Expanded access protocol for the use of tecovirimat for the treatment of monkeypox infection
| ISRCTN | ISRCTN43307947 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN43307947 |
| Secondary identifying numbers | 1-20 |
- Submission date
- 04/06/2021
- Registration date
- 09/08/2021
- Last edited
- 10/05/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Mpox (monkeypox) is a serious disease that causes fever and chills, fatigue, aching of the head, muscles, and back. It also causes lymph nodes to swell, and the skin to be scattered with lesions or scabs. This may last for 2−4 weeks. In some cases, mpox can cause long-lasting effects, even after recovery, and in a minority of cases may even be fatal. At the moment there is no treatment available that can cure mpox, but the drug tecovirimat might help patients recover more quickly and get better sooner. As there are no alternative treatments, the main aim of this study is to provide patients with access to this drug, but the researchers also hope to collect some additional information about how it works that will help them understand whether tecovirimat could help more patients in the future.
Who can participate?
Patients admitted to Hôpital de District de Mbaïki with laboratory-confirmed mpox infection
What does the study involve?
If patients agree to participate, on admission they will be asked about their health and other medicines that they might be taking. All patients will be offered an HIV test and all females of child-bearing potential will be offered a pregnancy test. These tests are voluntary.
Patients will stay at the hospital and take tecovirimat twice a day for 14 days. Tecovirimat is a tablet that must be taken with food. Patients will then have follow-up visits with a doctor 15 days and 28 days after they first started taking tecovirimat.
Five blood samples will be taken in total. One sample will be taken before patients start taking tecovirimat and further samples will be taken on days 4, 8, 14 and 28. These blood samples will be used to look at how the body reacts to tecovirimat.
The researchers will also collect some information about patients while they are taking tecovirimat to help them to decide whether they can use this medicine for other people in the future. This information will be collected on admission, throughout treatment and at the two follow-up visits patients will attend after they have finished taking tecovirimat. The researchers would also like to take some photos of the rashes or blisters that have been caused by mpox.
What are the possible benefits and risks of participating?
It is hoped that tecovirimat will help patients get better, but the researchers don’t know that it definitely will. It is hoped that the information collected will help other people in the future. However, because tecovirimat is not normally used to treat mpox, there may be risks that are not known at this time. The side effects the researchers know about are headache, stomach ache, nausea and/or vomiting. There may be other side effects that are not known yet and the researchers don’t know what effect tecovirimat has in pregnancy. Patients may also feel a small scratch when blood samples are taken.
Where is the study run from?
1. Institut Pasteur de Bangui (Central African Republic)
2. Oxford University (UK)
When is the study starting and how long is it expected to run for?
September 2019 to January 2024
Who is funding the study?
1. African Coalition for Epidemic Research Response
2. UK Foreign, Commonwealth and Development Office and Wellcome Trust (UK) (ref: 215091/Z/18/Z)
3. Bill & Melinda Gates Foundation (USA) (ref: OPP1209135)
Who is the main contact?
Emmanuel Rivalyn Nakouné Yandoko
enakouney@gmail.com
Contact information
Scientific
Tropical Medicine
New Richards Building
University of Oxford
Old Road Campus
Roosevelt Drive
Oxford
OX3 7LG
United Kingdom
| Phone | +44 (0)1865 612965 |
|---|---|
| piero.olliaro@ndm.ox.ac.uk |
Public
Tropical Medicine
New Richards Building
University of Oxford
Old Road Campus
Roosevelt Drive
Oxford
OX3 7LG
United Kingdom
| Phone | +44 (0)1865 612965 |
|---|---|
| josephine.bourner@ndm.ox.ac.uk |
Study information
| Study design | Single-centre expanded access protocol |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Expanded access protocol |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Expanded access protocol for the use of tecovirimat for the treatment of monkeypox infection |
| Study hypothesis | This is an Expanded Access Protocol that aims to provide access to tecovirimat (TPOXX) to patients with monkeypox. There is currently no satisfactory alternative treatment for patients with monkeypox and enrolment to clinical trials is not possible at this time. As well as providing access to TPOXX, the protocol also aims to generate information about its safety and effectiveness that could help inform future use and clinical development. |
| Ethics approval(s) |
1. Approved 02/12/2019, Oxford Tropical Research Ethics Committee (OxTREC) (, , , United Kingdom; ; ), ref: (University of Oxford Research Services, University Offices, Wellington Square, Oxford, OX1 2JD, United Kingdom; +44 (0)1865 (2)82585; oxtrec@admin.ox.ac.uk), ref: 1-20 2. Approved 20/05/2020, Université de Bangui Faculté des Sciences de la Santé Comité d'Ethique et Scientifique [University of Bangui Faculty of Health Sciences Ethics and Scientific Committee] (Université de Bangui, Bangui, None available, Central African Republic; None available; not@available.com), ref: None available |
| Condition | Mpox (monkeypox) |
