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A Trial Looking at the Use of Camostat to Reduce Progression of Symptoms of Coronavirus (COVID-19) in People Who Have Tested Positive. (SPIKE-1)

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ClinicalTrials.gov Identifier: NCT04455815
Recruitment Status : Recruiting
First Posted : July 2, 2020
Last Update Posted : July 2, 2021
Sponsor:
Collaborator:
Latus Therapeutics
Information provided by (Responsible Party):
Cancer Research UK

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
COVID-19 Infection Drug: Camostat Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : September 25, 2020
Estimated Primary Completion Date : July 31, 2021
Estimated Study Completion Date : July 31, 2021

Arm Intervention/treatment
Experimental: Camostat
Patient to receive treatment with camostat tablets, 200mg four times daily (qds) for 14 days.
Drug: Camostat
Patient to receive treatment with camostat tablets, 200mg four times daily (qds) for 14 days.

No Intervention: Control arm
Patient to receive best supportive care.



Primary Outcome Measures :
  1. To further assess the safety and toxicity profile of camostat to support integration into a Phase III trial. [ Time Frame: Days 1 - 28 ]
    Number of camostat related AEs and SAEs by CTCAE Grade


Secondary Outcome Measures :
  1. To confirm PK parameter maximum concentration (Cmax) aligns with the established PK profile of camostat (4-(4-Guanidinobenzoyloxy) phenylacetic acid (GBPA)). [ Time Frame: Days 1 - 28 ]
    Cmax of GBPA as assessed by population estimates from population PK analysis.

  2. To confirm PK parameter time to maximum concentration (Tmax) aligns with the established PK profile of camostat (4-(4-Guanidinobenzoyloxy) phenylacetic acid (GBPA)). [ Time Frame: Days 1 - 28 ]
    Tmax of GBPA as assessed by population estimates from population PK analysis.

  3. To confirm PK parameter area under the concentration time curve (AUC) aligns with the established PK profile of camostat (4-(4-Guanidinobenzoyloxy) phenylacetic acid (GBPA)). [ Time Frame: Days 1 - 28 ]
    AUC of GBPA as assessed by population estimates from population PK analysis.

  4. To confirm PK parameter half-life (T1/2) aligns with the established PK profile of camostat (4-(4-Guanidinobenzoyloxy) phenylacetic acid (GBPA)). [ Time Frame: Days 1 - 28 ]
    T1/2 of GBPA as assessed by population estimates from population PK analysis.

  5. To assess the ability of camostat to reduce the requirement for COVID-19 related hospital admission in community patients with SARS-CoV-2 infection. [ Time Frame: Days 1 - 28 ]
    Number of community patients admitted to hospital due to COVID-19

  6. To evaluate the requirement for supplementary oxygen (non-invasive or mechanical invasive) in patients who have received camostat as treatment for SARS-CoV-2 infection. [ Time Frame: Days 1 - 28 ]
    Mean number of oxygen free days

  7. To evaluate the requirement for ventilation in patients who have received camostat as treatment for SARS-CoV-2 infection. [ Time Frame: Days 1 - 28 ]
    Mean number of ventilator-free days

  8. To evaluate efficacy of camostat by effect on COVID-19 related clinical improvement. [ Time Frame: Days 1 - 28 ]
    Mean time to worst point on the scale or deterioration of two points or more (from randomisation) on a 9-point category ordinal scale.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04455815


Contacts
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Contact: Kevin Dhaliwal, Professor 01312429180 Kev.Dhaliwal@ed.ac.uk

Locations
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United Kingdom
Chawton Park Surgery Recruiting
Alton, United Kingdom
Contact: Emma Bowen-Simpkins, Dr         
The University of Edinburgh Recruiting
Edinburgh, United Kingdom
Contact: Kevin Dhaliwal, Professor         
Church Avenue Medical Group Active, not recruiting
Harrogate, United Kingdom
Oxford University Hospitals NHS Foundation Trust Not yet recruiting
Oxford, United Kingdom
Contact: Tanya Baron, Dr         
Trafalgar Medical Practice Recruiting
Portsmouth, United Kingdom
Contact: Shruti Singh, Dr         
Preston Lantern Centre Recruiting
Preston, United Kingdom
Contact: Salman Karim, Dr         
Clarence Medical Centre Recruiting
Rhyl, United Kingdom
Contact: Selena Harris, Dr         
Velindre Cancer Centre Recruiting
Wales, United Kingdom
Contact: John Chester, Prof         
Eynsham Medical Centre Recruiting
Witney, United Kingdom
Contact: Emma Ladds, Dr         
Sponsors and Collaborators
Cancer Research UK
Latus Therapeutics
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Responsible Party: Cancer Research UK
ClinicalTrials.gov Identifier: NCT04455815    
Other Study ID Numbers: CRUKD/20/002
2020-002110-41 ( EudraCT Number )
First Posted: July 2, 2020    Key Record Dates
Last Update Posted: July 2, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Camostat
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypsin Inhibitors
Serine Proteinase Inhibitors