EU-SOLIDACT

PATIENT FAQs   

1. What is this research looking at exactly?

The EU-SolidAct trial platform has been set up to look at whether adding already well-known drugs (currently bemcentinib (AXL-SolidAct) to the state-of-the-art treatment can help people who have been hospitalised with moderate or severe SARS-CoV-2 (also called COVID-19) to recover. A previous arm of the trial has already been completed which looked at baricitinib for treatment of COVID-19 (Bari-SolidAct).

2. What is the purpose of this research?

One of the main problems seen in COVID-19 infections seems to be that the body sometimes “over-reacts” to the virus, causing severe inflammation within the tissues of the body, especially the lungs. This prevents the body from being able to heal itself effectively and can lead to further complications and prolong or stop recovery. Previous research in the United States has shown that baricitinib is able to help people who have been admitted with the severe forms of COVID-19, reducing the amount of time they spend in the hospital. The Bari-SolidAct trial looked to repeat this success in order to show the safety and efficacy of baricitinib, to see whether adding it to the state-of-the-art treatment EU patients receive helps them recover more quickly. The AXL-SolidAct arm of EU-SolidAct is looking at whether an AXL inhibitor, bemcentinib, might be able to speed recovery along by interrupting the virus’ ability to replicate inside the cells by not letting it enter the cell it is targeting in the first place.

3. Who is running the study?

The main project is being managed by Oslo University Hospital in Oslo, Norway, but many other centres from many countries are involved in the process, including Austria, Belgium, the Czech Republic, France, Germany, Greece, Hungary, Ireland, Italy, Luxembourg, Norway, Portugal, Slovakia, Spain, Switzerland, and Turkey.

4. Who can take part in the study?

Patients who have been admitted to the hospital with moderate to severe COVID-19 may be screened for their participation in EU-SolidAct studies if their hospital is taking part. Patients being admitted to hospitals who are not involved in the study will not be included.

Patients who cannot take part in our studies may include those who are unable to make an informed choice about their participation in the study, those who are below the age of consent, and those who may be pregnant.

5. What will happen to me if I am included in the study?

Our trials are double blind, randomised trials. This means that once you are included in the study, you will be randomly assigned to either the test drug arm of the trial (the “active” arm) or a placebo arm. All patients involved in the trial will receive the same state of the art treatment that any other patient would receive in their situation, but they will also receive the study drug. Your study doctor will explain how the treatments will be given and the timing, as well as any potential side effects you may experience.

6. Why is this trial randomised?

There are several reasons why we use randomisation in drug trials. The first is that it eliminates bias in who is picked to be part of the study. Eliminating bias is very important because it means that all patients are treated equally, which allows investigators to directly compare the results of the trial. It is important that we have both people who are receiving standard treatment plus the study drug and patients who are receiving just the standard treatment alone so that we can see whether there is a difference in the recovery between patients receiving the study drug and those who do not. It is also useful for reducing bias in how patients react to questions or in the effect of their expectations on potential results.

7. What are the possible benefits of being in the study?

Being involved in a drug trial means that you are part of the group of patients who help the doctors to identify whether a drug is helpful, but it also means you are able to take a more active role in planning your treatment. You may get a treatment before other people have been offered it.

8. What are some of the possible risks of taking part in the trial?

The drugs being tested are not a new drugs, so the potential side effects have been well described. Side effects of the drugs are generally known to be quite mild, but some people may feel uncomfortable or even experience some serious side effects. As well, it is not clear that the study drugs will work well in this situation, so it may prove to be just as good as the standard treatment. There is also a chance you will not be included in the active study arm, which means that you will not receive the study drug as part of your treatment plan. Additionally, after the trial, extra visits may be required of you to monitor your health and ensure that you are not experiencing any long-term effects from the drug.

9. Can I refuse to take part in the study?

Yes! You are never required to begin or to continue on with the study. You have the right to withdraw from the study at any time. You will not be pressured to continue in the study if you choose to leave it. If you would like to withdraw from this study, simply speak to your doctor who will help you understand your rights and talk to you about whether you would like your information to remain available to the study team.

