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

NCT ID: NCT04681430

Last Updated: 2022-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-08
• Study Completion Date: 2021-10-29

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.

Conditions

Corona Virus Infection; SARS-CoV-2 Infection; SARS-CoV-2 PCR Test Positive; SARS-CoV-2 Acute Respiratory Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

convalescent plasma (CP)

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

Group Type: EXPERIMENTAL

Convalescent plasma

Intervention Type: BIOLOGICAL

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

Standard of Care

Standard of care allowed

Group Type: OTHER

Standard of Care (SoC)

Intervention Type: OTHER

Control Arm for convalescent plasma (CP)

Camostat Mesilate

Tablets 600 mg per day in 3 doses over 7 days

Group Type: EXPERIMENTAL

Camostat Mesilate

Intervention Type: DRUG

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

Placebo camostat

Placebo Tablets in 3 doses over 7 days (blinded)

Group Type: PLACEBO_COMPARATOR

Placebo for Camostat Mesilate

Intervention Type: DRUG

Placebo Tablets over 7 days, split into 3 doses

Interventions

Convalescent plasma

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

Intervention Type: BIOLOGICAL

Camostat Mesilate

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

Intervention Type: DRUG

Placebo for Camostat Mesilate

Placebo Tablets over 7 days, split into 3 doses

Intervention Type: DRUG

Standard of Care (SoC)

Control Arm for convalescent plasma (CP)

Intervention Type: OTHER

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

UNKNOWN

Sponsor Role: collaborator

Heinrich-Heine University, Duesseldorf

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Verena Keitel-Anselmino, Prof.Dr.med.

Role: PRINCIPAL_INVESTIGATOR

Klinik für Gastroenterologie, Hepatologie und Infektiologie Universitätsklinikum Düsseldorf

Locations

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

Freiburg im Breisgau, Baden-Wurttemberg, 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, Hesse, Germany

Klinikum Dortmund

Dortmund, North Rhine-Westphalia, Germany

Universitätsklinikum Düsseldorf Klinik für Hepatologie und Infektiologie

Düsseldorf, North Rhine-Westphalia, Germany

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 34001215 (View on PubMed)

Other Identifiers

2020-004695-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RES-Q-HR

Identifier Type: -

Identifier Source: org_study_id