Spanish Version
DATA SHEET
CLINICAL TRIAL REGISTRATION (EC)
EC INS No:  PER-027-20
1. ORGANIZATION / APPLICANTE INSTITUTION
Name of Organization / Institution: PPD Peru S.A.C.   Type of Organization / Institution : Empresa / Compañia 
Legal Domicile : Av. República de Panamá 3461, Interior 1801 Urb. El palomar 
District: San Isidro  Province: Lima 
Departament: Lima 
Single Taxpayer No : 20515127071 
Telephone: +511 613-4100, +516134115   Fax:  
2. CLINICAL TRIAL GENERAL INFORMATION
Scientific title:
A RANDOMIZED, DOUBLE-BLIND, PLACEBO- CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF TOCILIZUMAB IN HOSPITALIZED PATIENTS WITH COVID-19 PNEUMONIA


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


Clinical Trial Registration Date Most recent Clinical Trial Update
24/06/2020  
Principal Sponsor :
1.- GENETECH, INC.  
Secondary Sponsor :
 
Funding Source
1.-  GENENTECH, INC.
Executing Company / Institution / Other
- PPD PERU S.A.C. Authorized with   197-2020-OGITT-INS Date 24/06/2020
Responsabilities
PPD Peru S.A.C.  
  Inform to the OGITT of the NIH when the first subject is enrolled in Peru, and the end date of enrollment in the country.
  Submit progress reports to the National Health Institute during the execution of the Clinical Trial.
  Submit to the OGITT of the NIH the final reports as well as the results, conclusions, and publication of the clinical trial
  Inform and describe the reasons for a suspension and cancellation of the clinical trial.
  Inform and describe the reasons for a suspension and cancellation of the clinical trial.
  Provide the facilities for the inspection of the execution of the clinical trial by the staff of the General Office of Research and Technology Transfer (OGITT) of the National Institute of Health.
ROCHE FARMA (PERU) S.A.  
  Others
  Notify to the OGITT of the NIH the adverse events and deviations as established in the Clinical Trials Regulation.
Study clinical phase: III  Protocol Code ML42528 
Secondary ID(s) :  
WHO UTN: NA
CLINICALTRIALS.GOV: NCT04372186
EUDRACT N°:NA
Study Design
This is a Phase III, randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of TCZ in combination with SOC compared with placebo in combination with SOC in hospitalized adult patients with COVID-19. The Sponsor intends to enroll approximately 379 patients that have been diagnosed with COVID-19 pneumonia and meet the entry criteria. 
Insurance policy due date 01/01/2021  Assignation method Randomized 
Non randomized 
Type of blinding Assignation
Simple  Double  Triple 
Open
Single arm        Parallel
Crossed                 Factorial
Others:
Purpose
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. 
Research Product Information
Name of the product Generic Name Type of product ATC
TOCILIZUMAB TOCILIZUMAB      L04
Name of the compare Generic Name Type of product ATC
TOCILIZUMAB PLACEBO TOCILIZUMAB PLACEBO      V03
Intervention(s) description:
Group name Type of group N° of participants Intervention(s) description
Tocilizumab (TCZ) Experimental
Control
30   Participants will receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose may be given if clinical symptoms worsen or show no improvement.
Tocilizumab Placebo Experimental
Control
30   Participants will receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose may be given if clinical symptoms worsen or show no improvement.
Inclusion Criteria
1) Documented informed consent by any patient capable of giving consent, or, when the patient is not capable of giving consent, by his or her legal/authorized representative 2) Age 18 years 3) Ability to comply with the study protocol 4) Hospitalized 5) COVID-19 pneumonia confirmed per a positive PCR of any specimen (e.g., respiratory, blood, urine, stool, other bodily fluid) and radiographic imaging (CT scan or chest X-ray) 6) Able to complete screening within 96 hours of hospital admission. 7) Blood oxygen saturation (SpO2) 94% while on ambient air 8) For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception 9) For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm.  
Exclusion Criteria