10. Does being involved in the study cost me anything?

No, there will not be any cost involved for you to take part in the study.

11. Can I stop the study treatment?

Yes, you may stop the treatment at any time. Simply speak to your study nurse or doctor who will help you withdraw from the study; they will remind you of your rights in regard to your data.

12. Can I take back my permission to be part of this study?

Yes. You may decide at any time to withdraw your permission to be part of this study. Speak to your study nurse or doctor who will help you withdraw and will talk to you about your rights regarding your data. After your release from hospital, as part of your treatment plan, your study nurse or doctor should ask you if you would like to continue as part of the project as a normal part of each interaction you have with them. You have the right to withdraw at any time without being pressured to continue.

13. Who can I talk to if I have questions?

You may speak to any nurse or doctor who is treating you at the hospital.

14. What information will be held about me and who will have access to it?

Information about your health condition, including your diagnosis, blood values and chart notes may be seen by the doctors and nurses involved in your treatment, as well as other relevant members of the health care team.

15. How will you keep my data private?

EU-SolidAct follows the guidelines for data security required by the European Union’s Data Protection Act as well as any relevant guidelines specific to your country. Your data will be recorded in a very safe electronic data system without your name or any information which can identify you directly. These data are accessed exclusively by trial researchers and persons responsible for monitoring the safety of the participants. As part of the reporting of the results of the study your data may be seen by analysts from other countries involved in the study, but they will not know the data belongs to you, and they cannot ask for this information.

Information contained in this section is for use with the EU-SolidAct baricitinb trial only. Information taken from this area should only be used by physicians working in this specific trial.

Biobanking | OSH Operating Manual (Document – Updated 13 Aug 2021)

Biobanking | Naso-oropharyngeal Samples (Document – Updated 13 Aug 2021)

Biobanking | EDTA-Plasma and Serum Samples (Document – Updated 13 Aug 2021)

Drug Handling | EU-SolidAct Drug Handling Manual (v1 – Document)

Drug Handling | Quick Guide to the IMP (Bari-SolidAct) (v1 – Document)

Drug Handling | SolidAct IMP Management (v1 – Document)

Drug Handling | IMP Accountability Log (Document – Template – Updated 27.10.21)

eCRF | eCRF User Guide for Clinical Sites (Document v1.1 Updated 01.04.22)

eCRF | eCRF User Guide (Video – External Link)

eCRF | 1. How to connect (Video – External Link)

eCRF | 2. Using the eCRF Dashboard (Video – External Link)

eCRF | 3. Creating a Patient (Video – External Link)

eCRF | 4. Patient Overview (Video – External Link)

eCRF | 5. Data Entry (Video – External Link)

eCRF | 6. Randomisation (Video – External Link)

eCRF | 7. Queries (Video – External Link)

eCRF | 8. Missing Data (Video – External Link)

eCRF | 9. AE and DRE (Video – External Link)

eCRF | 10. SAE (Video – External Link)

eCRF | 11. Unblinding (Video – External Link)

eCRF | Queries – Working with Queries for CRAs (Video – External Link)

eCRF | How to create PDs in the eCRF system (v1 – Document)

eCRF | Short eCRF User Guide (v1 – Document)

eCRF | Unblinding Certificate (Document – Template)

eCRF | Transfer a Patient’s eCRF (Document – Template)

Protocol | EU-SolidAct Protocol (v3.1- Document)

Protocol | AXL-SolidAct (v1.5 – Document)

Protocol | AXL-SolidAct Protocol Signature Page (v1.5 – Document)

Protocol | Algorithm for Inclusion and Exclusion (baricitinib) (v1 – Document)

Protocol | Quick Guide to Inclusion and Exclusion (v1 – Document)

Protocol | Transfer of patients (Document – Template)

Protocol | Prescreening Log Template (Document – Template)

Safety | Dose reduction and discontinuation of Baricitinib (v1 – Document)

Safety | EU-SolidAct SOP Safety Working Instructions (v4 – Document)

DRUG HANDLING/INVESTIGATIONAL MEDICAL PRODUCT (IMP):

Q: Is temperature monitoring required during IMP transit from where the IMP has been received to the ward? (This could be longer than 5 minutes as it will also involve awaiting handover of IMP to the Responsible ward staff)
A: Under normal conditions, it should not be necessary to do temperature monitoring during short transits. However, if the drug will be over normal room temperature for longer than a few minutes (e.g., during high summer or deep winter), you should use some form of temperature-controlled transport container to ensure the drug is kept at a stable temperature.

