protocol_id stringclasses 263
values | section_number stringlengths 1 12 | title stringlengths 1 1.88k | content stringlengths 0 866k | merged_titles listlengths 0 491 |
|---|---|---|---|---|
NCT02287233 | 12.0 | Use of Information | 12.0 Use of Information All information concerning venetoclax and AbbVie operations, such as AbbVie patent applications, formulas, manufacturing processes, basic scientific data, or formulation information, supplied by AbbVie and not previously published is considered confidential information. The information developed... | [] |
NCT02287233 | 13.0 | Completion of the Study | 13.0 Completion of the Study The investigator will conduct the study in compliance with the protocol and complete the study within the timeframe specified in the contract between the investigator and AbbVie. Continuation of this study beyond this date must be mutually agreed upon in writing by both the investigator and... | [] |
NCT02287233 | 14.0 | Investigator's Agreement | 14.0 Investigator's Agreement - 1. I have received and reviewed the Investigator's Brochure for venetoclax (ABT-199/GDC-0199) and the product label for cytarabine. - 2. I have read this protocol and agree that the study is ethical. - 3. I agree to conduct the study as outlined and in accordance with all applicable regu... | [] |
NCT02287233 | 15.0 | Reference List | 15.0 Reference List - 1. Friedman EJ, Fraser IP, Wang YH, et al. Effect of different durations and formulations of diltiazem on the single-dose pharmacokinetics of midazolam: how long do we go? J Clin Pharmacol. 2011;51:1651-70. - 2. Salem AH, Agarwal SK, Dunbar M, et al. Pharmacokinetics of venetoclax, a novel BCL-2 i... | [
"Appendix A. Responsibilities of the Clinical Investigator",
"Appendix B. List of Protocol Signatories",
"Appendix C. Sample List of Excluded and Cautionary Medications",
"Excluded During Ramp-Up Phase and Throughout Study:",
"Cautionary (Additional Guidance Noted in [Table](#page-52-1) 1):",
"Cautionary:... |
NCT02293837 | 1 | BACKGROUND AND RATIONALE | 1. BACKGROUND AND RATIONALE | [] |
NCT02293837 | 1.1 | BACKGROUND AND SCIENTIFIC RATIONALE | 1.1 BACKGROUND AND SCIENTIFIC RATIONALE | [] |
NCT02293837 | 1.1.1 | Type 1 diabetes (T1D) | 1.1.1 Type 1 diabetes (T1D) Type 1 diabetes (T1D) affects about 1 million people in North America, with an incidence of approximately 30,000 new cases per year (~15,000 children and ~15,000 adults—80 people per day—are diagnosed with T1D in the U.S)[.](#page-64-3) 1 Standard of care comprises multiple daily shots of ex... | [] |
NCT02293837 | 1.1.2 | Tocilizumab | 1.1.2 Tocilizumab IL-6 is a systemic cytokine, participating in proinflammatory pathways associated with immunity and autoimmunity. In addition, IL-6 plays an important role in the communication between the innate and adaptive immune systems, mediated through the development and function of regulatory T (Treg) and path... | [
"Efficacy"
] |
NCT02293837 | 1.2.2.1.7 | Clinical Use in Diabetes | 1.2.2.1.7 Clinical Use in Diabetes IL-6 has been linked to defects in insulin action characteristic of metabolic syndrome and type 2 diabetes, but studies on the metabolic effects of IL-6R blockade are sparse. In a small open-label study of non-diabetic RA patients, tocilizumab therapy resulted in a significant decreas... | [] |
NCT02293837 | 1.2.2.1.8 | Pediatric Experience with Tocilizumab | 1.2.2.1.8 Pediatric Experience with Tocilizumab As noted previously, tocilizumab is approved for use in children 2 years of age and older with sJIA and pJIA. Tocilizumab has been studied in two phase 3 clinical trials (WA18221 and WA19977) and a supportive phase 3 study (MRA316JP) performed in Japan with pediatric popu... | [] |
NCT02293837 | 1.3 | SUMMARY OF KNOWN AND POTENTIAL RISKS AND BENEFITS FOR HUMAN PARTICIPANTS | 1.3 SUMMARY OF KNOWN AND POTENTIAL RISKS AND BENEFITS FOR HUMAN PARTICIPANTS | [] |
NCT02293837 | 1.3.1 | Overview | 1.3.1 Overview Like any immunomodulating therapy, the primary risks of tocilizumab relate to infections; however, these are generally well tolerated and the use of this drug is increasing rapidly in the approved autoimmune indications (rheumatoid arthritis, systemic juvenile idiopathic arthritis, and polyarticular juve... | [] |
