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

NCT04681430 | Completed Phase 2 DMC

• 2 other identifiers: RES-Q-HR2020-004695-18
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 6

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.

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

Outcome Measures

Primary Outcomes (1)

• 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

  up to and including day 28

Secondary Outcomes (25)

• Cumulative number WHO categories 4b-8

  day 8, day 14, day 56 and day 90

• Cumulative number WHO categories 3-4a

  day 8, day 14, day 28, day 56 and day 90

• Not hospitalized

  at day 90

• All-cause mortality

  at day 90

• Reinfection

  up to day 90

Study Arms (4)

convalescent plasma (CP)

EXPERIMENTAL

Administration of 2 units of CP (neutralizing anti-SARS-CoV-2 antibody titer of at least 1:160) on day 1

Biological: Convalescent plasma

Standard of Care

OTHER

Standard of care allowed

Other: Standard of Care (SoC)

Camostat Mesilate

EXPERIMENTAL

Tablets 600 mg per day in 3 doses over 7 days

Drug: Camostat Mesilate

Placebo camostat

PLACEBO COMPARATOR

Placebo Tablets in 3 doses over 7 days (blinded)

Drug: Placebo for Camostat Mesilate

Interventions

Convalescent plasma BIOLOGICAL

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

convalescent plasma (CP)

Camostat Mesilate DRUG

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

Camostat Mesilate

Placebo for Camostat Mesilate DRUG

Placebo Tablets over 7 days, split into 3 doses

Placebo camostat

Standard of Care (SoC) OTHER

Control Arm for convalescent plasma (CP)

Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

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

Study Sites (6)

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

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

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

München, Bavaria, 81675, Germany

Location

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

Frankfurt am Main, Hesse, 60590, Germany

Location

Klinikum Dortmund

Dortmund, North Rhine-Westphalia, 44137, Germany

Location

Universitätsklinikum Düsseldorf Klinik für Hepatologie und Infektiologie

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, 45147, Germany

Location

Related Publications (1)

• 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.

  PMID: 34001215 DERIVED

MeSH Terms

Conditions

Coronavirus Infections; COVID-19

Interventions

camostat; Standard of Care

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Verena Keitel-Anselmino, Prof.Dr.med.

  Klinik für Gastroenterologie, Hepatologie und Infektiologie Universitätsklinikum Düsseldorf

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The camostat mesylate and its placebo group will be double blinded while the CP and its placebo will be open label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: December 23, 2020
• Study Start: January 8, 2021
• Primary Completion: October 29, 2021
• Study Completion: October 29, 2021
• Last Updated: February 10, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (6)