protocol_id stringclasses 263
values | section_number stringlengths 1 12 | title stringlengths 1 1.88k | content stringlengths 0 866k | merged_titles listlengths 0 491 |
|---|---|---|---|---|
NCT04315298 | 3 | HYPOTHESIS AND RATIONALE | 3. HYPOTHESIS AND RATIONALE | [] |
NCT04315298 | 3.1 | Hypotheses | 3.1. Hypotheses Phase 2: Treatment of patients hospitalized with COVID-19 with sarilumab will result in a greater reduction in serum CRP compared to the control. Phase 3 Cohort 1: Treatment of patients hospitalized with COVID-19 in the critical stratum on mechanical ventilation at baseline with sarilumab 400 mg will re... | [] |
NCT04315298 | 3.2 | Rationale | 3.2. Rationale | [] |
NCT04315298 | 3.2.1 | Rationale for Study Design | 3.2.1. Rationale for Study Design Currently, there are no specific COVID-19 treatments. SARS-CoV-2, the betacoronavirus that causes COVID-19, results in a similar acute lower respiratory disease caused by SARS-CoV that was identified in 2002 and the Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV). Many thera... | [] |
NCT04315298 | 3.2.2 | Rationale for Study Design Adaptation | 3.2.2. Rationale for Study Design Adaptation Adaptations of the Phase 3 portion of the study are based on interim Phase 2 results of this study [\(Table](#page-44-1) 1 and [Table](#page-45-0) 2). Sarilumab 400 and 200 mg IV reduced serum CRP by 79% and 77%, respectively, compared to 21% in the placebo arm in the modifi... | [] |
NCT04315298 | 3.2.3 | Rationale for Phase 2 and Phase 3 Cohort 1 Dose Selection | 3.2.3. Rationale for Phase 2 and Phase 3 Cohort 1 Dose Selection COVID-19 infection can be associated with a degree of pulmonary cytokine release and IL-6 has been shown to be a major contributor to the development of fever and hypoxemia. In the current study, both 200 and 400-mg doses of sarilumab (Kevzara®), an anti-... | [] |
NCT04315298 | 3.2.4 | Rationale for Phase 3 Cohorts 2 and 3 Dose Selection | 3.2.4. Rationale for Phase 3 Cohorts 2 and 3 Dose Selection As discussed above, preliminary, open-label data from the use of tocilizumab, initially at a 400 mg IV dose [\(Xu, 2020](#page-117-4)) supported assessment of IL-6R inhibition in patients with severe or critical COVID-19 patients. Subsequent studies with tocil... | [] |
NCT04315298 | 3.3 | Risk-Benefit for REGN88 (sarilumab, Kevzara®) | 3.3. Risk-Benefit for REGN88 (sarilumab, Kevzara®) Sarilumab is currently approved at 200 mg Q2W (SC) for the treatment of RA in multiple countries. The risks and adverse reactions are described in the approved prescribing information for sarilumab. There are currently no known published reports of IL-6R antagonists fo... | [] |
NCT04315298 | 4 | ENDPOINTS | 4. ENDPOINTS | [] |
NCT04315298 | 4.1 | Primary and Secondary Endpoints | 4.1. Primary and Secondary Endpoints Note that for the primary and secondary endpoints, patients will not be required to return to the hospital once discharged. A follow-up phone call will occur on Days 29 and/or 60, depending on when the patient is discharged. All patients will be contacted for an end of study (EOS) f... | [] |
NCT04315298 | 4.1.1 | Primary Endpoints | 4.1.1. Primary Endpoints
Phase 2: Percent change from baseline in CRP levels at Day 4 in patients with serum IL-6 level greater than the upper limit of normal.
