protocol_id stringclasses 263
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NCT02991144 | 6.2.3 | Study Product Accountability | 6.2.3 Study Product Accountability The investigator or designated personnel will maintain accurate records of receipt of all study product (DTX301), including dates of receipt. In addition, accurate records will be kept regarding when and how much study product is dispensed and used by each subject in the study. Reason... | [] |
NCT02991144 | 6.2.4 | Transmission of Infectious Agents | 6.2.4 Transmission of Infectious Agents Recombinant AAV vectors are nonreplicative and are not expected to pose a risk of transmission. However, all sexually active subjects must use approved contraception from the time of DTX301 dosing and for 52 weeks following administration (Section [4.1\)](#page-48-2). All subject... | [] |
NCT02991144 | 6.2.5 | Exposure to Radiation | 6.2.5 Exposure to Radiation Carbon-13 is a naturally occurring, stable isotope of carbon that emits no radioactivity, has no known adverse biological effects, and is safe to use in children and adults [\[Koletzko](#page-98-9) 1997; [Tuchman](#page-101-6) 2008b]. Detailed instructions for dose preparation and administra... | [] |
NCT02991144 | 6.3 | Treatment Schedule and Administration | 6.3 Treatment Schedule and Administration | [] |
NCT02991144 | 6.3.1 | Administration of [1- 13C]Sodium Acetate | 6.3.1 Administration of [1- 13C]Sodium Acetate Subjects will be administered [1- 13C]sodium acetate dissolved in 60 mL of water at the time points specified in the Schedule of Events [\(Table](#page-103-0) 15-1). The dose of [1- 13C]sodium acetate administered will be calculated using the subject's weight recorded at S... | [] |
NCT02991144 | 6.3.2 | Administration of DTX301 | 6.3.2 Administration of DTX301 Subjects will receive a single, peripheral IV infusion of DTX301, administered by qualified study personnel as designated by the investigator [\(Table](#page-103-0) 15-1). The dose will be determined by the cohort and candidate dose (Section [3.1\)](#page-38-1). The dose of DTX301 to be a... | [] |
NCT02991144 | 6.3.3 | Treatment Compliance | 6.3.3 Treatment Compliance [1- 13C]sodium acetate will be administered orally at the study site and observed by qualified personnel. The dose and time of administration will be recorded in the subject's eCRF. Adherence to baseline ammonia scavenger medication regimens and modifications to ammonia scavenger medication r... | [] |
NCT02991144 | 6.4 | Prior and Concomitant Therapy | 6.4 Prior and Concomitant Therapy Use of all prior and concomitant medications will be recorded in the subject's eCRF. The minimum requirement is that the drug name, the dates of administration, and the reason for use are to be recorded. This will include all prescription drugs, herbal products, vitamins, minerals, and... | [] |
NCT02991144 | 6.4.1 | Permitted Medications | 6.4.1 Permitted Medications The use of permitted medications (date, dosage, reason for therapy) will be recorded on the concomitant medication page in the eCRF. If a subject starts a new medication, including medications to alleviate complications associated with OTC deficiency and herbal supplements, it should be disc... | [] |
NCT02991144 | 6.4.2 | Prohibited Medications | 6.4.2 Prohibited Medications Use of any of the following medications is prohibited, unless the investigator feels these medications are medically indicated. If medically indicated, the use of prohibited medications (date, dosage, reason for therapy) will be recorded on the concomitant medication page in the eCRF: - Ano... | [] |
NCT02991144 | 7 | Withdrawal of Subjects From the Study | 7 Withdrawal of Subjects From the Study | [] |
NCT02991144 | 7.1 | Study Withdrawal | 7.1 Study Withdrawal Subjects may withdraw from the study at any time and for any reason without prejudice to their future medical care by the investigator or at the study site. Any subject who withdraws consent to participate in the study will be removed from further treatment and/or study observation immediately upon... | [] |
NCT02991144 | 7.2 | Subject Replacement | 7.2 Subject Replacement If a subject withdraws from the study after receiving DTX301, the subject will not be replaced. Subjects who withdraw from the study after signing the ICF, but before receiving DTX301, will be replaced and the replacement subject will be sequentially assigned to treatment with a new subject iden... | [] |
