Spanish Version
DATA SHEET
CLINICAL TRIAL REGISTRATION (EC)
EC INS No:  PER-032-20
1. ORGANIZATION / APPLICANTE INSTITUTION
Name of Organization / Institution: PAREXEL International Perú S.A   Type of Organization / Institution : Empresa / Compañia 
Legal Domicile : Amador Merino Reyna 307, OF 1401 
District: San Isidro  Province: Lima 27 
Departament: Lima 
Single Taxpayer No : 20492118134 
Telephone: 511-4210299 o al 996208053   Fax:  
2. CLINICAL TRIAL GENERAL INFORMATION
Scientific title:
A PHASE 2/3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF MAVRILIMUMAB (KPL-301) TREATMENT IN ADULT SUBJECTS HOSPITALIZED WITH SEVERE COVID-19 PNEUMONIA AND HYPER-INFLAMMATION


Public Title
A PHASE 2/3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF MAVRILIMUMAB (KPL-301) TREATMENT IN ADULT SUBJECTS HOSPITALIZED WITH SEVERE COVID-19 PNEUMONIA AND HYPER-INFLAMMATION


Clinical Trial Registration Date Most recent Clinical Trial Update
23/07/2020  
Principal Sponsor :
1.- KINIKSA PHARMACEUTICALS, LTD.  
Secondary Sponsor :
 