Phase 3 Cohort 1: Proportion of patients with at least a 1-point improvement in clinical status from baseline to Day 22 using the 7-point ordinal scale in pat... | [
"Phase 2:",
"Phase 3 Cohort 1:",
"Phase 3 Cohort 2:"
] |
NCT04315298 | 4.1.2 | Secondary Endpoints | 4.1.2. Secondary Endpoints The 7-point ordinal scale will be assessed as a secondary endpoint in Phase 2 and will be used for both Primary and Secondary endpoints in Phase 3. The ordinal scale is an assessment of the clinical status. The scale is as follows: - Death; - Hospitalized, requiring invasive mechanical ventil... | [] |
NCT04315298 | 4.1.2.1 | Phase 2 Secondary Endpoints: | 4.1.2.1. Phase 2 Secondary Endpoints:
Efficacy
Phase 2 Key Secondary Endpoints - 1. Time to improvement (2 points) in clinical status assessment from baseline on the 7-point ordinal scale in severe or critical patients with serum IL-6 levels greater than the upper limit of normal - 2. Time to improvement (2 points) i... | [
"Efficacy",
"Phase 2 Key Secondary Endpoints",
"Other Phase 2 Secondary Endpoints:"
] |
NCT04315298 | 4.1.2.2 | Phase 3 Secondary Endpoints | 4.1.2.2. Phase 3 Secondary Endpoints The Phase 3 secondary endpoints for Cohorts 1 and 2 are outlined in [Table](#page-56-0) 4. Table 4: Phase 3 Efficacy Endpoints | | Cohort 1: sarilumab 400 mg vs. placebo | Cohort 2: sarilumab800mgvs. placebo(receiving mechanicalventilation atbaseline) | | | |------------------------... | [] |
NCT04315298 | 4.1.2.3 | Safety Endpoints | 4.1.2.3. Safety Endpoints The secondary safety endpoints for Phase 2 and 3 are: - 1. Proportion of patients with serious adverse events - 2. Proportion of patients with Grade 4 neutropenia (ANC 3 ) - 5. Proportion of patients with hypersensitivity reactions - 6. Proportion of patients with infusion reactions - 7. Propo... | [] |
NCT04315298 | 4.1.3 | Exploratory Endpoints | 4.1.3. Exploratory Endpoints
Phase 2 and 3: The exploratory endpoints are: - 1. Qualitative and quantitative PCR for SARS-CoV-2 in OP/NP swab on Days 1, 4, and 29 - 2. Time to 2 consecutive negative OP/NP swab PCR results for SARS-CoV-2 - 3. Qualitative and quantitative PCR for SARS-CoV-2 in blood on Days 1, 4, and 29... | [
"Phase 2 and 3:",
"Phase 3 only:"
] |
NCT04315298 | 5 | STUDY VARIABLES | 5. STUDY VARIABLES | [] |
NCT04315298 | 5.1 | Demographic and Baseline Characteristics | 5.1. Demographic and Baseline Characteristics Baseline characteristics will include standard demography (eg, age, race, weight, height, etc), disease characteristics, medical history, and medication history for each patient. The site investigator will assess the patient for a history of chronic hypercapnic respiratory ... | [] |
NCT04315298 | 5.2 | Efficacy Variables | 5.2. Efficacy Variables The efficacy variables include serum CRP, body temperature, gas exchange/oxygen requirement, requirement for ventilation support, ICU admissions, days of hospitalization, 7-point ordinal scale score (to assess clinical status), and NEWS2 specified in the study endpoints (Section [4.1.1](#page-53... | [] |
NCT04315298 | 5.3 | Safety Variables | 5.3. Safety Variables Safety variables include incidence of AESIs, SAEs, and laboratory safety test results (white cell count including ANC, hemoglobin, platelets, creatinine, total bilirubin, ALT, AST). | [] |
NCT04315298 | 5.4 | Pharmacokinetic Variables | 5.4. Pharmacokinetic Variables The PK variable is the concentration of sarilumab and sIL-6R in serum at each time point specified in [Table](#page-77-0) 5. | [] |
NCT04315298 | 5.5 | Pharmacodynamic and Other Biomarker Variables | 5.5. Pharmacodynamic and Other Biomarker Variables Exploratory endpoint variables include measurement of SARS-CoV-2 in OP or NP swabs over time using RT-PCR. Qualitative (positive or negative) or relative quantitation of viral copies may be evaluated. Pharmacodynamic variables may include the time to reach a negative O... | [] |
NCT04315298 | 6 | STUDY DESIGN | 6. STUDY DESIGN | [] |
