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AGILE (Early Phase Platform Trial for COVID-19)

Phase 1
Active, not recruiting
Conditions
Covid19
Interventions
Drug: Molnupiravir
Drug: NHS standard of care as per COVID-19 treatment guidelines
Drug: Paxlovid
Registration Number
NCT04746183
Lead Sponsor
University of Liverpool
Brief Summary

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.

Detailed Description

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.

Candidate-Specific Trial 3 (CST-3A): Multicentre, Adaptive, Phase I trial to Determine the optimal dose, Safety and Efficacy of Nitazoxanide for the Treatment of COVID-19

Candidate-Specific Trial 3 (CST-3B): A Randomized, Multicentre, Seamless, Adaptive, Phase I/II trial to Determine the optimal dose, Safety and Efficacy of Nitazoxanide for the Treatment of COVID-19

Candidate-Specific Trial 5 (CST-5): Randomized, Multicentre, Seamless, Adaptive, Phase I/II Platform Study to Determine the Phase II dose of VIR-7832, and Evaluate the Safety and Efficacy of VIR-7831 and VIR-7832 for the Treatment of COVID-19

Candidate-Specific Trial 6 (CST-6): A Randomized, Multicentre, Seamless, Adaptive, Phase I/II Platform Study to Determine the Phase II dose and to Evaluate the Safety and Efficacy of intravenous Favipiravir for the Treatment of COVID-19

Candidate-Specific Trial 8 (CST-8): A Randomised, Multicentre, Seamless, Adaptive, Phase I Platform Study to Determine the recommended Phase II dose and Evaluate the Safety and Efficacy of antiviral combination of Molnupiravir and Paxlovid® for the Treatment of COVID-19

Candidate-Specific Trial 9 (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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
600
Inclusion Criteria

  1. Adults (≥18 years) with laboratory-confirmed* SARS-CoV-2 infection (PCR)

  2. Ability to provide informed consent signed by study patient or legally acceptable representative

  3. 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) .

  2. 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).

  3. 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:

  1. Has signs or symptoms of COVID-19 that began within 5 days of the planned first dose of study drug.

  2. Is in generally good health (except for current respiratory infection) and is free of uncontrolled chronic conditions.

  3. Is willing and able to comply with all study procedures and attending clinic visits through the 4th week.

  4. Has someone, aged ≥ 16 living in the same household during the dosing period.

CST-6 Additional inclusion criteria:

  1. 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)).
  2. Less than or equal to 14 days from onset of COVID-19 symptoms

CST-8 Inclusion Criteria:

  1. 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.

  2. 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:

  1. 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:

  2. 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:

  3. 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

Exclusion Criteria

  1. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >5 times the upper limit of normal (ULN)

  2. Stage 4 severe chronic kidney disease or requiring dialysis (i.e., estimated glomerular filtration rate <30 mL/min/1.73 m^2)

  3. Pregnant or breast feeding

  4. Anticipated transfer to another hospital which is not a study site within 72 hours

  5. Allergy to any study medication

  6. Patients taking other prohibited drugs (as outline in CST protocol) within 30 days or 5 times the half-life (whichever is longer) of enrolment

  7. Patients participating in another CTIMP trial

    N.B. The CST protocol exclusion criteria will take precedence over the master protocol exclusion criteria.

    CST-2 Exclusion Criteria:

    Additional criteria specific to this candidate are:

  8. Has a febrile respiratory illness that includes signs of pneumonia, or requires hospitalization, oxygenation, mechanical ventilation, or other supportive modalities.

  9. Has a platelet count less than 50x10^9/L, or lymphocytes less than 0.2x10^9/L, haemoglobin less than 10 g/dL, or has a disorder of the hematologic system including anaemic disorder or other blood dyscrasia, cancer of the hematologic system, history of bone marrow transplant, or other significant hematologic disease at screening.

