COVID-19 InfectionPhase 2SPIKE-1NCT04455815
A Trial Looking at the Use of Camostat in People Who Have Tested Positive for Coronavirus (COVID-19) (SPIKE-1)
A Phase 2 study testing Camostat in people with COVID-19 Infection, run by Cancer Research UK at 9 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19 Infection
- What is being tested?
- Camostat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 9 sitesUnited Kingdom
- Study dates
- 23 Sep 2020to 3 Mar 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient willing and able to give informed consent
- Adults, 18 years of age and above
- Symptomatic COVID-19 infection
- Evidence of current COVID-19 infection from a validated assay
Who cannot join
- The patient may not enter the trial if ANY of the following apply:
- Significant electrolyte disturbance (e.g. hyperkalaemia, potassium > site specific upper limit of normal)
- Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) and/or Alkaline Phosphatase (ALP) ≥ 2.5 x ULN
- 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).
- 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)
- Known hypersensitivity to camostat
Show all 19Show fewer
- Platelet count <100 x 10^9/L
- 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.
- 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.
- 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.)
- 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.)
- Significant cardiovascular disease (as assessed via the participant's medical record and history) as defined by:
- History of congestive heart failure requiring therapy (New York Heart Association [NYHA] III or IV)
- History of unstable angina pectoris or myocardial infarction up to 6 months prior to trial entry
- Presence of severe valvular heart disease
- Presence of a ventricular arrhythmia requiring treatment
- Known allergic reactions to components of camostat e.g., lactose intolerance
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United Kingdom9 sites
Chawton Park Surgery
Alton
The Royal Infirmary of Edinburgh
Edinburgh
Church Avenue Medical Group
Harrogate
John Radcliffe Hospital
Oxford
Preston Lantern Centre
Preston
Clarence Medical Centre
Rhyl
Trafalgar Medical Practice
Southsea
Velindre Hospital
Wales
Eynsham Medical Centre
Witney
About this study
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.
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.
Read the 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.
- Conditions
- COVID-19 Infection
- Being tested
- Camostat
- Keywords
- COVID-19, Coronavirus Infections, Respiratory Tract Infections, Pneumonia, Viral, Virus Diseases, Camostat, Protease Inhibitors, Enzyme Inhibitors, Serine Proteinase Inhibitors
- Medical subject headings
- COVID-19, Coronavirus Infections, Respiratory Tract Infections, Pneumonia, Viral, Virus Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CamostatDrug
Also called Camostat mesylate, Camostat mesilate
Patient to receive treatment with camostat tablets, 200mg four times daily (qds) for 14 days.
| Study group | Role | What they receive |
|---|---|---|
| Camostat | Experimental | Patient to receive treatment with camostat tablets, 200mg four times daily (qds) for 14 days. Receives: Drug: Camostat |
| Control arm | No intervention | Patient to receive best supportive care. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Camostat Related AEs and SAEs.
Number of AEs and SAEs assessed as related to camostat by the Investigator.
Measured: Days 1 - 28
Number of AEs by Severity Grade
Number of AEs by Severity Grade (mild, moderate, severe)
Measured: Days 1 - 28
Secondary outcomes (8)
PK Parameter Maximum Concentration (Cmax) of 4-(4-Guanidinobenzoyloxy)Phenylacetic Acid (GBPA).
Maximum concentration (Cmax) of GBPA as assessed by population estimates from population PK analysis.
Measured: Days 7 and 14
PK Parameter Time to Maximum Concentration (Tmax) of GBPA
Time to maximum concentration (Tmax) of GBPA, as assessed by population estimates from population PK analysis.
Measured: Days 7 and 14
PK Parameter Area Under the Curve (AUC) of GBPA
Area under the curve (AUC) of GBPA, as assessed by population estimates from population PK analysis.
Measured: Days 7 and 14
PK Parameter to Confirm Half-life (T1/2) of GBPA
Half-life (T1/2) of GBPA as assessed by population estimates from population PK analysis
Measured: Days 1 - 28
Number of Community Patients Admitted to Hospital Due to COVID-19
Number of patients who were recruited in community healthcare settings who were subsequently admitted to hospital due to COVID-19.
Measured: Days 1 - 28
Number of Oxygen Free Days
Number of days from Day 1 that each patient did not supplementary oxygen (median and range).
Measured: Days 1 - 28
Number of Ventilator - Free Days
Number of days from Day 1 that each patient did not require ventilation (median and range).
