AGILE: Seamless Phase I/IIa Platform for the Rapid Evaluation of Candidates for COVID-19 Treatment
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 600
- 试验地点
- 7
- 主要终点
- CST-9b
研究概览
简要总结
The AGILE platform master protocol allows incorporation of a range of identified and yet-to-be-identified candidates as potential treatments for adults with COVID-19 into the trial. Candidates will be added into the trial via candidate-specific trial (CST) protocols of this master protocol as appendices. Having one master protocol ensures different candidates are evaluated in the same consistent manor and opening up new trials for new candidates is more efficient. Inclusion of new candidates will be based on pre-clinical data, evidence in the clinical setting and GMP capabilities.
详细描述
AGILE is a multicentre, multi-arm, multi-dose, multi-stage open-label, adaptive, seamless phase I/II Bayesian randomised platform trial to determine the optimal dose, activity and safety of multiple candidate agents for the treatment of COVID-19.
This study allows for the assessment of many candidates at different doses, with the ability to add candidates as they are identified or drop them as their evaluation is completed. Promising candidates will move to an external trial for further evaluation in the phase II/III setting.
Each candidate will be evaluated in its own trial, randomising between candidate and control with 2:1 allocation in favour of the candidate. Each dose will be assessed for safety sequentially in cohorts of 6 patients. Once a phase II dose has been identified we will assess efficacy by seamlessly expanding into a larger cohort.
AGILE is completely flexible in that the core design in the master protocol (as has been explained above) can be adapted for each candidate based on prior knowledge of the candidate - i.e. population, primary endpoint and sample size can be amended. This will be detailed in each candidate-specific trial protocol of the master protocol.
Candidate-Specific Trial 2 (CST-2): Open-label 2:1 randomised controlled phase I of EIDD-2801 versus standard of care followed by a 1:1 blinded controlled parallel group Phase II trial of EIDD-2801 versus placebo. A phase I will be carried out to confirm the optimal dose in this group. Following a safety review, EIDD-2801 will be tested for efficacy in a blinded placebo controlled randomised phase II trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
CST-2: Phase I, open-label EIDD-2801 vs standard of care. Phase II, blinded controlled parallel group of EIDD-2801 vs placebo CST-3A: Phase Ia, open-label nitazoxanide CST-3B: Phase Ib, II, open label nitazoxanide vs standard of care CST-5: Phase I, blinded VIR-7832 vs placebo, Phase II, blinded VIR-7832 vs VIR-7831 vs placebo CST-6: Open label IV favipiravir vs standard of care CST-8: Open label Molnupiravir and Paxlovid® versus standard of care CST-9a: Open label ALG-097558 versus ALG-097558 + remdesivir versus standard of care CST-9b:Double Blind ALG-097558 versus matching placebo for ALG097558
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Master Protocol Inclusion Criteria:
- •Adults (≥18 years) with laboratory-confirmed* SARS-CoV-2 infection (PCR)
- •Ability to provide informed consent signed by study patient or legally acceptable representative
- •Women of childbearing potential (WOCBP) and male patients who are sexually active with WOCBP must agree to use a highly effective method of contraception (as outlined in the protocol) from the first administration of trial treatment, throughout trial treatment and for the duration outlined in the candidate-specific trial protocol after the last dose of trial treatment
- •If any CSTs are included in the community setting, the CST protocol will clarify whether patients with suspected SARS-CoV-2 infection are also eligible.
- •Standard additional criteria that may be applied per CST protocol:
- •Group A (severe disease) 4a. Patients with clinical status of Grades 4 (hospitalised, oxygen by mask or nasal prongs), 5 (hospitalised, on non-invasive ventilation, or high flow oxygen), 6 (hospitalised, intubation and mechanical ventilation) or 7 (ventilation and additional organ support - pressors, renal replacement therapy (RRT), extracorporeal membrane oxygenation (ECMO)), as defined by the WHO clinical severity score, 9-point ordinal scale.
- •Group B (mild-moderate disease) 4b. Ambulant or hospitalised patients with the following characteristics peripheral capillary oxygen saturation (SpO2) >94% RA N.B. The CST protocol inclusion criteria will take precedence over the master protocol inclusion criteria.