NCT02991144 | 8 | Study Assessments and Procedures | 8 Study Assessments and Procedures | [] |
NCT02991144 | 8.1 | Efficacy Assessments | 8.1 Efficacy Assessments Planned time points for all efficacy measurements in the study are listed in [Table](#page-103-0) 15-1. | [] |
NCT02991144 | 8.1.1 | Ureagenesis | 8.1.1 Ureagenesis The change from baseline in the rate of ureagenesis will be assessed at specified time points [\(Table](#page-103-0) 15-1). Planned time points for the collection of blood samples to determine the rate of ureagenesis are provided in Section [8.3.1.](#page-68-1) Subjects will fast for at least 6 hours,... | [] |
NCT02991144 | 8.1.2 | Plasma Ammonia Area Under the Curve from Time Zero to 24 Hours | 8.1.2 Plasma Ammonia Area Under the Curve from Time Zero to 24 Hours The change from baseline in plasma ammonia (AUC0-24) will be assessed at specified time points [\(Table](#page-103-0) 15-1). Planned time points for the collection of blood samples to determine plasma ammonia (AUC0-24) are provided in Section [8.3.2.]... | [] |
NCT02991144 | 8.2 | Safety Assessments | 8.2 Safety Assessments Planned time points for all safety assessments are listed in the Schedules of Events [\(Table](#page-103-0) 15-1 and [Table](#page-110-0) 15-2). Safety will be assessed based on AEs, SAEs, complete and targeted physical examination findings, vital sign measurements, ECG results, clinical laborato... | [] |
NCT02991144 | 8.2.1 | Physical Examination | 8.2.1 Physical Examination A complete or targeted physical examination will be performed at the time points specified in the Schedule of Events [\(Table](#page-103-0) 15-1). A complete physical examination will include assessments of the head, eyes, ears, nose, and throat; skin; and the endocrine metabolic, neurologica... | [] |
NCT02991144 | 8.2.2 | Vital Sign Measurements | 8.2.2 Vital Sign Measurements Vital sign measurements will be made at the time points specified in the Schedule of Events [\(Table](#page-103-0) 15-1). During the study, vital sign measurements are to be collected before any stimulating or anxiety-provoking procedures (eg, phlebotomy). Vital sign measurements will incl... | [] |
NCT02991144 | 8.2.3 | Electrocardiograms | 8.2.3 Electrocardiograms An ECG will be performed at the time points specified in the Schedule of Events [\(Table](#page-103-0) 15-1). • A single 12-lead ECG will be obtained at Screening, on Day 0 (baseline), at approximately 1 hour (±15 minutes) after the start of infusion on Day 1, and at Week 52, using an ECG machi... | [] |
NCT02991144 | 8.2.4 | Clinical Laboratory Analyses | 8.2.4 Clinical Laboratory Analyses Laboratory tests, including LFTs and coagulation panel, will be closely monitored throughout the duration of the study. At any point between scheduled visits, additional, unscheduled assessment for LFTs, plasma ammonia, or any other biomarker to assess subject safety and clinical stat... | [] |
NCT02991144 | 8.2.4.1 | Clinical Laboratory Parameters | 8.2.4.1 Clinical Laboratory Parameters The clinical laboratory parameters to be measured are listed in [Table 8-1.](#page-63-0) Samples are to be collected at the time points (±5 minutes) specified in the Schedules of Events [\(Table](#page-103-0) 15-1 and [Table](#page-110-0) 15-2). Table 8-1 Clinical Laboratory Param... | [] |
NCT02991144 | 8.2.4.1.1 | Elevation of Liver Function Tests | 8.2.4.1.1 Elevation of Liver Function Tests In clinical studies with AAV-mediated gene transfer, a transient rise in liver aminotransferases and concurrent decline in transgene expression has been observed [\[Manno](#page-99-5) 2006; [Nathwani](#page-99-8) 2011a; [Nathwani](#page-100-2) 2014]. This has been hypothesize... | [] |
NCT02991144 | 8.2.4.1.2 | Treatment for Possible Vector-Induced Hepatitis | 8.2.4.1.2 Treatment for Possible Vector-Induced Hepatitis The investigator, in conjunction with the Ultragenyx Pharmaceutical Inc. medical lead will consider starting oral steroid treatment, per protocol, for possible vector-induced hepatitis when a subject's ALT is greater than the ULN and is considered by the investi... | [] |