  10. Is experiencing adverse events or laboratory abnormalities that are Grade 3 or above based on the CTCAE scale.

  11. Has clinically significant liver dysfunction or renal impairment.

  12. Has history of Hepatitis C infection or concurrent bacterial pneumonia.

  13. Has received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 30 days prior to the first dose of study drug.

  14. In the opinion of the investigator, has significant end-organ disease as a result of relevant comorbidities: chronic kidney disease, congestive heart failure, peripheral vascular disease including diabetic ulcers.

  15. Has a SaO2<95% by oximetry or has lung disease that requires supplemental oxygen.

  16. Has any condition that would, in the opinion of the investigator, put the patient at increased risk for participation in a clinical study.

CST-8 Exclusion Criteria:

For the purpose of the combination CST8 candidate-specific trial the following exclusion criteria also apply:

  1. Swallowing difficulties
  2. Known medical history of active liver disease
  3. Receiving dialysis or have known moderate to severe renal impairments (defined as CKD stage 4 or 5 or current acute kidney injury or most recent eGFR in the past 6 months <30 ml/min/1.73m2)
  4. Currently taking Paxlovid® or molnupiravir at time of screening
  5. Oxygen saturation of <92% on room air, or on their standard home oxygen supplementation
  6. Taking a drug which would put subject at unacceptable risk due to interaction or is contraindicated as per SPC for each IMP

CST-9a Exclusion Criteria:

Exclusion criteria has been amended from master protocol as:

  1. Prior SARS-CoV-2 infection <90 days before enrolment and/or received any COVID-19 vaccine dose <90 days before enrolment
  2. Alanine aminotransferase (ALT) >3 times the upper limit of normal (ULN) or Active Liver disease
  3. History or current evidence of cirrhosis
  4. 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
  5. Pregnant or breast feeding
  6. Anticipated transfer to another hospital which is not a trial site within 72 hours
  7. Known allergy to any trial medication
  8. Swallowing difficulties
  9. Currently receiving ALG-097558, Paxlovid, molnupiravir or remdesivir or any SoC therapy for COVID-19 at the time of screening
  10. Received sotrovimab at any point during the current SARS-CoV-2 infection
  11. Oxygen saturations <94% on room air
  12. Urgent or expected need for nasal high-flow oxygen therapy or positive pressure ventilation, invasive mechanical ventilation or ECMO.
  13. 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.
  14. Participating in another CTIMP trial

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
CST-5 VIR-7831 Phase IIVIR-7831Phase II: 500 mg dose of VIR-7831 will be given by IV infusion.
CST-3A NitazoxanideNitazoxanidePhase 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
CST-5 VIR-7832 Phase IVIR-7832Phase 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.
CST3B NitazoxanideNitazoxanidePhase II experimental arm.
CST6 IV FavipiravirFavipiravirIV 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.
CST-8 Phase I Molnupiravir + Paxlovid®MolnupiravirMolnupiravir 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.
CST-8 Phase I Molnupiravir + Paxlovid®PaxlovidMolnupiravir 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.
CST-5 VIR-7832VIR-7832Phase II: 500 mg dose of VIR-7832 will be given by IV infusion.
CST-9a MonotherapyALG-097558Phase II: ALG-097558 600 mg twice a day orally for 5 days
CST-9a CombinationALG-097558Phase 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)
CST-9a CombinationALG-097558 and RemdesivirPhase 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)
CST-9a ControlNHS standard of care as per COVID-19 treatment guidelinesPhase II : standard of care
Primary Outcome Measures
NameTimeMethod
Master Protocol: Dose-finding/Phase I29 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)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)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.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.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-1929 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 II8 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 1111 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 1111 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 combination11 days from randomisation

Adverse events, serious adverse events, physical findings, vital signs, ECG and laboratory parameters

CST-9a: Change in viral titre overtime following administration of ALG-097558 alone and in combination with RDV versus Standard of Care (SoC)11 days from randomisation

Qualitative (and quantitative when possible) PCR for SARS-CoV-2 by nose and throat swab

CST-9a: Sustained symptom resolution29 days from randomisation

Symptom resolution evaluated through questionnaires

Secondary Outcome Measures
NameTimeMethod
Master Protocol: Safety assessed by rate of adverse eventsUp to 29 days from randomisation

Adverse event rate according to CTCAE v5

Master Protocol: To evaluate clinical improvementFrom randomisation to day 29

Proportion of patients with clinical improvement (as defined above) at day 8, 15 and day 29.

