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

SARS-CoV-2 Infection Clinical Trial

— RES-Q-HR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04681430
• Other study ID #: RES-Q-HR
• Secondary ID: 2020-004695-18
• Status: Completed
• Phase: Phase 2
• Start date: January 8, 2021
• Est. completion date: October 29, 2021

Study information

• Verified date: February 2022
• Source: Heinrich-Heine University, Duesseldorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: October 29, 2021
• Est. primary completion date: October 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Corona Virus Infection
• Coronavirus Infections
• COVID-19
• Infections
• Respiration Disorders
• Respiratory Tract Diseases
• SARS-CoV-2 Acute Respiratory Disease
• SARS-CoV-2 Infection
• SARS-CoV-2 PCR Test Positive

Intervention

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

Drug:
• Camostat Mesilate
Tablets over 7 days, daily dose of 600 mg split into 3 doses
• Placebo for Camostat Mesilate
Placebo Tablets over 7 days, split into 3 doses

Other:
• Standard of Care (SoC)
Control Arm for convalescent plasma (CP)

Locations

Country	Name	City	State
Germany	Klinikum Dortmund	Dortmund	North Rhine-Westphalia
Germany	Universitätsklinikum Düsseldorf Klinik für Hepatologie und Infektiologie	Duesseldorf	North Rhine Westphalia
Germany	Universitätsklinikum Essen	Essen	North Rhine-Westphalia
Germany	Universitätsklinikum Frankfurt Medizinische Klinik 2: Hämatologie, Onkologie, Hämostaseologie, Rheumatologie, Infektiologie/HIV	Frankfurt am Main	Hessen
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

Sponsors (2)

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

Country where clinical trial is conducted

Germany, 

Outcome

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