Bronchopulmonary PK of AT-527 [COVID-19]
Research type
Research Study
Full title
A phase 1, open-label, randomised study in healthy subjects to assess the bronchopulmonary pharmacokinetics, safety and tolerability of AT-527, a potential treatment for COVID-19 (21-003)
IRAS ID
296498
Contact name
Arantxa Horga
Contact email
Sponsor organisation
Atea Pharmaceuticals Inc
Eudract number
2021-001021-49
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Research Summary
The study medicine (AT-527) is an experimental new medicine for treating infections with certain types of viruses, including the COVID-19 virus. Once the virus enters the body, it quickly replicates (‘makes copies of itself’) inside cells in the lung, causing a viral infection. Most people infected with COVID-19 have only mild illness and recover without medical treatment. But some people, particularly older people or those with existing health problems can become seriously ill. The main symptoms of COVID-19 are: fever; dry cough; loss of/change in the sense of smell or taste; tiredness; and aching muscles.
We’ll give up to 24 healthy participants, aged 18-65 years, repeated doses of the study medicine. We aim to find out it’s blood levels after dosing and whether it has any side effects after repeated dosing. In particular, we’ll do a procedure called bronchoscopy, to look into the lungs and take samples of lung fluid.
Participants will take up to 2 weeks to finish the study. They’ll make two outpatient visits and stay on the ward for 4 nights in a row.
A pharmaceutical company called Atea Pharmaceutical Inc is funding the study.The study will take place at 1 centre in London.
Summary of Results
Why did we do the study?
The study medicine (AT-527) is an experimental new medicine for the treatment of infections with certain types of viruses, including the COVID-19 virus. Once a virus enters the body, it quickly multiplies (‘makes copies of itself’) inside cells in the lung, causing a viral infection. Most people with COVID-19 have only a mild illness and recover without medical treatment, but some people, in particular the elderly or those with existing health problems, can become seriously ill. We hope the study medicine will be an improvement on existing treatments and cause fewer side effects.
We tested repeated doses of the study medicine in healthy volunteers, to find out its side effects, and how much of the study medicine and its breakdown products gets into the lungs and blood. We needed to test the study medicine in healthy people before we could test it in patients.
Who organised the study and when did it take place?
The doctors and support staff of HMR, London, UK organised the study. A pharmaceutical company – Atea Pharmaceuticals, Boston, MA USA (the ‘sponsor’) – paid for the study.
The study took place at HMR (London) from 15 April 2021 until 27 August 2021. We completed the study as planned.
Who took part in the study and what treatments did they take?
24 healthy volunteers, aged 18–65 years, took part in the study. They took repeated doses of study medicine (275, 550, or 825 mg) by mouth, as tablets, for up to 3.5 days (up to 7 doses in total).
All participants had a procedure called a bronchoscopy to give samples of lung fluid. A bronchoscopy involves passing a flexible tube with a mini video camera at the end into the air passages in your lungs, while they are lightly sedated.
What were the results of the study?
Side effects
Side effects are unwanted medical events (such as headache) that happen during the study and are reported because the study doctor believes the side effects may have been related to the study medicine. In this study, we found out the following.
• There were no serious side effects – those are side effect that are life threatening or required someone to go to hospital.
• Not all people in the study had side effects.
• The only side effect that the study doctor considered to be caused by the study medicine was nausea, reported by 2 out of 24 people (8.3%) after taking 2 doses of the highest dose.
Other results
• The study medicine was safe and well tolerated at the doses tested.
• The study medicine was broken down in the body into its 4 transformed products, 3 of which were measured in the blood. The blood levels of the study medicine and its breakdown products were within the blood levels that were safe in previous studies.
• The body got rid of the study medicine within about 6 hours after the last dose in most people, but some people who took higher doses of the study medicine still had the study medicine in their blood 12 hours after their last dose.
• The breakdown products of the study medicine were found in the blood and/or lung fluid, as expected based on previous studies in animals. The body got rid of the breakdown products from the blood more slowly than it got rid of the study medicine.
• Breakdown products stayed in the lung fluid up to 12 h after the last dose, and 1 breakdown product was found in fluid from the upper airways.
How has the study helped patients and researchers?
The results of this study will be used to decide the doses to be tested in patients with COVID-19.
Are there plans for further studies?
Studies of AT-527 (the study medicine) are ongoing and further trials are planned in patients with COVID-19.
Where can I find more information about the study?
You can find out more detailed information about this study at https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C01%7Cedgbaston.rec%40hra.nhs.uk%7C1e049a05f2124c09478108db91b40e03%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638263974733036343%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=%2FgmFemw8syKvvOfbaJmYfHTK%2FbEdX7l%2BL%2F8VZky%2B3VI%3D&reserved=0.
If you would like more general information about clinical trials, the UK Clinical Research Collaboration (UKCRC) booklet ‘Understanding Clinical Trials’ has information about medical research, and questions you might want to ask. If you’d like to read it, please visit https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.ukcrc.org%2Fwp-content%2Fuploads%2F2014%2F03%2FiCT_Booklet.pdf&data=05%7C01%7Cedgbaston.rec%40hra.nhs.uk%7C1e049a05f2124c09478108db91b40e03%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638263974733036343%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=hwnL6EIyBMdnXnXbPoG580M%2FZo0Zn3jlFAEWsY6UzAI%3D&reserved=0.REC name
West Midlands - Edgbaston Research Ethics Committee
REC reference
21/WM/0088
Date of REC Opinion
9 Apr 2021
REC opinion
Further Information Favourable Opinion