NCT02293837 | 1.3.2 | Risks | 1.3.2 Risks | [] |
NCT02293837 | 1.3.2.1 | Opportunistic Infections and Serious Infections | 1.3.2.1 Opportunistic Infections and Serious Infections Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, protozoal, or other opportunistic pathogens have been reported in patients receiving immunosuppressive agents including tocilizumab for rheumatoid arthritis. | [] |
NCT02293837 | 1.3.2.2 | Gastrointestinal Perforations | 1.3.2.2 Gastrointestinal Perforations A total of 30 cases of medically confirmed serious GI perforation (primarily as complications of diverticulitis in RA patients, but also including those related to malignancy) were reported in clinical trials, corresponding to a rate of 0.2 per 100 patient-years. No GI perforations... | [] |
NCT02293837 | 1.3.2.3 | Laboratory Abnormalities | 1.3.2.3 Laboratory Abnormalities
Neutrophils Treatment with tocilizumab in RA was associated with a higher incidence of neutropenia. An observed decrease in neutrophils occurs in about half the subjects in trials, occurred largely within the normal range, and was reversible upon interruption/discontinuation of TCZ. Ou... | [
"Neutrophils",
"Platelets",
"Lipids"
] |
NCT02293837 | 1.3.2.4 | Immunosuppression | 1.3.2.4 Immunosuppression The impact of treatment with tocilizumab on the development of malignancies is not known. Tocilizumab is an immunosuppressant, and treatment with this class of drugs may result in an increased risk of malignancies. In the 6-month double-blind studies in RA, the rate of malignant neoplasms was ... | [] |
NCT02293837 | 1.3.2.5 | Hypersensitivity Reactions, Including Anaphylaxis | 1.3.2.5 Hypersensitivity Reactions, Including Anaphylaxis Hypersensitivity reactions, including anaphylaxis and death, have been reported in association with infusion of tocilizumab. Anaphylaxis and other hypersensitivity reactions that required treatment discontinuation were reported in 0.1% (3 out of 2644) of RA pati... | [] |
NCT02293837 | 1.3.2.6 | Other Potential Risks | 1.3.2.6 Other Potential Risks
Demyelinating Disorders The impact of treatment with tocilizumab on demyelinating disorders is not known, but multiple sclerosis and chronic inflammatory demyelinating polyneuropathy were reported rarely in RA clinical studies.
Vaccinations Live vaccines should not be given concurrently ... | [
"Demyelinating Disorders",
"Vaccinations",
"Viral Reactivation",
"Anti-TCZ Antibodies",
"Drug Interaction"
] |
NCT02293837 | 1.3.3 | Potential Risks and Benefits of Trial Participation for Children | 1.3.3 Potential Risks and Benefits of Trial Participation for Children As noted in section 1.3.2.1.8, tocilizumab has been used in pediatric populations and is approved for treatment of both sJIA and pJIA for children age 2 and older in many countries. For children receiving placebo, the study procedures including bloo... | [] |
NCT02293837 | 1.3.4 | Benefits of Trial Participation | 1.3.4 Benefits of Trial Participation In this study, all participants will receive intensive diabetes management aimed at achieving near-normal metabolic control per the standard ADA guidelines.[45](#page-66-3) Although intensive diabetes management is recommended for all patients with T1DM, it is not always available ... | [] |
NCT02293837 | 2 | OBJECTIVES | 2. OBJECTIVES | [] |
NCT02293837 | 2.1 | PRIMARY OBJECTIVE | 2.1 PRIMARY OBJECTIVE Determine whether tocilizumab will slow the progression of the autoimmune destruction of ß cells and lead to the preservation of C-peptide secretion in T1DM. | [] |
NCT02293837 | 2.2 | SECONDARY OBJECTIVES | 2.2 SECONDARY OBJECTIVES - 1. Longitudinal analysis of HbA1c, insulin dose (units/kg) and blood glucose by treatment group. - 2. Determine the efficacy and safety of tocilizumab in participants with T1DM. - 3. Determine how the ratio of Treg/Teff is altered with tocilizumab treatment | [] |
NCT02293837 | 2.3 | EXPLORATORY OBJECTIVES | 2.3 EXPLORATORY OBJECTIVES
Mechanistic studies: 1. Investigate the mechanism of action for tocilizumab in the maintenance of ß-cell function and determine whether the loss of tolerance associated with this disease is reversed.
Metabolic: - 1. Determine whether treatment with tocilizumab improves blood glucose and HbA... | [
"Mechanistic studies:",
"Metabolic:"
] |
NCT02293837 | 3 | STUDY DESIGN | 3. STUDY DESIGN | [] |
NCT02293837 | 3.1 | DESCRIPTION | 3.1 DESCRIPTION This trial will be conducted in the US and Australia as a multi-center, prospective, double-blind, placebo-controlled, 2:1 randomized, phase 2 clinical trial for individuals with recent-onset T1DM aged 6−45 years old. 78 eligible pediatric subjects (6-17 years old) and at least 30 eligible adult subject... | [
"678'<'85\\$7,21"
] |
NCT02293837 | 3.3 | STUDY ENDPOINTS | 3.3 STUDY ENDPOINTS | [] |
NCT02293837 | 3.3.1 | Primary Endpoint | 3.3.1 Primary Endpoint The primary endpoint is a MMTT-stimulated mean 2-hour C-peptide AUC at week 52. The mean 2-hour C-peptide AUC, measured in pmol/ml, is computed by dividing the total AUC by 120 minutes. | [] |
NCT02293837 | 3.3.2 | Secondary Endpoints | 3.3.2 Secondary Endpoints
Efficacy: - 1. MMTT-stimulated mean 2-hour C-peptide AUC at weeks 12, 24, and 104. - 2. MMTT-stimulated mean 2-hour C-peptide AUC assessed longitudinally at weeks 12, 24, 39, 52, 78, and 104. - 3. MMTT-stimulated peak and 4-hour C-peptide AUC at weeks 52 and 104 for subjects ≥12 years old. - ... | [
"Efficacy:",
"Safety:",
"Mechanistic"
] |
NCT02293837 | 3.3.3 | Exploratory Endpoints | 3.3.3 Exploratory Endpoints
Mechanistic: - 1. Determine effect of TCZ on measures of immune cell number and function such as: - a. Changes in proportions and phenotype of Treg and Teff. - b. Changes in sensitivity of Teff to suppression by Treg. - c. Changes in circulating B cell compartment and activation state of in... | [
"Mechanistic:",
"Metabolic:"
] |
NCT02293837 | 3.4 | RATIONALE FOR SELECTION OF DRUG, ROUTE, DOSE, AND REGIMEN | 3.4 RATIONALE FOR SELECTION OF DRUG, ROUTE, DOSE, AND REGIMEN The dose of 8 mg/kg every 4 weeks via the IV route is the FDA and Australian, Therapeutic Goods Administration (TGA)-approved dose for adults in rheumatoid arthritis and will be used for adults and children ≥ 30kg in this study. For children <30 kg, TCZ will... | [] |
NCT02293837 | 3.5 | PREMATURE TERMINATION OR SUSPENSION OF THE TRIAL | 3.5 PREMATURE TERMINATION OR SUSPENSION OF THE TRIAL | [] |
NCT02293837 | 3.5.1 | Ongoing Review | 3.5.1 Ongoing Review As described in Section 10.1 of the protocol, this clinical trial is conducted through the NIAID NIH-funded Cooperative Agreement awarded to the Benaroya Research Institute at Virginia Mason (Seattle, WA) (BRI) to support the Immune Tolerance Network (ITN), a collaborative network for clinical rese... | [] |
NCT02293837 | 3.5.2 | Stopping Rules | 3.5.2 Stopping Rules | [] |
NCT02293837 | 3.5.2.1 | Study-related Adverse Events | 3.5.2.1 Study-related Adverse Events If any of the following events occur, enrollment will be suspended and the DSMB chair will be notified such that a review of safety data will determine if enrollment in the study will be stopped and/or administration of investigational study medication should be halted: - Any death ... | [] |
NCT02293837 | 4 | ELIGIBILITY | 4. ELIGIBILITY | [] |
NCT02293837 | 4.1 | INCLUSION CRITERIA | 4.1 INCLUSION CRITERIA Patients must meet all of the following criteria to be eligible for this study: - 1. Male or female aged 6-45 years inclusive who meet the American Diabetes Association T1DM criteria. - 2. Diagnosis of T1DM within 100 days of enrollment (V0). - 3. Positive for at least one diabetes-related autoan... | [] |
NCT02293837 | 4.2 | EXCLUSION CRITERIA | 4.2 EXCLUSION CRITERIA Patients who meet any of the following criteria will not be eligible for this study: - 1. Severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies. - 2. History of malignancy or serious uncontrolled cardiovascular, nervous system, pulmonary, renal, or gastrointestinal di... | [] |
NCT02293837 | 4.3 | PREMATURE TERMINATION OF A PARTICIPANT FROM THE STUDY | 4.3 PREMATURE TERMINATION OF A PARTICIPANT FROM THE STUDY Withdrawal of consent. Participants who withdraw consent for further treatment. These participants will be asked if they would be willing to complete safety and outcome assessments and visits. Failure to return. Participants who do not return for visits and who ... | [] |
NCT02293837 | 5 | STUDY MEDICATIONS | 5. STUDY MEDICATIONS | [] |
NCT02293837 | 5.1 | INVESTIGATIONAL MEDICATION | 5.1 INVESTIGATIONAL MEDICATION ACTEMRA® (tocilizumab) is the investigational agent and will be provided to the clinical research sites by the Sponsor. For sites in the US, commercially-labeled licensed product will be obtained by the Sponsor from either the manufacturer (Genentech, Inc. a member of the Roche group, loc... | [] |
NCT02293837 | 5.1.1 | Formulation and Packaging | 5.1.1 Formulation and Packaging  | [] |
NCT02293837 | 5.1.2 | Reconstitution | 5.1.2 Reconstitution  | [] |
NCT02293837 | 5.1.3 | Dosage, Preparation, and Administration | 5.1.3 Dosage, Preparation, and Administration For those with weight ≥ 30 kg, tocilizumab will be administered at a dose of 8 mg/kg every four weeks as an IV infusion not to exceed 800 mg. For those with weight < 30 kg, tocilizumab will be administered at a dose of 10 mg/kg. Dosing will be according to the individual's ... | [] |
NCT02293837 | 5.2 | DOSE MODIFICATION AND MANAGEMENT OF ADVERSE EVENTS | 5.2 DOSE MODIFICATION AND MANAGEMENT OF ADVERSE EVENTS | [] |
NCT02293837 | 5.2.1 | Overview | 5.2.1 Overview Clinical evaluation including history and directed physical exam, review of adverse events and laboratory values from previous visit will be done prior to each infusion. | [] |
NCT02293837 | 5.2.2 | Hematologic Abnormalities and Bleeding Events | 5.2.2 Hematologic Abnormalities and Bleeding Events Decreases in neutrophil and platelet counts have been observed following treatment with TCZ in combination with MTX. The risk mitigation strategies for neutropenia and thrombocytopenia are summarized in Table 2 and Table 3, respectively. Table 2. Neutropenia Risk Miti... | [] |
NCT02293837 | 5.2.3 | Blood Chemistry Abnormalities | 5.2.3 Blood Chemistry Abnormalities Elevations in ALT and AST have been observed during treatment with the study medications. The recommended dose modification strategies for elevations in ALT and AST are summarized in Table 4. Table 4. Liver Function Tests Risk Mitigation | ALT/AST | Action | |------------------|-----... | [] |
NCT02293837 | 5.2.4 | Infections | 5.2.4 Infections Tocilizumab should not be administered in patients with active infection including localized infections, or who report febrile illness within prior 48 hours. These subjects will be rescheduled for another day within the study dosing window. If the patient remains ill during the study window, the dose w... | [] |
NCT02293837 | 5.2.5 | Elevated Lipids | 5.2.5 Elevated Lipids Tocilizumab will not be administered in subjects with fasting LDL cholesterol ≥160 mg/dL or ≥4.1 mmol/L. Subjects with LDL values between 100 and 160 may be considered for treatment with lipid lowering agents. | [] |
NCT02293837 | 5.2.6 | Hypersensitivity or Anaphylaxis | 5.2.6 Hypersensitivity or Anaphylaxis An infusion/dose reaction is defined as an adverse event occurring during and within 24 hours after the infusion or subcutaneous injection of tocilizumab. This may include hypersensitivity reactions or anaphylactic reactions. Signs of a possible hypersensitivity reaction include bu... | [] |
NCT02293837 | 5.3 | DISCONTINUATION OF STUDY MEDICATION IN AN INDIVIDUAL PARTICIPANT | 5.3 DISCONTINUATION OF STUDY MEDICATION IN AN INDIVIDUAL PARTICIPANT The dosing and administration of investigational medication according to study specification will be discontinued for an individual participant if any of the following criteria is met: - Anaphylaxis or hypersensitivity reaction. - A confirmed demyelin... | [] |
NCT02293837 | 5.4 | CONCOMITANT MEDICATIONS | 5.4 CONCOMITANT MEDICATIONS | [] |
NCT02293837 | 5.4.1 | Prohibited Medications | 5.4.1 Prohibited Medications Participants will be instructed not to use the following medications: - Agents that are known to significantly influence insulin sensitivity or secretion. - Medications known to affect the laboratory measurement of C-peptide (i.e. Strensiq® (asfotase alfa)). - Non-insulin pharmaceuticals fo... | [] |
NCT02293837 | 5.5 | DRUG ACCOUNTABILITY | 5.5 DRUG ACCOUNTABILITY Under US code of federal regulations (21CFR 312.62), Australian TGA regulations and ICH E6 Good Clinical Practice guidelines, an investigator is required to maintain adequate records of the disposition of the investigational product, including the date and quantity of drug that was received, the... | [] |
NCT02293837 | 5.6 | ASSESSMENT OF COMPLIANCE WITH STUDY MEDICATION | 5.6 ASSESSMENT OF COMPLIANCE WITH STUDY MEDICATION Tocilizumab will be administered intravenously by trained medical staff; compliance, therefore, will be monitored by the medical staff and documented on the CRF. | [] |
NCT02293837 | 6 | STUDY PROCEDURES | 6. STUDY PROCEDURES | [] |
NCT02293837 | 6.1 | INTENSIVE DIABETES MANAGEMENT | 6.1 INTENSIVE DIABETES MANAGEMENT During the study period, all participants will receive "intensive" management of their diabetes, and HbA1C will be assessed at every visit to evaluate metabolic control. The goal of treatment will be to maintain the HbA1C levels within the currently recommended ADA age-specific target ... | [] |
NCT02293837 | 6.2 | VISIT WINDOWS | 6.2 VISIT WINDOWS | [] |
NCT02293837 | 6.2.1 | Scheduled Visits | 6.2.1 Scheduled Visits The initial treatment should begin within 100 days from the day of diagnosis and within 37 days of the screening MMTT. Subsequent treatment visits are every 4 weeks. The treatment visits (V0-V6) must occur within 7 days on either side of the target date. However, consecutive doses must be 21 days... | [] |
NCT02293837 | 6.3 | RANDOMIZATION, MASKING, AND UNMASKING | 6.3 RANDOMIZATION, MASKING, AND UNMASKING | [] |
NCT02293837 | 6.3.1 | Randomization | 6.3.1 Randomization Participants who sign the informed consent and meet the eligibility criteria will be randomly assigned in a 2:1 ratio to either the experimental or control group. A central automated randomization system will be used for treatment assignment and to create a unique identifier for each new study parti... | [] |
NCT02293837 | 6.3.2 | Masking to treatment assignment | 6.3.2 Masking to treatment assignment Masking will be maintained throughout the study for all study participants and study personnel, except the pharmacists. | [] |
NCT02293837 | 6.3.3 | Unmasking | 6.3.3 Unmasking Unmasking before the study is completed will occur if a participant's well-being is threatened and the investigator believes unmasking is necessary to protect the participant. Unmasking may also occur in the case of pregnancy (participant or partner pregnancy) at the request of the pregnant woman. Befor... | [] |
NCT02293837 | 6.4 | GENERAL ASSESSMENTS | 6.4 GENERAL ASSESSMENTS Informed consent: Written informed consent will be obtained from the participant before any study assessments or procedures are performed. - Eligibility criteria: Eligibility for study participation will be assessed during the screening period. - Medical history: This includes T1DM time of diagn... | [] |
NCT02293837 | 6.5 | CLINICAL LABORATORY ASSESSMENTS | 6.5 CLINICAL LABORATORY ASSESSMENTS Clinical laboratory blood draws are to be performed after vital signs are assessed and prior to study drug infusion during the treatment period. Participants will periodically undergo blood draws for both clinical and immunologic tests. Blood volumes drawn will be based on participan... | [
"Central laboratory assessments:"
] |
NCT02293837 | 6.6 | PHARMACOKINETIC ASSESSMENTS | 6.6 PHARMACOKINETIC ASSESSMENTS All participants will have PK samples taken at the time points listed in [Table 6.](#page-43-1) Table 6: Pharmacokinetic Samples | | Time Points | | | | | | | | | |-----------------|---------------------------------------------------------------|---------------------------------|--|--|--... | [] |
NCT02293837 | 6.7 | METABOLIC ASSESSMENTS | 6.7 METABOLIC ASSESSMENTS - MMTT: A 2-hour MMTT is to be performed at weeks 12, 24, 39, and 78. A 4 hour MMTT is to be performed at weeks -1 (screening), 52, and 104 for subjects ≥12 years old (for subjects <12 years old, a 2-hour MMTT will be performed instead. - HbA1c - Glucose (glucometer readings) - Continuous gluc... | [] |
NCT02293837 | 6.8 | MECHANISTIC ASSESSMENTS | 6.8 MECHANISTIC ASSESSMENTS Mechanistic samples drawn during the study drug treatment period are collected prior to study drug infusion. See section 7 for detailed discussion of additional mechanistic assays. | [] |
NCT02293837 | 7 | TOLERANCE ASSAYS | 7. TOLERANCE ASSAYS | [] |
NCT02293837 | 7.1 | MECHANISTIC HYPOTHESIS | 7.1 MECHANISTIC HYPOTHESIS The primary mechanistic hypotheses are that anti-IL6R therapy in T1D will promote T regulatory cell activity, suppress innate immune responses, and alter B cell activity. Studies will address multiple questions but will be prioritized based on the amount of blood available. Questions to be ad... | [] |
NCT02293837 | 7.2 | RETENTION OF SAMPLES | 7.2 RETENTION OF SAMPLES Specimens collected in this trial may be used to reevaluate biologic responses as new research tools become available. Samples collected from this study in the United States, will be stored centrally at the ITN sample repository for future analysis. Samples collected in Australia will be stored... | [] |
NCT02293837 | 7.2.1 | Sample Types | 7.2.1 Sample Types Samples will be collected under the auspices of the clinical sites as outlined in the schedule of events (Appendix 1). | [] |
NCT02293837 | 7.3 | MECHANISTIC ASSAYS | 7.3 MECHANISTIC ASSAYS The following assay methodologies may be used to address the mechanistic hypotheses: - Multi-chromatic flow cytometry on banked PBMCs to monitor the changes in number and phenotype of various immune cell subsets including T cells, B cell subsets and innate cells. Flow cytometry may also be used t... | [] |
NCT02293837 | 8 | ADVERSE EVENTS | 8. ADVERSE EVENTS | [] |
NCT02293837 | 8.1 | OVERVIEW | 8.1 OVERVIEW The investigator is responsible for the detection and documentation of events meeting the criteria and definition of an AE (adverse event) or SAE (serious adverse event) as described in Section 8.2 in this protocol. All AEs and SAEs will be recorded in the source documents and on the appropriate electronic... | [] |
NCT02293837 | 8.2 | DEFINITIONS | 8.2 DEFINITIONS | [] |
NCT02293837 | 8.2.1 | Disease-specific Adverse Event | 8.2.1 Disease-specific Adverse Event For the purposes of this study, major hypoglycemic events will be recorded in the eCRF. Major hypoglycemic events are defined as: Blood glucose concentration < 40 mg/dL; (Grades 3–5, NCI-CTCAE version 4.03), or Hypoglycemic events involving seizure or loss of consciousness (coma), o... | [] |
NCT02293837 | 8.2.2 | Adverse Event | 8.2.2 Adverse Event An adverse event (AE) is any occurrence or worsening of an undesirable or unintended sign, symptom, laboratory finding, or disease that occurs during participation in the trial. An AE will be followed until it resolves or until 30 days after a participant terminates from the study, whichever comes f... | [] |
NCT02293837 | 8.2.3 | Suspected Adverse Reaction and Adverse Reaction | 8.2.3 Suspected Adverse Reaction and Adverse Reaction Suspected adverse reaction (SAR) means any adverse event for which there is a reasonable possibility that the study drug caused the adverse event. For the purposes of safety reporting, 'reasonable possibility' means there is evidence to suggest a causal relationship... | [] |
NCT02293837 | 8.2.4 | Serious Adverse Event | 8.2.4 Serious Adverse Event An AE or SAR is considered "serious" if, in the view of either the investigator or DAIT, NIAID it results in any of the following outcomes (21 CFR 312.32(a))/(ICH E2A): - Death: A death that occurs during the study or that comes to the attention of the investigator during the protocol-define... | [] |
NCT02293837 | 8.2.5 | Adverse Events of Special Interest (AESIs) | 8.2.5 Adverse Events of Special Interest (AESIs) Adverse Events of Special Interest (AESIs) are identified for ACTEMRA® (tocilizumab) and will be collected and reported as study-specific AEs or SAEs in this trial. Investigators should use their clinical judgement to identify events falling in any of the following categ... | [] |
NCT02293837 | 8.2.6 | Unexpected Adverse Reaction | 8.2.6 Unexpected Adverse Reaction A SAR is considered "unexpected" when its nature (specificity), or severity, or rate of occurrence is not consistent with applicable product information as described in the safety information provided in the developmental core safety information section of the current F. Hoffman La-Roc... | [] |
NCT02293837 | 8.3 | COLLECTING AND RECORDING ADVERSE EVENTS | 8.3 COLLECTING AND RECORDING ADVERSE EVENTS | [] |
NCT02293837 | 8.3.1 | Methods of Collection | 8.3.1 Methods of Collection All adverse events (AEs) will be collected and recorded from visit -1 until the time the participant completes the study, or prematurely withdraws from the study. All serious adverse events (SAEs) will be collected from visit -1 until 30 days after the participant completes the study, or 90 ... | [] |
NCT02293837 | 8.3.2 | Specific Instructions for Recording Adverse Events | 8.3.2 Specific Instructions for Recording Adverse Events Correct medical terminology/concepts should be used when reporting AEs and SAEs. Avoid colloquialisms and abbreviations.