NCT02991144 | 8.2.5 | Other Laboratory Parameters | 8.2.5 Other Laboratory Parameters Where applicable, details for the preparation and shipment of samples are included in the laboratory manual. | [] |
NCT02991144 | 8.2.5.1 | Neutralizing Antibodies to Adeno-Associated Virus Serotype 8 | 8.2.5.1 Neutralizing Antibodies to Adeno-Associated Virus Serotype 8 Samples for neutralizing antibodies to AAV8 will be collected at the time points specified in the Schedule of Events [\(Table](#page-103-0) 15-1) to monitor for a humoral immune response to AAV8. The assay will be performed using a research method (a ... | [] |
NCT02991144 | 8.2.5.2 | Adeno-Associated Virus Serotype 8 Binding Antibody Immunoglobulin G Assay | 8.2.5.2 Adeno-Associated Virus Serotype 8 Binding Antibody Immunoglobulin G Assay Samples for the AAV8 binding antibody immunoglobulin G (IgG) assay will be collected at the time points specified in the Schedule of Events [\(Table](#page-103-0) 15-1) to monitor for circulating anti-AAV8 antibodies. The assay will be pe... | [] |
NCT02991144 | 8.2.5.3 | Anti-Ornithine Transcarbamylase Antibody Assay | 8.2.5.3 Anti-Ornithine Transcarbamylase Antibody Assay Samples for the anti-OTC antibody assay will be collected at the time points specified in the Schedule of Events [\(Table](#page-103-0) 15-1) to monitor for circulating anti-OTC antibodies. The assay will be performed using a research method (ELISA). | [] |
NCT02991144 | 8.2.5.4 | Viral Shedding | 8.2.5.4 Viral Shedding Saliva, urine, and stool will be collected at the time points specified in the Schedules of Events [\(Table](#page-103-0) 15-1 and Table 15-2) to monitor for the presence of shed virus. The presence of DTX301 will be determined . Subjects will be given an appropriate container to collect a stool ... | [] |
NCT02991144 | 8.3 | Pharmacokinetics and Pharmacodynamic Assessments | 8.3 Pharmacokinetics and Pharmacodynamic Assessments | [] |
NCT02991144 | 8.3.1 | Ureagenesis | 8.3.1 Ureagenesis The conversion of the stable isotope [1- 13C]sodium acetate to [13C]urea will be determined by gas chromatography mass spectrometry [\[Tuchman](#page-101-6) 2008b]. Blood samples will be collected in precooled heparinized tubes before dosing (time 0) and at approximately 0.5, 1, 1.5, 2, 3, and 4 hours... | [] |
NCT02991144 | 8.3.2 | Plasma Ammonia Area Under the Curve from Time Zero to 24 Hours | 8.3.2 Plasma Ammonia Area Under the Curve from Time Zero to 24 Hours The AUC0-24 of plasma ammonia will be determined at Baseline (Day 0) and over time to Week 52 after administration of DTX301 [\(Table](#page-103-0) 15-1). Two samples will be collected at time 0 and at approximately 2, 4, 8, 12, 16, 20, and 24 hours (... | [] |
NCT02991144 | 8.3.3 | Orotic Acid Excretion | 8.3.3 Orotic Acid Excretion The excretion of orotic acid will be determined over a 24-hour period. Urine samples will be collected approximately every 6 hours (× 4) at Baseline (Day 0) and over time to Week 52 after administration of DTX301 [\(Table](#page-103-0) 15-1). Details for the preparation and shipment of sampl... | [] |
NCT02991144 | 8.4 | Quality-of-Life Assessment | 8.4 Quality-of-Life Assessment | [] |
NCT02991144 | 8.4.1 | PROMIS Questionnaire | 8.4.1 PROMIS Questionnaire Subjects will be asked to complete the Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire (Appendix [15.2.1\)](#page-111-1) on Day 0 (predose) and then at Weeks 6, 12, 24, and 52 during the study [\(Table](#page-103-0) 15-1). NOTE: The PROMIS questionnaire should ... | [] |
NCT02991144 | 8.5 | Neuropsychological Tests | 8.5 Neuropsychological Tests All neuropsychological tests will be administered to English speaking subjects (at a minimum) in a nonfasted state. All neuropsychological tests are to be administered by appropriately qualified individuals as determined by sponsor or representative. The subject's plasma ammonia level shoul... | [] |
NCT02991144 | 8.5.1 | Intelligence | 8.5.1 Intelligence Subjects will be asked to complete the Vocabulary and Matrix Reasoning subtests from the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II) at Baseline only [\(Table](#page-103-0) 15-1). The WASI-II provides general measure of cognitive function in subjects aged 6 to 89 years. The V... | [] |
NCT02991144 | 8.5.2 | Motor Function | 8.5.2 Motor Function  | [] |
