Covid19
Conditions
Keywords
antiviral
Brief summary
The investigators are conducting a pilot trial where they will study safety, efficacy and compliance in a cohort of ambulatory patients in the Ghent region with confirmed COVID-19 infection, in both an early stage of disease, defined as less than 5 days of symptoms and who at presentation do not meet any criteria for hospitalisation as well as asymptomatic individuals with a PCR CT value below 30. The primary endpoint is to assess the efficacy of the drug in terms of change from day 0 to day 5 in respiratory (oropharyngeal swab RT-PCR) log10 viral load. The aim of the study is to assess whether Camostat, a serine protease inhibitor available in an oral formulation has the potential to be studied as an antiviral drug in a large scale ambulatory setting to prevent transmission by decreasing viral load, to prevent symptoms after exposure (PEP) in asymptomatic individuals or to prevent disease progression in the occurrence of early symptomatology.
Detailed description
Core study After eligibility assessment participants will be randomized and will receive the study drugs. We will define D1 as the first dose of the medication which can be the morning, midday or evening dose. They will be treated for 5 consecutive days. In patients with a positive PCR at D5 (CT value with threshold below 30) and/or presence of clinical symptoms after exclusion of hospitalization criteria (flowchart emergency department appendix 4), the treatment will be extended up to D10 at the same dosage in both treatment arms for 5 consecutive days: D6 and D10). Follow-up will be as follows: * D1-\>D14 (D28): The study participants will be asked to fill in daily questionnaires assessing symptoms (cfr daily self-score). They will receive a kit enabling to monitor heart rate (HR), respiratory rate (RR), temperature and oxygen saturation 3 times per day (every 4-8 hours, preferentially at the timing of medication intake at D1 to D5 or D10). * Compliance and tolerance will be assessed during the treatment period, D0-\>D5 (or D0-\>D10 if the treatment is prolonged). * During the study D1-D28: If indicated in the opinion of the investigator, a physical exam and biochemistry will be performed through a consultation at the clinic. This can be requested at any time during the study based on clinical symptoms or signs. * Consultation at D0, D5, (D10) and D28 at our COVID consultation facility. This will be done by a study nurse and/or a study physician.
Interventions
DRUGCamostat
Standard of care (SOC) + Camostat mesilate (Foipan) 100mg 3 tablets 3 times a day for 5 consecutive days (D1-\>D5);
DRUGPlacebo
SOC + placebo 500 mg 3 tablets 3 times a day for five consecutive days (D1-\>D5).
Sponsors
University Hospital, Ghent
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
double blinded placebo controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Aged ≥18 * Willing to participate and fill out a daily symptom diary * Willing to take the parameters such as blood oxygenation and temperature * Willing to attend follow-up visits both by phone as at the clinic * Capable of understanding the commitment in the trial * Signed informed consent * Signs and symptoms suggestive of COVID disease in absence of hospitalization criteria as defined by the flowchart used at the emergency department of our institution (appendix 4), present for maximum 5 days and confirmed by PCR. * OR documented COVID-19 infection by PCR with CT value below the threshold of 30 in asymptomatic individuals. * For women of childbearing potential\*: they should be willing to use highly effective method of contraception during treatment and until the end of study defined as having a failure rate of less than 1% per year when used consistently and correctly. Such methods include: * combined (estrogen and progestogen containing) hormonal contraception * associated with inhibition of ovulation: oral, intravaginal or transdermal * progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable or implantable * intrauterine device (IUD) and intrauterine hormone-releasing system ( IUS) * bilateral tubal occlusion * vasectomised partner * sexual abstinence * For men of reproductive potential\*\*: condom should be used as contraception during treatment and until the end of study when having a partner of childbearing potential * a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. * a man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy.
