Pharmacy and Poisons Board
Protocol No: ECCT/20/06/02 Date of Protocol: 02-06-2020
Study Title:

A RANDOMIZED, DOUBLE-BLIND, Placebo-Controlled, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF TOCILIZUMAB IN HOSPITALIZED PATIENTS WITH COVID‑19 PNEUMONIA
The EMPACTA Covid19 study (Protocol ML42528) has been amended to add an optional long-term follow-up sub-study.
 
There is limited evidence on the long-term effects of COVID-19 infection. This is due to the recent onset of the pandemic and, therefore, there has not been an opportunity to study patients who have recovered from the infection. Therefore, the purpose of this optional sub-study will be to follow patients who participated in Study ML42528 or other Genentech/Roche sponsored study that evaluates patients with COVID-19 associated pneumonia for approximately 12 months after completing or discontinuing from one of these studies. This is in order to understand the long-term sequelae of resolved COVID-19 associated pneumonia.
Study Objectives:

Objectives and Endpoints

This study will evaluate the efficacy and safety of tocilizumab (TCZ) compared with a placebo in combination with SOC in hospitalized patients with COVID-19 pneumonia.  To enhance the understanding of the clinical profile of tocilizumab for patients who belong to high-risk and minority populations, an emphasis will be placed on including minority-enrolling sites.  Specific objectives and corresponding endpoints for the study are outlined below.

Efficacy Objectives

Primary Efficacy Objective

The primary efficacy objective for this study is to evaluate the efficacy of TCZ compared with placebo in combination with standard of care (SOC) for the treatment of COVID-19 pneumonia on the basis of the following endpoint:

  • Cumulative proportion of patients with death or requiring mechanical ventilation by Day 28

 

Secondary Efficacy Objective

The secondary efficacy objective for this study is to evaluate the efficacy of TCZ compared with placebo in combination with SOC for the treatment of COVID-19 pneumonia on the basis of the following endpoints:

  • Time to improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status
  • Time to clinical failure, defined as the time to death, mechanical ventilation, intensive care unit (ICU) admission, or withdrawal (whichever occurs first)
  • Mortality rate by Day 28
  • Time to hospital discharge or “ready for discharge” (e.g., awaiting social disposition) as evidenced by, for example, normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or £2L supplemental oxygen

 

Exploratory Efficacy Objective

The exploratory efficacy objective for this study is to evaluate the efficacy of TCZ compared with placebo in combination with SOC for the treatment of COVID-19 pneumonia on the basis of the following endpoints:

  • Change from baseline in inflammatory markers levels (high sensitivity C-reactive protein [hs-CRP]/C-reactive protein [CRP], D-dimer, and ferritin) over time
  • Cumulative proportion of patients requiring CPAP or BIPAP by Day 28

 

Safety Objective

The safety objective for this study is to evaluate the safety of TCZ compared with placebo in combination with SOC for the treatment of COVID-19 pneumonia on the basis of the following endpoints:

  • Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
  • Incidence of any post-treatment bacterial and/or fungal infection
  • Incidence of any post-treatment acute kidney injury (defined by 50% increase of creatinine from baseline)
Laymans Summary:

There are currently no drugs licensed for the treatment of patients with COVID-19. Given the results of available data, Tocilizumab, along with standard of care (SOC) supportive treatment, could provide benefit, offering the potential to treat COVID-19 in hospitalized populations more effectively than current Standard Of Care (best practice supportive treatment) alone. Extensive safety data has previously been generated on the use of Tocilizumab in other indications e.g. for rheumatoid arthiritis as registered in Kenya. Therefore, this study will look at comparing a combination of Tocilizumab with Standard Of Care supportive treatment to assess safety and efficacy of Tocilizumab in hospitalized patients with COVID-19 pneumonia, and this rationale is justified to address the high unmet need and burden of disease in this severely ill population for which there is no current known better treatment options. 

 
1 Dear EEC reviewers, There is no change to the protocol or study design. This is a notification of final EC-approved ICFs, rendering use of ICF Version 4 as the final approved consent form that will be used for patients. Following the concurrent and extensive review by the PPB EEC and AKUH EC, there was one additional change requested by the AKUH EC to be made to the ICFs. This was to change the phrase "standard of care" to "best practice" as the EC clarified that there is no current standard of care for covid19, and the care provided to patients should be worded as best practice of clinical care currently known. The EC reviewed and approved site specific addendum and ICF's Version-4 are attached in the notification section of this amendment for your records. Many thanks Kind regards, Dr. Huwaida. Bulhan-Betts, Clinical Operations Lead, Roche-Kenya Ltd. +254-780-888997 / +254-791-088107 huwaida.bulhan-betts@roche.com
3 Since little is currently known about the long term consequences of Covid19 pneumonia on the body systems, the protocol has been amended to include a follow-up period of 12-months, where the patients will be evaluated for any long term consequences of the disease process.
Abstract of Study:

PROTOCOL SYNOPSIS

TITLE:

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE SAFETY AND EFFICACY OF TOCILIZUMAB IN HOSPITALIZED PATIENTS WITH COVID‑19 PNEUMONIA

PROTOCOL NUMBER:

ML42528

VERSION NUMBER:

2

Eudract Number:

2020-001154-22

IND NUMBER:

148225

NCT NUMBER:

NCT04372186

TEST PRODUCT:

Tocilizumab (RO4877533)

PHASE:

Phase III

INDICATION:

COVID-19 pneumonia

SPONSOR:

Genentech, Inc.

 

Objectives and Endpoints

This study will evaluate the efficacy and safety of tocilizumab (TCZ) compared with a placebo in combination with SOC in hospitalized patients with COVID-19 pneumonia.  To enhance the understanding of the clinical profile of tocilizumab for patients who belong to high-risk and minority populations, an emphasis will be placed on including minority-enrolling sites.  Specific objectives and corresponding endpoints for the study are outlined below.

Efficacy Objectives

Primary Efficacy Objective

The primary efficacy objective for this study is to evaluate the efficacy of TCZ compared with placebo in combination with standard of care (SOC) for the treatment of COVID-19 pneumonia on the basis of the following endpoint:

  • Cumulative proportion of patients with death or requiring mechanical ventilation by Day 28

 

Secondary Efficacy Objective

The secondary efficacy objective for this study is to evaluate the efficacy of TCZ compared with placebo in combination with SOC for the treatment of COVID-19 pneumonia on the basis of the following endpoints:

  • Time to improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status
  • Time to clinical failure, defined as the time to death, mechanical ventilation, intensive care unit (ICU) admission, or withdrawal (whichever occurs first)
  • Mortality rate by Day 28
  • Time to hospital discharge or “ready for discharge” (e.g., awaiting social disposition) as evidenced by, for example, normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or £2L supplemental oxygen

 

Exploratory Efficacy Objective

The exploratory efficacy objective for this study is to evaluate the efficacy of TCZ compared with placebo in combination with SOC for the treatment of COVID-19 pneumonia on the basis of the following endpoints:

  • Change from baseline in inflammatory markers levels (high sensitivity C-reactive protein [hs-CRP]/C-reactive protein [CRP], D-dimer, and ferritin) over time
  • Cumulative proportion of patients requiring CPAP or BIPAP by Day 28

 

Safety Objective

The safety objective for this study is to evaluate the safety of TCZ compared with placebo in combination with SOC for the treatment of COVID-19 pneumonia on the basis of the following endpoints:

  • Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
  • Incidence of any post-treatment bacterial and/or fungal infection
  • Incidence of any post-treatment acute kidney injury (defined by 50% increase of creatinine from baseline)
3

No changes to the study objectives. They remain the same.