<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04455815</url>
  </required_header>
  <id_info>
    <org_study_id>CRUKD/20/002</org_study_id>
    <secondary_id>2020-002110-41</secondary_id>
    <nct_id>NCT04455815</nct_id>
  </id_info>
  <brief_title>A Trial Looking at the Use of Camostat in People Who Have Tested Positive for Coronavirus (COVID-19) (SPIKE-1)</brief_title>
  <acronym>SPIKE-1</acronym>
  <official_title>A Randomised Phase II Trial in Early COVID-19, Assessing Use of Camostat by Blocking SARS-CoV-2 Spike Protein-initiated Membrane Fusion.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cancer Research UK</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Latus Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Cancer Research UK</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase II randomised, multicentre, prospective, open label clinical trial. The trial&#xD;
      aims to recruit patients who test positive for COVID-19 who have mild symptoms and therefore&#xD;
      can treat their symptoms in the community. Patients who test positive for COVID-19 at&#xD;
      hospital may also be able to participate.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Coronavirus-induced disease 2019 (COVID-19) caused by SARS-CoV-2 infection is a highly&#xD;
      contagious disease with a high and unpredictable morbidity and mortality, for which there is&#xD;
      currently no specific treatment. Progression from a mild fatigue, fever and cough, to severe&#xD;
      respiratory failure requiring mechanical ventilation may occur 1 to 2 weeks into the disease.&#xD;
      This provides a window of opportunity in which patients in the early phase of the disease&#xD;
      could be treated with a disease-modifying agent, to halt disease progression, prevent&#xD;
      hospital admissions with respiratory failure and prevent death.&#xD;
&#xD;
      Camostat is a serine protease inhibitor in clinical use in Japan since 1985 to treat patients&#xD;
      with chronic pancreatitis (inflammation of the pancreas) and has an acceptable safety&#xD;
      profile. Camostat has been shown to inhibit SARS-CoV-2 entry into epithelial cells in vitro.&#xD;
      A trial of this repurposed drug for treatment of COVID-19 in humans is urgently required to&#xD;
      assess its impact on disease progression to respiratory failure and whether it can reduce&#xD;
      mortality.&#xD;
&#xD;
      This trial will recruit up to 100 patients. Patients will be randomised into a treatment arm&#xD;
      (camostat tablets) or control arm (best supportive care). Community patients will be called&#xD;
      daily at home for 14 days by the clinical trial team to collect symptoms and record the&#xD;
      general well-being of the patient. For those patients recruited from hospital, visits will&#xD;
      continue in hospital, where feasible, until discharge when home visits will be able to&#xD;
      continue. The primary aim of this trial is to further assess the safety and toxicity profile&#xD;
      of camostat to support integration into a Phase III trial. Secondary aims are to determine if&#xD;
      camostat can reduce the clinical progression of COVID-19 and therefore the need for hospital&#xD;
      admission and supplemental oxygen as well as include collection of patient reported health&#xD;
      status, severity of symptoms and biological markers of the virus and confirm PK profile for&#xD;
      the active metabolite of camostat. As the understanding of COVID-19 develops and improves,&#xD;
      the inclusion criteria may be adapted to support the trial outcomes. Patients will be&#xD;
      recruited through various settings which may include primary care 'COVID-19 hub' clinics,&#xD;
      COVID-19 community-based testing centres, identification through other hospital departments,&#xD;
      NHS digital, Test and Trace (or equivalent) or other clinical environments.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor decision&#xD;
  </why_stopped>
  <start_date type="Actual">September 25, 2020</start_date>
  <completion_date type="Actual">March 3, 2022</completion_date>
  <primary_completion_date type="Actual">March 3, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of camostat related AEs and SAEs.</measure>
    <time_frame>Days 1 - 28</time_frame>
    <description>Number of camostat related AEs and SAEs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of AEs by severity grade</measure>
    <time_frame>Days 1 - 28</time_frame>
    <description>Number of AEs by severity grade (mild, moderate, severe)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PK parameter Maximum concentration (Cmax) of 4-(4-Guanidinobenzoyloxy)phenylacetic acid (GBPA).</measure>
    <time_frame>Days 7 and 14</time_frame>
    <description>Maximum concentration (Cmax) of GBPA as assessed by population estimates from population PK analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter time to maximum concentration (Tmax) of GBPA, as assessed by population estimates from population PK analysis.</measure>
    <time_frame>Days 7 and 14</time_frame>
    <description>Time to maximum concentration (Tmax) of GBPA, as assessed by population estimates from population PK analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter area under the curve (AUC) of GBPA</measure>
