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

Phase 2

Completed

• Conditions: SARS-CoV-2 PCR Test Positive; Corona Virus Infection; SARS-CoV-2 Acute Respiratory Disease; SARS-CoV-2 Infection
• Interventions: Biological: Convalescent plasma; Other: Standard of Care (SoC); Drug: Placebo for Camostat Mesilate; Drug: Camostat Mesilate

• Registration Number: NCT04681430
• Lead Sponsor: Heinrich-Heine University, Duesseldorf

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.

Study Timeline

• Study First Submitted: 2020-12-17
• Study First Submitted QC: 2020-12-22
• Study First Posted: 2020-12-23
• Study Start: 2021-01-08
• Primary Completion: 2021-10-29
• Study Completion: 2021-10-29
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-09
• Last Update Posted: 2022-02-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
convalescent plasma (CP)	Convalescent plasma	Administration of 2 units of CP (neutralizing anti-SARS-CoV-2 antibody titer of at least 1:160) on day 1
Standard of Care	Standard of Care (SoC)	Standard of care allowed
Placebo camostat	Placebo for Camostat Mesilate	Placebo Tablets in 3 doses over 7 days (blinded)
Camostat Mesilate	Camostat Mesilate	Tablets 600 mg per day in 3 doses over 7 days

Primary Outcome Measures

Name	Time	Method
WHO ordinal Covid-19 scale up to day 28	up to and including 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

Secondary Outcome Measures

Name	Time	Method
All-cause mortality	at day 90	All-cause mortality at day 90
Mortality	at day 28	All-cause mortality at day 28
Cumulative number WHO categories 4b-8	day 8, day 14, day 56 and day 90	Cumulative number of persons in the respective treatment arms versus SoC/placebo in WHO categories 4b-8
Oxygen therapy	number of days with oxygen therapy up to day 90	Duration of oxygen therapy (in days)
Cumulative number WHO categories 3-4a	day 8, day 14, day 28, day 56 and day 90	Cumulative number of persons in the respective treatment arms versus SoC/placebo in WHO categories 3-4a
Reinfection	up to day 90	Number of patient with SARS-CoV-2 reinfection up to day 90
patients with dexamethasone treatment	up to day 90	The proportion of patients on dexamethasone therapy
negative SARS-CoV-2-PCR test	until day of first negative test up to day 90	Time to first negative SARS-CoV-2-PCR (polymerase chain reaction)
Not hospitalized	at day 90	Cumulative number of participants not hospitalized at day 90
SAEs	up to day 90	Cumulative incidence of Serious Adverse Events (SAE) per group within 90 days follow up
chronic pulmonary disease as sequelae from COVID-19	at day 90	Number of patient with COVID-19 associated chronic pulmonary disease
COVID-19 WHO status of patients at start of dexamethasone treatment	up to day 90	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
Number of ventilation days per participant up to day 90	up to day 90	Number of ventilation days per participant up to day 90
Secondary sclerosing cholangitis (SSC)	at day 90	Number of patient with secondary sclerosis cholangitis at day 90
patients with remdesivir treatment	up to day 90	The proportion of patients with remdesivir therapy
resolution of COVID-19 symptoms	until day of resolution up to day 90	Time to resolution of COVID-19 related symptoms (e.g. fever)
COVID-19 pneumonia	up to day 90	Frequency of occurrence of COVID-19 pneumonia
hospital stay and intensive care	up to day 90	Duration of hospital stay (in days), duration in intensive care/intermediate care (IMC) (in days)
SARS-CoV-2 antibody IgG concentrations	on day 8, day 14, day 90	SARS-CoV-2 antibody concentrations (IgG in g/l) in serum on day 8, day 14, day 90
COVID-19 WHO status of patients at start of remdesivir treatment	up to day 90	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
Grade 3/4 AEs	up to day 90	Cumulative incidence of grade 3/4 Adverse Events (AE) per group
Percentage of participants requiring mechanical ventilation	up to day 90	Percentage of participants in each group with need for mechanical ventilation
SARS-CoV-2 antibody IgA concentrations	on day 8, day 14, day 90	SARS-CoV-2 antibody concentrations (IgA in g/l) in serum on day 8, day 14, day 90
SARS-CoV-2 neutralizing antibody titers	on day 8, day 14, day 90	SARS-CoV-2 neutralizing antibody titers in serum on day 8, day 14, day 90
Plasma treatment screening failures	up to day 8 (End of treatment)	Number of screening failures due to the lack of a suitable plasma preparation

Trial Locations

Locations (6)

Universitätsklinikum Frankfurt Medizinische Klinik 2: Hämatologie, Onkologie, Hämostaseologie, Rheumatologie, Infektiologie/HIV; 🇩🇪 Frankfurt am Main, Hessen, Germany

Klinikum Dortmund; 🇩🇪 Dortmund, North Rhine-Westphalia, Germany

Universitätsklinikum Essen; 🇩🇪 Essen, North Rhine-Westphalia, Germany

Universitätsklinikum Düsseldorf Klinik für Hepatologie und Infektiologie; 🇩🇪 Duesseldorf, North Rhine Westphalia, Germany

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