PROphylaxis for paTiEnts at Risk of COVID-19 infecTion -V

  • STATUS
    Recruiting
  • End date
    Mar 11, 2022
  • participants needed
    1500
  • sponsor
    Cambridge University Hospitals NHS Foundation Trust
Updated on 11 May 2021

Summary

COVID-19 (novel coronavirus-induced disease) was declared a global pandemic by the WHO on 11th March 2020. Currently there are no drugs proven to prevent COVID-19 or to reduce the severity of illness if given as prophylaxis. Although vaccines are now available, there remains a need for other prophylactic agents until vaccine use becomes widespread globally and effectiveness and durability is established, particularly in immunocompromised individuals. Efforts are underway to repurpose established drugs with well understood drug interactions and safety profiles.

The PROTECT-V is a platform clinical trial and aims to enrol patients at particularly high risk of COVID-19 and its complications. the first agent to be tested is nasal nicolosamide treatment as a prophylactic measure that either might prevent the disease from occurring or may reduce the number of cases where the disease becomes serious or life-threatening. PROTECT-V is a randomised, double blind, placebo controlled event driven trial.

Patients will be eligible for recruitment to the trial if they fall within one of the following vulnerable populations: a)patients receiving dialysis, b)kidney transplant patients, c)patients with vasculitis or glomerulonephritis.

Approximately 1500 participants will be randomised to active treatment or placebo, stratified by PROTECT sub-population, age and participating sites. Enrolment to the trial will be via an online platform following informed consent with a face to face screening visit. Subsequent assessments, aside from an in person end of trial visit, will be done via email or telephone together with utilising the routine collected health data thus reducing the burden to participants as well as reducing their exposure to COVID-19.

Description

The first arm of PROTECT-V is a double-blind placebo controlled trial of prophylactic niclosamide (UNI911) against SARS-CoV2 infection in vulnerable populations. The trial will enrol vulnerable patients with kidney or autoimmune diseases, including patients in receipt of dialysis, kidney transplant recipients, individuals with vasculitis and glomerular disease receiving immunosuppression.

Participant Identification and Consent

Potential participants can be identified via a number of avenues including advertisements, word of mouth, trial specific invitation letter, face to face and existing cohort studies.

  • The PROTECT website will contain the information from the approved patient information sheet.
  • Additional information, including the detailed Participant Information Sheets will be available from the local site study team and on the study website.

Consent will be obtained by the Principal Investigator at each trial site or by a suitably qualified and delegated health professional and member of the research team at each site.

Screening Assessment

The screening and baseline visits may be readily combined in those patients who agree to participation in the trial. Screening will be conducted at participating sites. Participants attending the screening visit will be given a unique ID number to be used in all CRFs.

All eligible participants who proceed to randomisation will be provided with the trial specific Patient ID Card which includes details of the trial IMP and contact details of the local study team and Sponsor.

Randomisation

The PI or suitably qualified and delegated member of the study team will confirm the eligibility of a participant by entering their screening data into the PROTECT eCRF web portal. Once the full screening details have been entered and eligibility confirmed, the participant will be randomised.

Randomisation 1:1 to niclosamide or placebo nasal spray will be carried out using a web-based randomisation system (Sealed Envelope) accessible via password-protected access. Randomisation will be stratified by PROTECT disease sub-group, age and site using a stratified block randomisation method.

Immediate allocation of treatment will be performed, with documentation of the decision in a blinded confirmatory email. The system will allocate the participant treatment pack code(s) which will relate uniquely to the first supply of IMP. Different treatment pack code(s) for every subsequent order of IMP supply will be allocated by the randomisation system.

Participants and site teams will remain blinded to treatment allocation. The allocated blinded IMP supply will be collected by participants when possible or sent at least 3-monthly to their home by courier.

Trial assessments

The following sections describe the schedule of assessments that will be completed by participants. Further details are available in the trial procedures manual (TPM).

Research-specific face-to-face visits as part of their trial participation will be kept to a minimum and aligned with routine clinical follow up whenever possible, as healthcare contact needs to be minimised during the COVID-19 pandemic. Therefore, telephone follow-up and self-reporting of symptoms will be utilised.

The first 70 dialysis participants will be included in a Population PK cohort. These participants will have additional assessments.

Data on the primary endpoint (COVID-19 infection) will be captured on a monthly basis via linkage with PHE and by direct reporting by sites or by participants. All subsequent assessments will consist of self-completed questionnaires online or through telephone calls from the local trial team. Data will be collected in real time through linkage with NHS Digital or equivalent, ONS, ICNARC or other routine data sources as necessary. Data on death will be reported by sites or obtained via linkage.

Telephone consultations - weeks 1,2,3, 4 and 6 (3 days)

Participants will be telephoned by the local PI or research nurse and asked about the treatment received and symptoms suggestive of potential side effects of niclosamide/placebo or of COVID-19 infection, once every week for the first 4 weeks and then again on the sixth week of the trial. If concerns are raised about potential side effects of niclosamide/placebo, the information will be reviewed by the PI and a decision made whether to continue IMP. Participants will be asked to keep a diary of IMP administration with reasons for any missed doses. This will initially be provided in paper format but will also be incorporated in the PROTECT smartphone app to provide participants with the option of electronic IMP diaries if they prefer. The app will also allow participants to set reminders and confirm when a given dose has been taken.