- •CST-2 Inclusion Criteria:
- •For the purpose of the EIDD-2801 candidate-specific trial the following inclusion criteria have been amended from the Master protocol to:
- •1. Male or female ≥ 60 years old or ≥50 years old with at least one well controlled comorbidity: cardiovascular disease, chronic lung disease (e.g. COPD, or pulmonary hypertension), immune deficiency (taking the equivalent of 20 mg prednisone daily, chemotherapy, or immune modulating biologic therapies), diabetes (treated with insulin or oral medications), BMI≥30, or hypertension requiring medication with laboratory confirmed SARS-CoV-2 infection (PCR) .
- •3. Women of childbearing potential (WOCBP) and male patients who are sexually active with WOCBP must agree to use two effective methods of contraception, one of which should be highly effective (as outlined in the protocol). For women, from the first administration of trial treatment, throughout trial and up to 50 days after the last follow up visit (50 days after day 29) and for men with female partners of child bearing potential, from the first administration until 100 days after last follow up visit (100 days after day 29).
- •4. Group B (mild-moderate disease): Ambulant with the following characteristics peripheral capillary oxygen saturation (SpO2) >94% RA (NB this differs to the Master Protocol which also includes hospitalised patients in this group).
- •Additional criteria specific to this candidate are:
- •5. Has signs or symptoms of COVID-19 that began within 5 days of the planned first dose of study drug.
- •6. Is in generally good health (except for current respiratory infection) and is free of uncontrolled chronic conditions.
- •7. Is willing and able to comply with all study procedures and attending clinic visits through the 4th week.
- •8. Has someone, aged ≥ 16 living in the same household during the dosing period.
- •CST-6 Additional inclusion criteria:
- •Group A (severe disease). Patients with clinical status of Grades 5 (hospitalised, oxygen by mask or nasal prongs), 6 (hospitalised, on non-invasive ventilation, or high flow oxygen as defined by the WHO Clinical Progression Scale (WHO, 2020)).
- •Less than or equal to 14 days from onset of COVID-19 symptoms
- •CST-8 Inclusion Criteria:
- •For the purpose of CST-8, criteria 1 has been amended from the Master Protocol to:
- •Adults (≥18 years) outpatients positive lateral flow test at screening or baseline Day 1, who are within 5 days of symptom onset prior to the planned first dose of study drug.
- •Criteria 3 has been amended from the Master Protocol to:
- •Women of childbearing potential (WOCBP) and male participants who are sexually active with WOCBP must agree to use a highly effective method of contraception (as outlined in section 5.5 of the Master Protocol) for the duration of the treatment and for six weeks following the last dose.
- •Additional criteria specific to CST-8 are:
- •Initial onset of COVID-19 signs/symptoms within 5 days prior to the day of randomisation and at least 1 of the current specified COVID-19 signs/symptoms (listed on the NHS website) present on the day of randomisation
- •Is willing and able to comply with all study procedures and attending clinic visits
- •CST-9a Inclusion Criteria:
- •For the purpose of CST-9a, criteria 1 has been amended from the Master Protocol to:
- •Adults (>/= 18 years of age) with a positive SARS-CoV-2 lateral flow test on screening or Day 1, 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 are with mild- moderate disease severity at enrolment.
- •Criterion 2 has been amended from the Master Protocol to:
- •Ability to provide informed consent signed by trial participant or legally acceptable representative and are willing and able to comply with all trial procedures and attending clinic visits
- •Criterion 3 has been amended from the Master Protocol to:
- •Women of childbearing potential (WOCBP) and male participants who are sexually active with WOCBP must agree to use two effective methods of contraception, one of which must be highly effective for the duration of the treatment and for 90 Days following the last dose
- •Master Protocol
排除标准
- •Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >5 times the upper limit of normal (ULN)
- •Stage 4 severe chronic kidney disease or requiring dialysis (i.e., estimated glomerular filtration rate <30 mL/min/1.73 m^2)
- •Pregnant or breast feeding
- •Anticipated transfer to another hospital which is not a study site within 72 hours
- •Allergy to any study medication
- •Patients taking other prohibited drugs (as outline in CST protocol) within 30 days or 5 times the half-life (whichever is longer) of enrolment
- •Patients participating in another CTIMP trial
- •N.B. The CST protocol exclusion criteria will take precedence over the master protocol exclusion criteria.
