General information Section to complete general information about the trial: scientific and public title, protocol identifiers, sponsors and Source(s) of Monetary or Material Support.
Scientific title:
Safety and efficacy of the anti-CD6 itolizumab monoclonal antibody produced in CHO in the treatment of moderate or severe patients with SARS-CoV-2 pneumonia. (COVID-19)
Secondary indentifying numbers:
Issuing authority of the secondary identifying numbers:
Source(s) of monetary or material support:
Center of Molecular Immunology (CIM), Cuban Ministry of Public Health (MINSAP)
Authorization for beginning Section to complete information about the regulatory approval of clinical trial: regulatory agency name, approval date and reference number in the agency.
Regulatory instance to authorize the initiation of the study:
Center for State Control of Drugs, Medical Devices and Equipment (CECMED)
Principal investigator Section to complete information about Email address, telephone number and postal address of the Principal Investigator.
Medical Specialty :
Master in Medical Emergencies. Second Degree Specialist in Internal Medicine. Associate Professor
Affiliation:
Military Hospital Manuel Fajardo Rivero
Postal address:
Nueva Abel Santa Maria. Villa Clara Province
Telephone:
+53-42206061
+53-42206064
Clinical sites to participate Section to complete the data related to the clinical sites involved in the trial: site and responsible investigator for every site.
Countries of recruitment:
Recruitment status Section to complete information about the recruitment status and the date of first enrolment subject
Date of first enrollment:
Health condition and Intervention Section to complete information about the primary medical condition(s) or problem(s) studied and, a characteristics of the intervention(s).
Health condition(s) or Problem(s) studied:
Health condition(s) code:
Coronavirus Infections
SARS Virus
Coronaviridae Infections
Nidovirales Infections
Betacoronavirus
Severe Acute Respiratory Syndrome
Health condition keyword:
Intervention(s):
Itolizumab monoclonal antibody by intravenous route (IV). Administration must be very slow. The infusion should last at least 6 hours (approximately 25 drops / minute or less), following sterility and aseptic standards. It will use pre-infusion medication approximately 30 minutes (± 10 minutes) before the start of itolizumab administration.
Each vial of itolizumab, produced in India, contains 100 mg of the monoclonal antibody in lyophilized form. The product must be reconstituted in 1.1mL of water for injection, leaving a concentration of 100 mg / mL of the monoclonal antibody. The calculated dose of itolizumab is diluted in 500 ml of saline, 0.9%.
Pre-infusion medication: Hydrocortisone 100 mg IV or methylprednisolone 8 mg IV (or equivalent short-acting glucocorticoid) and diphenhydramine (or equivalent of an alternative antihistamine) 25 mg by intramuscular or intravenous route. Subjects already receiving systemic corticosteroid therapy (such as dexamethasone, methylprednisolone, or prednisone at a dose of ≥25 mg / day or equivalent) do not require glucocorticoid medication prior to infusion.
If occurs an adverse event during the infusion, it is recommended decrease or close the drip until the event disappears. Then, the treatment will restart. Itolizumab does not contain preserve in the formulation, so it should be used immediately after preparing the infusion, discarding any unused remnants. Itolizumab diluted in 0.9% saline infusion is physically and chemically stable for 12 hours at temperatures below 25 degrees Celsius. If these limits are exceeded, the infusion must be discarded.
If patient no improves the symptoms and signs of the systemic inflammatory disease, the patient may receive additional doses of itolizumab up to a maximum of 4 doses, with intervals of 3 to 7 days after the preceding dose.
Intervention code:
Antibodies, Monoclonal, Humanized
Antibodies, Monoclonal
Infusions, Intravenous
Outcomes and Timepoint Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.
Primary outcome(s):
Security outcomes:
1- Serious adverse events: From the total number of patients who will receive treatment, the percentage that developed serious adverse events will be calculated, according to the CTCAE v5.0 classification. Measurement time: Upon discharge of the patient.
2- Clinical and laboratory adverse events: The frequency distribution of AD appearance, type of event and body system will be determined. Duration, intensity, result, attitude and causal relationship of the AE will be identified. Measurement time: Upon discharge of the patient.
Effect outcomes:
3- Rate of deceased patients in 14 days following the use of the drug. Measurement time: Upon discharge of the patient.
4- Rate of patients with disease progression (worsening in clinical status classification). Measurement time: Upon discharge of the patient.
Key secondary outcomes:
1- Proportion of Patients at Risk of Progression According to the CALL Index. Measurement time: Upon discharge of the patient.
2- Proportion of patients with high risk according to the MINSAP classification. Measurement time: Upon discharge of the patient.
3- Length of stay in intensive care. Measurement time: Upon discharge of the patient.
4- Hospital stay time. Measurement time: Upon discharge of the patient.