Q: Is temperature monitoring required whilst the IMP is being stored on the ward for 2 weeks?
A: Yes, there should be temperature monitoring during the weeks the drug is stored on the ward.

Q: Is it acceptable for sites to use their own temperature monitoring logs?
A: Yes, as long as it covers the information in NorCRIN template 2.13.2 (see Investigator Site File section 7.5)

Q: Electronic prescriptions: is it acceptable to print and sign these to use as source documents?
A: Yes, printed electronic prescriptions can be used as the source for the prescription, but we suggest printing the randomisation e-mail received from ENNOV / eCRF system as source for which kit the patient has been randomised to.

Q: What is the missed dose procedure?
A: A dose should only be replaced if it can be visually confirmed that the patient did not receive the dose, either due to vomiting with visible tablet remains or due to tablets getting stuck in the NG tube (if applicable in your arm of the trial). No other missed/skipped doses should be replaced.

Q: The protocol states, “The dose of study intervention and study subject identification will be confirmed at the time of dosing by a member of the study site staff other than the person administering the study intervention.” What exactly is being asked for here – a two-nurse administration?
A: Yes. For baricitinib, this is suggested in the Investigational Brochure (IB). Otherwise, sites should follow local procedures (double check simultaneously, delayed second check, etc).

Q: Drug reconciliation: Can you give us some guidance on when this is to occur?
A: Continuously, i.e., when IMPs are received, dispensed, returned or destroyed.

Q: Is the “Drug reconciliation log” completed by the monitor or the pharmacist?
A: The drug reconciliation log / accountability log at site level should be completed by the pharmacist or site staff responsible for the IMP and checked by the monitor.

Q: What will happen when the IMP arrives in the ward? Who can administer study drug?
A: It may be necessary for clinical staff (non-study staff) to be allowed to deliver the IMP.  The PI should make the clinical staff in the ICU / ward aware of the study. The drug should be documented on the patient’s chart as you would with normal medications.

Q: If a patient does not have a nasogastric (NG) tube in and becomes NPO should a tube be put in just for IMP administration?
A: NG tube should only be placed on clinical indication and not for the trial per se.

Q: How will pharmacists receive information about kit numbers after randomisation?
A: If the IMP is stored at a pharmacy, the prescription will indicate which kit number to dispense to the patient.

Q: Can you give some clarification around what will happen on weekends if a patient’s results indicate the dosage needs to be changed?
A: It should be possible to contact study staff locally so that dose modifications can be performed even during weekends. These arrangements must be made locally at each site.

SAFETY/AE REPORTING:

Q: Who can report AEs and SAEs in the eCRF?
A: AEs and SAEs can be reported by all investigators at a site, not only the PI.

Q: The assessments in section 8 of the protocol ‘Safety Assessments’: are these only required if an AE has occurred?
A: Please see the Bari-SolidAct protocol, schedule of assessments 1.3. Safety biochemistry samples should be taken regularly whether AE has occurred or not.

Q: Urine pregnancy test at day 30: should sites provide a kit to patients?
A: The sites will receive pregnancy tests together with the delivery of study drugs for the first patients, and yes, the sites should provide a test to the patient when required.

Q: Baseline pregnancy test: is a urine test sufficient or will a blood test also be required?
A: A blood test is required.

BIOBANKING/LAB:

Q: In cases where a lab member is not part of study staff, who should the lab contact person be?
A: If biobanking is planned, staff with experience in lab work should be included locally.

