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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital Hf

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

3 Jun 2021 → 23 Jan 2023

Decision date (initial)

2022-05-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

European Union’s Horizon 2020 Research and Innovation Program under grant agreement No 101015736 · Eli Lilly (providing baricitinib and matching placebo)

External identifiers

EU CT number

2022-500385-99-00

EudraCT number

2021-000541-41

WHO UTN

U1111-1278-9084

ClinicalTrials.gov

NCT04891133

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

Master Protocol Number: 3.1 dated 28 November 2022

Phase 3 objectives

* Part A, moderate disease. The primary objective is to determine the effect of therapeutic interventions on occurrence of disease progression in hospitalized patients with moderate COVID-19.

* Part B, severe disease. The primary objective is to determine the effect of therapeutic interventions on occurrence of death in hospitalized patients with severe or critical COVID-19.

* Baricitinib-specific protocol v. 3.1 dated 28 November 2022: The primary objective is to determine the effect of baricitinib vs. placebo added to SoC on occurrence of death in hospitalized immunocompromised patients with severe or critical COVID-19.

Secondary objectives 10

1. Master Protocol: 1. to determine the effect of therapeutic interventions on other clinical endpoints
2. Master Protocol: 2. to determine the effect of therapeutic interventions on viral clearance
3. Master Protocol: 3. to determine the effect of therapeutic interventions on biochemical parameters
4. Master Protocol: 4. to assess the safety impact of therapeutic interventions on major serious adverse events
5. Master Protocol: 5. to determine the effect of therapeutic interventions on patient reported outcomes.
6. Baricitinib Protocol: 1. To compare the efficacy of baricitinib vs. placebo on disease progression, time to sustained recovery and time to first hospital discharge
7. Baricitinib Protocol: 2. To compare baricitinib vs. placebo on major SAE
8. Baricitinib Protocol: 3. To compare baricitinib vs. placebo on patient reported
9. Baricitinib Protocol: 4. To compare the efficacy of baricitinib vs. placebo on viral clearance
10. Baricitinib Protocol: 5. To compare the efficacy of baricitinib vs. placebo on markers of systemic inflammation

Conditions and MedDRA coding

SARS-CoV II infection (Coronavirus disease)

Study design 1 period

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Master Protocol: GI1. ≥ 18 years of age.
2. Baricitinib Protocol: GI4. Informed consent by the participant or legally authorized representative.
3. Baricitinib Protocol: GI5B: Severe/critical disease state defined as fulfilling at least one of the following criteria: 1. SpO2<90% on room air, or 2. SpO2 90-94% with a downwards trend and/or signs of respiratory distress*, or 3. Need of oxygen by NIV (CPAP, BIPAP), high flow or non-rebreather mask, or 4. Need of mechanical ventilation/ECMO *persistently increased respiratory rate, use of accessory muscles, inability to complete full sentences. Clinical judgement must be applied to determine whether a low oxygen saturation is indicative of disease progression or severity or is habitual for a given patient (i.e., with underlying chronic lung disease). NIV=non-invasive ventilation. CPAP= Continuous Positive Airway Pressure, BPAP= Bi-level Positive Airway Pressure, ECMO = extracorporeal membrane oxygenation.
4. Baricitinib Protocol: SI-01. Immunocompromised patients defined as the presence of at least one of the following conditions9: 1. Hematological malignancy or pre-malignancy, except acute leukemia or history of lymphoma 2. Organ transplant recipients, except recipients of bone marrow or solid organ transplant last 6 months, or with transplant rejection last 6 months 3. HIV positive with CD4 count < 350 cells and on stable antiretroviral therapy 4. Primary immunodeficiency 5. Rheumatoid arthritis, lupus, vasculitis, inflammatory bowel disease or other autoimmune disorder for which a patient is being treated with systemic immunosuppressive medication including but not limited to active treatment for solid tumor and hematologic malignancies, immunosuppressive therapy for solid-organ transplant, active treatment with high-dose corticosteroids (20 or more mg of prednisone or equivalent per day when administered for 2 or more weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, tumor necrosis factor (TNF) blockers, mTOR inhibitors, and other biologic agents that are immunosuppressive or immunomodulatory
5. Master Protocol: GI2. Laboratory-confirmed SARS-CoV-2 infection (new infection or reinfection) as determined by PCR not more than 14 days old.
6. Master Protocol: GI3. Admitted to hospital.
7. Master Protocol: GI4. Informed consent by the participant or legally authorized representative.
8. Master Protocol: GI5A: Moderate disease state defined as hospitalised patients without oxygen therapy or oxygen by mask or nasal prongs needed, or GI5B: Severe/critical disease state defined as fulfilliing at least one of the following criteria: 1. SpO2<90% on room air, or 2. SpO2 90-94% with a downwards trend and/or signs of respiratory distress*, or 3. Need of oxygen by NIV (CPAP, BIPAP), high flow or non-rebreather mask, or 4. Need of mechanical ventilation/ECMO *persistently increased respiratory rate, use of accessory muscles, inability to complete full sentences. Clinical judgement must be applied to determine whether a low oxygen saturation is indicative of disease progression or severity or is habitual for a given patient (i.e., with underlying chronic lung disease). NIV=non-invasive ventilation. CPAP= Continuous Positive Airway Pressure, BPAP= Bi-level Positive Airway Pressure, ECMO = Extracorporeal membrane oxygenation.
9. Master Protocol: GI5B: Severe/critical disease state defined as fulfilling at least one of the following criteria: 1. SpO2<90% on room air, or 2. SpO2 90-94% with a downwards trend and/or signs of respiratory distress*, or 3. Need of oxygen by NIV (CPAP, BIPAP), high flow or non-rebreather mask, or 4. Need of mechanical ventilation/ECMO.
10. Baricitinib Protocol: GI1. > 18 years of age.
11. Baricitinib Protocol: GI2. Laboratory-confirmed SARS-CoV-2 infection (new infection or reinfection) as determined by PCR in any specimen not more than 14 days old.
12. Baricitinib Protocol: GI3. Admitted to hospital
13. Baricitinib Protocol SI-02. Elevation of 2 or more inflammatory markers above the following cutoffs: Ferritin > 700 ug/l; LDH > 400 U/L; CRP >75 mg/L