NCT04315298 | 6.1 | Study Description and Duration | 6.1. Study Description and Duration This study is an adaptive Phase 2/3, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of sarilumab in hospitalized adults with severe or critical COVID-19. As part of the Phase 3 adaptation plan, the Phase 3 portion of the study will include 3 co... | [
"Randomization",
"1. Severe disease",
"2. Critical disease:",
"3. Multi-system organ dysfunction:",
"4. Immunocompromised",
"Dosing",
"Phase 3 Cohort 1:",
"Phase 3 Cohort 2:",
"Day 1",
"Day 2 through 7",
"Days 8 through 14",
"Days 15 through 21",
"Phase 3 Cohort 3:",
"Safety",
"Assessmen... |
NCT04315298 | 6.1.1 | Study Stopping Rules | 6.1.1. Study Stopping Rules | [] |
NCT04315298 | 6.1.1.1 | Individual Patient Stopping Rules | 6.1.1.1. Individual Patient Stopping Rules For an individual patient, an investigator should assess potential benefit-risk to determine if study drug should be interrupted or discontinued for suspected drug-related events of infusion-related reactions. Refer to Section [8.3](#page-70-5) for details. | [] |
NCT04315298 | 6.1.1.2 | Study Level Stopping Rules | 6.1.1.2. Study Level Stopping Rules An independent data monitoring committee (IDMC) will actively monitor interim data to review the ongoing safety of patients and can make recommendations about early study closure or changes to the conduct of the study. The Sponsor may decide to stop or make adaptations to the study b... | [] |
NCT04315298 | 6.1.2 | End of Study Definition | 6.1.2. End of Study Definition The end of study is defined as the date the last patient completes the last study assessment (in the hospital or via a follow-up phone call if the patient was discharged from the hospital before Day 60), withdraws from the study, or is lost to follow-up (ie, the study patient can no longe... | [] |
NCT04315298 | 6.2 | Planned Timing of Analysis | 6.2. Planned Timing of Analysis The first analysis of data is planned for safety and efficacy monitoring when the first approximately 12 patients are randomized, receive a study drug, and have at least 7 days of follow-up. Data, including deaths, on these first 12 patients as well as all patients enrolled in the study ... | [] |
NCT04315298 | 6.3 | Study Committees | 6.3. Study Committees | [] |
NCT04315298 | 6.3.1 | Independent Data Monitoring Committee | 6.3.1. Independent Data Monitoring Committee An IDMC will actively monitor interim data to review the ongoing safety of patients and can make recommendations about early study closure or changes to the protocol. The IDMC members will include 2 to 4 physicians with relevant medical specialty training and 1 statistician.... | [] |
NCT04315298 | 7 | SELECTION, WITHDRAWAL, AND REPLACEMENT OF PATIENTS | 7. SELECTION, WITHDRAWAL, AND REPLACEMENT OF PATIENTS | [] |
NCT04315298 | 7.1 | Number of Patients Planned | 7.1. Number of Patients Planned The total sample size for Phase 2 will be approximately 460 to include patients with all baseline IL-6 levels. Based on results from Phase 2 data, sample size for Phase 3 was re-calculated. For Cohort 1 of the Phase 3 portion of this study, the total sample size will be approximately 1,4... | [] |
NCT04315298 | 7.2 | Study Population | 7.2. Study Population Hospitalized adult (≥18 years old) male and female patients with COVID-19. | [] |
NCT04315298 | 7.2.1 | Inclusion Criteria | 7.2.1. Inclusion Criteria A patient must meet the following criteria to be eligible for inclusion in the study: - 1. Male or female adult ≥18 years of age at time of enrollment - 2. Hospitalized (or documentation of a plan to admit to the hospital if the patient is in an emergency department) with illness of any durati... | [
"• Severe disease",
"• Critical disease",
"• Multi-system organ dysfunction",
"• Immunocompromised"
] |
NCT04315298 | 7.2.2 | Exclusion Criteria | 7.2.2. Exclusion Criteria A patient who meets any of the following criteria will be excluded from the study: - 1. In the opinion of the investigator, not expected to survive for more than 48 hours from screening. - 2. Presence of any of the following abnormal laboratory values at screening: ANC less than 2000 mm3 , AST... | [
