Tofacitinib in Hospitalized Patients With COVID-19 Pneumonia

NCT ID: NCT04469114

Last Updated: 2021-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 289 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-16
• Study Completion Date: 2021-01-09

Brief Summary

Tofacitinib suppresses pro-inflammatory signaling that may be important pathogenetically to progression to more severe lung disease and acute respiratory distress syndrome (ARDS) in patients with COVID-19. The purpose of the study is to assess the safety and efficacy of tofacitinib plus standard pharmacologic and supportive measures in treating hospitalized participants with COVID-19 pneumonia.

Detailed Description

COVID-19 is a viral disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that can cause severe pneumonia and ARDS. Respiratory viral load may peak within 5 days after onset, while symptoms are still mild. Many patients rapidly (within 1 to 2 weeks of infection) develop dyspnea and pneumonia and require hospitalization for respiratory support.

Preliminary clinical data from COVID-19 patients indicate that severe symptoms with SARS-CoV-2 infection are associated with an exaggerated immune response driven by interleukin (IL)-6 IL-10, tumor necrosis factor (TNF)α, and other cytokines. The ultimate result is progressive destruction of the alveolar epithelium leading to pneumonia and/or ARDS. Moreover, the exudative phase of ARDS is thought to be due to an influx of myeloid cells (neutrophils and macrophages) and elevations of inflammatory cytokines, with higher levels of both IL-6 and IL-8 levels being correlated with increased mortality. Therefore, immunomodulatory therapy may be beneficial in reducing the deleterious effects of lung inflammation and mitigating progressive lung injury.

Tofacitinib is an inhibitor of Janus kinase (JAKs) 1 and 3, with partial selectivity to JAK 2. Tofacitinib suppresses pro-inflammatory signaling that may be important pathogenetically to progression to more severe lung disease and ARDS in patients with COVID-19.

The purpose of the study is to assess the safety and efficacy of tofacitinib plus standard pharmacologic and supportive measures in treating hospitalized participants with COVID-19 pneumonia.

Participants with laboratory confirmed SARS-CoV-2 infection as determined by a positive PCR, who have agreed to participate, will be screened within 72h hours after admission to the hospital to determine eligibility.

Eligible participants will be randomized on Day 1 to the tofacitinib plus standard of care treatment group or the placebo plus standard of care treatment group in a 1:1 ratio, stratified by site. Participants will receive treatment for up to 14 days or until discharge from the hospital, whichever is earlier.

Participants will be assessed daily (up to Day 28) while hospitalized for clinical, safety, and laboratory parameters. Follow-up visits will occur on Day 14 and on Day 28.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Tofacitinib

Tofacitinib 10mg twice daily for 14 days or until hospital discharge

Group Type: EXPERIMENTAL

Tofacitinib 10 mg

Intervention Type: DRUG

Tofacitinib 10mg administered orally twice daily for 14 days or until hospital discharge

Placebo

Placebo twice daily for 14 days or until hospital discharge

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Tofacitinib-matching placebo administered orally twice daily for 14 days or until hospital discharge

Interventions

Tofacitinib 10 mg

Tofacitinib 10mg administered orally twice daily for 14 days or until hospital discharge

Intervention Type: DRUG

Placebo

Tofacitinib-matching placebo administered orally twice daily for 14 days or until hospital discharge

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female participants older than 18 years

2. Laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR) prior to Day 1.

3. Evidence of pneumonia assessed by radiographic imaging (chest x-ray or chest CT scan).

4. Hospitalized for less than 72 hours and receiving supportive care for COVID-19

Exclusion Criteria

1. Require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) on Day 1 at the time of randomization

2. History of or known current thrombosis. Only if current thrombosis is suspected by the investigator, imaging testing is recommended (per local guidance) to exclude thrombosis.

3. Have a personal or first-degree family history of blood clotting disorders.

4. Participants who are immunocompromised, with known immunodeficiencies, or taking potent immunosuppressive agents (eg, azathioprine, cyclosporine).

5. Participants with any current malignancy or lymphoproliferative disorders that requires active treatment

6. Severe hepatic impairment, defined as Child-Pugh class C.

7. Severe anemia (hemoglobin <8 g/dL).

8. Absolute lymphocyte count <500 cells/mm;

9. Absolute neutrophil count <1000 cells/mm.

10. Known allergy to tofacitinib.

11. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk associated with study participation or, in the investigator's judgment, make the participant inappropriate for the study.