Exclusion criteria 21

1. Master Protocol: GE1. Anticipated transfer to another non-trial hospital within 72 hours
2. Baricitinib Protocol: GE1. Anticipated transfer to another non-trial hospital within 72 hours.
3. Baricitinib Protocol: SE-01. Patients receiving Janus kinase (JAK) inhibitors (including baricitinib) for any indication at screening.
4. Baricitinib Protocol: SE-20. Have received tocilizumab or sarilumab for any indication 4 weeks prior to screening. Note: Tocilizumab as rescue therapy will be allowed in patients with clinical progression after inclusion, see section 6.8 concomitant medication. If tocilizumab or other immunosuppressive rescue therapy is started, IMP should be discontinued.
5. Baricitinib Protocol: SE-21. Patients with recent changes in immunosuppressive therapy that could interfere with the potential effect of baricitinib. Note: An assessment of the total level of immunosuppression, hematological parameters (SE-13 and SE-14), drug half-lives, drug-drug interactions, and underlying medical conditions (SE-22) must be performed as part of the risk/benefit evaluation. *Recipients of bone marrow transplant or solid organ transplant last 6 months, or with transplant rejection last 6 months, should not be included. *Organ transplant recipients receiving triple immunosuppression can only be included if the anti-metabolite (mycophenolic acid or mTOR inhibitor) has been temporarily discontinued per clinical practice. IMP should be discontinued once triple immunosuppression is restarted.
6. Baricitinib Protocol: SE-22. Any medical condition that in the opinion of the investigator poses an inacceptable risk of serious infection or aggravation of the medical condition by participating in the trial. Note: Patients with acute leukemia or history of lymphoma should not be included. Cancer patients under active treatment, HIV positive individuals with detectable HIVRNA, or other patient group associated with high risk of serious infection or aggravation of the medical condition should only be included if, in the judgement of the investigator, the potential benefit outweighs the potential risk.
7. Baricitinib Protocol: SE-03. Have received dexamethasone 6 mg daily (or alternative regimens with equivalent of corticosteroids) for more than 4 days prior to screening as part of SoC for severe/critical COVID-19.
8. Baricitinib Protocol: SE-04. Had COVID-related symptoms > 21 days or hospitalized > 7 days.
9. Baricitinib Protocol: SE-05. Strong inhibitors of organic anion transporter 3 [OAT3] (e.g., probenecid) that cannot be discontinued at study entry.
10. Baricitinib Protocol: SE-07. Have received any live vaccine within 4 weeks before screening, or intend to receive a live vaccine during the study (until day 90 (+/- 14 days)). Note: Use of non-live (inactivated) vaccinations, including COVID-19 vaccinations, is allowed for all participants.
11. Baricitinib Protocol: SE-08. Are using or will use extracorporeal blood purification (EBP) device to remove proinflammatory cytokines from the blood such as a cytokine absorption or filtering device, for example, CytoSorb®.
12. Baricitinib Protocol: SE-09. Have diagnosis of current active tuberculosis (TB) or, if known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening tests required).
13. Baricitinib Protocol: SE-10. Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID- 19) that in the opinion of the investigator could constitute a risk when taking investigational product.
14. Baricitinib Protocol: SE-12. Have a history of venous thromboembolism (VTE) (deep vein thrombosis [DVT] and/or pulmonary embolism [PE]) within 12 weeks prior to randomization or have a history of recurrent (>1) VTE (DVT/PE).
15. Baricitinib Protocol: SE-13. Neutropenia (absolute neutrophil count <1000 cells/microliters).
16. Baricitinib Protocol: SE-14. Lymphopenia (absolute lymphocyte count <200 cells/microliters).
17. Baricitinib Protocol: SE-15. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 times ULN.
18. Baricitinib Protocol: SE-16. Subjects with estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease [MDRD]) <30 millilitre/minute/1.73 meters squared are excluded.
19. Baricitinib Protocol: SE-17. Known hypersensitivity to baricitinib or any of its excipients.
20. Baricitinib Protocol: SE-18. Are pregnant or breastfeeding, or intend to become pregnant or breastfeed during the study. Note: Women of child bearing potential (WOCBP) can only be included based on a negative pregnancy test and WOCBP must comply with requirements regarding highly effective contraception. Refer to section Protocol section 10.1 for contraception requirements.
21. Baricitinib Protocol: SE-19 Participation in any therapeutic clinical trials investigating immunomodulators for COVID-19.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Master Protocol: Part A, moderate disease: Occurrence of disease progression, defined as a progression of disease state from moderate (WHO score 4-5) to severe/critical (WHO score 6-9) or death (WHO score 10) within 14 days.
2. Master Protocol: Part B, severe disease: Occurrence of death within 60 days.
3. Baricitinib Protocol: Occurrence of death within 60 days.