- •CST-9a Exclusion Criteria:
- •Exclusion criteria has been amended from master protocol as:
- •Prior SARS-CoV-2 infection <90 days before enrolment and/or received any COVID-19 vaccine dose <90 days before enrolment
- •Alanine aminotransferase (ALT) >3 times the upper limit of normal (ULN) or Active Liver disease
- •History or current evidence of cirrhosis
- •Receiving dialysis or have known moderate to severe renal impairment (defined as CKD stage 4 or 5) or current acute kidney injury on most recent eGFR in the past 6 months
- •Pregnant or breast feeding
- •Anticipated transfer to another hospital which is not a trial site within 72 hours
- •Known allergy to any trial medication
- •Swallowing difficulties
- •Currently receiving ALG-097558, Paxlovid, molnupiravir or remdesivir or any SoC therapy for COVID-19 at the time of screening
- •Received sotrovimab at any point during the current SARS-CoV-2 infection
- •Oxygen saturations <94% on room air
- •Urgent or expected need for nasal high-flow oxygen therapy or positive pressure ventilation, invasive mechanical ventilation or ECMO.
- •Participants who have taken or require treatment with a comedication that is a strong CYP450 3A4 inhibitor (atazanavir, clarithromycin, itraconazole, posaconazole, voriconazole, nefazodone, nelfinavir, grapefruit juice, HIV protease inhibitors), strong CYP450 3A4 inducers (rifampin, phenytoin, carbamazepine, St. John's Wort) or sensitive substrates of CYP450 2C8 and 2B6 (repaglinide, rosiglitazone, paclitaxel, bupropion) within at least 2 weeks or 5 half-lives (whichever is longer) before the planned first dose of study drug.
- •Participating in another CTIMP trial
- •CST-9b Exclusion criteria:
- •Prior SARS-CoV-2 infection diagnosed <90 days before enrolment and/or received any COVID-19 vaccine dose <90 days before enrolment
- •Alanine aminotransferase (ALT) >3 times the upper limit of normal (ULN) or Active Liver disease
- •History or current evidence of cirrhosis
- •Receiving dialysis or have known severe renal impairment defined as CKD stage 5 (an eGFR <15 mL/min/1.73 m2 at screening, or current acute kidney injury in most recent eGFR in past 6 months.
- •Pregnant or breast feeding
- •Anticipated transfer to another hospital which is not a trial site within 72 hours
- •Known allergy to any trial medication
- •Swallowing difficulties
- •Currently receiving ALG-097558, Paxlovid, molnupiravir or remdesivir or any standard of care antiviral therapy for COVID-19 at the time of screening
- •Received sotrovimab at any point during the current SARS-CoV-2 infection prior to enrolment
- •Oxygen saturations <94% on room air. NOTE: Participants on stable oxygen therapy, including use of NIPPV (non-invasive positive pressure ventilation), for a pre-existing medical condition (e.g., COPD) may be included with oxygen saturation of <94% on room air, provided there is no new increased oxygen requirement.
- •Urgent or expected need for nasal high-flow oxygen therapy or positive pressure ventilation, invasive mechanical ventilation or ECMO.
- •Participants who have taken or require treatment with a comedication that is a strong CYP450 3A4 inhibitor (atazanavir, clarithromycin, itraconazole, posaconazole, voriconazole, nefazodone, nelfinavir, grapefruit juice, HIV protease inhibitors), strong CYP450 3A4 inducers (rifampin, phenytoin, carbamazepine, St. John's Wort) or sensitive substrates of CYP450 2C8 and 2B6 (repaglinide, rosiglitazone, paclitaxel, bupropion) within at least 2 weeks or 5 half-lives (whichever is longer) before the planned first dose of study drug.
- •Participating in another CTIMP trial within 5 half-lives of the last administered dose of an investigational medicinal product.
- •Participants eligible for other antiviral treatment according to DHSC criteria, or those otherwise eligible for CST9a.
研究组 & 干预措施
CST-2 EIDD-2801 Phase Ib
EIDD-2801 (also known as MK-4482, molnupiravir). Phase Ib: EIDD-2801 will be administered orally, twice daily (BID) for 10 doses (5 or 6 days). The starting dose will be established based on safety and pharmacokinetics from the EIDD-2801-1001-US/UK study, and dose escalations may occur as described in this CST.
干预措施: CST-2: EIDD-2801 (Drug)
CST-9a Combination
Phase II: ALG-097558 600 mg twice a day orally for 5 days in combination with IV remdesivir for 3 days (200 mg day 1, 100 mg day 2 and 3)
干预措施: ALG-097558 and Remdesivir (Drug)
CST-9a Control
Phase II : standard of care
干预措施: NHS standard of care as per COVID-19 treatment guidelines (Drug)
CST-2 Control
Phase 1b only (standard of care)
CST-2 Placebo
Phase II placebo blinded controlled
干预措施: CST-2: Placebo (Drug)
CST-5 Placebo Phase I
Phase I: placebo blinded controlled
干预措施: CST-5: Placebo (Drug)
CST3B Control
Standard of care
CST6 Control
Standard of care
CST-2 EIDD-2801 Phase II
EIDD-2801 (also known as MK-4482, molnupiravir).
Phase II: As per Phase Ib, with the dose determined by the recommended phase II dose.
干预措施: CST-2: EIDD-2801 (Drug)
CST-8 Phase I Molnupiravir + Paxlovid® Control
Standard of care
CST-5 Placebo Phase II
Phase II: placebo blinded controlled
干预措施: CST-5: Placebo (Drug)
CST-9b: placebo for ALG097558
干预措施: Placebo (Drug)
CST-3A Nitazoxanide
Phase Ia Nitazoxanide will be administered orally, initially twice daily (BID) for 14 doses (7 days). The starting dose will be 1500mg BID based on existing dose information, but dose adaptations may occur
干预措施: Nitazoxanide (Drug)
CST-5 VIR-7831 Phase II
Phase II: 500 mg dose of VIR-7831 will be given by IV infusion.
干预措施: VIR-7831 (Drug)
CST-5 VIR-7832
Phase II: 500 mg dose of VIR-7832 will be given by IV infusion.
干预措施: VIR-7832 (Drug)
CST-9a Monotherapy
Phase II: ALG-097558 600 mg twice a day orally for 5 days
干预措施: ALG-097558 (Drug)
CST-8 Phase I Molnupiravir + Paxlovid®
Molnupiravir 800mg Twice a day (BD) in combination with Paxlovid® (300mg nirmatrelvir + ritonavir 100mg) twice a day (BD) for 5 days as starting dose, with a de-escalation protocol reducing in increments of molnupiravir to 600mg BD, then 400mg BD if required. The dose of Paxlovid® will be fixed for all cohorts.
干预措施: Paxlovid (Drug)
CST6 IV Favipiravir
IV Favipiravir twice daily for 7 days. Starting dose 600 mg twice daily. Dose escalation to 1200 mg twice daily, 1800 twice daily, 2400 twice daily.
干预措施: Favipiravir (Drug)
CST-5 VIR-7832 Phase I
Phase I: Single doses of VIR-7832 will be administered by intravenous (IV) infusion. The starting dose will be 50 mg, and dose escalations of 150 and 500 mg are anticipated.
干预措施: VIR-7832 (Drug)
CST-9a Combination
Phase II: ALG-097558 600 mg twice a day orally for 5 days in combination with IV remdesivir for 3 days (200 mg day 1, 100 mg day 2 and 3)
干预措施: ALG-097558 (Drug)
CST3B Nitazoxanide
Phase II experimental arm.
干预措施: Nitazoxanide (Drug)
CST-9b: ALG-097558
twice daily dose for 5 days
干预措施: ALG-097558 (Drug)
CST-8 Phase I Molnupiravir + Paxlovid®
Molnupiravir 800mg Twice a day (BD) in combination with Paxlovid® (300mg nirmatrelvir + ritonavir 100mg) twice a day (BD) for 5 days as starting dose, with a de-escalation protocol reducing in increments of molnupiravir to 600mg BD, then 400mg BD if required. The dose of Paxlovid® will be fixed for all cohorts.
