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

Summary

COVID-19 (SARS-CoV2 virus) 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, for whom vaccine responses may be suboptimal. Efforts are underway to repurpose established drugs with well understood drug interactions and safety profiles.

PROTECT-V is a platform trial to test prophylactic interventions against SARS-CoV2 infection in vulnerable patient populations at particularly high risk of COVID-19 and its complications, seeking to identify treatments that either might prevent the disease from occurring or may reduce the number of cases where the disease becomes serious or life-threatening.

In PROTECT-V, multiple agents can be evaluated on the same platform across vulnerable populations, with the option of adding additional treatments at later time points as these become available. The expectation is for as many sites as possible to recruit to all available trial treatments at any time, however, the platform structure and randomisation/data collection systems allow sites to open the trial treatment arms according to their capacity.

The trial opened with intranasal niclosamide and matched placebo, aiming to recruit 1500 vulnerable renal patients in February 2021. A parallel study protocol, was conducted in India, sponsored by The George Institute. Recruitment of around 750 Indian patients was completed in with the rest of the study arm recruitment in November 2022. The Niclosamide arm of the study was completed in June 2023.

The second agent, intranasal and inhaled ciclesonide and matched placebo, was meant to be added to the platform in mid-2022 in the same renal patient population however it was unable to be included due to other factor.

Sotrovimab and matched placebo have been added to the platform in August 2022 which aim to recruit approximately 800-1000 patients from the main study population with additional patient groups with primary immunodeficiency, any Haematology or Oncology patient who is currently receiving or has received chemotherapy or who is immunocompromised as a result of their disease or treatment, those with a diagnosis of an autoimmune or inflammatory disease receiving immunosuppression and also haematopoietic stem cell transplant recipients.

Conditions

• Covid19

Interventions

DRUG

Niclosamide

140μL of a 1% niclosamide ethanolamine solution in each nostril twice daily, equivalent to 1.4mg of niclosamide ethanolamine salt per nostril twice daily, approximately 12 hours apart. Total daily dose 5.6mg niclosamide ethanolamine salt (4.7mg free niclosamide acid). Treatment duration will be 6-9 months or up to 28 days after COVID-19 diagnosis unless hospitalised. Participants hospitalised with a diagnosis of COVID-19 should stop the randomised treatment immediately.

DRUG

Placebo

140μL of a matching placebo solution in each nostril twice daily. Treatment duration will be 6-9 months or up to 28 days after COVID-19 diagnosis unless hospitalised. Participants hospitalised with a diagnosis of COVID-19 should stop the randomised treatment immediately.

DRUG

Ciclesonide

Participants will be prescribed ciclesonide once daily, administered as follows: Two puffs (320 μg) inhaled via mouth sequentially One puff (160 μg) inhaled via nose Treatment duration will be 6-9 months or up to 28 days after COVID-19 diagnosis unless hospitalised. Participants hospitalised with a diagnosis of COVID-19 should stop the randomised treatment immediately.

DRUG

Placebo

Matched placebo: two puffs inhaled via mouth sequentially and one puff inhaled via nose. Treatment duration will be 6-9 months or up to 28 days after COVID-19 diagnosis unless hospitalised. Participants hospitalised with a diagnosis of COVID-19 should stop the randomised treatment immediately.

DRUG

Sotrovimab

There will be a single infusion of sotrovimab administered at the beginning of the study. 500mg of sotrovimab solution (8mL) will be diluted in 42mL of 0.9% sodium chloride and administered by intravenous infusion. 50mLs to be infused over 30 minutes with a 0.2 micrometre inline filter. Four vials will be required for a 2000 mg dose.

DRUG

Placebo

There will be a single infusion placebo, in the form of 100mL 0.9% sodium chloride, administered at the beginning of the study.

Sponsors & Collaborators

• Life Arc

  collaborator UNKNOWN

• Kidney Research UK (KRUK)

  collaborator UNKNOWN

• UNION therapeutics

  collaborator INDUSTRY

• Addenbrookes Charitable Trust

  collaborator OTHER

• GlaxoSmithKline

  collaborator INDUSTRY

• National Institute for Health Research, United Kingdom

  collaborator OTHER_GOV

• Cambridge University Hospitals NHS Foundation Trust

  lead OTHER

Principal Investigators

• Rona Smith, Dr · Cambridge University Hospitals NHS Foundation Trust

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-02-19

Primary Completion

2025-04-16

Completion

2025-04-16

Countries

• United Kingdom

Study Locations