"Phase 3 Cohort 2 only:"
] |
NCT04315298 | 7.3 | Premature Withdrawal from the Study | 7.3. Premature Withdrawal from the Study A patient has the right to withdraw from the study at any time, for any reason, and without repercussion. The investigator and/or sponsor have the right to withdraw a patient from the study if it is no longer in the interest of the patient to continue in the study, or if the pat... | [] |
NCT04315298 | 7.4 | Replacement of Patients | 7.4. Replacement of Patients Patients prematurely discontinued from the study will not be replaced. | [] |
NCT04315298 | 8 | STUDY TREATMENTS | 8. STUDY TREATMENTS | [] |
NCT04315298 | 8.1 | Investigational Treatment | 8.1. Investigational Treatment In Phase 2 and Phase 3 Cohort 1, all patients randomized and dosed will receive 1 of the following: - Sarilumab 200 mg IV for 1-hour - Sarilumab 400 mg IV for 1-hour - Placebo IV for 1-hour For Phase 3 Cohort 2, all patients randomized and dosed will receive 1 of the following: - Sariluma... | [] |
NCT04315298 | 8.2 | Dose Modification and Study Treatment Discontinuation Rules | 8.2. Dose Modification and Study Treatment Discontinuation Rules | [] |
NCT04315298 | 8.2.1 | Dose Modification | 8.2.1. Dose Modification Eligible patients will receive repeat dosing per the criteria outlined in Section [6.1.](#page-60-0) Per the recommendation of the IDMC, as of 27 Apr 2020, patients will no longer receive sarilumab 200 mg or be eligible for repeat dosing of 200 mg and patients in the severe and MSOD strata will... | [] |
NCT04315298 | 8.2.2 | Study Drug Discontinuation | 8.2.2. Study Drug Discontinuation Study drug may be temporarily withheld if ANC 3or ALT >5x ULN, or at the discretion of the investigator according to the instructions in Section [6.1.](#page-60-0) Study drug may be continued if, upon repeat testing, ANC >500/mm3and ALT ≤5x ULN. Patients who opt to withdraw from the st... | [] |
NCT04315298 | 8.3 | Management of Acute Reactions | 8.3. Management of Acute Reactions | [] |
NCT04315298 | 8.3.1 | Acute Intravenous Infusion Reactions | 8.3.1. Acute Intravenous Infusion Reactions Emergency equipment and medication for the treatment of infusion reactions must be available for immediate use. All Grade ≥2 infusion-related reactions must be reported as AESIs (see Section [10.1.3](#page-90-1) and Section [10.2.4](#page-92-0)) and graded using the grading s... | [] |
NCT04315298 | 8.3.1.1 | Interruption of the Intravenous Infusion | 8.3.1.1. Interruption of the Intravenous Infusion The infusion should be interrupted if any of the following AEs are observed: - sustained/severe cough - rigors/chills - rash, pruritus (itching) - urticaria (hives, welts, wheals) - diaphoresis (sweating) - hypotension - dyspnea (shortness of breath) - vomiting - flushi... | [] |
NCT04315298 | 8.3.1.2 | Termination of the Intravenous Infusion | 8.3.1.2. Termination of the Intravenous Infusion The infusion should be terminated and NOT restarted if any of the following adverse events occur: - anaphylaxis\ - laryngeal/pharyngeal edema - severe bronchospasm - chest pain - seizure - severe hypotension - other neurological symptoms (confusion, loss of consciousness... | [] |
NCT04315298 | 8.4 | Method of Treatment Assignment | 8.4. Method of Treatment Assignment In the Phase 2 study and Cohort 1 of the Phase 3 study, patients will be randomized in a ratio of 2:2:1 to receive sarilumab 400 mg IV, or sarilumab 200 mg IV or placebo, in a stratified manner. In Phase 3, Cohort 2, patients will be randomized in a ratio of 1:1 to receive sarilumab ... | [
"Phase 2 and Phase 3 Cohort 1:"
] |
NCT04315298 | 8.5 | Blinding | 8.5. Blinding A pharmacist or qualified personnel at the site, not otherwise associated with the conduct of the study, will reconstitute the drug for IV administration. The drug infusion solution must be provided in identical form for active and placebo treatments, so that they remain indistinguishable to both study pe... | [
"Blinding of CRP Assessment Results"
] |