    <time_frame>Days 7 and 14</time_frame>
    <description>Area under the curve (AUC) of GBPA, as assessed by population estimates from population PK analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter to confirm half-life (T1/2) of GBPA</measure>
    <time_frame>Days 1 - 28</time_frame>
    <description>Half-life (T1/2) of GBPA as assessed by population estimates from population PK analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of community patients admitted to hospital due to COVID-19</measure>
    <time_frame>Days 1 - 28</time_frame>
    <description>Number of community patients admitted to hospital due to COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of oxygen free days</measure>
    <time_frame>Days 1 - 28</time_frame>
    <description>Number of oxygen free days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of ventilator - free days</measure>
    <time_frame>Days 1 - 28</time_frame>
    <description>Number of ventilator - free days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to worst point on the scale or deterioration of two points or more (from randomisation) on 9 point category ordinal scale ranging from '0 - Uninfected, no clinical or virological evidence of infection' to '8 - Death'</measure>
    <time_frame>Days 1 - 28</time_frame>
    <description>Median time and range to worst point on the scale or deterioration of two points or more (from randomisation) on 9 point category ordinal scale. The scale was described in the protocol as follows: '0 - Uninfected, no clinical or virological evidence of infection, 1 - Ambulatory, no limitation of activities, 2 - Ambulatory, limitation of activities, 3 - Hospitalised - mild disease, no oxygen therapy, 4 - Hospitalised - mild disease, oxygen by mask or nasal prongs, 5 - Hospitalised - severe disease, non-invasive, ventilation or high-flow oxygen, 6 - Hospitalised - severe disease, intubation and mechanical ventilation, 7 - Hospitalised - severe disease, ventilation and additional organ support - vasopressors, renal replacement therapy (RRT), extracorporeal membrane oxygenation (ECMO), 8 - Death'</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>COVID-19 Infection</condition>
  <arm_group>
    <arm_group_label>Camostat</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient to receive treatment with camostat tablets, 200mg four times daily (qds) for 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patient to receive best supportive care.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Camostat</intervention_name>
    <description>Patient to receive treatment with camostat tablets, 200mg four times daily (qds) for 14 days.</description>
    <arm_group_label>Camostat</arm_group_label>
    <other_name>Camostat mesylate</other_name>
    <other_name>Camostat mesilate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient willing and able to give informed consent&#xD;
&#xD;
          2. Adults, 18 years of age and above&#xD;
&#xD;
          3. Symptomatic COVID-19 infection&#xD;
&#xD;
          4. Evidence of current COVID-19 infection from a validated assay&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        The patient may not enter the trial if ANY of the following apply:&#xD;
&#xD;
          1. Significant electrolyte disturbance (e.g. hyperkalaemia, potassium &gt; site specific&#xD;
             upper limit of normal)&#xD;
&#xD;
          2. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) and/or Alkaline&#xD;
             Phosphatase (ALP) &gt; 2.5 x ULN&#xD;
&#xD;
          3. Any condition that, in the Investigator's opinion, would not make the patient a good&#xD;
             candidate for the clinical trial or would prevent adequate compliance with trial&#xD;
             therapy e.g. mild cognitive impairment (unable to follow instructions for&#xD;
             self-assessment readings as assessed by the Investigator).&#xD;
&#xD;
          4. Patients on long term supplementary oxygen requirement (patients for whom hospital&#xD;
             admission would not be considered e.g. care plan in the community is in place, are not&#xD;
             excluded)&#xD;
&#xD;
          5. Known hypersensitivity to camostat&#xD;
&#xD;
          6. Platelet count &lt;100 x 10^9/L&#xD;
&#xD;
          7. Co-enrolment with a Clinical Trial of an Investigational Medicinal Product (CTIMP)&#xD;
             will not be permitted. Co-enrolment with a clinical investigation of a Medical Device&#xD;
             or a non-interventional clinical study will be considered on a study-by-study basis&#xD;
             and in discussion with the relevant Chief Investigators and Sponsors and industrial&#xD;
             collaborators.&#xD;
&#xD;
          8. Co-enrolment involving non-interventional research (including questionnaire or tissue&#xD;
             only studies) will be allowed provided this is not expected to affect the outcomes of&#xD;
             both studies or place undue burden upon participants and their families.&#xD;
&#xD;
          9. Female patients who are able to become pregnant (or are already pregnant or&#xD;
             lactating). However, those patients who are of child bearing potential and have a&#xD;
