A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, STUDY EVALUATING THE EFFICACY AND SAFETY OF OTILIMAB IV IN PATIENTS WITH SEVERE PULMONARY COVID-19 RELATED DISEASE
Public Title
INVESTIGATING OTILIMAB IN PATIENTS WITH SEVERE PULMONARY COVID-19 RELATED DISEASE
Clinical Trial Registration Date
Most recent Clinical Trial Update
21/08/2020
Principal Sponsor :
1.- GLAXOSMITHKLINE RESEARCH & DEVELOPMENT LIMITED
Secondary Sponsor :
Funding Source
1.- GLAXOSMITHKLINE PERÚ S.A.
Executing Company / Institution / Other
- GLAXOSMITHKLINE PERÚ S.A.
-
Authorized with 324-2020-OGITT-INS Date 21/08/2020
Responsabilities
Others
GLAXOSMITHKLINE PERÚ S.A.
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
Notify to the OGITT of the NIH the adverse events and deviations as established in the Clinical Trials Regulation.
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.
Study clinical phase:
II
Protocol Code
214094
Secondary ID(s) :
WHO UTN:
NA
CLINICALTRIALS.GOV:
NA
EUDRACT N°:
2020-01759-42
Study Design
This study is a multi-center, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of otilimab for the treatment of severe pulmonary COVID-19 related disease. The study population consists of hospitalized participants with new onset hypoxia requiring significant oxygen support or requiring invasive mechanical ventilation (≤48 hours before dosing). All participants will receive standard of care as per institutional protocols, in addition to study treatment.
Insurance policy due date
31/12/2020
Assignation method
Randomized
Non randomized
Type of blinding
Assignation
Simple
Double
Triple
Open
Single arm
Parallel
Crossed
Factorial
Others:
Purpose
To compare the efficacy of otilimab 90 mg IV versus placebo.
Research Product Information
Name of the product
Generic Name
Type of product
ATC
OTILIMAB
Otilimab
L03
Name of the compare
Generic Name
Type of product
ATC
PLACEBO DE OTILIMAB
Placebo de Otilimab
V03
Intervention(s) description:
Group name
Type of group
N° of participants
Intervention(s) description
Otilimab
Experimental
Control
400
Participants receive a blinded 1-hour infusion of Otilimab 90 mg IV in addition to standard of care.
Otilimab placebo
Experimental
Control
400
Participants receive a blinded 1-hour infusion of Otilimab placebo 90 mg IV in addition to standard of care.
Inclusion Criteria
1) Age ≥18 years and ≤79 years
2) Have positive SARS-CoV-2 result
3) Be hospitalized due to diagnosis of pneumonia (chest X-ray or computerized tomography [CT] scan)
4) Be developing new onset of oxygenation impairment requiring any of the following: high-flow oxygen (≥15L/min); non-invasive ventilation (e.g. CPAP, iPAP); mechanical ventilation ≤48h prior to dose
5) Have increased biological markers of systemic inflammation.
6) No gender restriction
7) Female participants must meet and agree to abide by the contraceptive criteria.
8) Capable of giving written informed consent. If participants are not capable of giving written informed consent, alternative consent procedures.
For more details check the protocol
Exclusion Criteria
1) Progression to death is imminent and inevitable within the next 48 hours, irrespective of the provision of treatments, in the opinion of the investigator.
2) Multiple organ failure according to the investigator’s judgement or a Sequential Organ Failure assessment (SOFA score) >10 if in the ICU
3) Extracorporeal membrane oxygenation (ECMO) hemofiltration/dialysis, or high dose (>0.15ug/kg/min) noradrenaline (or equivalent) or more than one vasopressor
4) Current serious or uncontrolled medical condition or abnormality of clinical
5) Untreated systemic bacterial, fungal, viral, or other infection
6) Known active tuberculosis (TB), history of untreated or incompletely treated active or latent TB, suspected or known extrapulmonary TB
7) Known HIV regardless of immunological status
8) Known HBsAg and/or anti-HCV positive
9) Currently receiving radiotherapy, chemotherapy or immunotherapy for malignancy
10) Received immunosuppressant therapy including but not limited to cyclosporin, azathioprine, tacrolimus, mycophenolate, JAK inhibitors within the last 3 months prior to randomization
11) Received monoclonal antibody therapy (e.g. tocilizumab, sarilumab) within the past 3 months prior to randomization
12) History of allergic reaction, including anaphylaxis to any previous treatment with an anti-GM-CSF therapy
For more details check the protocol
Worldwide enrolment start date
28/05/2020
Enrolment start date in Peru (Initial)
01/08/2020
Enrolment start date in Peru
08/10/2020
Peru enrolment status
Without starting enrollment
Enrollment stopped
In enrollment
Enrollment closed
Clinical Trial Total Duration
15 months
Medical Speciality
PNEUMOLOGY
Studied Condition (CIE-10 code)
-J128 Other viral pneumonia
Number of subjects to be included in all the countries
800
Number of subjects to be included in Peru (initial)
Number of subjects to be included in Peru (posterior)
35
35
Countries where the enrolment is conducted :
- India
- Japan
- Belgium
- Spain
- France
- Poland
- United Kindgdom
- Sweden
- Nederland
- South Africa
- Argentina
- Brazil
- Canada
