Low-dose Tocilizumab for COVID-19

(COVIDOSE-2 Trial)

Overseen By Pankti D Reid, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must not be taking: Bruton's inhibitors, JAK2 inhibitors

Disqualifiers: Mechanical ventilation, Vasopressors, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different doses of tocilizumab, a medication that might help people with severe COVID-19 pneumonia recover faster by reducing inflammation. The trial seeks to identify the most effective dose, given limited supplies. Participants will receive either a smaller dose, a larger dose, or standard care to determine which option best aids recovery and reduces the chance of death within 28 days. Those hospitalized with COVID-19, who have a fever and lung problems visible in scans, might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

You may need to stop taking certain medications to participate in this trial. Specifically, you cannot be on certain immunosuppressive agents, some targeted therapies, or scheduled antipyretic medications like acetaminophen or ibuprofen. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tocilizumab is generally safe for COVID-19 patients. Studies have found that a single dose is usually well-tolerated, with only a small increase in blood urea nitrogen (BUN), a kidney function marker. In larger safety studies, 40% of patients using tocilizumab experienced infections, compared to 32% of those given a placebo. Serious infections were slightly less common in the placebo group at 23%, compared to 19% for those taking tocilizumab. These results suggest that while some risks exist, tocilizumab is considered safe enough for treating COVID-19 in certain situations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about low-dose tocilizumab for COVID-19 because it offers a potentially safer and more targeted approach to managing inflammation without the high doses typically associated with more severe side effects. Unlike the standard treatments that primarily focus on antiviral or supportive care, tocilizumab specifically blocks the IL-6 receptor, a key player in the inflammatory response seen in severe COVID-19 cases. This targeted action could help reduce the overwhelming immune response that leads to complications, with the added benefit of using lower doses to minimize potential side effects. By exploring various low doses, researchers aim to find the sweet spot where effectiveness meets safety, possibly offering a more tolerable treatment option for patients.

What evidence suggests that this trial's treatments could be effective for COVID-19?

Studies have shown that tocilizumab can help treat severe COVID-19 pneumonia by reducing inflammation, a part of the body's response to infection. It achieves this by blocking a protein called interleukin-6. Some studies found that tocilizumab, especially when combined with steroids, can lower the risk of death in COVID-19 patients. In this trial, participants in Sub-study A will receive either 40mg or 120mg of tocilizumab, or no tocilizumab as part of the standard of care. Sub-study B will test doses of 40mg, 120mg, or a standard dose of 400mg or 8mg/kg. Initial findings suggest that even small doses, like 40mg or 120mg, might still be helpful. Overall, research supports tocilizumab as a useful option for managing severe COVID-19 symptoms. ^{4 6 7 8 9}

Who Is on the Research Team?

Pankti D Reid, MD, MPH

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for hospitalized adults over 18 with COVID-19, fever, and lung issues seen on X-rays or CT scans. They must have a positive SARS-CoV-2 test and be able to consent. People with severe liver disease, low blood counts, certain drug treatments (like immunosuppressives), other active infections, extreme liver enzyme levels, history of transplants or diverticulitis, those on strong heart drugs or ventilators can't join.

Inclusion Criteria

I am currently in the hospital.

You have a positive test for an active COVID-19 infection.

I can sign the consent form myself or have someone who can do it for me.

Exclusion Criteria

I have had Hepatitis B or C but am not currently undergoing treatment.

I have had a bone marrow or solid organ transplant.

Your absolute neutrophil count is less than 500 per microliter.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive low-dose tocilizumab or standard of care for COVID-19 pneumonitis

4 weeks

Weekly monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

Bi-weekly follow-up visits

Long-term follow-up

Participants are monitored for long-term outcomes and overall survival

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Tocilizumab

Trial Overview The study tests two doses of Tocilizumab (40mg and 120mg) against standard care in patients with severe COVID-19 pneumonia. It's an open-label trial where recovery time is the main goal; survival after 28 days is also tracked. Patients are grouped by whether they're getting remdesivir or steroids too.

How Is the Trial Designed?

Group I: Sub-study B, Tocilizumab 40mg Experimental Treatment 1 Intervention

Patient assigned to Sub-study B by primary treating physicians. Patient enrolled on trial sub-study B and randomized to receive standard of care tocilizumab 40mg.

Group II: Sub-study B, Tocilizumab 120mg Experimental Treatment 1 Intervention

Patient assigned to Sub-study B by primary treating physicians. Patient enrolled on trial sub-study B and randomized to receive standard of care tocilizumab 120mg.

Group III: Sub-study A, Tocilizumab 40mg Experimental Treatment 1 Intervention

Patient assigned to Sub-study A by primary treating physicians. Patient enrolled on trial sub-study A and randomized to receive tocilizumab 40mg.

Group IV: Sub-study A, Tocilizumab 120mg Experimental Treatment 1 Intervention

Patient assigned to Sub-study A by primary treating physicians. Patient enrolled on trial sub-study A and randomized to receive tocilizumab 120mg.

Group V: Sub-study B, Tocilizumab 400mg or 8mg/kg Standard of Care Active Control 1 Intervention

Patient assigned to Sub-study B by primary treating physicians. Patient enrolled on trial sub-study B and randomized to receive standard of care tocilizumab dose (400mg or 8mgkg).

Group VI: Sub-study A, Tocilizumab-Free Standard of Care Active Control 1 Intervention

Patient assigned to Sub-study A by primary treating physicians. Patient enrolled on trial sub-study A and randomized to receive no tocilizumab.

Tocilizumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Approved in United States as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Approved in Canada as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Approved in Japan as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Citations

1. actemrahcp.com actemrahcp.com/coronavirus/efficacy.html

Efficacy Data for COVID-19 - ACTEMRA® (tocilizumab) ACTEMRA Was Evaluated in 4 Clinical Studies That Included ~3,000 Patients Hospitalized With COVID-191,3-7. The efficacy of ACTEMRA for the treatment of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10084735/

Low dose vs high dose tocilizumab in COVID-19 patients ... Tocilizumab has been shown to decrease mortality when used concomitantly with steroids in COVID-19 with 8 mg/kg (max 800 mg) being the standard ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04479358

Low-dose Tocilizumab Versus Standard of Care in ... Study Overview. Brief Summary. Tocilizumab is an effective treatment for severe coronavirus disease 2019 (Covid-19) pneumonia and related inflammation.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1876034125002229

Safety and efficacy of tocilizumab in COVID-19 This study confirms tocilizumab's position as a valuable therapeutic agent for COVID-19 complications while highlighting the necessity for judicious patient ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2028700

Tocilizumab in Hospitalized Patients with Severe Covid-19 ... The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia.

6. actemrahcp.com actemrahcp.com/coronavirus/safety.html

Important Safety Information - ACTEMRA® (tocilizumab) In the pooled safety population, the rates of infection/serious infection events were 40%/19% in patients receiving ACTEMRA versus 32%/23% receiving placebo.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8953525/

Safety of Tocilizumab in COVID-19 Patients and Benefit ... All of these data indicated the safety of a single dose of tocilizumab in COVID-19 patients except the slight increase in the blood BUN level, which could ...

8. actemra.com actemra.com/safety.html

Important Safety Information | ACTEMRA® (tocilizumab) Learn about the important safety information for ACTEMRA® (tocilizumab), a treatment option for RA, COVID-19, GCA, SSc-ILD, SJIA, and PJIA.

9. fda.gov fda.gov/media/150345/download

REVOKED_Genentech Actemra tocilizumab FAQs 12212022 FDA has authorized the emergency use of Actemra in certain children (2 years and less than 18 years of age) hospitalized with COVID-19 based ...