NCT04315298 | 8.6 | Emergency Unblinding | 8.6. Emergency Unblinding Unblinding of treatment assignment for a patient may be necessary due to a medical emergency or any other significant medical event and when a treatment decision is contingent on knowing the patient's treatment assignment. Study drug will be discontinued for patients whose treatment has been u... | [] |
NCT04315298 | 8.7 | Treatment Logistics and Accountability | 8.7. Treatment Logistics and Accountability | [] |
NCT04315298 | 8.7.1 | Packaging, Labeling, and Storage | 8.7.1. Packaging, Labeling, and Storage Sarilumab for injection, 175 mg/mL will be provided as open-label supplies packaged in boxes. Each box will contain 1 prefilled syringe or vial. Each box will be labeled with a 1-panel, open label printed in black. The product identity and strength, container number, directions f... | [] |
NCT04315298 | 8.7.2 | Supply and Disposition of Treatments | 8.7.2. Supply and Disposition of Treatments Study drug will be shipped at a temperature of 2ºC to 8ºC to the investigator or designee at regular intervals or as needed during the study. At specified time points during the study (eg, interim site monitoring visits), at the site close-out visit, and following drug reconc... | [] |
NCT04315298 | 8.7.3 | Treatment Accountability | 8.7.3. Treatment Accountability All drug accountability records must be kept current. The investigator must be able to account for all opened and unopened study drug. These records should contain the dates, quantity, and study medication - dispensed to each patient - disposed of at the site or returned to the sponsor o... | [] |
NCT04315298 | 8.7.4 | Treatment Compliance | 8.7.4. Treatment Compliance All drug compliance records must be kept current and made available for inspection by the sponsor and regulatory agency inspectors. | [] |
NCT04315298 | 8.8 | Concomitant Medications | 8.8. Concomitant Medications Any treatment administered from the first dose of study drug to the final study assessment will be considered concomitant medication. This includes medications that were started before the study and are ongoing during the study. If the local standard of care per written policies or guidelin... | [
"CYP Substrates"
] |
NCT04315298 | 8.8.1 | Prohibited and Permitted Medications | 8.8.1. Prohibited and Permitted Medications Patients may continue their normal regimen of medications and procedures, except for those specified in the exclusion criteria for study enrollment (Section [7.2.2\)](#page-67-0). Patients who receive a prohibited medication will not be eligible for re-dosing of study drug. | [] |
NCT04315298 | 9 | STUDY SCHEDULE OF EVENTS AND PROCEDURES | 9. STUDY SCHEDULE OF EVENTS AND PROCEDURES | [] |
NCT04315298 | 9.1 | Schedule of Events | 9.1. Schedule of Events Study assessments and procedures are presented by study period/day in [Table](#page-77-0) 5. Table 5: Schedule of Events | Study Procedure | ScreeningVisit1 | BaselineVisit1 | Daily Follow-up Until Hospital Discharge | | | | | EOS2 | |-------------------------------------------------------------... | [] |
NCT04315298 | 9.1.1 | Footnotes for the Schedule of Events Table | 9.1.1. Footnotes for the Schedule of Events Table - 1. Screening and baseline may occur on the same day. Assessments that are noted for both visits should only be assessed once. Medical history should include collecting onset of pneumonia symptoms. Body temperature, SpO2, and FiO2 must be collected at randomization. - ... | [] |
NCT04315298 | 9.1.2 | Early Termination from the Study | 9.1.2. Early Termination from the Study Patients who are withdrawn from the study before the primary endpoint assessment (Day 29) may be asked to provide a final blood draw sample for PK analysis before withdrawing from the study [\(Table](#page-77-0) 5) and to allow for re-contact at the end of the trial (Day 60 follo... | [] |
NCT04315298 | 9.2 | Study Procedures | 9.2. Study Procedures | [] |