             negative serum or urine pregnancy test before enrolment and agree to use two forms of&#xD;
             contraception (one effective form plus a barrier method [oral, injected or implanted&#xD;
             hormonal contraception and condom; intra-uterine device and condom; diaphragm with&#xD;
             spermicidal gel and condom]) or agree to sexual abstinence*, effective from the first&#xD;
             administration of camostat, throughout the trial and for 28 days afterwards are&#xD;
             considered eligible.&#xD;
&#xD;
             (*Abstinence is only considered to be an acceptable method of contraception when this&#xD;
             is in line with the preferred and usual lifestyle of the subject. Periodic abstinence&#xD;
             [e.g. calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are&#xD;
             not acceptable methods of contraception.)&#xD;
&#xD;
         10. Male patients with partners of child-bearing potential (unless they agree to take&#xD;
             measures not to father children by using a barrier method of contraception [condom&#xD;
             plus spermicide] or to sexual abstinence* effective from the first administration of&#xD;
             camostat, throughout the trial and for 28 days afterwards. Men with partners of&#xD;
             child-bearing potential must also be willing to ensure that their partner uses an&#xD;
             effective method of contraception for the same duration for example, hormonal&#xD;
             contraception, intrauterine device, diaphragm with spermicidal gel or sexual&#xD;
             abstinence). Men with pregnant or lactating partners must be advised to use barrier&#xD;
             method contraception (for example, condom plus spermicidal gel) to prevent exposure of&#xD;
             the foetus or neonate.&#xD;
&#xD;
             (*Abstinence is only considered to be an acceptable method of contraception when this&#xD;
             is in line with the preferred and usual lifestyle of the subject. Periodic abstinence&#xD;
             [e.g. calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are&#xD;
             not acceptable methods of contraception.)&#xD;
&#xD;
         11. Significant cardiovascular disease (as assessed via the participant's medical record&#xD;
             and history) as defined by:&#xD;
&#xD;
               1. History of congestive heart failure requiring therapy (New York Heart Association&#xD;
                  [NYHA] III or IV)&#xD;
&#xD;
               2. History of unstable angina pectoris or myocardial infarction up to 6 months prior&#xD;
                  to trial entry&#xD;
&#xD;
               3. Presence of severe valvular heart disease&#xD;
&#xD;
               4. Presence of a ventricular arrhythmia requiring treatment&#xD;
&#xD;
        Known allergic reactions to components of camostat e.g., lactose intolerance&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kevin Dhaliwal, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Edinburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chawton Park Surgery</name>
      <address>
        <city>Alton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Edinburgh</name>
      <address>
        <city>Edinburgh</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Church Avenue Medical Group</name>
      <address>
        <city>Harrogate</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oxford University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Oxford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Trafalgar Medical Practice</name>
      <address>
        <city>Portsmouth</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Preston Lantern Centre</name>
      <address>
        <city>Preston</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clarence Medical Centre</name>
      <address>
        <city>Rhyl</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Velindre Cancer Centre</name>
      <address>
        <city>Wales</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eynsham Medical Centre</name>
      <address>
        <city>Witney</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/spike-1-covid-19/</url>
    <description>A lay summary of the trial on the Health Research Authority website</description>
  </link>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>June 25, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>June 10, 2022</last_update_submitted>
  <last_update_submitted_qc>June 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>Coronavirus Infections</keyword>
  <keyword>Respiratory Tract Infections</keyword>
  <keyword>Pneumonia, Viral</keyword>
  <keyword>Virus Diseases</keyword>
  <keyword>Camostat</keyword>
  <keyword>Protease Inhibitors</keyword>
  <keyword>Enzyme Inhibitors</keyword>
  <keyword>Serine Proteinase Inhibitors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gabexate</mesh_term>
    <mesh_term>Camostat</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>January 5, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04455815
org study id: CRUKD/20/002
secondary id: 2020-002110-41
nct id: NCT04455815
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of camostat related AEs and SAEs.
