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

Sponsor

Heinrich-Heine University, Duesseldorf (Other)

Overall Status

Completed

CT.gov ID

NCT04681430

Collaborator

The Federal Ministry of Health, Germany (Bundesministerium für Gesundheit, BMG) (Other)

Enrollment

Locations

Arms

9.7

Actual Duration (Months)

3.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Corona Virus Infection SARS-CoV-2 Infection SARS-CoV-2 PCR Test Positive SARS-CoV-2 Acute Respiratory Disease	Biological: Convalescent plasma Drug: Camostat Mesilate Drug: Placebo for Camostat Mesilate Other: Standard of Care (SoC)	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

The camostat mesylate and its placebo group will be double blinded while the CP and its placebo will be open label.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 8, 2021

Actual Primary Completion Date :

Oct 29, 2021

Actual Study Completion Date :

Oct 29, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: convalescent plasma (CP) Administration of 2 units of CP (neutralizing anti-SARS-CoV-2 antibody titer of at least 1:160) on day 1	Biological: Convalescent plasma transfusion of convalescent plasma (CP) with neutralizing antibodies against anti-SARS-CoV-2 ((titer of at least 1:160)
Other: Standard of Care Standard of care allowed	Other: Standard of Care (SoC) Control Arm for convalescent plasma (CP)
Experimental: Camostat Mesilate Tablets 600 mg per day in 3 doses over 7 days	Drug: Camostat Mesilate Tablets over 7 days, daily dose of 600 mg split into 3 doses
Placebo Comparator: Placebo camostat Placebo Tablets in 3 doses over 7 days (blinded)	Drug: Placebo for Camostat Mesilate Placebo Tablets over 7 days, split into 3 doses

Outcome Measures

Primary Outcome Measures

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

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
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
Not hospitalized [at day 90]
Cumulative number of participants not hospitalized at day 90
All-cause mortality [at day 90]
All-cause mortality at day 90
Reinfection [up to day 90]
Number of patient with SARS-CoV-2 reinfection up to day 90
Secondary sclerosing cholangitis (SSC) [at day 90]
Number of patient with secondary sclerosis cholangitis at day 90
chronic pulmonary disease as sequelae from COVID-19 [at day 90]
Number of patient with COVID-19 associated chronic pulmonary disease
patients with remdesivir treatment [up to day 90]
The proportion of patients with remdesivir therapy
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
patients with dexamethasone treatment [up to day 90]
The proportion of patients on dexamethasone therapy
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
resolution of COVID-19 symptoms [until day of resolution up to day 90]
Time to resolution of COVID-19 related symptoms (e.g. fever)
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)
Oxygen therapy [number of days with oxygen therapy up to day 90]
Duration of oxygen therapy (in days)
COVID-19 pneumonia [up to day 90]
Frequency of occurrence of COVID-19 pneumonia
Percentage of participants requiring mechanical ventilation [up to day 90]
Percentage of participants in each group with need for mechanical ventilation
Number of ventilation days per participant up to day 90 [up to day 90]
Number of ventilation days per participant up to day 90
hospital stay and intensive care [up to day 90]
Duration of hospital stay (in days), duration in intensive care/intermediate care (IMC) (in days)
Mortality [at day 28]
All-cause mortality at day 28
SAEs [up to day 90]
Cumulative incidence of Serious Adverse Events (SAE) per group within 90 days follow up
Grade 3/4 AEs [up to day 90]
Cumulative incidence of grade 3/4 Adverse Events (AE) per group
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 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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Individuals (female, male, diverse) ≥ 18 years with SARS-CoV-2 infection, confirmed by PCR before study enrollment
SARS-CoV-2 positive PCR ≤ 3 days old (date of NP swab)
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.
Ability to provide written informed consent
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:

Age <18 years
Unable to give informed consent
Pregnant women or breast-feeding mothers
Previous transfusion reaction or other contraindication to a plasma transfusion
Known hypersensitivity to camostat mesylate and/or severe pancreatitis
Volume stress due to CP administration would be intolerable
Known IgA deficiency
Life expectancy < 6 months
Duration SARS-CoV-2 typical symptoms > 3 days
SARS-CoV-2 PCR detection older than 3 days
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).
Previously or currently hospitalized due to SARS-CoV-2
Previous antiviral therapy for SARS-CoV-2
alanine aminotransferase (ALT) or aspartate transferase (AST) > 5 times upper limit of normal (ULN) at screening
Liver cirrhosis > Child A (patients with Child B/C cirrhosis are excluded from the trial)
Chronic kidney disease with GFR < 30 ml/min
Concurrent or planned anticancer treatment during trial period
Accommodation in an institution due to legal orders (§40(4) AMG).
Any psycho-social condition hampering compliance with the study protocol.
Evidence of current drug or alcohol abuse.
Use of other investigational treatment within 5 half-lives of enrollment is prohibited
Previous use of convalescent plasma for COVID-19
Concomitant proven influenza A infection
Patients with organ or bone marrow transplant in the three months prior to Screening Visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Abteilung Infektiologie Klinik für Innere Medizin II Department Innere Medizin Universitätsklinikum Freiburg	Freiburg im Breisgau	Baden-Württemberg	Germany	79106
2	Klinik und Poliklinik für Innere Medizin II Klinikum rechts der Isar Technische Universität München	München	Bavaria	Germany	81675
3	Universitätsklinikum Frankfurt Medizinische Klinik 2: Hämatologie, Onkologie, Hämostaseologie, Rheumatologie, Infektiologie/HIV	Frankfurt am Main	Hessen	Germany	60590
4	Universitätsklinikum Düsseldorf Klinik für Hepatologie und Infektiologie	Duesseldorf	North Rhine Westphalia	Germany	40225
5	Klinikum Dortmund	Dortmund	North Rhine-Westphalia	Germany	44137
6	Universitätsklinikum Essen	Essen	North Rhine-Westphalia	Germany	45147

Sponsors and Collaborators

Heinrich-Heine University, Duesseldorf
The Federal Ministry of Health, Germany (Bundesministerium für Gesundheit, BMG)

Investigators

Principal Investigator: Verena Keitel-Anselmino, Prof.Dr.med., Klinik für Gastroenterologie, Hepatologie und Infektiologie Universitätsklinikum Düsseldorf