NCT02991144 | 8.5.3 | Executive Function | 8.5.3 Executive Function  | [] |
NCT02991144 | 8.5.4 | Memory | 8.5.4 Memory  Page 72 of 126 | [] |
NCT02991144 | 8.6 | Genotyping | 8.6 Genotyping | [] |
NCT02991144 | 8.6.1 | Ornithine Transcarbamylase Genotyping | 8.6.1 Ornithine Transcarbamylase Genotyping At Baseline, subjects will be asked to provide a single whole-blood sample for OTC genotyping. The objective of this research is to provide a background understanding to the etiology of the subject's OTC deficiency and to investigate any relationship between genetic factors a... | [] |
NCT02991144 | 8.7 | Other Assessments | 8.7 Other Assessments | [] |
NCT02991144 | 8.7.1 | Demographic, Medical, and Ornithine Transcarbamylase Deficiency History Assessments | 8.7.1 Demographic, Medical, and Ornithine Transcarbamylase Deficiency History Assessments As allowed by local laws and regulations, the following demographic data may be captured on the appropriate page in the eCRF: date of birth, sex, race, and ethnicity. Medical, medication, and OTC deficiency medical history will be... | [] |
NCT02991144 | 8.7.2 | Ammonia Scavenger Use and Dietary Protein Intake | 8.7.2 Ammonia Scavenger Use and Dietary Protein Intake The use of ammonia scavenger therapy and dietary protein intake will be reviewed and recorded at each visit [\(Table](#page-103-0) 15-1). Changes to baseline treatment cannot occur until there is evidence of transgene expression reflected by continued evidence of m... | [] |
NCT02991144 | 9 | Safety Monitoring and Reporting | 9 Safety Monitoring and Reporting | [] |
NCT02991144 | 9.1 | Adverse Events and Serious Adverse Events | 9.1 Adverse Events and Serious Adverse Events Adverse events will be assessed from the time the subject signs the ICF through the end of study/early withdrawal visit. At every study visit, subjects will be asked a standard nonleading question to elicit any medically related changes in their well-being. In addition to s... | [] |
NCT02991144 | 9.1.1 | Definitions | 9.1.1 Definitions | [] |
NCT02991144 | 9.1.1.1 | Adverse Events | 9.1.1.1 Adverse Events The investigator is responsible for reporting all AEs that are observed or reported during the study, regardless of their relationship to study product or their clinical significance. An AE is defined as any untoward medical occurrence in a subject enrolled into this study regardless of its causa... | [] |
NCT02991144 | 9.1.1.2 | Serious Adverse Events | 9.1.1.2 Serious Adverse Events An SAE is defined as any event that: - Results in death - Is immediately life-threatening - Requires inpatient hospitalization or prolongation of existing hospitalization. - NOTE: Hospitalization due to hyperammonemic crisis (HAC [Section [3.2.6\]](#page-47-0)) will be considered an SAE. ... | [] |
NCT02991144 | 9.1.2 | Safety Reporting | 9.1.2 Safety Reporting | [] |
NCT02991144 | 9.1.2.1 | Adverse Events | 9.1.2.1 Adverse Events All AEs reported or observed during the study will be recorded on the AE page in the eCRF. Information to be collected includes drug treatment, dose, event term, time of onset, investigator-specified assessment of severity and relationship to study product, corticosteroid regimen, [1- 13C] sodium... | [] |
NCT02991144 | 9.1.2.2 | Serious Adverse Events | 9.1.2.2 Serious Adverse Events Any AE that meets SAE criteria (Section [9.1.1.2\)](#page-74-0) or any of the safety stopping criteria (Section [3.2.7\)](#page-47-1) must be reported by the study site to PPD Pharmacovigilance (PVG) Department immediately (ie, within 24 hours) after the time study site personnel first le... | [] |
NCT02991144 | 9.1.2.2.1 | Expedited Reporting | 9.1.2.2.1 Expedited Reporting The sponsor is responsible for reporting serious, unexpected, suspected adverse drug reactions (SUSARs) involving the study product(s) to all regulatory authorities and participating investigators in accordance with International Council for Harmonisation (ICH) guidelines and/or local regu... | [] |
NCT02991144 | 9.1.3 | Assessment of Severity/Toxicity | 9.1.3 Assessment of Severity/Toxicity The severity/toxicity, or intensity, of an AE refers to the extent to which an AE affects the subject's daily activities. The intensity of the AE will be rated as Grade 1, 2, 3, 4, or 5 using the most current version of the National Cancer Institute (NCI) CTCAE [[NCI CTCAE 2018\]](... | [] |
NCT02991144 | 9.1.4 | Assessment of Causality | 9.1.4 Assessment of Causality The investigator's assessment of an AE's relationship to study product is part of the documentation process, but it is not a factor in determining what is or is not reported in the study. If there is any doubt as to whether a clinical observation is an AE, the event should be reported. The... | [] |
NCT02991144 | 9.1.5 | Follow-Up of Subjects Reporting Adverse Events | 9.1.5 Follow-Up of Subjects Reporting Adverse Events All AEs must be reported in detail on the appropriate page in the eCRF and followed to satisfactory resolution, until the investigator deems the event to be chronic or not clinically significant, or until the subject is considered to be stable. | [] |
NCT02991144 | 9.2 | Procedures for Handling Special Situations | 9.2 Procedures for Handling Special Situations | [] |
NCT02991144 | 9.2.1 | Pregnancy | 9.2.1 Pregnancy A serum pregnancy test will be performed on all female study subjects of childbearing potential during Screening. A urine pregnancy test will be performed on all female study subjects of childbearing potential at each visit specified in the Schedule of Events [\(Table](#page-103-0) 15-1). Pregnancy is n... | [] |
NCT02991144 | 9.2.2 | Treatment Noncompliance | 9.2.2 Treatment Noncompliance | [] |
NCT02991144 | 9.2.2.1 | Overdose Management | 9.2.2.1 Overdose Management An overdose is any dose of study product given to or taken by a subject that intentionally or unintentionally exceeds the dose, based on body weight (kg), described in Section [3.1.](#page-38-1) Overdoses without signs or symptoms do not need to be recorded as AEs; in case of any AEs associa... | [] |
NCT02991144 | 9.2.2.2 | Medication Errors | 9.2.2.2 Medication Errors A medication error is defined as a mistake made in prescribing, dispensing, administration, or use of the study product. The treatment will be open-label and is to be administered by trained medical personnel at the study site. | [] |
NCT02991144 | 9.3 | Data Monitoring Committee | 9.3 Data Monitoring Committee An independent DMC will be responsible for monitoring safety data from the study. The DMC will meet after all subjects in Cohort 1, all subjects in Cohort 2, and the initial 3 subjects in Cohort 3 have completed Week 12 of the study to review the safety data and to provide their recommenda... | [] |
NCT02991144 | 10 | Statistical and Analytical Plan | 10 Statistical and Analytical Plan A statistical analysis plan (SAP) will be written and will provide a detailed description of the statistical methods and expand on the details provided in this protocol. Additional analyses may be added. | [] |
NCT02991144 | 10.1 | Dose-Finding Algorithm and Process | 10.1 Dose-Finding Algorithm and Process Dose finding for DTX301 will be accomplished through a CRM algorithm as described in Section [10.5.1.](#page-82-0) The operational process is as follows: - Data sources and methodologies used to determine the parameter values of the prior distributions of the toxicity model - Dat... | [] |
NCT02991144 | 10.2 | Primary Endpoints | 10.2 Primary Endpoints The primary endpoint is the incidence of AEs, treatment-emergent AEs, and SAEs (Section [9.1\)](#page-73-1). | [] |
NCT02991144 | 10.3 | Secondary Endpoints | 10.3 Secondary Endpoints The secondary endpoints are: - The change from baseline in the rate of ureagenesis (Section [8.1.1\)](#page-59-2) - The change from baseline in AUC0-24 for plasma ammonia (Section [8.1.2\)](#page-59-3) | [] |
NCT02991144 | 10.4 | Exploratory Endpoints | 10.4 Exploratory Endpoints The exploratory endpoints are: - The number of hyperammonemic crises (HAC) (Section [8.2.4.1\)](#page-62-0) - The change from baseline in urinary orotic acid secretion (Section [8.3.3\)](#page-69-0) - The change from baseline in serum glutamine and glutamate (Section [8.2.4.1\)](#page-62-0) -... | [] |
NCT02991144 | 10.5 | Statistical Analysis Methodology | 10.5 Statistical Analysis Methodology Dose-finding modeling will be conducted through specialized software that has been validated by PPD. SAS® software (SAS Institute, Inc., Cary, North Carolina, United States) Version 9.2 or later will be used for general data manipulation and statistical analyses. Continuous variabl... | [] |