1) Known severe allergic reactions to TCZ or other monoclonal antibodies 2) Active tuberculosis (TB) infection 3) Suspected active bacterial, fungal, viral, or other infection (besides COVID-19) 4) In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments 5) Have received oral anti-rejection or immunomodulatory drugs (including TCZ) with the past 3 months 6) Participating in other drug clinical trials (participation in COVID-19 anti-viral trials may be permitted if approved by Medical Monitor) 7) Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination 8) Treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization (investigational COVID-19 antivirals may be permitted if approved by Medial Monitor) 9) Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator´s judgment, precludes the patient´s safe participation in and completion of the study 10) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 10 x upper limit of normal (ULN) detected within 24 hours at screening (per local lab) 11) Absolute neutrophil count (ANC) < 1000/mL at screening (per local lab) 12) Platelet count < 50,000/mL at screening (per local lab)  
Worldwide enrolment start date 09/06/2020 
Enrolment start date in Peru (Initial) 21/06/2020  Enrolment start date in Peru 03/07/2020 
Peru enrolment status Without starting enrollment
Enrollment stopped
  In enrollment
  Enrollment closed 
Clinical Trial Total Duration 17  months Medical Speciality INTERNAL MEDICINE 
Studied Condition (CIE-10 code) -J128 Other viral pneumonia  
Number of subjects to be included in all the countries 379 
Number of subjects to be included in Peru (initial) Number of subjects to be included in Peru (posterior)
60 60
Countries where the enrolment is conducted :
- Kenya - South Africa - Brazil
- Mexico - Peru - United States
Number of participants per gender (Initial) Female: 0 
Male : 0 
Number of participants per gender (Posterior) Female: 0 
Male : 0
Range of age of subjects to be included : - Adults (18-64 years) Yes   No
- Elderly (>= 65 years) Yes   No
- Under 18 years Yes   No
  If yes, specify:
  - In Utero Yes  No
  - Preterm newborn infants (up to gestational age < 37 weeks) Yes  No
  - Newborns (0-27 días) Yes  No
  - Infants and toddlers (28 days-23 months) Yes  No
  - Children (2 - 11 years) Yes  No
  - Adolescents (12 - 17 years) Yes  No
Subjects' treatment time 1  day(s) Subjects' follow up time 60  day(s)
Primary Outcome  
Name of the outcome Metric or method of measurement Time point for the outcome
Cumulative proportion of patients with death or requiring mechanical ventilation by Day 28 The primary efficacy objective for this study is to evaluate the efficacy of TCZ plus SOC compared with placebo plus SOC. Time to death or the first utilization of mechanical ventilation after randomization will be compared between the TCZ group and the placebo group using the stratified log-rank test with age group (age 60, age 60 years) as the stratification factor. The cumulative proportion of patients with death or requiring mechanical ventilation at Day 28 will be estimated using the Kaplan-Meier method. Day 28 
Secondary Outcome
Name of the outcome Metric or method of measurement Time point for the outcome
Time to improvement in ordinal clinical status Defined as time from randomization to the time when at least a 2-category improvement in the 7-category ordinal scale is observed. Assessment of patient status using an ordinal scale will be recorded at baseline and once daily in the morning (between approximately 8 am and 12 pm) while hospitalized. 60 days 
Time to clinical failure Defined as the time to first occurrence on study of death, mechanical ventilation, ICU admission, or withdrawal, whichever occurs first For up to 60 days. 
Mortality rate at Day 28 Difference in mortality rate at Day 28 will be compared using the Cochran-Mantel-Haenszel test statistic stratified by age group (age 60, age 60 years). The difference in proportions and its 95% CI for the treatment group comparison will be presented. Day 28 
Time to hospital discharge or “ready for discharge” “Ready for discharge” defined as normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or 2L supplemental oxygen. Up to 60 days. 
3. RESEARCH SITE, PRINCIPAL INVESTIGATOR, ETHICS COMMITTEE
Research site where the clinical trial will be conducted Principal Investigator Institutional Research Ethics Committee (CIEI) that approved the trial for the site Observations
Research Institution RCI Research site Full name RCEI Ethics Committe Name Status Approval date End approval date Term Telephone number Email addrees
HOSPITAL MILITAR CENTRAL "CORONEL LUIS ARIAS SCHEREIBER" RCI 301 CENTRO DE INVESTIGACIÓN DEL HOSPITAL MILITAR
VICTORIA CHAVEZ MIÑANO