Funding Source
1.-  KINIKSA PHARMACEUTICALS, LTD.
Executing Company / Institution / Other
- PAREXEL INTERNATIONAL PERÚ S.A Authorized with   249-2020-OGITT-INS Date 23/07/2020
Responsabilities
PAREXEL International Perú S.A  
  Others
  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 KPL-301-C203 
Secondary ID(s) :  
WHO UTN: U1111-1254-5493
CLINICALTRIALS.GOV: NCT0444746
EUDRACT N°:2020-002426-82
Study Design
This is a prospective, Phase 2/3, interventional, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of mavrilimumab (KPL-301) treatment in adult subjects hospitalized with severe COVID-19 pneumonia and hyper-inflammation. Approximately 573 subjects, divided into 2 cohorts, will be enrolled and randomized in a 1:1:1 allocation ratio to receive a single IV infusion of mavrilimumab (10 mg/kg or 6 mg/kg) or placebo. Cohort 1 will include non-intubated hospitalized subjects who require supplemental oxygen to maintain SpO2 ≥ 92%, ie, “non-ventilated” subjects. Cohort 2 will include hospitalized subjects for whom mechanical ventilation was recently initiated (within 48 hours prior to randomization), ie, “ventilated” subjects). The initial Phase 2 part of the study will enroll approximately 156 subjects, and the Phase 3 part will enroll approximately 417 subjects. There will be a seamless transition in enrollment of subjects in both cohorts between the Phase 2 and Phase 3 portions of the study. For each cohort, once the last subject in Phase 2 is enrolled, all subsequent subjects will be considered Phase 3 subjects. This will allow for continued enrollment during the analysis of the Phase 2 cohort-specific data. Once the last subject in Phase 2 completes Day 15, primary efficacy and safety analyses of the Phase 2 data will be conducted by the Sponsor. Following demonstration of efficacy and safety in Phase 2, the Phase 3 portion of the study will be continued/completed. A sample size adjustment and other potential changes in the Phase 3 study design may be considered. The primary endpoint in both cohorts will be assessed for both the Phase 2 and Phase 3 parts of the study using the NIAID scale for clinical improvement.[9] Subject clinical status will be assessed daily using this 8-point ordinal scale: 
Insurance policy due date 04/06/2021  Assignation method Randomized 
Non randomized 
Type of blinding Assignation
Simple  Double  Triple 
Open
Single arm        Parallel
Crossed                 Factorial
Others:
Purpose
The primary objective of this study is to evaluate the clinical efficacy of a single intravenous (IV) dose of mavrilimumab (10 mg/kg or 6 mg/kg) relative to placebo in adult subjects hospitalized with severe COVID-19 pneumonia and hyper-inflammation to reduce progression to respiratory failure or death. 
Research Product Information
Name of the product Generic Name Type of product ATC
MAVRILIMUMAB mavrilimumab      L04
Name of the compare Generic Name Type of product ATC
PLACEBO CLORURO DE SODIO 0.9% Placebo Cloruro de Sodio 0.9%      V07
Intervention(s) description:
Group name Type of group N° of participants Intervention(s) description
placebo-controlled study to evaluate the efficacy and safety of mavrilimumab (KPL-301) treatment in adult subjects hospitalized with severe COVID-19 pneumonia and hyper-inflammation Experimental
Control
573   Mavrilimumab (KPL-301, formerly known as CAM-3001) is a recombinant human monoclonal immunoglobulin G (IgG)4 antibody, which modulates activity of granulocyte-macrophage colony-stimulating factor (GM-CSF) by binding to the alpha subunit of its receptor (GMCSFRα). Mavrilimumab is a sterile, clear to opalescent, colorless to slightly brown-yellow liquid, free from visible particles and is formulated at 150 mg/mL in 50 mM sodium acetate, 70 mM sodium chloride, 4% weight/volume trehalose dihydrate, 0.05% weight/volume polysorbate 80 with a pH of 5.8. It is supplied by Kiniksa Pharmaceuticals as a liquid in accessorized pre-filled syringes or in vials for parenteral administration. Please see the Pharmacy Manual for additional details Subjects will receive a single IV infusion of either 10 mg/kg or 6 mg/kg mavrilimumab or placebo over approximately 60 minutes. Total dose may not exceed 1000 mg, which was approximately the maximum dose administered in the Phase 1 study with IV infusion. Dosing will be based on body weight obtained at Screening. Additional details regarding mavrilimumab
Inclusion Criteria
Subjects must meet all the following inclusion criteria to be eligible for enrollment in the study. 1. Subject (or legally authorized representative) is able and willing to provide informed consent, which includes compliance with study requirements and restrictions listed in the consent form. Consent must be performed per institutional regulations. 2. Age of ≥ 18 years 3. Positive SARS-CoV-2 (2019-nCoV) test within 14 days prior to randomization 4. Hospitalized for SARS-CoV-2 (2019-nCoV) 5. Bilateral pneumonia on chest x-ray or computed tomography (CT) 6. Active fever or recently documented fever within 72 hours prior to randomization (≥100.4°F or ≥38°C) 7. At least one of the following: • Ferritin > 500 ng/mL • CRP > 5 mg/dL • D-dimer > 1,000 ng/mL • LDH > 250 U/L 8. Cohort 1: Receiving any form of non-invasive ventilation OR oxygenation to maintain SpO2 ≥ 92% and not-intubated [examples include nasal cannula, face mask, venturi mask, high-flow nasal cannula, and non-invasive ventilation (NIV) or non-invasive positive pressure ventilation (NIPPV)] 9. Cohort 2: Recently ventilated with mechanical ventilation beginning within 48 hours prior to randomization 
Exclusion Criteria
Subjects who meet any of the following exclusion criteria will not be eligible for study enrollment. General Exclusion Criteria 1. Onset of COVID-19 symptoms > 14 days from randomization 2. Hospitalized > 7 days prior to randomization 3. [For Cohort 1 only] Need for invasive mechanical ventilation 4. Need for ECMO 5. Serious prior or concomitant illness that in the opinion of the Investigator precludes the subject from enrolling in the trial, including (but not limited to): • History of pulmonary alveolar proteinosis (PAP) • History of immunodeficiency (congenital or acquired) • History of solid-organ or bone marrow transplant • Current systemic autoimmune or autoinflammatory disease(s) requiring systemic immune-modulating drugs • History of or active cancer within the last 10 years - except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured • Severe and uncontrolled pulmonary disease other than COVID-19 pneumonia (eg, asthma, chronic obstructive pulmonary disease [COPD], or others) • Pre-existing severe left ventricular systolic dysfunction (ie, left ventricular ejection fraction [LVEF] < 35%) • Known active tuberculosis (TB) determined by history and local standard of care, or history of incompletely treated TB or at high risk for latent TB (exposure or prior incarceration) • Concomitant uncontrolled systemic bacterial or fungal infection • Concomitant respiratory viral infection other than COVID-19 that, in the opinion of the Investigator, represents a higher mortality risk (eg, SARS, MERS) • History of chronic liver disease with portal hypertension 6. Recent treatment with cell-depleting biological therapies (eg, anti-CD20) within 12 months, cell-depleting biological therapies (such as anti-TNF, anakinra, anti-IL-6 receptor [eg, tocilizumab], or abatacept) within 8 weeks (or 5 half-lives, whichever is longer), treatment with alkylating agents within 12 weeks, treatment with cyclosporine A, azathioprine, cyclophosphamide, mycophenolate mofetil (MMF), COVID-19-immune plasma, or other immunosuppressant within 4 weeks prior to randomization 7. Recent treatment with intramuscular live (attenuated) vaccine within 4 weeks prior to randomization 8. Corrected QT interval by Federicia method (QTcF) on Screening ECG ≥450ms 9. Chronic or recent (within 1 month) corticosteroid use > 10 mg/day 10. Enrolled in another investigational study of a medical intervention within 30 days prior to randomization 11. Known hypersensitivity to mavrilimumab or any of its excipients 12. In the opinion of the Investigator, unable to comply with the requirements to participate in the study 13. Female subjects must be: • postmenopausal, defined as at least 12 months post cessation of menses (without an alternative medical cause), or • permanently sterile following documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal ligation or having a male partner with vasectomy as affirmed by the subject, or • nonpregnant, nonlactating, and if sexually active having agreed to use a highly effective method of contraception (ie, hormonal contraceptives associated with inhibition of ovulation or intrauterine device [IUD], or intrauterine hormone-releasing system [IUS], or sexual abstinence) from Screening Visit until Day 90. 14. Male subjects must have documented vasectomy or if sexually active must agree to use a highly effective method of contraception with their partners of childbearing potential (ie, hormonal contraceptives associated with the inhibition of ovulation or intrauterine device [IUD], or intrauterine hormone-releasing system [IUS], or sexual abstinence) from Screening until Day 90. Male subjects must agree to refrain from donating sperm during this time period. 15. At Screening blood tests, any of the following: • Aspartate transaminase (AST) > 5 × ULN • Alanine transaminase (ALT) > 5 × ULN • Hemoglobin < 7.5 g/dL • Neutrophils < 1,500/mm3 • Absolute platelet count < 50,000/mm3 • Creatinine clearance (CrCl) < 30 mL/min by Cockcroft-Gault formula 
Worldwide enrolment start date 15/06/2020 
Enrolment start date in Peru (Initial) 22/07/2020  Enrolment start date in Peru 28/09/2020 
Peru enrolment status Without starting enrollment
Enrollment stopped
  In enrollment
  Enrollment closed 
Clinical Trial Total Duration 10  months Medical Speciality  
Studied Condition (CIE-10 code) -J22 Unspecified acute lower respiratory infection  
Number of subjects to be included in all the countries 573 
Number of subjects to be included in Peru (initial) Number of subjects to be included in Peru (posterior)
115 115
Countries where the enrolment is conducted :
- Ireland - Italy - United Kindgdom
- South Africa - Chile - 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  month(s) Subjects' follow up time 2  month(s)
Primary Outcome  
Name of the outcome Metric or method of measurement Time point for the outcome
Cohort 1 (non-ventilated subjects) Proportion of subjects alive and without respiratory failure at Day 15, where respiratory failure is defined as the need for high flow oxygen (HFO), non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO). Respiratory failure status will be evaluated based on the National Institute of Allergy and Infectious Diseases (NIAID) clinical outcome 8-point ordinal scale. Subjects whose clinical outcome meets NIAID categories 2 or 3 will be considered as having respiratory failure. 1. Death; 2. Hospitalized, on invasive mechanical ventilation or ECMO; 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized, limitation on activities and/or requiring home oxygen; 8. Not hospitalized, no limitations on activities. Cohort 2 (ventilated subjects) The primary efficacy endpoint is mortality rate, defined as the proportion of subjects who die by Day 15. 
Secondary Outcome
Name of the outcome Metric or method of measurement Time point for the outcome
Key Secondary Endpoints Key secondary efficacy endpoints will be examined based on the hierarchical order as specified below: Cohort 1 (non-ventilated subjects) 1. Time to return to room air by Day 15 Defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first. Subjects who die before Day 15 will be censored at Day 15. 2. Time to 2-point clinical improvement by Day 15 Defined as time from randomization to a 2-point improvement on the NIAID 8-point ordinal scale, or discharge from the hospital, whichever comes first. Subjects who die before Day 15 will be censored at Day 15. 3. Mortality rate at Day 29 Cohort 2 (ventilated subjects) 1. Time to 1-point clinical improvement by Day 15 Defined as time from randomization to a 1-point improvement on the NIAID 8-point ordinal scale, or discharge from the hospital, whichever comes first. Subjects who die before Day 15 will be censored at Day 15 2. Mortality rate at Day 29 
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 CAYETANO HEREDIA RCI 363 Departamento de enfermedades infecciosas, tropicales y dermatológicas
CARLOS RAFAEL SEAS RAMOS