Two-Weekly self-reporting - week 8 onwards

Participants will be asked to complete a short questionnaire regarding COVID-19 self-assessment/reporting and potential side effects of niclosamide/placebo, once every two weeks during trial conduct via email (linking to the PROTECT data portal), via the PROTECT smartphone app, in paper form via mail, or via telephone interview. Participants receiving in centre haemodialysis may be assessed during their dialysis sessions. The intention of two-weekly self-reporting is to provide participants with the opportunity to

  • indicate any symptoms suggestive of COVID-19 infection and/or positive result of COVID-19 test,
  • adverse effects of IMP administration,
  • report new concomitant medications
  • report vaccination against COVID-19

If a participant has not submitted data electronically for a period of 6 weeks, they will be contacted by the local study team for a telephone interview to minimise loss to follow up.

Pharmacokinetic Assessment

Population Pharmacokinetic (PK) assessment will be conducted in the first 30 participants receiving niclosamide for safety purposes, to exclude the unlikely possibility of accumulation of niclosamide during the course of the trial in patients receiving dialysis only. Given that participants and investigators will be blinded to treatment allocation, PK samples will maintain blinding by including the first 70 dialysis patients in the PK sampling cohort. Including 70 participants is necessary to exclude the scenario where a chance imbalance in treatment allocation early in the study results in fewer than 30 participants allocated to niclosamide. These participants will be identified as the 'PK Cohort'.

The PK Cohort will have a blood sample taken at the start of dialysis, before taking the IMP. PK Cohort participants receiving dialysis in the afternoon or evening may take the morning dose of IMP, but should omit the evening dose until the PK sample has been obtained. The procedure for obtaining PK samples is described in the trial procedures manual.

PK samples will be obtained 7 (3) days after the date of first IMP dose (or coincident with the 3rd dialysis session post-dating randomisation), 14 (3) days and 21 (3) days after date of first dose.

Unscheduled assessment - "suspected COVID-19 infection"

Should an individual develop symptoms suggestive of COVID-19 infection, which are listed in the Participant Information Sheet, they must arrange a COVID-19 test via the NHS Test and Trace system, booking online or calling 119 to organise an appointment at their nearest testing facility.

Participants should continue taking trial medication until advised to stop by a member of the trial team or admitted to hospital. Participants must follow the current public health guidance for "suspected COVID-19 infection" at that time.

Final safety assessment

PROTECT is an event driven trial. The anticipated median treatment duration per participant is 6-9 months. However, the trial may conclude while some participants are in the trial for less than 6 months if the required number of events are observed. Upon completion of the trial, participants will be notified by email, PROTECT smartphone application or by telephone depending on participant preference. Participants will be asked to stop taking IMP and acknowledge receipt of end-of-trial notification.

A final safety assessment will be conducted in person, 4-6 weeks after the final treatment (defined as the day of notification of end of trial or date of last dose administered). Participants will be asked to return all completed medication diaries and IMP bottles for compliance assessment at this visit. Participants will be asked a series of questions to identify any additional adverse events or adverse reactions experienced since their last follow up assessment and a blood sample will be taken for a SARS-CoV2 total antibody assay, to detect asymptomatic cases of COVID-19 infection.

Duration of study

PROTECT is an event driven trial. The median anticipated treatment period is 6 months with a maximum treatment period of 9 months. Last follow-up visit will be scheduled 4-6 weeks after last dose.

Treatment withdrawal

Participants will be withdrawn at the discretion of the PI/CI if continuation in the trial is deemed to be against the participant's best interest.

Treatment will be withdrawn if:

  • Participants become pregnant
  • Participant is hospitalized for COVID-19
  • Participant experiences unacceptable drug reaction such as:
  • Moderate or severe pain in the nose
  • Severe itch or burning sensation in the nose
  • Spontaneous nose bleeding as result of nasal ulceration
  • Oedema that prevents breathing through the nose Participants who have been withdrawn from the trial treatment and are experiencing ongoing toxicity will be followed up until the adverse reaction comes to its conclusion. In the event of a Participant being withdrawn from the trial treatment, they will continue to receive the most appropriate standard of care treatment available under the guidance of their treating clinician.

Treatment period

Participants will continue allocated treatment until one of the following occurs:

  1. The required number of the primary outcome events have occurred
  2. The participant is hospitalised with COVID-19 (see 4.10.2.)
  3. 28 Days after a diagnosis of COVID-19 if hospitalisation is not required

Diagnosis of COVID-19

Participants may receive a diagnosis of COVID-19 during the course of participation in the trial, either as a result of routine testing or prompted by suggestive symptoms. Any participant diagnosed with COVID-19 should continue with their randomised treatment for 28 days after the date of diagnosis, unless hospitalised. Participants hospitalised with a diagnosis of COVID-19 should stop the randomised treatment immediately.

Details
Condition COVID19
Treatment Placebo, Niclosamide
Clinical Study IdentifierNCT04870333
SponsorCambridge University Hospitals NHS Foundation Trust
Last Modified on11 May 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Be aged 18 years or older
Have given written informed consent
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)

Exclusion Criteria

Inability to provide informed consent or to comply with trial procedures
COVID-19 at time of enrolment - either positive SARS CoV-2 swab (PCR) or symptoms highly suggestive of COVID-19 infection
Known chronic liver disease or hepatic dysfunction as evidenced by ALT or AST > 3x upper limit of the normal range
Allergy to niclosamide or history of significant adverse reaction to niclosamide or related compounds, or to any of the excipients used
Significant structural nasal disease in the opinion of the investigator
Pregnant, trying to conceive, unwilling to use contraception or breastfeeding
Participation in another interventional prophylactic or vaccine trial against COVID-19
Patients remain eligible for enrolment if they have received SARS-COV-2 vaccination as part of routine care
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note