time frame: Days 1 - 28
description: Number of camostat related AEs and SAEs
measure: Number of AEs by severity grade
time frame: Days 1 - 28
description: Number of AEs by severity grade (mild, moderate, severe)
measure: PK parameter Maximum concentration (Cmax) of 4-(4-Guanidinobenzoyloxy)phenylacetic acid (GBPA).
time frame: Days 7 and 14
description: Maximum concentration (Cmax) of GBPA as assessed by population estimates from population PK analysis
measure: PK parameter time to maximum concentration (Tmax) of GBPA, as assessed by population estimates from population PK analysis.
time frame: Days 7 and 14
description: Time to maximum concentration (Tmax) of GBPA, as assessed by population estimates from population PK analysis
measure: PK parameter area under the curve (AUC) of GBPA
time frame: Days 7 and 14
description: Area under the curve (AUC) of GBPA, as assessed by population estimates from population PK analysis
measure: PK parameter to confirm half-life (T1/2) of GBPA
time frame: Days 1 - 28
description: Half-life (T1/2) of GBPA as assessed by population estimates from population PK analysis
measure: Number of community patients admitted to hospital due to COVID-19
time frame: Days 1 - 28
description: Number of community patients admitted to hospital due to COVID-19
measure: Number of oxygen free days
time frame: Days 1 - 28
description: Number of oxygen free days
measure: Number of ventilator - free days
time frame: Days 1 - 28
description: Number of ventilator - free days
measure: Time to worst point on the scale or deterioration of two points or more (from randomisation) on 9 point category ordinal scale ranging from '0 - Uninfected, no clinical or virological evidence of infection' to '8 - Death'
time frame: Days 1 - 28
description: Median time and range to worst point on the scale or deterioration of two points or more (from randomisation) on 9 point category ordinal scale. The scale was described in the protocol as follows: '0 - Uninfected, no clinical or virological evidence of infection, 1 - Ambulatory, no limitation of activities, 2 - Ambulatory, limitation of activities, 3 - Hospitalised - mild disease, no oxygen therapy, 4 - Hospitalised - mild disease, oxygen by mask or nasal prongs, 5 - Hospitalised - severe disease, non-invasive, ventilation or high-flow oxygen, 6 - Hospitalised - severe disease, intubation and mechanical ventilation, 7 - Hospitalised - severe disease, ventilation and additional organ support - vasopressors, renal replacement therapy (RRT), extracorporeal membrane oxygenation (ECMO), 8 - Death'
arm group label: Camostat
arm group type: Experimental
description: Patient to receive treatment with camostat tablets, 200mg four times daily (qds) for 14 days.
arm group label: Control arm
arm group type: No Intervention
description: Patient to receive best supportive care.
intervention type: Drug
intervention name: Camostat
description: Patient to receive treatment with camostat tablets, 200mg four times daily (qds) for 14 days.
arm group label: Camostat
other name: Camostat mesylate
other name: Camostat mesilate
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kevin Dhaliwal, Professor
role: Principal Investigator
affiliation: University of Edinburgh
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United Kingdom
url: https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/spike-1-covid-19/
description: A lay summary of the trial on the Health Research Authority website
responsible party type: Sponsor
mesh term: Infections
mesh term: COVID-19
mesh term: Gabexate
mesh term: Camostat
sharing ipd: No
submitted: January 5, 2023