NCT04315298 | 9.2.1 | Procedures Performed Only at the Screening/Baseline | 9.2.1. Procedures Performed Only at the Screening/Baseline The following procedures will be performed for the sole purpose of determining study eligibility or characterizing the baseline characteristics of the study population: demographics, medical history, timing of COVID-19 infection, prior therapy, pregnancy status... | [] |
NCT04315298 | 9.2.2 | Efficacy Procedures | 9.2.2. Efficacy Procedures | [] |
NCT04315298 | 9.2.2.1 | C-Reactive Protein | 9.2.2.1. C-Reactive Protein Serum CRP will be measured at each site's local laboratory according to the schedule in [Table](#page-77-0) 5. See Section [9.2.3.5](#page-86-0) for details. | [] |
NCT04315298 | 9.2.2.2 | Body Temperature | 9.2.2.2. Body Temperature Body temperature measurement will occur before taking antipyretics or more than 4 hours after last dose of antipyretics. Body temperature will be measured to monitor the patient's status regarding fever per the schedule in [Table](#page-77-0) 5. Temperature may be measured using the following ... | [] |
NCT04315298 | 9.2.2.3 | Oxygen Administration and Oxygenation | 9.2.2.3. Oxygen Administration and Oxygenation Supplemental oxygen/FiO2 use will be measured to monitor the patient's status regarding gas exchange per the schedule in [Table](#page-77-0) 5. As applicable, the following will be recorded: - Oxygen delivery device (eg, nasal cannula, simple face mask, non-rebreather mask... | [] |
NCT04315298 | 9.2.2.4 | Clinical Status Assessment (7-Point Ordinal Scale) | 9.2.2.4. Clinical Status Assessment (7-Point Ordinal Scale) Cohort 1: A Clinical Status Assessment (7-point ordinal scale) [\(Peterson, 2017](#page-116-9)) should be assessed in the morning to consider the worst assessments for the previous day (ie, midnight to midnight; 00:00 – 00:00 [24-hour clock]). If it is the fir... | [
"Cohort 2:"
] |
NCT04315298 | 9.2.2.5 | NEWS2 Scoring System | 9.2.2.5. NEWS2 Scoring System The NEWS2 scoring system [\(Table](#page-84-0) 6) is a composite score derived from respiratory rate (per minute), SpO2 Scale 1 (%) or SpO2 Scale 2 (%), Use of air or oxygen (?), Systolic blood pressure (mm Hg), Pulse (per minute), Consciousness, and Temperature (°C). The NEWS2 score will ... | [] |
NCT04315298 | 9.2.3 | Safety Procedures | 9.2.3. Safety Procedures | [] |
NCT04315298 | 9.2.3.1 | Vital Signs | 9.2.3.1. Vital Signs Vital signs, including blood pressure, pulse, and respiration, will be collected and recorded at the time points according to [Table](#page-77-0) 5. Predose body temperature should be recorded on the vital signs eCRF. | [] |
NCT04315298 | 9.2.3.2 | Limited Physical Examination | 9.2.3.2. Limited Physical Examination A targeted physical examination including lung auscultation will be performed at time point according to [Table](#page-77-0) 5. Care should be taken to examine and assess any abnormalities that may be present, as indicated by the patient's medical history. | [] |
NCT04315298 | 9.2.3.3 | Electrocardiogram | 9.2.3.3. Electrocardiogram If feasible, a standard 12-lead ECG will be performed at time points according to [Table](#page-77-0) 5. An historical ECG from the present hospital admission (including ED stay) may be used. The ECG strips or reports will be retained with the source. | [] |
NCT04315298 | 9.2.3.4 | Targeted Medication Review | 9.2.3.4. Targeted Medication Review The patient's medications will be reviewed and recorded, including but not limited to use of: - antipyretics, such as aspirin, acetaminophen, ibuprofen, and other non-steroidal anti-inflammatory drugs (NSAIDs) - warfarin - cyclosporine A - theophylline - digoxin - antiepileptics, suc... | [] |
NCT04315298 | 9.2.3.5 | Laboratory Testing | 9.2.3.5. Laboratory Testing Serum CRP will be measured at each site's local laboratory according to the schedule in [Table](#page-77-0) 5. All patients should have white blood cell count, platelet count, AST, and ALT measured prior to randomization (see Section [7.2.2\)](#page-67-0). If these laboratory tests were not ... | [
"Blood Chemistry",
"Hematology/Coagulation",
"Other Laboratory Tests",
"Screening:",
"Safety:",
"Biomarkers/Research Samples:"
] |