干预措施: Molnupiravir (Drug)
结局指标
主要结局
CST-9b
时间窗: 11 Days from randomisation
AEs, SAEs
CST-9b
时间窗: 11 days from randomisation
Dose Limiting Toxicity (DLT) using CTCAE version 5 (grades 3 and above) up to and including Day 11
CST-9a: Sustained symptom resolution
时间窗: 29 days from randomisation
Symptom resolution evaluated through questionnaires
CST-9a: Change in viral titre overtime following administration of ALG-097558 alone and in combination with RDV versus Standard of Care (SoC)
时间窗: 11 days from randomisation
Qualitative (and quantitative when possible) PCR for SARS-CoV-2 by nose and throat swab
Master Protocol: Dose-finding/Phase I
时间窗: 29 days from randomisation
Determination of a dose(s) for efficacy evaluation. Dose limiting toxicities (Safety and Tolerability of drug under study - CTCAE v5 Grade ≥3 adverse events)
Master Protocol: Efficacy evaluation/Phase II - Severe patients (Group A)
时间窗: 29 days from randomisation
Determination of activity and safety. In severe patients (Group A): time to clinical improvement. Improvement will be determined according to the WHO Clinical Progression Scale; improvement is defined as a minimum 2-step change from randomisation in the scale up to day 29 post-randomisation.
Master Protocol: Efficacy evaluation/Phase II - Mild to moderate patients (Group B)
时间窗: 15 days from randomisation
Determination of activity and safety. In mild to moderate patients (Group B): pharmacodynamics of drug under study, defined as time to negative viral titres in nose and/or throat swab, measured up to 15 days post-randomisation.
CST-2 Phase I: To determine the safety and tolerability of multiple ascending doses of EIDD-2801 to recommend dose for phase II.
时间窗: 7 days from randomisation
Dose limiting toxicity (DLT) using CTCAE version 5 (grades 3 and above) over 7 days. CTCAE grading related to platelets and/or lymphocytes
CST-2 Phase II: To determine the ability of EIDD-2801 to reduce serious complications of COVID-19 including hospitalization, reduction in SAO2<92%, or death.
时间窗: 29 days from randomisation
Progression of disease (SpO2\<92% based on at least 2 consecutive recordings on the same day) or hospitalization or death up to day 29
CST6 Phase I: To determine the safety and tolerability of multiple doses of IV Favipiravir in patients with COVID-19
时间窗: 29 days from randomisation
Adverse events and serious adverse events
CST6 Phase I: To determine the maximum safe dose of IV Favipiravir for efficacy evaluation in phase II
时间窗: 8 days from randomisation
Dose limiting toxicities (Safety and Tolerability of IV Favipiravir- CTCAE v5 Grade ≥3 adverse events)
CST-8 Phase I: Dose Limiting Toxicities up to and including Day 11
时间窗: 11 days from randomisation
Dose limiting toxicities (Safety and Tolerability of molnupiravir and Paxlovid® combination - CTCAE v5 Grade ≥3 adverse events) up to and including Day 11
CST-9a: Dose limiting toxicities up to and including Day 11
时间窗: 11 days from randomisation
Dose limiting toxicities (Safety and Tolerability of ALG-097558 and ALG-097558 plus remdesivir combination - CTCAE v5 Grade ≥3 adverse events) up to and including Day 11
CST-9a: to determine the safety and tolerability of ALG-097558 and ALG-097558 plus remdesivir combination
时间窗: 11 days from randomisation
Adverse events, serious adverse events, physical findings, vital signs, ECG and laboratory parameters
次要结局
- Master Protocol: Safety assessed by rate of adverse events(Up to 29 days from randomisation)
- Master Protocol: To evaluate clinical improvement(From randomisation to day 29)
- Master Protocol: To evaluate clinical improvement using WHO clinical progression scale(From randomisation to day 15)
- CST-9b(11 days from randomisation)
- CST-9b(29 Days from randomisation)
- CST-9b(11 Days from randomisation)
- Master Protocol: To evaluate clinical improvement using WHO clinical progression scale(From randomisation to day 29)
- Master Protocol: To evaluate clinical improvement using SpO2/FiO2(From randomisation to day 29)
- Master Protocol: To evaluate discharge(From randomisation to day 29)
- Master Protocol: To evaluate admission to ICU(From randomisation to day 29)
- Master Protocol: To evaluate safety further (WCC)(From randomisation to day 29)
- Master Protocol: To evaluate safety further (Hg)(From randomisation to day 29)
- Master Protocol: To evaluate safety further (platelets)(From randomisation to day 29)
