma/Camostat Mesylate Early in SARS-CoV-2 Q-PCR (COVID-19) Positive High-risk Individuals
Official title: Reconvalescent Plasma / Camostat Mesylate Early in Sars-CoV-2 Q-PCR (COVID-19) Positive High-risk Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Corona Virus Infection
SARS-CoV-2 Infection
SARS-CoV-2 PCR Test Positive
SARS-CoV-2 Acute Respiratory Disease
Keywords: SARS-CoV-2
Covid-19
camostat mesilate
reconvalescent plasma
TMPRSS2
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
Collaborators: name: The Federal Ministry of Health, Germany (Bundesministerium für Gesundheit, BMG)
First posted: 2020-12-23
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is a multicenter trial that will be conducted in approx. 10 - 15 centers in Germany.

At each center, patients will be randomized into four groups: two treatment groups and two control groups. The randomization rate in this study is two to one (2:1) in favor to therapy, i.e.

included patients have twice the chance to receive interventional therapy than placebo / SoC.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: WHO ordinal Covid-19 scale up to day 28
timeFrame: up to and including day 28
Secondary outcomes:
measure: Cumulative number WHO categories 4b-8
timeFrame: day 8, day 14, day 56 and day 90
measure: Cumulative number WHO categories 3-4a
timeFrame: day 8, day 14, day 28, day 56 and day 90
measure: Not hospitalized
timeFrame: at day 90
measure: All-cause mortality
timeFrame: at day 90
measure: Reinfection
timeFrame: up to day 90
measure: Secondary sclerosing cholangitis (SSC)
timeFrame: at day 90
measure: chronic pulmonary disease as sequelae from COVID-19
timeFrame: at day 90
measure: patients with remdesivir treatment
timeFrame: up to day 90
measure: COVID-19 WHO status of patients at start of remdesivir treatment
timeFrame: up to day 90
measure: patients with dexamethasone treatment
timeFrame: up to day 90
measure: COVID-19 WHO status of patients at start of dexamethasone treatment
timeFrame: up to day 90
measure: resolution of COVID-19 symptoms
timeFrame: until day of resolution up to day 90
measure: negative SARS-CoV-2-PCR test
timeFrame: until day of first negative test up to day 90
measure: Oxygen therapy
timeFrame: number of days with oxygen therapy up to day 90
measure: COVID-19 pneumonia
timeFrame: up to day 90
measure: Percentage of participants requiring mechanical ventilation
timeFrame: up to day 90
measure: Number of ventilation days per participant up to day 90
timeFrame: up to day 90
measure: hospital stay and intensive care
timeFrame: up to day 90
measure: Mortality
timeFrame: at day 28
measure: SAEs
timeFrame: up to day 90
measure: Grade 3/4 AEs
timeFrame: up to day 90
measure: SARS-CoV-2 antibody IgA concentrations
timeFrame: on day 8, day 14, day 90
measure: SARS-CoV-2 antibody IgG concentrations
timeFrame: on day 8, day 14, day 90
measure: SARS-CoV-2 neutralizing antibody titers
timeFrame: on day 8, day 14, day 90
measure: Plasma treatment screening failures
timeFrame: up to day 8 (End of treatment)
Other outcomes:
Locations:
city: Freiburg im Breisgau
country: Germany
facility: Abteilung Infektiologie Klinik für Innere Medizin II Department Innere Medizin Universitätsklinikum Freiburg
state: Baden-Württemberg
city: München
country: Germany
facility: Klinik und Poliklinik für Innere Medizin II Klinikum rechts der Isar Technische Universität München
state: Bavaria
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt Medizinische Klinik 2: Hämatologie, Onkologie, Hämostaseologie, Rheumatologie, Infektiologie/HIV
state: Hessen
city: Duesseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf Klinik für Hepatologie und Infektiologie
state: North Rhine Westphalia
city: Dortmund
country: Germany
facility: Klinikum Dortmund
state: North Rhine-Westphalia
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: North Rhine-Westphalia
Study officials:
affiliation: Klinik für Gastroenterologie, Hepatologie und Infektiologie Universitätsklinikum Düsseldorf
name: Verena Keitel-Anselmino, Prof.Dr.med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Keitel V, Jensen B, Feldt T, Fischer JC, Bode JG, Matuschek C, Bolke E, Budach W, Plettenberg C, Scheckenbach K, Kindgen-Milles D, Timm J, Muller L, Kolbe H, Stohr A, Calles C, Hippe A, Verde P, Spinner CD, Schneider J, Wolf T, Kern WV, Nattermann J, Zoufaly A, Ohmann C, Luedde T; RES-Q-HR Trial Team. Reconvalescent plasma/camostat mesylate in early SARS-CoV-2 Q-PCR positive high-risk individuals (RES-Q-HR): a structured summary of a study protocol for a randomized controlled trial. Trials. 2021 May 17;22(1):343. doi: 10.1186/s13063-021-05181-0.