Master Protocol: To evaluate clinical improvement using WHO clinical progression scaleFrom randomisation to day 29

Time to a one point change on the WHO Clinical Progression Scale

Master Protocol: To evaluate clinical improvement using SpO2/FiO2From randomisation to day 29

The ratio of the oxygen saturation to fractional inspired oxygen concentration (SpO2/FiO2)

Master Protocol: To evaluate dischargeFrom randomisation to day 29

Proportion of patient discharged at days 8, 15 and 29

Master Protocol: To evaluate admission to ICUFrom randomisation to day 29

Admission rate to ICU

Master Protocol: To evaluate safety further (WCC)From randomisation to day 29

White cell count on day 1, 3, 5, 8, 11 (while hospitalised); and Day 15 and 29

Master Protocol: To evaluate safety further (Hg)From randomisation to day 29

Haemoglobin on day 1, 3, 5, 8, 11 (while hospitalised); and Day 15 and 29

Master Protocol: To evaluate safety further (platelets)From randomisation to day 29

Platelets on day 1, 3, 5, 8, 11 (while hospitalised); and Day 15 and 29

Master Protocol: To evaluate safety further (creatinine)From randomisation to day 29

Creatinine on day 1, 3, 5, 8, 11 (while hospitalised); and Day 15 and 29

Master Protocol: To evaluate safety further (ALT)From randomisation to day 29

ALT on day 1, 3, 5, 8, 11 (while hospitalised); and Day 15 and 29

Master Protocol: To evaluate overall mortalityFrom randomisation to day 29

Mortality at Days 8, 15 and 29. Time to death from randomisation

Master Protocol: To evaluate the number of oxygen-free daysFrom randomisation to day 29

Duration (days) of oxygen use and oxygen-free days

Master Protocol: To evaluate ventilator-free daysFrom randomisation to day 29

Duration (days) of mechanical ventilation and mechanical ventilation-free days

Master Protocol: To evaluate incidence of new mechanical ventilation useFrom randomisation to day 29

Incidence of new mechanical ventilation use

Master Protocol: To evaluate National Early Warning Score (NEWS)2/qSOFAFrom randomisation to day 29

NEWS2/qSOFA assessed daily while hospitalised

Master Protocol: To evaluate translational outcomes (Viral Load)From randomisation to day 29

Change in viral load over time

Master Protocol: To evaluate translational outcomes (Baseline SARS-COV-2)From randomisation to day 29

Change in viral load over time

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

Concentrations of EIDD-2801 and -1931 in plasma

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

Qualitative (and quantitative when possible) PCR for SARS-CoV-2 by nasal swab.

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

Patient Reported Outcome Measures (FLU-PRO).

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

WHO Progression Scale at day 15 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 (NEWS2)From randomisation to Day 29

NEWS2 (National Early Warning Score2) assessed during study clinic visit on days 15 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 (mortality)From randomisation to Day 29

Mortality at Days 15 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 (death)From randomisation to Day 29

Time from randomisation to death

CST-6 Additional: To characterise the pharmacokinetics (PK) of multiple doses of IV FavipiravirFrom randomisation to Day 8

Plasma PK parameters of IV Favipiravir

CST-6 Additional: To investigate the ability of IV Favipiravir to reduce the duration of signs and symptoms of COVID-19 in-patientsRandomisation to Day 15 and Day 29