- Master Protocol: To evaluate safety further (creatinine)(From randomisation to day 29)
- Master Protocol: To evaluate safety further (ALT)(From randomisation to day 29)
- Master Protocol: To evaluate overall mortality(From randomisation to day 29)
- Master Protocol: To evaluate the number of oxygen-free days(From randomisation to day 29)
- Master Protocol: To evaluate ventilator-free days(From randomisation to day 29)
- Master Protocol: To evaluate incidence of new mechanical ventilation use(From randomisation to day 29)
- Master Protocol: To evaluate National Early Warning Score (NEWS)2/qSOFA(From randomisation to day 29)
- Master Protocol: To evaluate translational outcomes (Viral Load)(From randomisation to day 29)
- Master Protocol: To evaluate translational outcomes (Baseline SARS-COV-2)(From randomisation to day 29)
- CST-2 Additional: Pharmacokinetic Objective: To define PK of EIDD-2801 and EIDD-1931 in plasma following multiple doses administered to patients with COVID-19.(Samples collected on Day 1 and Day 5 post-randomisation)
- CST-2 Additional: Virologic Objective: To assess the difference in viral clearance (time to negative PCR) between EIDD-2801 and control.(Swabs taken on Day 1 (day of randomisation), 3, 5, 8, 11, 15, 22 and 29)
- CST-2 Additional: Clinical Objective: To determine the ability of EIDD-2801 to reduce the duration of signs and symptoms of COVID-19 in patients (FLU-PRO)(From randomisation to Day 29)
- CST-2 Additional: Clinical Objective: To determine the ability of EIDD-2801 to reduce the duration of signs and symptoms of COVID-19 in patients (WHO Scale).(From randomisation to Day 29)
- CST-2 Additional: Clinical Objective: To determine the ability of EIDD-2801 to reduce the duration of signs and symptoms of COVID-19 in patients (NEWS2)(From randomisation to Day 29)
- CST-2 Additional: Clinical Objective: To determine the ability of EIDD-2801 to reduce the duration of signs and symptoms of COVID-19 in patients (mortality)(From randomisation to Day 29)
- CST-2 Additional: Clinical Objective: To determine the ability of EIDD-2801 to reduce the duration of signs and symptoms of COVID-19 in patients (death)(From randomisation to Day 29)
- CST-6 Additional: To characterise the pharmacokinetics (PK) of multiple doses of IV Favipiravir(From randomisation to Day 8)
- CST-6 Additional: To investigate the ability of IV Favipiravir to reduce the duration of signs and symptoms of COVID-19 in-patients(Randomisation to Day 15 and Day 29)
- CST-6 Additional: To investigate the effect of IV Favipiravir on SARS-CoV-2 viral load(From randomisation to Day 29)
- CST-8: Assess feasibility for late phase study by reviewing any recorded AEs and SAEs(From randomisation to Day 29)
- CST-8: Assess feasibility for late phase study by reviewing hospitalisation or death up to Day 29(From randomisation to Day 29)
- CST-8: Measure concentrations of IMP re evidence of virological efficacy(From randomisation to Day 11)
- CST-8: Measure PK of each drug within the combination(From randomisation to Day 11)
- CST8: Review evidence of virological efficacy via viral elimination slopes(From baseline to Day 11)
- CST8: Vital signs (Heart Rate) at Screening, Baseline/Day 1, Day 3, Day 5 and Day 11(From randomisation to Day 11)
- CST-8: Vital signs (Blood Pressure) at Screening, Baseline/Day 1, Day 3, Day 5 and Day 11(From randomisation to Day 11)
- CST-8: Vital signs (Respiratory Rate) at Screening, Baseline/Day 1, Day 3, Day 5 and Day 11(From randomisation to Day 11)
- CST-8: Vital signs (Temperature) at Screening, Baseline/Day 1, Day 3, Day 5 and Day 11(From randomisation to Day 11)
- CST-8: Vital signs (Oxygen Saturation) at Screening, Baseline/Day 1, Day 3, Day 5 and Day 11(From randomisation to Day 11)
- CST-9a: incidence of rebound SARS-CoV-2 infection(From randomisation to Day 29)
- CST-9a: Measure PK of ALG-097558 plus remdesivir in plasma(Day 1 to day 3)
- CST-9a: establish disease progression endpoints including visits to emergency department, hospitalisations, all- cause mortality(From randomisation to Day 29)
- CST-9a: Symptom improvement in subgroup of severely immunosuppressed participants or with high baseline viral titre(From randomisation to Day 29)
- CST-9: Viral dynamics in subgroup of severely immunosuppressed participants or with high baseline viral titre(From randomisation to Day 29)