NCT04315298 | 9.2.4 | Drug Concentration and Measurements | 9.2.4. Drug Concentration and Measurements Samples for measurement of sarilumab and sIL-6R in serum will be collected at visits listed in [Table](#page-77-0) 5. These samples will be analyzed either by the Sponsor or a central laboratory. | [] |
NCT04315298 | 9.2.5 | Pharmacodynamic and Exploratory Biomarker Procedures | 9.2.5. Pharmacodynamic and Exploratory Biomarker Procedures In this study, research assessments will be performed to explore how sarilumab may modify the clinical manifestations and pathology associated with COVID-19 and how the IL-6 signaling pathway may be modulated. Biomarker samples will be collected at time points... | [] |
NCT04315298 | 10 | SAFETY EVALUATION AND REPORTING | 10. SAFETY EVALUATION AND REPORTING | [] |
NCT04315298 | 10.1 | Recording and Reporting Adverse Events | 10.1. Recording and Reporting Adverse Events | [] |
NCT04315298 | 10.1.1 | General Guidelines | 10.1.1. General Guidelines The investigator must promptly record all serious clinical events and AESIs occurring during the study data collection, from the time of signing the ICF to the end of study. Medical conditions that existed or were diagnosed prior to the signing of the Informed Consent will be recorded as part... | [] |
NCT04315298 | 10.1.2 | Reporting Procedure | 10.1.2. Reporting Procedure All SAEs and AESIs (serious and non-serious) must be reported with investigator's assessment of the event's seriousness, severity, and causality to the blinded study drug. A detailed narrative summarizing the course of the event, including its evaluation, treatment, and outcome should be pro... | [] |
NCT04315298 | 10.1.3 | Events that Require Expedited Reporting to Sponsor | 10.1.3. Events that Require Expedited Reporting to Sponsor The following events also require reporting to the sponsor (or designee) within 24 hours of learning of the event: - SAEs. - Adverse Events of Special Interest (AESI; serious and nonserious): Adverse events of special interest for this study include the followi... | [] |
NCT04315298 | 10.2 | Definitions | 10.2. Definitions | [] |
NCT04315298 | 10.2.1 | Adverse Event | 10.2.1. Adverse Event An AE is any untoward medical occurrence in a patient administered a study drug which may or may not have a causal relationship with the study drug. Therefore, an AE is any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease which is temporally associated w... | [] |
NCT04315298 | 10.2.2 | Serious Adverse Event | 10.2.2. Serious Adverse Event An SAE is any untoward medical occurrence that at any dose: - Results in death includes all deaths, even those that appear to be completely unrelated to study drug (eg, a car accident in which a patient is a passenger). - Is life-threatening in the view of the investigator, the patient is ... | [] |
NCT04315298 | 10.2.3 | Adverse Events of Special Interest | 10.2.3. Adverse Events of Special Interest An adverse event of special interest (AESI; serious or non-serious) is one of scientific and medical interest specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate. Such an event... | [] |
NCT04315298 | 10.2.4 | Infusion Reactions | 10.2.4. Infusion Reactions Infusion reactions are defined as any relevant AE that occurs during the infusion or within 2 hours after the infusion is completed. | [] |
NCT04315298 | 10.2.5 | Severity | 10.2.5. Severity The severity of AEs will be graded using the NCI-CTCAE v5. Adverse events not listed in the NCI-CTCAE v5 will be graded according to the following scale: Table 7: Grading System for Adverse Events Not Listed in NCI-CTCAE | Grade | Severity | Description | | |-------|------------------|-----------------... | [] |
NCT04315298 | 10.2.6 | Causality | 10.2.6. Causality The investigator must provide causality assessment as whether or not there is a reasonable possibility that the drug caused the adverse event, based on evidence or facts, his/her clinical judgment, and the following definitions. The causality assessment must be made based on the available information ... | [
"• Related:",
"• Not Related:",
"• Related:",
"• Not Related:"