NCT02991144 | 10.5.1 | Determination of the Optimal Biological Dose | 10.5.1 Determination of the Optimal Biological Dose | | The CRM uses the Bayesian method to model the probability of experiencing a DLT for each given | |--------|---------------------------------------------------------------------------------------------------| | | dose in order to determine the next dose. A DLT is d... | [] |
NCT02991144 | 10.5.2 | Efficacy Analysis | 10.5.2 Efficacy Analysis | [] |
NCT02991144 | 10.5.2.1 | Ureagenesis | 10.5.2.1 Ureagenesis The change from baseline in the rate of ureagenesis (presented in µmol/kg/hr and the relative percentage to normal healthy adults [300 µmol/kg/hr]) will be determined for all subjects at Weeks 6, 12, 20, 24, and 52 [\(Table](#page-103-0) 15-1). During Screening, assessment of rate of ureagenesis ma... | [] |
NCT02991144 | 10.5.2.2 | Plasma Ammonia Area Under the Curve from Time Zero to 24 Hours | 10.5.2.2 Plasma Ammonia Area Under the Curve from Time Zero to 24 Hours The change from baseline in the plasma ammonia area under the curve (AUC0-24) and the time-normalized plasma ammonia, defined as plasma ammonia AUC0-24 divided by actual hours from zero to 24 hours, after IV administration of DTX301 will be determi... | [] |
NCT02991144 | 10.5.3 | Safety Analyses | 10.5.3 Safety Analyses All subjects who receive DTX301 will be included in the safety analysis. | [] |
NCT02991144 | 10.5.3.1 | Adverse Events | 10.5.3.1 Adverse Events All statistical analyses of safety outcomes will be descriptive. The incidence of AEs and treatment-emergent AEs will be summarized for each dosing cohort by severity and relationship to study product. Serious AEs will be presented for each dosing cohort by relationship to study product. Summary... | [] |
NCT02991144 | 10.5.3.2 | Physical Examination Findings | 10.5.3.2 Physical Examination Findings Complete and targeted physical examination findings will be summarized by visit and dosing cohort. | [] |
NCT02991144 | 10.5.3.3 | Vital Sign Measurements | 10.5.3.3 Vital Sign Measurements Vital sign measurements (heart rate, blood pressure [systolic and diastolic], and respiratory rate) will be summarized over time in terms of absolute values and changes from baseline by visit and dosing cohort. Height and weight will be summarized. | [] |
NCT02991144 | 10.5.3.4 | Electrocardiogram Results | 10.5.3.4 Electrocardiogram Results Electrocardiogram data will be summarized by visit and dosing cohort. Each ECG will be classified as "abnormal" or "normal," and the relevance of the abnormality will be summarized as "clinically significant" or "not clinically significant." Version 06 25 February 2020 Page 86 of 126 | [] |
NCT02991144 | 10.5.3.5 | Clinical Laboratory Assessment Results | 10.5.3.5 Clinical Laboratory Assessment Results For all laboratory assessments with continuous results, absolute values and changes from baseline will be summarized by visit and dosing cohort. For laboratory tests with categorical results, shifts from baseline will be summarized by visit and dosing cohort. Chemistry va... | [] |
NCT02991144 | 10.5.3.6 | Other Laboratory Results | 10.5.3.6 Other Laboratory Results Neutralizing antibodies (AAV8) and AAV8-binding antibody IgG assay results will be listed by time point and dosing cohort. Anti-OTC antibody assay and viral shedding results will be listed by time point and dosing cohort. | [] |
NCT02991144 | 10.5.4 | Neuropsychological Tests | 10.5.4 Neuropsychological Tests Changes in responses to the PROMIS mental health measurements and (Section [8.4\)](#page-69-1) will be summarized by visit and dosing cohort as outlined in the SAP. Results of the other neuropsychological tests will be listed by visit and dosing cohort. | [] |
NCT02991144 | 10.5.5 | Quality-of-Life Assessment | 10.5.5 Quality-of-Life Assessment Associations between QoL and dose will be undertaken using tabular summaries and appropriate statistical methods as outlined in the SAP. | [] |
NCT02991144 | 10.5.6 | Other Analyses | 10.5.6 Other Analyses Summary statistical analyses will be provided for demographics, medical history, OTC deficiency medical history, prior and concomitant medications, use of ammonia scavengers, and dietary protein intake. A summary of subject disposition will be prepared. | [] |
