Tofacitinib in Hospitalized Patients With COVID-19 Pneumonia

NCT04469114 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: 34810620.0.1001.0071
• Study Type: interventional
• Target: 289
• Locations: 1 country
• Sites: 17

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.

Conditions

Covid19

Outcome Measures

Primary Outcomes (1)

• Death or respiratory failure until Day 28

  1, 2 or 3 on the 8-point National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity. The minimum value is 1 (worst outcome) and the maximum value is 8 (best outcome). 1. Death. 2. Hospitalized, on invasive mechanical ventilation or ECMO. 3. Hospitalized, on non-invasive ventilation or high-flow oxygen devices. 4. Hospitalized, requiring supplemental oxygen. 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise). 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care. 7. Not hospitalized, limitation on activities and/or requiring home oxygen. 8. Not hospitalized, with no limitations on activities.

  28 days

Secondary Outcomes (11)

• National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14

  14 days

• Status of alive and not on mechanical ventilation or ECMO at Day 14 and 28 NIAID ordinal scale of disease severity at Day 14

  14 and 28 days

• Status of requiring supplemental oxygen at Day 28

  28 days

• Status of being alive and not hospitalized at Day 14 and 28

  14 and 28 days

• National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14 NIAID ordinal scale of disease severity at Day 28

  28 days

Study Arms (2)

Tofacitinib

EXPERIMENTAL

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

Drug: Tofacitinib 10 mg

Placebo

PLACEBO COMPARATOR

Placebo twice daily for 14 days or until hospital discharge

Drug: Placebo

Interventions

Tofacitinib 10 mg DRUG

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

Tofacitinib

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants older than 18 years
• Laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR) prior to Day 1.
• Evidence of pneumonia assessed by radiographic imaging (chest x-ray or chest CT scan).
• Hospitalized for less than 72 hours and receiving supportive care for COVID-19

You may not qualify if:

• Require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) on Day 1 at the time of randomization
• 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.
• Have a personal or first-degree family history of blood clotting disorders.
• Participants who are immunocompromised, with known immunodeficiencies, or taking potent immunosuppressive agents (eg, azathioprine, cyclosporine).
• Participants with any current malignancy or lymphoproliferative disorders that requires active treatment
• Severe hepatic impairment, defined as Child-Pugh class C.
• Severe anemia (hemoglobin \<8 g/dL).
• Absolute lymphocyte count \<500 cells/mm;
• Absolute neutrophil count \<1000 cells/mm.
• Known allergy to tofacitinib.
• 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.
• 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.
• 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.
• Have received estrogen-containing contraception or treatment with herbal supplements within 48 hours prior to the first dose of study intervention.
• Have received treatment with corticosteroids equivalent to prednisone or methylprednisolone \>20 mg/day for equal or more than 14 consecutive days prior to screening.

Sponsors & Collaborators

• Hospital Israelita Albert Einstein: lead
• Pfizer: collaborator

Study Sites (17)

Centro de Pesquisa Clínica do Coração

Aracaju, Brazil

Location

Hospital Universitário São Francisco de Assis Na Providência de Deu

Bragança Paulista, Brazil

Location

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

Bragança Paulista, Brazil

Location

Hospital do Coração do Brasil

Brasília, Brazil

Location

Instituto de Pesquisa Clínica de Campinas

Campinas, Brazil

Location

Hospital Regional do Litoral Norte

Caraguatatuba, Brazil

Location

Unimed Fortaleza Sociedade Corporativa Médica LTD

Fortaleza, Brazil

Location

Hospital Regional Jorge Rossmann

Itanhaém, Brazil

Location

Hospital Bruno Born

Lajeado, Brazil

Location

Hospital São Vicente de Paulo

Passo Fundo, Brazil

Location

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, Brazil

Location

Hospital Regional de Registro

São José dos Campos, Brazil

Location

Hospital Regional de São José dos Campos

São José dos Campos, Brazil

Location

Beneficência Portuguesa

São Paulo, Brazil

Location

BP Mirante

São Paulo, Brazil

Location

Hospital Israelita Albert Einstein

São Paulo, Brazil

Location

Instituto do Coração

São Paulo, Brazil

Location

Related Publications (3)

• 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.

  PMID: 39504090 DERIVED

• 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.

  PMID: 35695334 DERIVED

• 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.

  PMID: 34133856 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2020
• First Posted: July 13, 2020
• Study Start: September 16, 2020
• Primary Completion: January 9, 2021
• Study Completion: January 9, 2021
• Last Updated: August 9, 2021

Record last verified: 2020-07

Locations

BR (17)