This is a phase II randomised, multicentre, prospective, open label clinical trial. The trial aims to recruit patients who test positive for COVID-19 who have mild symptoms and therefore can treat their symptoms in the community. Patients who test positive for COVID-19 at hospital may also be able to participate.
Coronavirus-induced disease 2019 (COVID-19) caused by SARS-CoV-2 infection is a highly
contagious disease with a high and unpredictable morbidity and mortality, for which there is
currently no specific treatment. Progression from a mild fatigue, fever and cough, to severe
respiratory failure requiring mechanical ventilation may occur 1 to 2 weeks into the disease.
This provides a window of opportunity in which patients in the early phase of the disease
could be treated with a disease-modifying agent, to halt disease progression, prevent
hospital admissions with respiratory failure and prevent death.
Camostat is a serine protease inhibitor in clinical use in Japan since 1985 to treat patients
with chronic pancreatitis (inflammation of the pancreas) and has an acceptable safety
profile. Camostat has been shown to inhibit SARS-CoV-2 entry into epithelial cells in vitro.
A trial of this repurposed drug for treatment of COVID-19 in humans is urgently required to
assess its impact on disease progression to respiratory failure and whether it can reduce
mortality.
This trial will recruit up to 100 patients. Patients will be randomised into a treatment arm
(camostat tablets) or control arm (best supportive care). Community patients will be called
daily at home for 14 days by the clinical trial team to collect symptoms and record the
general well-being of the patient. For those patients recruited from hospital, visits will
continue in hospital, where feasible, until discharge when home visits will be able to
continue. The primary aim of this trial is to further assess the safety and toxicity profile
of camostat to support integration into a Phase III trial. Secondary aims are to determine if
camostat can reduce the clinical progression of COVID-19 and therefore the need for hospital
admission and supplemental oxygen as well as include collection of patient reported health
status, severity of symptoms and biological markers of the virus and confirm PK profile for
the active metabolite of camostat. As the understanding of COVID-19 develops and improves,
the inclusion criteria may be adapted to support the trial outcomes. Patients will be
recruited through various settings which may include primary care 'COVID-19 hub' clinics,
COVID-19 community-based testing centres, identification through other hospital departments,
NHS digital, Test and Trace (or equivalent) or other clinical environments.
Drug: Camostat
Patient to receive treatment with camostat tablets, 200mg four times daily (qds) for 14 days.
Other Name: Array
Inclusion Criteria:
1. Patient willing and able to give informed consent
2. Adults, 18 years of age and above
3. Symptomatic COVID-19 infection
4. Evidence of current COVID-19 infection from a validated assay
Exclusion Criteria:
The patient may not enter the trial if ANY of the following apply:
1. Significant electrolyte disturbance (e.g. hyperkalaemia, potassium > site specific
upper limit of normal)
2. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) and/or Alkaline
Phosphatase (ALP) > 2.5 x ULN
3. Any condition that, in the Investigator's opinion, would not make the patient a good
candidate for the clinical trial or would prevent adequate compliance with trial
therapy e.g. mild cognitive impairment (unable to follow instructions for
self-assessment readings as assessed by the Investigator).
4. Patients on long term supplementary oxygen requirement (patients for whom hospital
admission would not be considered e.g. care plan in the community is in place, are not
excluded)
5. Known hypersensitivity to camostat
6. Platelet count <100 x 10^9/L
7. Co-enrolment with a Clinical Trial of an Investigational Medicinal Product (CTIMP)
will not be permitted. Co-enrolment with a clinical investigation of a Medical Device
or a non-interventional clinical study will be considered on a study-by-study basis
and in discussion with the relevant Chief Investigators and Sponsors and industrial
collaborators.
8. Co-enrolment involving non-interventional research (including questionnaire or tissue
only studies) will be allowed provided this is not expected to affect the outcomes of
both studies or place undue burden upon participants and their families.
9. Female patients who are able to become pregnant (or are already pregnant or
lactating). However, those patients who are of child bearing potential and have a
negative serum or urine pregnancy test before enrolment and agree to use two forms of
contraception (one effective form plus a barrier method [oral, injected or implanted
hormonal contraception and condom; intra-uterine device and condom; diaphragm with
spermicidal gel and condom]) or agree to sexual abstinence*, effective from the first
administration of camostat, throughout the trial and for 28 days afterwards are
considered eligible.
(*Abstinence is only considered to be an acceptable method of contraception when this
is in line with the preferred and usual lifestyle of the subject. Periodic abstinence
[e.g. calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are
not acceptable methods of contraception.)
10. Male patients with partners of child-bearing potential (unless they agree to take
measures not to father children by using a barrier method of contraception [condom
plus spermicide] or to sexual abstinence* effective from the first administration of
camostat, throughout the trial and for 28 days afterwards. Men with partners of
child-bearing potential must also be willing to ensure that their partner uses an
effective method of contraception for the same duration for example, hormonal
contraception, intrauterine device, diaphragm with spermicidal gel or sexual
abstinence). Men with pregnant or lactating partners must be advised to use barrier
method contraception (for example, condom plus spermicidal gel) to prevent exposure of
the foetus or neonate.
(*Abstinence is only considered to be an acceptable method of contraception when this
is in line with the preferred and usual lifestyle of the subject. Periodic abstinence
[e.g. calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are
not acceptable methods of contraception.)
11. Significant cardiovascular disease (as assessed via the participant's medical record
and history) as defined by:
1. History of congestive heart failure requiring therapy (New York Heart Association
[NYHA] III or IV)
2. History of unstable angina pectoris or myocardial infarction up to 6 months prior
to trial entry
3. Presence of severe valvular heart disease
4. Presence of a ventricular arrhythmia requiring treatment
Known allergic reactions to components of camostat e.g., lactose intolerance
Chawton Park Surgery
Alton, United Kingdom
The University of Edinburgh
Edinburgh, United Kingdom
Church Avenue Medical Group
Harrogate, United Kingdom
Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom
Trafalgar Medical Practice
Portsmouth, United Kingdom
Preston Lantern Centre
Preston, United Kingdom
Clarence Medical Centre
Rhyl, United Kingdom
Velindre Cancer Centre
Wales, United Kingdom
Eynsham Medical Centre
Witney, United Kingdom
Kevin Dhaliwal, Professor, Principal Investigator
University of Edinburgh