12. Suspected or known active systemic bacterial, fungal, or viral infections (with the exception of COVID-19) including but not limited to: active herpes zoster infection; known active tuberculosis or history of inadequately treated tuberculosis; known B hepatitis, C hepatitis, or HIV.

13. Have received any of these within 4 weeks prior to the first dose of study intervention: any JAK inhibitors, potent immunosuppressants, or any biologic agents including IL-6 inhibitors (eg, tocilizumab) or IL-1 inhibitors (eg, anakinra) within the past 30 days; any potent cytochrome P450 inducer, such as rifampin, within the past 28 days or 5 half-lives, whichever is longer.

14. Have received estrogen-containing contraception or treatment with herbal supplements within 48 hours prior to the first dose of study intervention.

15. Have received treatment with corticosteroids equivalent to prednisone or methylprednisolone >20 mg/day for equal or more than 14 consecutive days prior to screening.

16. Current participation in other trials.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Hospital Israelita Albert Einstein

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Centro de Pesquisa Clínica do Coração

Aracaju, , Brazil

Hospital Universitário São Francisco de Assis Na Providência de Deu

Bragança Paulista, , Brazil

Irmandade do Sr. Bom Jesus dos Passos da Santa Casa de Misericórdia de Bragança Paulista

Bragança Paulista, , Brazil

Hospital do Coração do Brasil

Brasília, , Brazil

Instituto de Pesquisa Clínica de Campinas

Campinas, , Brazil

Hospital Regional do Litoral Norte

Caraguatatuba, , Brazil

Unimed Fortaleza Sociedade Corporativa Médica LTD

Fortaleza, , Brazil

Hospital Regional Jorge Rossmann

Itanhaém, , Brazil

Hospital Bruno Born

Lajeado, , Brazil

Hospital São Vicente de Paulo

Passo Fundo, , Brazil

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, , Brazil

Hospital Regional de Registro

São José dos Campos, , Brazil

Hospital Regional de São José dos Campos

São José dos Campos, , Brazil

Beneficência Portuguesa

São Paulo, , Brazil

BP Mirante

São Paulo, , Brazil

Hospital Israelita Albert Einstein

São Paulo, , Brazil

Instituto do Coração

São Paulo, , Brazil

Countries

Brazil

References

Guimaraes PO, Damiani LP, Tavares CAM, Halpern ASR, Deuring JJ, Rizzo LV, Berwanger O. Laboratory profiles of patients hospitalized with COVID-19 pneumonia treated with tofacitinib or placebo: a post hoc analysis from the STOP-COVID trial. Einstein (Sao Paulo). 2024 Nov 4;22:eAO0821. doi: 10.31744/einstein_journal/2024AO0821. eCollection 2024.

Reference Type: DERIVED

PMID: 39504090 (View on PubMed)

Kramer A, Prinz C, Fichtner F, Fischer AL, Thieme V, Grundeis F, Spagl M, Seeber C, Piechotta V, Metzendorf MI, Golinski M, Moerer O, Stephani C, Mikolajewska A, Kluge S, Stegemann M, Laudi S, Skoetz N. Janus kinase inhibitors for the treatment of COVID-19. Cochrane Database Syst Rev. 2022 Jun 13;6(6):CD015209. doi: 10.1002/14651858.CD015209.

Reference Type: DERIVED

PMID: 35695334 (View on PubMed)

Guimaraes PO, Quirk D, Furtado RH, Maia LN, Saraiva JF, Antunes MO, Kalil Filho R, Junior VM, Soeiro AM, Tognon AP, Veiga VC, Martins PA, Moia DDF, Sampaio BS, Assis SRL, Soares RVP, Piano LPA, Castilho K, Momesso RGRAP, Monfardini F, Guimaraes HP, Ponce de Leon D, Dulcine M, Pinheiro MRT, Gunay LM, Deuring JJ, Rizzo LV, Koncz T, Berwanger O; STOP-COVID Trial Investigators. Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med. 2021 Jul 29;385(5):406-415. doi: 10.1056/NEJMoa2101643. Epub 2021 Jun 16.

Reference Type: DERIVED

PMID: 34133856 (View on PubMed)

Other Identifiers

34810620.0.1001.0071

Identifier Type: -

Identifier Source: org_study_id