RCEI-305 COMITÉ NACIONAL TRANSITORIO DE ÉTICA EN INVESTIGACIÓN PARA LA EVALUACIÓN Y SUPERVISIÓN DE ÉTICA DE LOS ENSAYOS CLÍNICOS DE LA ENFERMEDAD COVID-19 - COMITÉ NACIONAL TRANSITORIO DE ÉTICA EN INVESTIGACIÓN PARA LA EVALUACIÓN Y SUPERVISIÓN DE ÉTICA DE LOS ENSAYOS CLÍNICOS DE LA ENFERMEDAD COVID-19Approved 19/06/2020 18/06/2021127126450  
Co-Investigator
- Giovanna Rosa Trujillo Velita
- Miluska Daniela Delgado Flores
 
HOSPITAL NACIONAL HIPÓLITO UNANUE RCI-542 HOSPITAL NACIONAL HIPÓLITO UNANUE
JOHAN ALEXANDER AZAÑERO HARO


RCEI-305  COMITÉ NACIONAL TRANSITORIO DE ÉTICA EN INVESTIGACIÓN PARA LA EVALUACIÓN Y SUPERVISIÓN DE ÉTICA DE LOS ENSAYOS CLÍNICOS DE LA ENFERMEDAD COVID-19 - COMITÉ NACIONAL TRANSITORIO DE ÉTICA EN INVESTIGACIÓN PARA LA EVALUACIÓN Y SUPERVISIÓN DE ÉTICA DE LOS ENSAYOS CLÍNICOS DE LA ENFERMEDAD COVID-19 Approved 21/06/2020  21/06/2021    - Research Site Extension R.D. 208-2020-OGITT-INS with date 02/07/2020  
Co-Investigator
 
HOSPITAL MARIA AUXILIADORA RCI-260 CENTRO DE INVESTIGACIONES MÉDICAS - HOSPITAL MARÍA AUXILIADORA
MARIA ANGELICA PAREDES MORENO


RCEI-305  COMITÉ NACIONAL TRANSITORIO DE ÉTICA EN INVESTIGACIÓN PARA LA EVALUACIÓN Y SUPERVISIÓN DE ÉTICA DE LOS ENSAYOS CLÍNICOS DE LA ENFERMEDAD COVID-19 - COMITÉ NACIONAL TRANSITORIO DE ÉTICA EN INVESTIGACIÓN PARA LA EVALUACIÓN Y SUPERVISIÓN DE ÉTICA DE LOS ENSAYOS CLÍNICOS DE LA ENFERMEDAD COVID-19 Approved 21/06/2020  21/06/2021    - Research Site Extension R.D. 207-2020-OGITT-INS with date 02/07/2020  
Co-Investigator
 
HOSPITAL CAYETANO HEREDIA RCI-363 DEPARTAMENTO DE ENFERMEDADES INFECCIOSAS, TROPICALES Y DERMATOLÓGICAS
FERNANDO ALONSO MEJIA CORDERO