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 30/06/2020 30/06/202007126450  
Co-Investigator
 
HOSPITAL III EMERGENCIAS GRAU RCI-31 CENTRO DE LA UNIDAD DE INFECTOLOGÍA
HUMBERTO DELFIN VASQUEZ CUBAS


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 20/07/2020  20/07/2021    - Research Site Extension R.D. 362-2020-OGITT-INS with date 03/09/2020  
Co-Investigator
 
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 - COMITÉ NACIONAL TRANSITORIO DE ÉTICA EN INVESTIGACIÓN PARA LA EVALUACIÓN Y SUPERVISIÓN DE ÉTICA DE LOS ENSAYOS CLÍNICOS DE LA ENFERMEDAD COVID-19 Approved 20/07/2020  20/07/2021    - Research Site Extension R.D. 378-2020-OGITT-INS with date 10/09/2020  
Co-Investigator
 
CLÍNICA PROVIDENCIA RCI-358 CENTRO DE INVESTIGACIÓN DE ENFERMEDADES RESPIRATORIAS
CARLOS ALBERTO IBERICO BARRERA


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 24/07/2020  20/07/2021    - Research Site Extension R.D. 401-2020-OGITT-INS with date 24/09/2020  
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
 
URL NAP
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
Rosmery Osorio Ubaldo rosmery.osorioubaldo@parexel.com 4231923 Yes Yes Yes
AUTHORIZATION STATUS
AUTHORIZED    ACTIVE
TYPE AND NUMBER OF AUTHORIZATION   DOCUMENT R.D.  249-2020-OGITT-INS AUTHRORIZATION   DOCUMENT DATE (dd/mm/aaaa): 23/07/2020  (Validity date from:23/07/2020)
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. 362-2020-OGITT-INS
03/09/2020

Research Site Extension
R.D. 378-2020-OGITT-INS
10/09/2020
10/09/2020

Research Site Extension
R.D. 401-2020-OGITT-INS
24/09/2020

Clinical Trial Amendment Report
 1141-2020-OGITT-INS
02/10/2020

Clinical Trial Amendment Report
 1224-2020-OGITT/INS
19/10/2020

Clinical Trial Progress Report
 
23/10/2020 12:22:31 p.m.

Clinical Trial Progress Report
 
23/10/2020 12:22:50 p.m.

Clinical Trial Progress Report
 
23/10/2020 12:23:01 p.m.

Clinical Trial Progress Report
 
23/10/2020 12:23:15 p.m.

Extension / Modification of Supply List
R.D. 482-2020-OGITT/INS
09/11/2020