Secondary endpoints 17

1. Master Protocol: 1.1 Occurrence of disease progression, defined as a progression of disease state from moderate (WHO score 4-5) to severe/critical/death (WHO score 6-10) or from severe/critical (WHO score 6-9) to death within 28 days.
2. Master Protocol: 1.2 Time from randomization to sustained recovery, defined as being discharged from the index hospitalization, followed by being alive and at home for 14 consecutive days within 90 days.
3. Master Protocol: 1.3 Time from randomization to first hospital discharge within 90 days.
4. Master Protocol: 1.4 Disease state on a 5-point scale defined as 1. Mild (WHO score 1-3) or better, 2. Moderate (WHO score 4-5), 3. Severe (WHO score 6), 4. Critical (WHO score 7-9) or 5. Death at Day 15 and 29.
5. Master Protocol: 1.5 Time from randomization to recovery defined as no need for oxygen.
6. Master Protocol: 1.6 SpO2/FiO2-ratio at day 3, 5 and 8.
7. Master Protocol: 2. Viral clearance as assessed by SARS-CoV-2 PCR in oropharyngeal specimens during hospitalization.
8. Master Protocol: 3. Biochemical parameters including inflammatory markers (C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin, D-dimer, leukocyte subsets and cytokine panels) during hospitalisation.
9. Master Protocol: 4. Occurence of serious adverse events leading to study treatment discontinuation or death.
10. Master Protocol: 5. The Oslo COVID-19 QLQ-PW80 subscale scores at Day 91.
11. Baricitinib Protocol: 1. Occurrence of disease progression, defined as a progression from severe (WHO score 6) to critical/death (WHO score 7-10) or from critical (WHO score 7-9) to death within 28 days.
12. Baricitinib Protocol: 2. Time from randomization to sustained recovery, with sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days within 90 days
13. Baricitinib Protocol 3. Time from randomization to first hospital discharge within 90 days.
14. Baricitinib Protocol: 4. Disease state on a 5 point scale defined as 1. Mild (WHO score 1-3) or better, 2. Moderate (WHO score 4-5), 3. Severe (WHO score 6), 4. Critical (WHO score 7-9) or 5. Death at Day 15 and 29.
15. Baricitinib Protocol: 5. Occurrence of serious adverse events leading to study treatment discontinuation or death.
16. Baricitinib Protocol: 6. Viral clearance as assessed by SARS-CoV-2 PCR in oropharyngeal specimens during hospitalization.
17. Baricitinib Protocol: 7. Inflammatory markers (C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin, Ddimer, leukocyte subsets and cytokine panels) during hospitalisation.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital Hf

Sponsor organisation

Oslo University Hospital Hf

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital Hf

Contact name

Dr Inge Christoffer Olsen

Public contact point

Organisation

Oslo University Hospital Hf

Contact name

Thale Patrick-Brown

Locations

14 EU/EEA countries · 78 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications