Efficacy of Tocilizumab on Patients With COVID-19

NCT04356937 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 2020P001159
• Study Type: interventional
• Target: 243
• Locations: 1 country
• Sites: 3

Brief Summary

This is a randomized, double blind, multi-center study to evaluate the effects of tocilizumab compared to placebo on patient outcomes in participants with confirmed SARS-CoV-2 infection and evidence of systemic inflammation. The aim of this study is to test the effect of Tocilizumab on multi-organ dysfunction in a phase 3 randomized controlled trial among hospitalized patients with COVID-19 infection. Specifically, as compared to placebo, we will test whether tocilizumab is associated with a reduction in multi-organ dysfunction among hospitalized COVID-19 adult patients with elevated inflammatory measures. Multi-organ dysfunction will be measured as the incidence of the following composite endpoint (mechanical ventilation, renal replacement therapy, mechanical support, need for inotropes or vasopressors, liver dysfunction (increased bilirubin), and all-cause mortality). We will also assess multiple pre-specified secondary (exploratory) endpoints and safety endpoints. We hypothesize that, as compared to placebo, tocilizumab will reduce transfer to the ICU, need for mechanical ventilation, increase rates of hospital discharge in patients diagnosed with severe COVID-19 infection and evidence of exaggerated inflammatory response.

Conditions

SARS-CoV 2

Outcome Measures

Primary Outcomes (1)

• Mechanical Ventilation or Death

  Time from administration of the investigational agent (or placebo) to requiring mechanical ventilation and intubation, or death for subjects who die prior to intubation. The percentages of patients who have been intubated or died as of day 14 and day 28 are estimated from the Kaplan-Meier curve.

  28 days

Secondary Outcomes (2)

• Clinical Worsening on Ordinal Scale

  28 days

• Discontinuation of Supplemental Oxygen Among Patients Receiving it at Baseline

  28 days

Other Outcomes (6)

• Duration of Supplemental Oxygen

  28 days

• Duration of Mechanical Ventilation

  28 days

• Mortality

  28 days

Study Arms (2)

Tocilizumab

EXPERIMENTAL

Review effect of Tocilizumab on multi-organ dysfunction in a phase 3 randomized controlled trial among hospitalized patients with COVID-19 infection. Participants will receive an intravenous (IV) injection of 8 mg/kg (not to exceed 800 mg) tocilizumab.Specifically, as compared to placebo, we will test whether tocilizumab is associated with a reduction in multi-organ dysfunction among hospitalized COVID-19 adult patients with elevated inflammatory measures.

Drug: Tocilizumab

Standard of care plus placebo

PLACEBO COMPARATOR

Participants will receive an placebo intravenous (IV) injection of 8 mg/kg (not to exceed 800 mg).Specifically, as compared to placebo, we will test whether tocilizumab is associated with a reduction in multi-organ dysfunction among hospitalized COVID-19 adult patients with elevated inflammatory measures.

Drug: Placebos

Interventions

Tocilizumab DRUG

Patients will receive the standard treatment for COVID-19 per MGH guidance and also be randomized (2:1) to one of the following arms: 1. Tocilizumab 8mg x 1 (n=185) 2. Standard of care/Placebo (n=93)

Also known as: Actemra

Tocilizumab

Placebos DRUG

Patients will receive the standard treatment for COVID-19 per MGH guidance and also be randomized (2:1) to one of the following arms: 1. Tocilizumab 8mg x 1 (n=185) 2. Standard of care/Placebo (n=93)

Standard of care plus placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who meet all of the following criteria will be eligible to participate in the study:
• Must have provided informed consent in a manner approved by the Investigator's Institutional Review Board (IRB) or Independent Ethics Committee (IEC) prior to any assessments. If a patient is unable to provide informed consent due to their medical condition, the patient's legally authorized representative may consent on behalf of the study patient, as permitted by local law and institutional Standard Operating Procedures;
• Age Range: 19-85 years old
• Male or female gender
• Confirmed SARS-CoV-2 infection by nasopharyngeal swab PCR or serum assay for IgM antibody
• Requiring hospital but not mechanical ventilation
• Oxygen supplementation not greater than 10L delivered by any device
• WITH evidence of severe COVID-19 (at least 2 of the following):
• Fever \> 38C within 72 hours
• Pulmonary infiltrate on CXR
• Need for supplemental O2 to maintain saturation \> 92%
• AND at least 1 of the following:
• Ferritin \> 500 ng/ml
• CRP \> 50 mg/L
• LDH \>250 U/L

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from participation in the study:
• Unable to provide verbal informed consent or have verbal agreement to participate through attestation and signature of a Witness required, as outlined in the Partners IRB's Table for Consenting in COVID Research that is More than Minimal Risk.
• Subjects between the ages of 79 and 86 will be excluded if they have NYHA Class III/IV heart failure, insulin-dependent diabetes mellitus, angina, or treatment of a malignancy (excluding non-melanoma skin cancer) within six months
• Uncontrolled bacterial, fungal, or non-COVID viral infection
• Active TB
• Any prior investigational immunosuppressive therapy within 28-days or 3 half-lives of the agent (for instance with biologic or JAK inhibitor)
• Any concurrent immunosuppressive medication that the PI believes would put the patient at higher risk
• Receipt of intravenous tocilizumab for the treatment of a non-COVID condition within three weeks of the first COVID symptom
• History of hypersensitivity to tocilizumab
• Any concurrent immunosuppressive medication that the PI believes would put the patient at higher risk
• Treatment with other biologic or small-molecule immunosuppressive therapy such as IL1R-antagonism, JAK inhibition, or other agents
• Treatment with convalescent plasma
• History of diverticulitis or bowel perforation
• ANC \<500, Platelets \<50,000\*
• AST/ALT \> 5X ULN

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Genentech, Inc.: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Newton-Wellesley Hospital

Newton, Massachusetts, 02462, United States

Location

Related Publications (1)

• Stone JH, Frigault MJ, Serling-Boyd NJ, Fernandes AD, Harvey L, Foulkes AS, Horick NK, Healy BC, Shah R, Bensaci AM, Woolley AE, Nikiforow S, Lin N, Sagar M, Schrager H, Huckins DS, Axelrod M, Pincus MD, Fleisher J, Sacks CA, Dougan M, North CM, Halvorsen YD, Thurber TK, Dagher Z, Scherer A, Wallwork RS, Kim AY, Schoenfeld S, Sen P, Neilan TG, Perugino CA, Unizony SH, Collier DS, Matza MA, Yinh JM, Bowman KA, Meyerowitz E, Zafar A, Drobni ZD, Bolster MB, Kohler M, D'Silva KM, Dau J, Lockwood MM, Cubbison C, Weber BN, Mansour MK; BACC Bay Tocilizumab Trial Investigators. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. N Engl J Med. 2020 Dec 10;383(24):2333-2344. doi: 10.1056/NEJMoa2028836. Epub 2020 Oct 21.

  PMID: 33085857 DERIVED

MeSH Terms

Interventions

tocilizumab

Results Point of Contact

• Title: DRAI Director of Clinical Trials
• Organization: Massachusetts General Hospital

JHSTONE@mgh.harvard.edu

617-726-7938

Study Officials

• John H Stone, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Subjects who meet all inclusion criteria and none of the exclusion criteria will be randomized 2:1 to tocilizumab or placebo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Prospective, multi-center, randomized,double blind, placebo-controlled trial

Study Record Dates

• First Submitted: April 19, 2020
• First Posted: April 22, 2020
• Study Start: April 20, 2020
• Primary Completion: July 13, 2020
• Study Completion: August 27, 2020
• Last Updated: July 27, 2021
• Results First Posted: July 27, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)