Exclusion criteria
* Inability to make a decision to participate * Pregnant or breast feeding * Inability to take oral medication * Inability to provide informed written consent * Known hypersensitivity towards Camostat or other Serine protease inhibitors * Any condition that, in the Investigator's opinion, prevents adequate compliance with study therapy. * Any COVID infection at risk for hospitalisation as described in the emergency department flowchart (cfr appendix 4) * With regard to exclusion of women of child-bearing potential, women who tell us they know they are pregnant are excluded. All women of child-bearing potential who test positive for pregnancy by urine test at first visit are excluded. * Severe chronic pancreatitis requiring suction of gastric juice, fasting or abstention from drinking * Postoperative reflux oesophagitis due to reflux or gastric juice * Postoperative reflux oesophagitis (if improvement of symptoms is not observed).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy in Terms of Viral Load or Surrogate After 5 Days of Treatment | 5 days | The primary endpoint is to assess the efficacy of the drug in terms of change from day 0 to day 5 in respiratory (oropharyngeal swab RT-PCR) surrogate market CT value. Higher values equate to better outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Clinical Improvement (in at Least 1 Point on the 5-point Likert Scale) of 5 Most Self-reported Symptoms | 28 days | Symptoms were daily measured by means of a self-report questionnaire. The top 5 self-reported symptoms during the whole study period were determined. Time to clinical improvement of these 5 most self-reported symptoms were compared between the camostat and placebo group. Additionally, potential risk factors are studied in order to influence clinical improvement. |
| Neutralizing Antibodies (NAbs) at Visit 28 | 28 days | The 50% neutralizing antibody titer (NT50) was compared between the camostat and placebo group |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Camostat camostat 100mg 3 tablets 3x/day D1-\>D5 (+ possible extension D6-\>D10)
Camostat: Standard of care (SOC) + Camostat mesilate (Foipan) 100mg 3 tablets 3 times a day for 5 consecutive days (D1-\>D5);
Camostat: Standard of care (SOC) + Camostat mesilate (Foipan) 100mg 3 tablets 3 times a day for 5 consecutive days (D6-\>D10); | 61 |
| Placebo Placebo 3 tablets 3x/day D1-\>D5 (+ possible extension D6-\>D10)
Placebo: SOC + placebo 500 mg 3 tablets 3 times a day for five consecutive days (D1-\>D5).
Placebo: SOC + placebo 500 mg 3 tablets 3 times a day for five consecutive days (D6-\>D10). | 29 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Camostat | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 38 years | 37 years | 38 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 59 Participants | 29 Participants | 88 Participants |
| Region of Enrollment Belgium | 61 participants | 29 participants | 90 participants |
| Sex: Female, Male Female | 33 Participants | 16 Participants | 49 Participants |
| Sex: Female, Male Male | 28 Participants | 13 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 61 | 0 / 29 |
| other Total, other adverse events | 59 / 61 | 23 / 29 |
| serious Total, serious adverse events | 3 / 61 | 1 / 29 |
Outcome results
Primary
Efficacy in Terms of Viral Load or Surrogate After 5 Days of Treatment
The primary endpoint is to assess the efficacy of the drug in terms of change from day 0 to day 5 in respiratory (oropharyngeal swab RT-PCR) surrogate market CT value. Higher values equate to better outcomes.
Time frame: 5 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Camostat | Efficacy in Terms of Viral Load or Surrogate After 5 Days of Treatment | 2.34 number of cycles | Standard Deviation 10.27 |
| Placebo | Efficacy in Terms of Viral Load or Surrogate After 5 Days of Treatment | 2.08 number of cycles | Standard Deviation 11.14 |
p-value: 0.511Mixed Models Analysis
Secondary
Neutralizing Antibodies (NAbs) at Visit 28
The 50% neutralizing antibody titer (NT50) was compared between the camostat and placebo group
Time frame: 28 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Camostat | Neutralizing Antibodies (NAbs) at Visit 28 | NT50 higher than the detection limit (≥40) | 38 Participants |
| Camostat | Neutralizing Antibodies (NAbs) at Visit 28 | NT50 below the detection limit (<40) | 23 Participants |
| Placebo | Neutralizing Antibodies (NAbs) at Visit 28 | NT50 higher than the detection limit (≥40) | 22 Participants |
| Placebo | Neutralizing Antibodies (NAbs) at Visit 28 | NT50 below the detection limit (<40) | 7 Participants |
Secondary
Number of Patients With Clinical Improvement (in at Least 1 Point on the 5-point Likert Scale) of 5 Most Self-reported Symptoms
Symptoms were daily measured by means of a self-report questionnaire. The top 5 self-reported symptoms during the whole study period were determined. Time to clinical improvement of these 5 most self-reported symptoms were compared between the camostat and placebo group. Additionally, potential risk factors are studied in order to influence clinical improvement.
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Camostat | Number of Patients With Clinical Improvement (in at Least 1 Point on the 5-point Likert Scale) of 5 Most Self-reported Symptoms | 22 Participants |
| Placebo | Number of Patients With Clinical Improvement (in at Least 1 Point on the 5-point Likert Scale) of 5 Most Self-reported Symptoms | 13 Participants |
p-value: 0.92195% CI: [0.48, 1.942]Regression, Cox