- Chile
- Colombia
- 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
2 month(s)
Primary Outcome
Name of the outcome
Metric or method of measurement
Time point for the outcome
To compare the efficacy of otilimab 90 mg IV versus placebo
To compare the efficacy of otilimab 90 mg IV versus placebo
28 days
Secondary Outcome
Name of the outcome
Metric or method of measurement
Time point for the outcome
All-cause mortality at Day 60
All-cause mortality at Day 60
60 days
Time to all-cause mortality up to Day 60
Time to all-cause mortality up to Day 60
60 days
Participants alive and free of respiratory failure at Day 7, 14, 42, and 60
Participants alive and free of respiratory failure at Day 7, 14, 42, and 60
60 days
Time to recovery from respiratory failure up to Day 28
Time to recovery from respiratory failure up to Day 28
28 days
Participants alive and independent of supplementary oxygen at Day 7, 14, 28, 42, and 60
Participants alive and independent of supplementary oxygen at Day 7, 14, 28, 42, and 60
60 days
Time to last dependence on supplementary oxygen up to Day 28
Time to last dependence on supplementary oxygen up to Day 28
28 days
Admission to ICU up to Day 28
Admission to ICU up to Day 28
28 days
Time to final ICU discharge up to Day 28
Time to final ICU discharge up to Day 28
28 days
Time to final hospital discharge up to Day 28
Time to final hospital discharge up to Day 28
28 days
Occurrence of adverse events (AEs) [up to Day 60]
Occurrence of adverse events (AEs) [up to Day 60]
60 days
Occurrence of serious adverse events (SAEs) [up to Day 60]
Occurrence of serious adverse events (SAEs) [up to Day 60]
60 days
Invasive mechanical ventilation (if not previously initiated)
Invasive mechanical ventilation (if not previously initiated)
28 days
Time to invasive mechanical ventilation (if not previously initiated)
Time to invasive mechanical ventilation (if not previously initiated)
28 days
Alive and not invasively mechanically ventilated
Alive and not invasively mechanically ventilated
28 days
Time to definitive extubation
Time to definitive extubation
28 days
Improvement of at least 2 points relative to baseline of Sequential Organ Failure Assessment (SOFA) score
Improvement of at least 2 points relative to baseline of Sequential Organ Failure Assessment (SOFA) score
28 days
Improvement relative to baseline in SpO2, FiO2, and SpO2/FiO2 ratio
Improvement relative to baseline in SpO2, FiO2, and SpO2/FiO2 ratio
28 days
Oxygen-free days
Oxygen-free days
28 days
Ventilator-free days
Ventilator-free days
28 days
Time to resolution of pyrexia (for at least 48h)
Time to resolution of pyrexia (for at least 48h)
28 days
Clinical status assessed using an ordinal scale assessed at Days 4, 7, 14, 28, 42, and 60.
Clinical status assessed using an ordinal scale assessed at Days 4, 7, 14, 28, 42, and 60.
60 days
Time to improvement of at least 2 categories relative to baseline on an ordinal scale
Time to improvement of at least 2 categories relative to baseline on an ordinal scale
60 days
Change in COVID-19 signs and symptoms
Change in COVID-19 signs and symptoms
60 days
Otilimab apparent clearance (CL/F) and other PK parameters as appropriate using sparse PK sampling
Otilimab apparent clearance (CL/F) and other PK parameters as appropriate using sparse PK sampling
14 days
Exposure-response relationship for key efficacy, safety and PD endpoints
Exposure-response relationship for key efficacy, safety and PD endpoints
28 days
Key markers of inflammation including, but not limited to CRP, serum ferritin and inflammatory cytokines as appropriate
Key markers of inflammation including, but not limited to CRP, serum ferritin and inflammatory cytokines as appropriate
28 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 NACIONAL ALBERTO SABOGAL SOLOGUREN DE LA RED ASISTENCIAL SABOGAL
RCI 78
Unidad de Investigación, Hospital Nacional IV Alberto Sabogal Sologuren, Essalud, Red Asistencial Sabogal
LUIS ENRIQUE HERCILLA VASQUEZ
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 - CNTEI
Approved
27/07/2020
26/07/2021
12
7126450
Co-Investigator
- Erika Cecilia Agurto Lescano
HOSPITAL NACIONAL EDGARDO REBAGLIATI MARTINS
RCI-403
UNIDAD DE INVESTIGACIÓN DE INFECTOLOGÍA 1
FERNANDO CRUZ MENDO URBINA
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 - CNTEI
Approved
07/08/2020
07/08/2021
- Research Site Extension R.D. 356-2020-OGITT-INS with date 02/09/2020
- Clinical Trial Research Site Closure Resolución Directoral223-2021-OGITT-INS with date27/05/2021
Co-Investigator
CLÍNICA INTERNACIONAL S.A.
RCI-307
UNIDAD DE INVESTIGACIÓN DE LA CLÍNICA INTERNACIONAL
JOSÉ LUIS CABRERA RIVERO
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 - CNTEI
Approved
07/08/2020
07/08/2021
- Research Site Extension R.D. 358-2020-OGITT-INS with date 02/09/2020
Co-Investigator
HOSPITAL MILITAR CENTRAL “LUIS ARIAS SCHEREIBER”
RCI-301
CENTRO DE INVESTIGACIÓN DEL HOSPITAL MILITAR CENTRAL
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 - CNTEI
Approved
17/08/2020
07/08/2021
- Research Site Extension R.D. 357-2020-OGITT-INS with date 02/09/2020
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