Measured: Days 1 - 28
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'
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'
Measured: Days 1 - 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2020
- Study start23 Sep 2020
- Primary completion29 Nov 2021
- Study completion3 Mar 2022
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19 InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cancer Research UK
- Sponsor type
- University, hospital or other
- Collaborators
- Latus Therapeutics
- Responsible party
- Sponsor
- Investigators
- Kevin Dhaliwal, Professor, Principal investigator, The Royal Infirmary of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04455815
- Sponsor's protocol ID
- CRUKD/20/002
- Other IDs
- 2020-002110-41
- Acronym
- SPIKE-1
- Status last verified
- Dec 2023
- First submitted
- 25 Jun 2020
- Last updated
- 11 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual de-identified patient data will be shared with researchers whose proposed use of the data is approved by a review committee of the Sponsor.
Publications
Halford S, Wan S, Dragoni I, Silvester J, Nazarov B, Anthony D, Anthony S, Ladds E, Norrie J, Dhaliwal K; CDD SPIKE-1 Project Team. SPIKE-1: A Randomised Phase II/III trial in a community setting, assessing use of camostat in reducing the clinical progression of COVID-19 by blocking SARS-CoV-2 Spike protein-initiated membrane fusion. Trials. 2021 Aug 19;22(1):550. doi: 10.1186/s13063-021-05461-9.
PubMed 34412682
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04455815
- Acronym / sponsor ID
- SPIKE-1 / CRUKD/20/002
- Conditions
- COVID-19 Infection
- Keywords
- COVID-19, Coronavirus Infections, Respiratory Tract Infections, Pneumonia, Viral, Virus Diseases, Camostat, Protease Inhibitors, Enzyme Inhibitors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Cancer Research UKUniversity, hospital or other
- Collaborators
- Latus Therapeutics
- Study start
- 23 Sep 2020 (actual)
- Primary completion
- 29 Nov 2021 (actual)
- Study completion
- 3 Mar 2022 (actual)
- First posted
- 2 Jul 2020 (actual)
- Results
- Posted 11 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Camostat | Experimental | Drug: CamostatPatient to receive treatment with camostat tablets, 200mg four times daily (qds) for 14 days. |
| Control arm | No intervention | –Patient to receive best supportive care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patient willing and able to give informed consent
- Adults, 18 years of age and above
- Symptomatic COVID-19 infection
- Evidence of current COVID-19 infection from a validated assay
Key exclusion criteria (19 listed)
- Significant electrolyte disturbance (e.g. hyperkalaemia, potassium > site specific upper limit of normal)
- Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) and/or Alkaline Phosphatase (ALP) ≥ 2.5 x ULN
- 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).
- 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)
- Known hypersensitivity to camostat
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CamostatAlso: Camostat mesylate, Camostat mesilatePatient to receive treatment with camostat tablets, 200mg four times daily (qds) for 14 days. | Drug | Camostat |
Primary outcome
Number of Camostat Related AEs and SAEs.
Time frame: Days 1 - 28
Number of AEs and SAEs assessed as related to camostat by the Investigator.
Number of AEs by Severity Grade
Time frame: Days 1 - 28
Number of AEs by Severity Grade (mild, moderate, severe)
8 secondary outcomes
PK Parameter Maximum Concentration (Cmax) of 4-(4-Guanidinobenzoyloxy)Phenylacetic Acid (GBPA).
Time frame: Days 7 and 14
PK Parameter Time to Maximum Concentration (Tmax) of GBPA
Time frame: Days 7 and 14
PK Parameter Area Under the Curve (AUC) of GBPA
Time frame: Days 7 and 14
PK Parameter to Confirm Half-life (T1/2) of GBPA
Time frame: Days 1 - 28
Number of Community Patients Admitted to Hospital Due to COVID-19
Time frame: Days 1 - 28
Number of Oxygen Free Days
Time frame: Days 1 - 28
Number of Ventilator - Free Days
Time frame: Days 1 - 28
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 34412682Halford S, Wan S, Dragoni I, Silvester J, Nazarov B, Anthony D, Anthony S, Ladds E, Norrie J, Dhaliwal K; CDD SPIKE-1 Project Team. SPIKE-1: A Randomised Phase II/III trial in a community setting, assessing use of camostat in reducing the clinical progression of COVID-19 by blocking SARS-CoV-2 Spike protein-initiated membrane fusion. Trials. 2021 Aug 19;22(1):550. doi: 10.1186/s13063-021-05461-9.
- A lay summary of the trial on the Health Research Authority websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual de-identified patient data will be shared with researchers whose proposed use of the data is approved by a review committee of the Sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin Dhaliwal, Professor principal investigator
The Royal Infirmary of Edinburgh
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Camostat in people with COVID-19 Infection, run by Cancer Research UK at 9 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Camostat Related AEs and SAEs. (time frame: Days 1 - 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04455815, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2023.