European DisCoVeRy for Solidarity: An Adaptive Pandemic and Emerging Infection Platform Trial (SolidAct)

The primary objective of the study is to evaluate the effect of **therapeutic interventions** on the occurrence of disease progression in hospitalized patients with moderate COVID-19 and on the occurrence of death in those with severe or critical COVID-19. Additionally, the study aims to assess the effect of **baricitinib** versus placebo, added to standard of care, on the occurrence of death in hospitalized immunocompromised patients with severe or critical COVID-19. These objectives are clinically relevant as they address critical outcomes in the management of COVID-19, potentially informing treatment strategies to reduce mortality and disease severity.

Secondary objectives include:

• Determining the effect of therapeutic interventions on other clinical endpoints, viral clearance, biochemical parameters, and patient-reported outcomes.
• Assessing the safety impact of therapeutic interventions on major serious adverse events.
• Comparing the efficacy of baricitinib versus placebo on disease progression, time to sustained recovery, time to first hospital discharge, major serious adverse events, patient-reported outcomes, viral clearance, and markers of systemic inflammation.

The clinical trial involves participants diagnosed with **SARS-CoV II infection (Coronavirus disease)**, focusing on hospitalized patients with moderate to severe or critical COVID-19. The study population includes both male and female subjects aged 18 years and older. Participants are selected based on laboratory-confirmed SARS-CoV-2 infection, with a requirement for hospital admission. The trial includes immunocompromised individuals, such as those with hematological malignancies, organ transplant recipients, and patients with autoimmune disorders under systemic immunosuppressive treatment. The sponsor has not provided the total number of participants. The trial population is characterized by a vulnerable group, considering the severe health implications of the disease and the immunocompromised status of some participants. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **baricitinib** in hospitalized patients with severe or critical **COVID-19**. This is a Phase 3, randomized, double-blind, placebo-controlled trial. The trial aims to assess the effect of baricitinib, in addition to standard of care (SoC), on the occurrence of death in immunocompromised patients. The trial is expected to last until May 18, 2023, with recruitment having started on April 22, 2022. Participants will be involved in the study for a maximum treatment period of 14 days, with a maximum daily dose of 4 mg of baricitinib, administered orally in the form of film-coated tablets.

The study includes several key visits: an initial screening visit, follow-up visits, and an end-of-study visit. During the screening visit, eligibility criteria are assessed, including age (≥18 years), laboratory-confirmed SARS-CoV-2 infection, and hospitalization status. Participants must also exhibit elevated inflammatory markers and meet specific criteria for severe or critical disease. Informed consent is required. Follow-up visits will monitor disease progression, adverse events, and biochemical parameters. The end-of-study visit will evaluate the primary and secondary endpoints, including the occurrence of death within 60 days and disease progression within 28 days.

Participants may be withdrawn from the study if they experience serious adverse events leading to treatment discontinuation or if they no longer meet the inclusion criteria. The trial's primary endpoints focus on the occurrence of death within 60 days, while secondary endpoints include disease progression, time to recovery, and viral clearance. The trial is not classified as low intervention, given the investigational nature of baricitinib in this specific patient population. The study is conducted under a master protocol, with specific objectives for moderate and severe disease states, ensuring a comprehensive evaluation of therapeutic interventions in the context of the ongoing pandemic.

The clinical trial involves the administration of **Olumiant** 2 mg film-coated tablets, which contain the active substance **baricitinib**. Baricitinib is a chemical compound, also known by its synonyms LY-3009104 and INCB-028050. The pharmaceutical form of the medication is a film-coated tablet, designed for **oral use**. The maximum daily dose is 4 mg, with a total maximum dose of 56 mg over a treatment period of 14 days. The tablets used in the trial are manufactured, packaged, and labeled specifically for clinical trial use, differing from commercial tablets in debossing and other specifications. The trial tablets are provided by ELI LILLY NEDERLAND B.V. and are identical in unit formula to the commercial version, ensuring consistency in the active substance.

In addition to the experimental medication, a **placebo** is used to match the film-coated baricitinib 2 mg tablets. The placebo is designed to mimic the appearance of the active medication, ensuring blinding in the trial. The placebo does not contain any active substance and is used to compare the effects of baricitinib against a non-active treatment. The placebo is administered in the same manner as the active medication, maintaining the integrity of the study design.

Efficacy in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the occurrence of disease progression from moderate to severe/critical or death within 14 days for patients with moderate COVID-19, and the occurrence of death within 60 days for patients with severe or critical COVID-19. Specifically, for the **baricitinib** protocol, the primary endpoint is the occurrence of death within 60 days in hospitalized immunocompromised patients with severe or critical COVID-19.

Secondary endpoints will further evaluate efficacy by measuring the occurrence of disease progression within 28 days, time from randomization to sustained recovery, and time to first hospital discharge within 90 days. Additional assessments include disease state on a 5-point scale at Day 15 and 29, SpO2/FiO2-ratio at specific timepoints, viral clearance via SARS-CoV-2 PCR, and biochemical parameters such as inflammatory markers during hospitalization. The occurrence of serious adverse events leading to study treatment discontinuation or death will also be monitored. The Oslo COVID-19 QLQ-PW80 subscale scores at Day 91 will be used to assess quality of life outcomes.