RCEI-305  COMITÉ NACIONAL TRANSITORIO DE ÉTICA EN INVESTIGACIÓN PARA LA EVALUACIÓN Y SUPERVISIÓN DE ÉTICA DE LOS ENSAYOS CLÍNICOS DE LA ENFERMEDAD COVID-19 - COMITÉ NACIONAL TRANSITORIO DE ÉTICA EN INVESTIGACIÓN PARA LA EVALUACIÓN Y SUPERVISIÓN DE ÉTICA DE LOS ENSAYOS CLÍNICOS DE LA ENFERMEDAD COVID-19 Approved 21/06/2020  21/06/2021    - Research Site Extension R.D. 206-2020-OGITT-INS with date 02/07/2020  
Co-Investigator
 
HOSPITAL NACIONAL SERGIO E. BERNALES RCI-105 CENTRO DE INVESTIGACIÓN EN ENFERMEDADES NEUMOLÓGICAS
EPIFANIO SANCHEZ GARAVITO


RCEI-305  COMITÉ NACIONAL TRANSITORIO DE ÉTICA EN INVESTIGACIÓN PARA LA EVALUACIÓN Y SUPERVISIÓN DE ÉTICA DE LOS ENSAYOS CLÍNICOS DE LA ENFERMEDAD COVID-19 - COMITÉ NACIONAL TRANSITORIO DE ÉTICA EN INVESTIGACIÓN PARA LA EVALUACIÓN Y SUPERVISIÓN DE ÉTICA DE LOS ENSAYOS CLÍNICOS DE LA ENFERMEDAD COVID-19 Approved 27/06/2020  27/06/2021    - Research Site Extension R.D. 215-2020-OGITT-INS with date 09/07/2020  
Co-Investigator
 
COMPLETION DATE:
4. IPD SHARING STATEMENT
Is there a plan for sharing of deidentified individual clinical trial participant-level data (IPD) to other researchers (including data dictionaries)?
Yes   No Non decided
In case the answer is affirmative, describe the Plan.
 
Additional information that will be shared. Study protocol
Statistical Analysis Plan
Informed Consent Form
Clinical Study report
Others: ________________
Describe briefly when this information will be available and how it can be obtained
 
URL https://ensayosclinicos-repec.ins.gob.pe/
5. CLINICAL TRIAL CONTACT PERSONS INFORMATION
Full Name E-mail Telephone Type of queries to be resolved
Information to general public Administrative Consultations Scientific Consultations
John Cabanillas Tejada john.cabanillas@ppdi.com 6134182/998111515 Yes Yes Yes
Elena Camacho Ruiz elena.camacho@ppdi.com 6134165 / 987505039 Yes Yes Yes
Dario Diaz Rojas dario.diaz@ppdi.com 6134145/967767545 Yes Yes Yes
AUTHORIZATION STATUS
AUTHORIZED    ACTIVE
TYPE AND NUMBER OF AUTHORIZATION   DOCUMENT R.D.  197-2020-OGITT-INS AUTHRORIZATION   DOCUMENT DATE (dd/mm/aaaa): 24/06/2020  (Validity date from:24/06/2020)
SUMMARY EVALUATION REPORT
APPROVED PROCEDURES
TYPE OF PROCEDURE TYPE AND NUMBER OF RESOLUTION / OFFICIAL LETTER DATE OF RESOLUTION / OFFICIAL LETTER VALIDITY DATE ANNULATION
FROM

TO

 

Research Site Extension
R.D. 208-2020-OGITT-INS
02/07/2020

Research Site Extension
R.D. 207-2020-OGITT-INS
02/07/2020

Research Site Extension
R.D. 206-2020-OGITT-INS
02/07/2020

Research Site Extension
R.D. 215-2020-OGITT-INS
09/07/2020

Clinical Trial Progress Report
R.D. 
22/09/2020 04:41:23 p.m.

Clinical Trial Progress Report
R.D. 
22/09/2020 04:41:37 p.m.

Clinical Trial Progress Report
R.D. 
22/09/2020 04:41:57 p.m.

Clinical Trial Progress Report
R.D. 
22/09/2020 04:42:12 p.m.