| Intervention | All patients who receive a laboratory-confirmed diagnosis of monkeypox will be eligible to access treatment with tecovirimat. If patients agree to participate, on admission they will be asked about their health and other medicines that they might be taking. All patients will be offered an HIV test and all females of child-bearing potential will be offered a pregnancy test. These tests are voluntary. Patients will stay at the hospital and take tecovirimat twice a day for 14 days. Tecovirimat is a tablet that must be taken with food. Tecovirimat dosage is based on age and weight: Adults: 600 mg (three 200 mg capsules) twice daily for 14 days Paediatric patients weighing 13 kg or more: 13 kg to less than 25 kg: 200 mg (one capsule) of tecovirimat twice daily for 14 days 25 kg to less than 40 kg: 400 mg (two capsules) of tecovirimat twice daily for 14 days 40 kg or more: 600 mg (three capsules) of tecovirimat twice daily for 14 days Patients will then have follow-up visits with a doctor 15 days and 28 days after they first started taking TPOXX. Five blood samples will be taken in total. One sample will be taken before patients start taking tecovirimat and further samples will be taken on days 4, 8, 14 and 28. These blood samples will be used to look at how the body reacts to tecovirimat. The researchers will also collect some information about patients while they are taking tecovirimat to help them to decide whether they can use this medicine for other people in the future. This information will be collected on admission, throughout treatment and at the two follow-up visits patients will attend after they have finished taking tecovirimat. The researchers would also like to take some photos of the rashes or blisters that have been caused by monkeypox. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Tecovirimat |
| Primary outcome measure | Expanded Access Programs (EAPs) do not use or assess outcome measures in their analysis. This is because EAPs are primarily conducted to provide patients with access to drugs that would not normally be available and this is done outside of a clinical trial setting. EAPs cannot measure outcomes for a variety of reasons: a) only limited research data on safety and efficacy is collected, b) sample sizes are too small and there’s too much heterogeneity for any inferences to be made, c) unlike a clinical trial, the data collected as part of an EAP wouldn’t normally support the regulatory process. So while research data is collected as part of an EAP, outcome measures aren’t evaluated as they would not yield any meaningful analyses. The data collected to monitor efficacy has been described under 'Secondary outcome measures'. |
| Secondary outcome measures | 1. Total number, type and location of lesions measured clinically/visually at days 1 – 14 and 28 2. Temperature measured using a thermometer at days 1 to 14 3. Degree of incapacity measured assessed clinically at days 1 to 15 and 28 4. Complications: (1) gastrointestinal (diarrhoea or vomiting), (2) upper respiratory (includes runny nose and sore throat), (3) lower respiratory (includes wheeze, cough, and respiratory distress), (4) systemic (includes lymphadenopathy, muscle ache, back pain, headache); (5) ocular (keratitis, corneal ulceration); (6) neurological (confusion, seizures) assessed clinically at days 1 – 15 and 28 5. Whether the subject has survived with or without sequelae or succumbed to disease, assessed clinically at day 15 (after completion of treatment) and day 28 6. Viral load and serology: total exposure to the virus in the bloodstream over the course of treatment (area under the curve), maximum viral load, time to clearance of viral DNA from the blood, and antibody responses, measured using blood (5 ml) collected prior to the first dose and then on days 4, 8, 14 and 28 |
| Overall study start date | 19/09/2019 |
| Overall study end date | 18/01/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | All |
| Sex | Both |
| Target number of participants | 30 |
| Participant inclusion criteria | 1. Male and female patients weighing ≥13 kg 2. Present with monkeypox disease as determined by clinical signs and symptoms that include a characteristic rash preceded by fever. Blood and lesion swab will be taken for confirmation by qPCR positivity for monkeypox virus DNA. 3. Close contacts of patients with confirmed monkeypox who develop fever may be tested by qPCR (prior to or after rash development) and if positive would be eligible for treatment |
| Participant exclusion criteria | Subjects taking repaglinide |
| Recruitment start date | 01/08/2021 |
| Recruitment end date | 22/12/2023 |
Locations
Countries of recruitment
- Central African Republic
Study participating centre
-
Central African Republic
Sponsor information
University/education
University Offices
Wellington Square
Oxford
OX1 2JD
England
United Kingdom
| Phone | +44 (0)1865 616546 |
|---|---|
| denis.murphy@admin.ox.ac.uk | |
| Website | http://www.ox.ac.uk/ |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Research organisation
No information available
Government organisation / National government
- Alternative name(s)
- Foreign, Commonwealth & Development Office, Foreign, Commonwealth & Development Office, UK Government, FCDO
- Location
- United Kingdom
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Wellcome, WT
- Location
- United Kingdom
Government organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Bill & Melinda Gates Foundation, Gates Foundation, BMGF, B&MGF, GF
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/12/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. The study protocol and other documents are currently not available at this point in time. |
| IPD sharing plan | The datasets generated and/or analysed during the current study will be published as a supplement to the results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 09/05/2024 | 10/05/2024 | Yes | No |
Editorial Notes
10/05/2024: Publication reference added.
11/04/2024: The following changes were made:
1. The overall study end date was changed from 01/04/2024 to 18/01/2024.
2. The recruitment end date was changed from 01/03/2024 to 22/12/2023.
13/09/2023: The following changes were made to the study record:
1. The recruitment end date was changed from 01/06/2023 to 01/03/2024.
2. The overall study end date was changed from 30/06/2023 to 01/04/2024.
3. The intention to publish date was changed from 01/09/2023 to 01/12/2024.
30/11/2022: The International Severe Acute Respiratory and Emerging Infection Consortium was removed and UK Foreign, Commonwealth and Development Office and Wellcome Trust and Bill & Melinda Gates Foundation were added as funders.
29/11/2022: The record has been updated to include 'mpox'.
20/06/2022: IPD sharing statement added.
08/06/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/06/2022 to 01/06/2023.
2. The overall trial end date was changed from 30/06/2022 to 30/06/2023.
18/06/2021: Trial's existence confirmed by Oxford Tropical Research Ethics Committee and Université de Bangui Faculté des Sciences de la Santé Comité d'Ethique et Scientifique.