Q: Is there any flexibility on day 3 for biobanking? If not it could limit days the site can recruit where there is no weekend cover.
A: The biobank assessment has a window of +/- 1 day (exept baseline which should be performed before first dose of IMP). If not possible to assess the patient during weekends, the Saturday assessment could be performed on Friday, and the Sunday assessment could be performed on Monday.

CLINICAL:

Q: Guidance is required around window for schedule of assessments. Is there a limit on the days a patient can be recruited if a cheduled event falls on a weekend? For example patients will not be able to be recruited on a Thursday as the day 3 assessment will not be possible at our clinic.
A: Each of the assessments (including biobank and lab) has a window of +/- 1 day. If it is not possible to assess the patient during the weekend, the Saturday assessment could be performed on Friday, and the Sunday assessment could be performed on Monday.

Q: What days does renal function need to be documented? Does a renal function calculation need to be done and documented over the weekend?
A: Renal function may be necessary for dose adjustment of IMP and will be noted in the protocol. It is possible to adjust time points for assessment with +/- 1 day, so that Saturday assessment could be done on a Friday, and the Sunday assessment could be performed on Monday.

Q: Corticosteroids: If a patient is started on oral corticosteroids after enrolment can they remain on the trial? Is this a PI decision?
A: For baricitinib, the patient can remain in the trial, but start or dose increase in steroids should be noted under conmeds in the eCRF along with an assessment of potential disease progression. For other arms, please consult the Sponsor team.

DOCUMENTS:

Q: Will an approved GP letter be provided?
A: No.

Q: Are financial disclosures required by the sponsor?
A: No, but they are required by the European Medicines Agency, and must be uploaded within the CTIS system. You will be asked to provide this form when you enter thre trial.

Results from Bari-SolidAct:

Article 1:

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial

Results from AXL-SolidAct (bemcentinib):

* No results to share yet.

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Clinical Leads:

• Marius Trøseid – Principal Investigator
• Jose R. Arribas – Co-Chief Investigator
• Dominique Costagliola – Chair of Trial Steering Committee

OUH Sponsor Team:

• Inge C. Olsen – Head of Operations
• Thale D.J.Hovdun Patrick-Brown – Study Manager and Drug and Biobanking Responsible
• Paul C. Meier – Study Financial Coordinator

Clinical Leads:

• Robert Breitkopf – Austria
• Maya Hites – Belgium
• Michael Rezek – Czechia
• Julien Poissy – France (baricitinib)
• Karine Lacombe – France (bemcentinib)
• Bernd Muelhbauer – Germany
• Sotirios Tsiodras – Greece
• Edit Hajdu – Hungary
• Brian Kent – Ireland
• Fulvia Mazzaferri – Italy (baricitinib)
• Jean Reuter – Luxembourg
• Aleksander Rygh Holten – Norway (baricitinib)
• Kristian Tonby –  Norway (bemcentinib)
• José Artur Paiva – Portugal
• Monika Halanova – Slovakia
• José Rodriguez Baño – Spain
• Mattias Briel – Switzerland
• Qian Zhou – Switzerland Basel
• Ahmet Çağkan İnkaya – Turkey
• Serhat Ünal – Turkey

Monitoring

• Helen Heyerdahl – Lead Monitor

Inserm Biometrics Team:

• Lambert Assoumou – Head of Biometrics
• Aliou Balde – Trial Statistician
• Lydie Beniguel – Data/Project Manager
• Lucie de  Gastines – Data/Project Management

Inserm Pharmacovigilence team:

• Alpha Bell Diallo – Head of Pharmacovigilence
• Vida Terzic – Trial Pharmacovigilence Officer

ECRIN Operations Team:

• Sigrun Hjelle – ECRIN Project Manager
• Marta Del Alamo – ECRIN Project Manager

Allied Operational Members

• Katerine Nezvalova-Henriksen – Consultant Pharmacist, Norway
• Victoria Charlotte Simensen – Coordinator, Independent Ethics and Scientific Advisory Board (IESAB)