Agile CST-9a
Title
AGILE Platform; Seamless Phase I/IIa Platform for the Rapid Evaluation of Candidates for COVID-19 treatment
Candidate Specific Trial -9a (CST-9a): A Multicentre, Adaptive Phase II Platform Trial to Evaluate the Safety, Efficacy and Virological response of ALG-097558 as monotherapy and in combination with Remdesivir in high-risk population for the Treatment of COVID-19 disease.
Description
This trial is an open label randomised controlled adaptive trial with twice daily dose of ALG-097558 versus twice daily dose of ALG-097558 in combination with Remdesivir) versus standard-of-care therapy in participants will have mild-moderate SARS-CoV-2 infection and be considered at greater risk of disease progression based on UK DHSC criteria for COVID-19 treatment.
Objectives
Primary Objectives:
Phase 1:
Safety Objective: Determine the safety and tolerability of ALG-097558 alone and in combination with the nucleoside analogue Remdesivir (RDV)
Efficacy Objective: Two co-primary endpoints are utilised:
i) to determine change in viral titre overtime following administration of ALG-097558 alone and in combination with RDV versus Standard of Care (SoC).
ii) to determine time to sustained symptom resolution following administration of ALG-097558 alone and in combination with RDV versus Standard of Care (SoC), defined as time from the first dose to the time when symptoms are rated as absent for two consecutive days.
Secondary Objectives:
- To establish the pharmacokinetics of ALG-097558 + RDV in plasma
- To establish disease progression endpoints including visits to emergency department, hospitalisations, all- cause mortality
- To evaluate the incidence of rebound SARS-CoV-2 infection
- Symptom improvement in subgroup of severely immunosuppressed participants or with high baseline viral titre (defined as Ct value of <22)
- Viral dynamics in subgroup of severely immunosuppressed participants or with high baseline viral titre (defined as Ct value of < 22)
- To evaluate time to, and proportion of, clinical improvement.
Exploratory Objectives:
- To characterise pharmacokinetics of ALG-097558 in tears, saliva, and nasal secretions
- To characterise genetic variability in SARS-CoV-2 before and during treatment
- To evaluate changes in culturable virus during treatment
- To characterise time dependent changes in host response to infection or drug exposure
Trial Design
Trial Status
Open for recruitment.
Population
Adults (>/= 18 years of age) with a positive SARS-CoV-2 lateral flow test, who are at high risk (as defined in UK DHSC criteria) of progressing to severe COVID-19 disease, within 3 days of symptom onset, with at least one symptom of COVID-19 infection present on the day of randomization, and with mild- moderate disease severity at enrolment.
Trial Manager:
Babitha Jeevith
Programme Managers
Helen Reynolds
Michelle Tetlow
Justin Chiong
Data Manager
Michelle Stackpole
Trial Statistician
Jones Ashley
Contact Information
SAE reporting:
Press releases, video clips and other external websites
(University of Southampton cannot accept responsibility for external websites)
AGILE website (press section) – https://www.agiletrial.net/for-press/
Why is this trial being done
You have suspected or confirmed COVID-19, which is caused by the SARS-CoV-2 coronavirus.
The trial drug ALG-097558, is an experimental new medicine for treating COVID-19. This trial aims to assess whether ALG-097558 may be useful for patients with COVID-19 when given alone or in combination with Remdesivir and if either of these treatments turn out to be more effective than treatment with the usual standard of care (as determined by your doctor).
ALG-097558 is now being tested on a larger population after successful trials in healthy volunteers. ALG-097558 has already been extensively tested in healthy volunteers. Animal studies were also conducted at doses many times higher than the highest dose planned for this trial. You will receive ALG-097558 either alone or with a drug called Remdesivir (RDV). This Trial is the first time both trial drugs, ALG-097558 and RDV, are being given to people with COVID-19 as a combination of antivirals.
What is the purpose of this trial?
The aims of this trial are to determine the following:
- The safety of the trial drugs and any side effects that might be associated with them
- How much of the trial drugs get into the bloodstream
- How quickly the body removes the trial drugs
- How well the trial drugs might be able to reduce complications of COVID-19
- How the trial drug affects the body’s response to COVID-19
Any changes in the amount of virus present from the start of treatment
There is limited data on the trial drug ALG-097558 and its effect in treating COVID-19. However, in an early phase trial of ALG-097558 in a heathy volunteer population, ALG-097558 was well-tolerated, with a favourable safety profile and minimal side effects.
Design of the study:
This is an open-label trial. You will be randomized to receive the trial drug alone, the trial drug in combination with RDV, or SoC. Before receiving any treatment, you will be informed of your treatment allocation and schedule.
Trial drug alone (ALG-097558)
The trial drug ALG-097558 will be administered at a dose of 600 mg (6 x 100 mg tablets) twice a day (12 hours apart) for a total of 5 days of dosing (a total of 10 doses). The first dose will be taken in the clinic or while you are in hospital. The rest of the medication will be taken at home or in the hospital by yourself. You will be asked to record taking your doses in a diary (for more information see sections below on Diary Completion).
Trial drug (ALG-097558) in combination with IV RDV
The trial drug ALG-097558 will be given together with IV RDV. Dosing will be as follows:
- ALG-097558 600 mg (6 x 100 mg tablets) twice a day, 12 hours apart, for a total of 5 days (10 doses in total).
- RDV 200 mg administered as a drip into your vein on Day 1 and 100 mg on Days 2 and 3 – you will continue to receive this in hospital for as long as you are an in-patient.
If you are an outpatient or have been discharged from hospital the IV RDV treatment will be given in the clinic. On the days when RDV is also given, the dose of ALG-097558 will be taken just after the RDV is given.
The dose level for ALG-097558 is based on the results of a previously completed trial in healthy volunteer participants. The dose level for RDV is based on dosing recommended/approved by MHRA and regulators in the United States. It has also been tested in other trials for COVID-19 treatments.
Standard of Care (SoC) alone
If you are randomised to SOC arm, you will receive the usual NHS treatment available (this is known as ‘standard of care’) but we will still follow you up regardless of which group you are in. This is so we can compare the results for all the treatments given.
What the trial involves:
The trial involves 5-6 visits to the Clinical Research Facility/ unit. If you are hospitalized when enrolled in the trial, some of the visits may take place during that time and follow-up visits will be continued after you are discharged. These visits will include the Screening visit, a baseline visit (Day 1, which may be combined with screening), and further clinic visits at Days 3, 5, 8 and 11.
Are there any financial costs or payments?
You will be compensated £1020 for your time and inconvenience or £1170 if you are assigned to the treatment arm and require pharmacokinetics samples. Travel expenses related to the trial will also be reimbursed.
What will happen to the results of the research trial?
When the trial ends, the results will be analysed and presented at national/international meetings before being published in a medical journal. In addition, Aligos Therapeutics, Inc. may use the results and any publications of the results in regulatory or commercial materials related to its development of the trial drug. The confidentiality of all patients will be maintained. You will not be personally identified in any reports or publications resulting from the trial. 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.
No, taking part in the trial 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. You can take as long as you need to decide.
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 choose not to participate in this trial, you will receive the usual NHS treatment your doctor thinks most appropriate for you. This may include medications like nirmatrelvir (Paxlovid), sotrovimab, molnupiravir, and RDV. Your doctor will work with you to determine the best course of treatment.