E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary aim of the trial is to determine if nasal niclosamide reduces the risk of confirmed symptomatic COVID-19 infection in vulnerable renal and immunosuppressed patients participating in the study. |
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E.2.2 | Secondary objectives of the trial |
The trial also aims to: 1) Determine if nasal niclosamide increases the time to confirmed SARS-Cov-2 infection from the date of randomisation including incidental asymptomatic cases in the vulnerable populations taking part in the study. 2) Determine if nasal niclosamide increases the proportion of individuals with antibodies to SARS-Cov-2 at the end of the trial in the vulnerable populations taking part in the study. 3) Determine the safety of nasal niclosamide in this patient population 4) Determine if nasal niclosamide reduces mortality and severity of COVID-19 infection in the vulnerable populations taking part in the study. 5) Determine if nasal niclosamide reduces the occurrence of other influenza infections in the vulnerable populations taking part in the study. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
ο Be aged 18 years or older ο Have given written informed consent to participate ο Be a member of one of the following vulnerable patients populations - Dialysis – including in centre haemodialysis, home haemodialysis and peritoneal dialysis - Kidney transplant receiving at least one of the immunosuppressive medications listed below - Vasculitis (according to Chapel Hill Consensus Conference 2012 definitions) receiving at least one of the immunosuppressive medications listed below - Glomerulonephritis receiving at least one of the immunosuppressive medications listed below
Ciclosporin Tacrolimus Azathioprine Mycophenolate Mofetil or Mycophenolic Acid Belatacept Methotrexate Tocilizumab Abatacept Leflunomide Prednisolone current dose > 20mg daily for 8 weeks Anti-TNF (infliximab, adalimumab, etanercept) Belimumab Cyclophosphamide (within the last 6 months) Rituximab (in the last 12 months) Alemtuzumab (in the last 12 months)
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E.4 | Principal exclusion criteria |
ο Inability to provide informed consent or to comply with trial procedures ο COVID-19 at time of enrolment – either positive SARS CoV-2 swab (PCR) or symptoms highly suggestive of COVID-19 infection ο Previous confirmed COVID-19 ο Known chronic liver disease or hepatic dysfunction as evidenced by ALT or AST > 3x upper limit of the normal range ο Allergy to niclosamide or history of significant adverse reaction to niclosamide or related compounds, or to any of the excipients used ο Significant structural nasal disease in the opinion on the investigator ο Pregnant, trying to conceive, unwilling to use contraception or breastfeeding ο Participation in another prophylactic or vaccine trial against COVID-19
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome for PROTECT is the time to confirmed symptomatic COVID-19 infection. The risk of confirmed symptomatic COVID-19 infection in the niclosamide arm compared to the placebo arm will be summarised in terms of hazard ratio and infection rates after 3, 6 and 9 months.
Definition of the primary outcome event
The primary outcome event is defined as the presence of both • PCR confirmed SARS-CoV2 and • One or more symptoms in keeping with COVID-19, including: o Respiratory (Cough +/- sputum and shortness of breath) o Constitutional (Pyrexia/chills, myalgia/arthralgia, fatigue, rash, headache, confusion) o Gastrointestinal (nausea/vomiting, diarrhoea, abdominal pain, loss of appetite)
The date (time) of the primary outcome event is defined as the date of the confirmed COVID-19 test.
The primary endpoint will be censored at the date of last treatment administered for participants who have not experienced the primary outcome event.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 38 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 16 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 16 |