This is a multicentre, randomised, open-label, adaptive clinical study on the safety and efficacy of treatments for COVID-19 in patients treated on an out-patient basis. As there is no validated animal model for COVID-19, the efficacy of any potential treatment remains speculative beyond what is known about their pharmacokinetic and in-vitro data.

Several repurposed drugs are currently being tested in severe cases or as prophylaxis, and the results may become available by the time the present study is initiated. At the same time, a number of other drug candidates are being evaluated for in-vitro efficacy or in small proof-ofconcept studies.In view of the rapidly evolving landscape in Africa, it was decided to select an adaptive design for the study in order to allow for the flexibility of adding or dropping arms or adjusting the randomisation ratio based on the data as it becomes available.

Additionally, given that the control arm in the study may not be acceptable in some countries, it was decided to adopt a master platform-based approach to be allow for integration of data from all sites in the interim analyses, irrespective of their ability to have randomised patients in all treatment arms..

In the context of COVID-19, and at the time of protocol development, patients may spontaneously present to hospital for diagnosis in various clinical contexts 

• asymptomatic, but perceived as at risk;

• with viral syndrome without uncomplicated pneumonia, i.e. presence of fatigue, irregular fever, chills, muscle pain, sore throat, rhinitis, etc.;

• with uncomplicated pneumonia, i.e. SpO2 > 94%, crackles on auscultation, irregular breathing difficulties but respiratory rate < 30/min;

• moderate to severe pneumonia with SpO2 < 93%, with our without mental confusion, with our without respiratory rate > 30/min, with our without BP < 90/60mm Hg.

All patients will be tested for the presence of SARS-CoV-2 using the available molecular assay. Different strategies will apply among the afore-mentioned four categories of patients who test positive for SARS-CoV-2:

• asymptomatic patients will not be randomised but will be monitored by the medical team for disease progression based on national guidelines;

• patients with viral syndrome, without uncomplicated pneumonia will be randomised in the study;

• patients with uncomplicated pneumonia will be randomised in the study; and

• patients with moderate to severe pneumonia will be hospitalised and potentially referred to other studies such as SOLIDARITY*.

Clinical Study Phase III

Study Design- Multicentre, randomised, open-label, adaptative master protocol / platform study

Primary Objective

The primary objective is to compare the efficacy of alternative treatment strategies versus control on the risk of progression to severe respiratory disease

Secondary Objectives

The secondary objectives are:

• To compare the safety of each study arm to control, up to Day 21 of follow-up

• To compare the rate of hospitalisations due to COVID-19 in each study arm versus control

• To compare the time to hospitalisation due to COVID-19 in each study arm versus control

• To compare the disease-free rate in each study arm versus control

• To compare the death rate in each study arm versus control

• To compare time to worsening of SpO2 < 93in each study arm versus control

• To compare the capacity to prevent severe progression between study arms

• To identify risk factors for severe progression

• To assess efficacy in sub-groups of patients e.g. with pre-existing conditions/co-morbidities, by age group, sex, BMI, timeframe between onset of symptoms and randomisation

Dose Doses used are within those for the registered indications of the IPs

Route of Administration Oral

Duration of Treatment Up to 14 days depending on the treatment arm

Study Duration Patient participation in the master study will be 22 days.

Indication Mild / Moderate COVID-19