] |
NCT04315298 | 10.3 | Safety Monitoring | 10.3. Safety Monitoring The investigator will monitor the safety of study patient at his/her site(s) as per the requirements of this protocol and consistent with current Good Clinical Practice (GCP). Any questions or concerns should be discussed with the sponsor in a timely fashion. The sponsor will monitor the safety ... | [] |
NCT04315298 | 10.4 | Notifying Health Authorities, Institutional Review Board, and Investigators | 10.4. Notifying Health Authorities, Institutional Review Board, and Investigators During the study, the sponsor and/or the CRO will inform health authorities, IRBs, and the participating investigators of any SUSARs (Suspected Unexpected Serious Adverse Reactions) occurring in other study centers using the active study ... | [] |
NCT04315298 | 11 | STATISTICAL PLAN | 11. STATISTICAL PLAN This section provides the basis for the statistical analysis plans (SAPs) for the study. There will be 2 separate SAPs for this study; one will be for Phase 2 and second for Phase 3. The SAPs will be revised prior to the end of each portion of the study (Phase 2 or Phase 3) to accommodate amendment... | [] |
NCT04315298 | 11.1 | Statistical Hypothesis | 11.1. Statistical Hypothesis
Phase 2 Portion of the Study For the Phase 2 portion of the study, the hypothesis to be tested is the superiority of sarilumab versus placebo with respect to the primary endpoint of percent change from baseline in CRP levels at Day 4 (Section [4.1.1](#page-53-0) and Section [11.4.3.1\)](#p... | [
"Phase 2 Portion of the Study",
"Phase 3 Portion of the Study (Prior to Adaptation)",
"Phase 3 Portion of the Study (Post-Adaptations)",
"Cohort 1",
"Cohort 2"
] |
NCT04315298 | 11.2 | Justification of Sample Size | 11.2. Justification of Sample Size For the Phase 2 portion of the study, approximately 200 patients (80 in each of the 2 sarilumab dose groups and 40 on placebo) are required in all disease severity strata with high baseline IL-6 levels to test for superiority of sarilumab versus placebo with respect to percent change ... | [
"Phase 3 Portion of the Study (Prior to Adaptations)",
"Phase 3 Portion of the Study (Post-Adaptations)"
] |
NCT04315298 | 11.3 | Analysis Sets | 11.3. Analysis Sets | [] |
NCT04315298 | 11.3.1 | Efficacy Analysis Sets | 11.3.1. Efficacy Analysis Sets ITT population: The intention-to-treat (ITT) population includes all randomized patients who received at least one dose of the study drug. Analysis of the ITT population will be done according to the initial treatment assigned to the patient (as randomized). ITT population will be used fo... | [] |
NCT04315298 | 11.3.2 | Safety Analysis Set | 11.3.2. Safety Analysis Set Safety population: The safety population includes all randomized patients who received at least one dose of the study drug. Analysis of the Safety population will be done according to the treatment received (as treated). Determination of "as treated" will be based on the actual study drug re... | [] |
NCT04315298 | 11.3.3 | Pharmacokinetic Analysis Sets | 11.3.3. Pharmacokinetic Analysis Sets The PK analysis population includes all patients who received any study drug and who had at least 1 non-missing result following the first dose of study drug. | [] |
NCT04315298 | 11.4 | Statistical Methods | 11.4. Statistical Methods For continuous variables, descriptive statistics will include the following information: the number of patients reflected in the calculation (n), mean, standard deviation, Q1, median, Q3, minimum, and maximum. For categorical or ordinal data, frequencies and percentages will be displayed for e... | [] |
NCT04315298 | 11.4.1 | Patient Disposition | 11.4.1. Patient Disposition The following will be provided: - The total number of screened patients: met the inclusion criteria regarding the target indication and signed the ICF - The total number of randomized patients: received a randomization number - The total number of patients who discontinued the study, and the... | [] |
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