Diagnosis vs. Signs and Symptoms If known at the time of reporting, a diagnosis should be reported rather than individual signs and symptoms ... | [
"Diagnosis vs. Signs and Symptoms",
"Deaths",
"Preexisting Medical Conditions",
"Hospitalizations for Medical or Surgical Procedures"
] |
NCT02293837 | 8.3.3 | Recording AEs | 8.3.3 Recording AEs Throughout the study, the investigator will record all symptomatic AEs on the appropriate eCRF regardless of their severity or relation to study participation and asymptomatic AEs of grade 3 or above. The investigator will treat participants experiencing AEs appropriately and observe them at suitabl... | [] |
NCT02293837 | 8.3.4 | Recording SAEs | 8.3.4 Recording SAEs Serious AEs will be recorded on the SAE eCRF and Health Authorities will be notified as outlined in Section 8.5. | [] |
NCT02293837 | 8.4 | GRADING AND ATTRIBUTION OF ADVERSE EVENTS | 8.4 GRADING AND ATTRIBUTION OF ADVERSE EVENTS | [] |
NCT02293837 | 8.4.1 | Grading of Major Hypoglycemic and Hyperglycemic Events | 8.4.1 Grading of Major Hypoglycemic and Hyperglycemic Events For this study of participants with type 1 diabetes, the NCI-CTCAE will not be used to grade hypoglycemia and hyperglycemia. Please refer to the grading criteria for major hypoglycemic and hyperglycemic events below. In this study, non-major hypoglycemic and ... | [
"Major hypoglycemic events will be graded as follows:"
] |
NCT02293837 | 8.4.2 | Grading for All Other Adverse Events | 8.4.2 Grading for All Other Adverse Events The study site will grade the severity of AEs experienced by study participants according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE, v 4.03) manual and provides a common language to describe levels of... | [] |
NCT02293837 | 8.4.3 | Attribution | 8.4.3 Attribution Adverse events will be categorized for their relation to tocilizumab. The principal investigator will make the initial determination of the relation, or attribution, of an AE to study drug and will record the initial determination on the appropriate eCRF and/or SAE reporting form. Infusion reactions o... | [] |
NCT02293837 | 8.5 | REPORTING SERIOUS ADVERSE EVENTS | 8.5 REPORTING SERIOUS ADVERSE EVENTS | [] |
NCT02293837 | 8.5.1 | Reporting SAEs to the Global Study Sponsor (DAIT, NIAID, NIH) | 8.5.1 Reporting SAEs to the Global Study Sponsor (DAIT, NIAID, NIH) The following process for reporting a SAE ensures compliance with 21CFR 312 and ICH guidelines. After learning that a participant has experienced a SAE, the investigator or designee will report the SAE via the electronic SAE report form (SAE eCRF) with... | [] |
NCT02293837 | 8.5.2 | Reporting SAEs to Health Authorities | 8.5.2 Reporting SAEs to Health Authorities After the SAE has been reported by the principal investigator and assessed by the Global Study Sponsor (DAIT, NIAID, NIH). In the US, the IND sponsor (DAIT, NIAID, NIH) must report an event to the FDA using one of these two options: - Standard reporting (report in the IND annu... | [] |
NCT02293837 | 8.5.3 | Reporting SAEs to the DSMB | 8.5.3 Reporting SAEs to the DSMB The Study Global Sponsor (DAIT, NIAID, NIH) will provide the DSMB with data of all SAEs on a regular basis, including quarterly reports of all SAEs. Major hypoglycemic events that require emergency care will also be reported to the DSMB in an expedited fashion regardless of whether they... | [] |
NCT02293837 | 8.5.4 | Reporting of Adverse Events to IRBs/ECs | 8.5.4 Reporting of Adverse Events to IRBs/ECs All investigators must report adverse events, including expedited reports, in a timely fashion to their respective IRBs/ECs in accordance with applicable regulations and guidelines. All Safety Reports to the FDA or the appropriate Health Authorities shall be distributed by ... | [] |
NCT02293837 | 8.5.5 | Reporting AEs to Genentech, Inc. | 8.5.5 Reporting AEs to Genentech, Inc. The DAIT, NIAID will provide Genentech, Inc. with data for AEs of Special Interest (AESIs) and SAEs on an ongoing basis as specified in the protocol-specific safety management plan part B.
Distribution as follows: 1. DAIT SACCC (Rho Federal) will forward a notification including ... | [
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NCT02293837 | 8.5.6 | Reporting Pregnancy | 8.5.6 Reporting Pregnancy The investigator should be informed immediately of any pregnancy in the participant or a partner pregnancy of a male participant occurring from randomization through the end of the follow-up period (two-year study period). All available pregnancy information should be entered into the electron... | [] |
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