WHO Progression Scale (WHO, 2020)

CST-6 Additional: To investigate the effect of IV Favipiravir on SARS-CoV-2 viral loadFrom randomisation to Day 29

Viral load change from baseline over time

CST-8: Assess feasibility for late phase study by reviewing any recorded AEs and SAEsFrom randomisation to Day 29

Review of any adverse events

CST-8: Assess feasibility for late phase study by reviewing hospitalisation or death up to Day 29From randomisation to Day 29

Death and hospitalisation up to Day 29

CST-8: Measure concentrations of IMP re evidence of virological efficacyFrom randomisation to Day 11

PK concentrations of both IMPs and their circulating metabolites in plasma.

CST-8: Measure PK of each drug within the combinationFrom randomisation to Day 11

PK concentrations of both IMPs and their circulating metabolites in plasma.

CST8: Review evidence of virological efficacy via viral elimination slopesFrom baseline to Day 11

Qualitative (and quantitative when possible) PCR for SARS-CoV-2 by nose and throat swab

CST8: Vital signs (Heart Rate) at Screening, Baseline/Day 1, Day 3, Day 5 and Day 11From randomisation to Day 11

Vital sign measure 1 heart rate (beats/min) - to be part of aggregated review of pt vitals to assess safety and tolerability.

CST-8: Vital signs (Blood Pressure) at Screening, Baseline/Day 1, Day 3, Day 5 and Day 11From randomisation to Day 11

Vital sign measure 2 Blood Pressure (mmHG) - to be part of aggregated review of pt vitals to assess safety and tolerability.

CST-8: Vital signs (Respiratory Rate) at Screening, Baseline/Day 1, Day 3, Day 5 and Day 11From randomisation to Day 11

Vital sign measure 3 respiratory rate (breaths/min) - to be part of aggregated review of pt vitals to assess safety and tolerability.

CST-8: Vital signs (Temperature) at Screening, Baseline/Day 1, Day 3, Day 5 and Day 11From randomisation to Day 11

Vital sign measure 4 temperature (degrees c) - to be part of aggregated review of pt vitals to assess safety and tolerability.

CST-8: Vital signs (Oxygen Saturation) at Screening, Baseline/Day 1, Day 3, Day 5 and Day 11From randomisation to Day 11

Vital sign measure 5 oxygen saturation (FiO2 as %) - to be part of aggregated review of pt vitals to assess safety and tolerability.

CST-9a: incidence of rebound SARS-CoV-2 infectionFrom randomisation to Day 29

Proportion of participants with clinical and/or virologic rebound

CST-9a: Measure PK of ALG-097558 plus remdesivir in plasmaDay 1 to day 3

PK concentrations of ALG-097558 and remdesivir and metabolites in plasma

CST-9a: establish disease progression endpoints including visits to emergency department, hospitalisations, all- cause mortalityFrom randomisation to Day 29

Death, hospitalisation, and hospital/GP visits

CST-9a: Symptom improvement in subgroup of severely immunosuppressed participants or with high baseline viral titreFrom randomisation to Day 29

Symptom improvement evaluated through questionnaires

CST-9: Viral dynamics in subgroup of severely immunosuppressed participants or with high baseline viral titreFrom randomisation to Day 29

Viral dynamics in subgroup of severely immunosuppressed participants or with high baseline viral titre

Trial Locations

Locations (6)

Manchester University NHS Foundation Trust

🇬🇧

Manchester, United Kingdom

Desmond Tutu Health Foundation

🇿🇦

Cape Town, South Africa

Ezintsha

🇿🇦

Johannesburg, South Africa

Kings College Hospital NHS Foundation Trust

🇬🇧

London, United Kingdom

University Hospital Southampton NHS Foundation Trust

🇬🇧

Southampton, United Kingdom

Liverpool University Hospitals NHS Foundation Trust

🇬🇧

Liverpool, United Kingdom

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