Selection criterias Section to complete information about the inclusion and exclusion criteria for participant selection, including age and gender.
Inclusion criteria:
1. Express voluntariness of the patient, family member or impartial witness.
2. Any gender and skin color
3. Age equal to or greater than 18 years
4. SARS-CoV-2 infection diagnosed by RT-PCR that presents any of the following characteristics:
4.1 Confirmed multifocal interstitial pneumonia or,
4.2 Need for oxygen therapy to maintain SO2> 93% or;
4.3 Worsening of lung involvement, defined as one of the following criteria:
4.3.1 Worsening of oxygen saturation> 3 percentage points or decrease in PaO2> 10%, with stable FiO2 in the last 24h.
4.3.2 Need to increase FiO2 in order to maintain a stable SO2 or new need for mechanical installation in the last 24 hours.
4.3.3 Increase in the number and / or extent of lung areas of consolidation.
FOR CONFIRMED CASES RT-PCR positive ASYMPTOMATIC high risk ”which would be:
1. Patients 65 years of age or older or;
2. or who have any of the risk factors associated with mortality in Covid-19 (obesity, complicated HT, ischemic heart disease, diabetes mellitus, COPD, cancer, kidney failure, severe malnutrition, and others considered by attending physicians).
This group will be kept under strict clinical surveillance
FOR CONFIRMED CASES RT-PCR positive SYMPTOMATIC RT-PCR positive “Moderate high risk”.
1. Patients who present manifestations of lower respiratory infection WITHOUT signs of severity (mild pneumonia) that are:
1.1 Patients 65 years of age or older; or
1.2 Patients who have any of the risk factors associated with mortality in Covid-19 (obesity, complicated HT, ischemic heart disease, diabetes mellitus, COPD, cancer, kidney failure, severe malnutrition, neutrophil / lymphocyte ratio> 4 and others that consider the attending physicians).
Important: These cases will be treated in a different room with the supervision of the intensivists. Each case will be evaluated individually. (If the disease has been evolving for 8 days or more, treatment with Heberferon should be discontinued, and prophylactic anticoagulant treatment should be indicated in cases that meet the criteria for such therapy).
Alternatively, itolizumab can be used in patients with suspected macrophage activation syndrome, according to the following criteria:
1. Need for oxygen therapy not less than 6L / min plus one of the following conditions:
1.1 Wheezing or choppy speech (cannot quickly count to 20 after a deep breath)
1.2 Respiratory rate greater than 22 breaths per minute with oxygen therapy at 6L / min
1.3 PO2: Partial pressure of arterial oxygen <65 mm Hg
1.4 Worsening of the radiological image
1.5 Fever ≥38ºC
1.6 Reduction in baseline values of hemoglobin, platelets or neutrophils or Hb <90 g / L, platelets <100 x109 / L, neutrophils <1 x109 / L or leukocytes <4 x109 / L.
1.7 Decrease in erythrocyte sedimentation in disagreement with C-reactive protein (pcr) (low erythrocyte sedimentation and CRP increases or is not modified)
1.8 Increase in the initial value of triglycerides or triglycerides greater than 3 mmol. / L.
1.9 Increase in the initial value of ferritin from 500 ng / ml or absolute value of ferritin ≥ 2000 ng / ml.
1.10 Aspartate aminotransferase transaminase ≥30 IU / L
1.11 Increase in D-dimer
1.12 Fibrinogen <2.5 g / L
1.13 Appearance of neurological manifestations
Exclusion criteria:
1- Pregnant or nursing women.
2- Under 18 years of age.
Study design Section to complete information about the characteristics of the study design.
Contact for public queries Section to complete information about Email address, telephone number and postal address of the contact who will respond to general queries, including information about current recruitment status
Specialty:
Biochemestry. Doctor of Health Sciences
Affiliation:
Center of Molecular Immunology
Contact for scientific queries Section to complete information about Email address, telephone number and postal address of the contact who will respond to scientific queries.
Specialty:
Biochemestry. Doctor of Health Sciences
Affiliation:
Cenrter of Molecular Immunology
Postal Address:
216 and 15. Atabey. Playa
Data Sharing Section to complete the data related to the data sharing plan.
Research Ethics Committees Section to complete the data related to the review ethics committees.
Name of Research Ethics Committees:
Military Hospital "Manuel Fajardo Rivero"
Status of evaluation date of Ethic Committee:
Postal address of Ethic Committee :
Abel Santa Maria. Santa Clara Villa Clara. Z.C:50100, Cuba
About study completion Section to complete the data related to the study completion.
Registration and Update Section to complete information about the name of Primary Registry, date of registration and the unique ID number assigned by the registry (RPCEC).
Date of Registration in Primary Registry:
Record Verification Date:
Link to the spanish version:
