The evaluation of efficacy and safety of Tocilizumab (AryoGen Pharmed Co.) in patients with COVID-19.
Design
This is a phase III, open-label, and single-arm study with the sample size of 500 patients.
Settings and conduct
This phase-III, single-arm, open-label, multi-center (9 cities of Iran) clinical trial will be conducted in patients with COVID-19 with a follow-up duration of 14 days. Tocilizumab will be administered to the eligible patients on day 1, and the outcomes will be investigated with the 14-day monitoring of the patients.
Participants/Inclusion and exclusion criteria
َAbility to comprehend and willingness to sign the Informed Consent Form for this study by the patient or his/her guardian; Patients aged≥18 years old; Patients with any of the following symptoms: fever (body temperature>37.8°C), shortness of breath, or cough and SpO2≤93%, with the confirmed diagnosis of SARS-CoV-2 infection based on PCR and/or radiography. Exclusion criteria include hypersensitivity to Tocilizumab or any components of the formulation, hepatic or renal disorders, bone marrow suppression, patients with a high risk of GI perforation, history of tuberculosis, hepatitis B or C, HIV, pregnancy and breastfeeding, and any other active infection.
Intervention groups
Intervention group: Intravenous (4-8 mg/kg) or subcutaneous (two PFS injections of 162 mg Tocilizumab for patients <100 kg and three PFS injections of 162 mg Tocilizumab for patients >100 kg) in addition to the standard treatment. In case of inadequate response, Tocilizumab would be re-administered in either form with a 12-hour interval between injections.
Main outcome variables
Proportion of participants with clinical response (body temperature <36.6°C armpit, <37.2°C oral, or <37.8°C rectal and SpO2>94% through day 14, sustained for at least 24 hours).
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20150303021315N17
Registration date:2020-04-12, 1399/01/24
Registration timing:registered_while_recruiting
Last update:2020-04-12, 1399/01/24
Update count:1
Registration date
2020-04-12, 1399/01/24
Registrant information
Name
Nassim Anjidani
Name of organization / entity
Orchid Pharmed
Country
Iran (Islamic Republic of)
Phone
+98 21 4347 3000
Email address
amini@orchidpharmed.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2020-03-15, 1398/12/25
Expected recruitment end date
2020-07-21, 1399/04/31
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of the safety and efficacy of Tocilizumab (AryoGen pharmed Co. Iran) in patients with COVID-19
Public title
Tocilizumab in COVID-19
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
َAbility to comprehend and willingness to sign the Informed Consent Form for this study by the patient or his/her guardian
Patients above 18 years old
Patients with fever higher than 37.8 °C, cough or shortness of breath accompanied by SpO2 ≤%93, who have a confirmed diagnosis of SARS-CoV-2 infection using PCR and/or radiography.
Serum Interleukin-6 level of 7 pg/ml or more
Exclusion criteria:
History of hypersensitivity to Tocilizumab or any components of the formulation
Hepatic disease (especially active hepatic diseases and hepatic impairment)
Patients with bone marrow suppression (defined as Absolute Neutrophil Count (ANC) below 2000/mm3 or platelet count below 100,000/mm3)
Patients with a high risk of gastrointestinal perforation or with distinct history of GI disorders, e.g., active peptic ulcer and diverticulitis
Patients with active or latent tuberculosis
Patients with history of active hepatitis B, hepatitis C, HIV, or any known immunodeficiency
Pregnant or lactating patients
Patients with any other active infection in addition to COVID-19
Patients with any other disease or disorder, which, in the opinion of the investigator will put the subject at risk, if they are enrolled
Renal impairment (GFR of below 30ml/min/1.73m2)
Age
From 18 years old
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
500
Randomization (investigator's opinion)
Not randomized
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Single
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
National Institution for Medical Research Development
Street address
No 21, Beesat St., West Fatemi St.
City
Tehran
Province
Tehran
Postal code
1419693111
Approval date
2020-03-13, 1398/12/23
Ethics committee reference number
IR.NIMAD.REC.1398.414
Health conditions studied
1
Description of health condition studied
COVID-19
ICD-10 code
U07.1
ICD-10 code description
COVID-19
Primary outcomes
1
Description
The proportion of participants with clinical response (normalization of fever and oxygen saturation through day 14). Fever normalization: Temperature <36.6 °C armpit, <37.2 °C oral, or <37.8 °C rectal, sustained for at least 24 hours; Oxygen saturation normalization: peripheral capillary oxygen saturation (SpO2) > 94% sustained for at least 24 hours.
Timepoint
day 1 through 14
Method of measurement
Physical Examination
Secondary outcomes
1
Description
Percent of patients with improvement in oxygenation
Timepoint
day 1 through 14
Method of measurement
Oxygen saturation test
2
Description
Changes in in laboratory data
Timepoint
Day 1 through 14
Method of measurement
Laboratory Test
3
Description
Mortality rate during the study
Timepoint
day 1 thorough 14
Method of measurement
Recording time of deaths
4
Description
Change in body temperature
Timepoint
Day 1 through 14
Method of measurement
Physical Examination
5
Description
Change in mean PaO2/FiO2
Timepoint
Day 1 through 14
Method of measurement
Clinical tests
6
Description
The lesions of the pulmonary segment numbers involved in pulmonary CT
Timepoint
Day 1 and 14
Method of measurement
CT scan
7
Description
Duration (days) of supplemental oxygenation
Timepoint
Day 1 through 14
Method of measurement
Clinical Evaluation
8
Description
Incidence of any adverse events (AEs) during the study
Timepoint
Day 1 through 14
Method of measurement
Clinical Evaluation
Intervention groups
1
Description
Intervention group: Intravenous (4-8 mg/kg) or subcutaneous (two PFS injections of 162 mg Tocilizumab for patients <100 kg and three PFS injections of 162 mg Tocilizumab for patients >100 kg) in addition to the standard treatment. In case of inadequate response, Tocilizumab would be re-administered in either form with a 12-hour interval between injections.