CST-8 Participant Information

Phase I Platform Study to Determine the Recommended Phase II dose and to Evaluate the Safety and Efficacy of Antiviral Combination of Molnupiravir and Paxlovid® for the Treatment of COVID-19

Why is this research being done?

You have suspected or confirmed COVID-19, which is caused by the SARS-CoV-2 coronavirus.

This Study is the first time both study drugs are being given to people with Covid-19 as a combination of antivirals. Each antiviral is separately licensed as treatment for COVID-19.

Molnupiravir has been approved as treatment for SARS-CoV-19 by the MHRA in November 2021 as it has shown in several trials to be safe and effective at reducing the risk of hospitalisation and death in people displaying up to moderate COVID-19 symptoms. Clinical trials indicate the most effective time for molnupiravir is during the early stages of infection.

Paxlovid® consists of nirmatrelvir and ritonavir. Paxlovid® is an antiviral medicine used for treating mild-to-moderate COVID-19. COVID-19 is caused by a virus. Paxlovid® stops the virus multiplying in cells and this stops the virus multiplying in the body. This can help your body to overcome the virus infection and may help you get better faster.

A full description of the risks associated with the study drugs would be provided by the research site as part of the screening, eligibility and consent process.

There are limited drugs of proven value against COVID-19 although there are several which may turn out to be helpful when added to the usual standard of care. This study aims to find out whether this combination of drugs are of any help.

What is the purpose of this study?

The AGILE study aims to assess several different treatments that may be useful for patients with COVID-19. These treatments have been recommended for testing by a team of experts (The Coronavirus Treatment Acceleration Program (CTAP)) based on strict criteria.

The aims of this Study are to determine, in people with COVID-19, the following:

To determine the safety and tolerability of dose combinations of molnupiravir and Paxlovid®

Establish feasibility for the combination of drugs to be trialled in a larger late phase clinical trial platform.
To evaluate preliminary evidence of whether the combination of drugs are effective in treating the virus.
To understand how each drug behaves within the combination.

At present, we don’t know whether this combination of drugs will be effective in treating COVID-19, although there is promising research showing both drugs to individually be effective in treating patients with early mild disease. Both drugs have undergone vigorous safety review in earlier studies. Side effects are any unwanted, or sometimes unpleasant reactions that may result from taking a drug or having a procedure. More information about this is explained further on in this information sheet.

The AGILE study for CST 8 – Molnupiravir and Paxlovid® is a Phase I study only.

What is a Phase I Clinical Trial?

Phase I studies are to establish the dosing levels that are safe and effective to use in patients with COVID-19. A small group of patients will participate in the phase I component of the study where they will receive different doses of the combined drugs. The doses chosen have already been used safely in previous studies and both drugs have already been licensed by the MHRA (Medicines and Healthcare products Regulatory Agency) in the UK.

Design of the study:

If you are given the study drugs, you will be administered a total of 10 doses of study drugs (over 5 days), with dosing of twice daily to take home for administration.

Dose:

The doses of the drugs you will be taking are molnupiravir 800mg (4 x 200mg capsules) twice a day for a total of 5 days (or 10 doses) to complete the course, alongside Paxlovid®

(2 x 150mg nirmatrelvir and 1 x 100mg ritonavir) twice daily for 5 days (10 doses). Before receiving the study drugs, you will be informed of your dosing schedule.

The dose levels of study drugs will be based on the results of the previously completed parts of the study. It is planned start treatment doses at the licensed doses for both drugs which have been tested to be considered safe for use in Covid-19. The dose levels to be studied in the remaining groups will depend upon the results from the previous groups but patients will have the potential to reduce the molnupiravir dose to either 600mg twice daily or 400mg twice daily if any adverse effects are found due to molnupiravir.

The study compares the study drugs with routine standard of care. The treatment group will receive the combination of molnupiravir and Paxlovid® medication and the control group will receive the standard of care as explained by your doctor. This means that some patients will receive the study drugs and some will not. Whether you receive study drugs will be determined by a process called randomisation. The randomisation for this phase of the study will be done in a 2:1 ratio. This means that for every 3 patients who enter the study, 2 patients will receive the study drugs, 1 patient will receive normal standard of care. The only way to make sure that the two groups of patients are as similar as possible is to have your treatment decided by chance. Therefore, neither you nor your doctors can choose which of these options you will be allocated.

What the study involves:

During the Study, the visits will take place as per table outlined below. These visits will include the Screening visit, a baseline visit (which may be on the same day as the screening visit), clinic visits at Day 3, 5, 11, as well as home swab tests (using kits provided) at Day 2 and Day 4 and a telephone call follow up at Day 29. You will also be contacted on Days 2 and 4 to ensure you have completed your home swab and taken your medication (if applicable).

Are there any financial costs or payments?

You will be paid the total amount of £650. In addition to being reimbursed travel expenses for any clinic visits. Please discuss any necessary travel arrangements with the study team prior to the visit.

What will happen to the results of the research study?

When the study ends, the results will be analysed and presented at national/international meetings before being published in a medical journal. The confidentiality of all patients will be maintained. You will not be personally identified in any reports or publications resulting from the study. If you would like to obtain a copy of the published results, please ask your doctor.

A detailed Participant Information Sheet and Consent Form would be provided by the research team at the clinic for discussion prior to screening you for eligibility.

Do I have to take part?

Taking part in the study is entirely voluntary and if you do not wish to participate this will not affect the standard of your treatment in any way. It is up to you to decide whether or not to take part. If you do decide to take part you will be given this information sheet to keep and asked to sign a consent form.

If you decide to take part you are still free to withdraw at any time without giving a reason. This will not affect the standard of care you receive.

If you do not wish to take part in this study, you will be offered whatever treatment your doctor thinks is best for you.

Visit Summary

	Screening	Day 1	Day 2	Day 3	Day 4	Day 5	Day 11	Day29
Visit Location	Clinic	Clinic	At Home	Clinic	At Home	Clinic	Clinic
Nose and Throat Swab	x	x	x	x	x	x	x
Blood Tests	x					x
Tear and Nasal Swab						x