NCT02991144 | 10.5.7 | Interim Analysis | 10.5.7 Interim Analysis An interim analysis may be conducted when 12 weeks of data are available for all subjects from at least 2 dosing cohorts. Results and their dissemination will be at the sponsor's discretion. A detailed plan for the analysis of the safety and efficacy data will be presented in the SAP. | [] |
NCT02991144 | 10.6 | Data Quality Assurance | 10.6 Data Quality Assurance Study sites will maintain source documentation and enter subject data in the eCRF as accurately as possible and will rapidly respond to any reported discrepancies. The eCRFs are accessed through Medidata Rave® (New York, New York, United States). This EDC system is validated and compliant wi... | [] |
NCT02991144 | 10.6.1 | Data Management | 10.6.1 Data Management As part of the responsibilities assumed by participating in the study, the investigator agrees to maintain adequate case histories for the subjects treated as part of the research under this protocol. The investigator agrees to maintain accurate eCRFs and source documentation as part of the case ... | [] |
NCT02991144 | 11 | Ethics | 11 Ethics | [] |
NCT02991144 | 11.1 | Institutional Review Board, Independent Ethics Committee, and Institutional Biosafety Committee | 11.1 Institutional Review Board, Independent Ethics Committee, and Institutional Biosafety Committee Federal regulations and the ICH guidelines require that approval be obtained from an IRB/IEC/IBC before participation of human subjects in research studies. Before study onset, the protocol, ICF, advertisements to be us... | [] |
NCT02991144 | 11.2 | Ethical Conduct of the Study | 11.2 Ethical Conduct of the Study The study will be performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki, ICH GCP, and all applicable local laws and regulations. | [] |
NCT02991144 | 11.3 | Subject Information and Consent | 11.3 Subject Information and Consent A written ICF in compliance with regulatory authority regulations and 21 CFR §50 shall be obtained from each subject before entering the study or performing any unusual or nonroutine procedure that involves risk to the subject. An ICF template may be provided by the sponsor to study... | [] |
NCT02991144 | 12 | Investigator's Obligations | 12 Investigator's Obligations The following administrative items are meant to guide the investigator in the conduct of the study but may be subject to change based on industry and government standard operating procedures, working practice documents, or guidelines. Any change will be reported to the IRB/IEC/IBC but will... | [] |
NCT02991144 | 12.1 | Confidentiality | 12.1 Confidentiality All laboratory specimens, evaluation forms, reports, and other records will be identified in a manner designed to maintain subject confidentiality. All records will be kept in a secure storage area with limited access. Clinical information will not be released without the written permission of the ... | [] |
NCT02991144 | 12.2 | Financial Disclosure and Obligations | 12.2 Financial Disclosure and Obligations Investigators are required to provide financial disclosure information to allow the sponsor to submit the complete and accurate certification or disclosure statements required under 21 CFR §54. In addition, the investigator must provide to the sponsor a commitment to promptly u... | [] |
NCT02991144 | 12.3 | Investigator Documentation | 12.3 Investigator Documentation Prior to beginning the study, the investigator will be asked to comply with ICH E6(R2) 8.2 and Title 21 of the CFR by providing the following essential documents, including but not limited to: - IRB/IEC/IBC approvals; - Original investigator-signed investigator agreement page of the prot... | [] |
NCT02991144 | 12.4 | Study Conduct | 12.4 Study Conduct The investigator agrees that the study will be conducted according to the principles of ICH E6(R2). The investigator will conduct all aspects of this study in accordance with all national, state, and local laws or regulations. Study information from this protocol will be posted on publicly available ... | [] |
NCT02991144 | 12.5 | Adherence to Protocol | 12.5 Adherence to Protocol The investigator agrees to conduct the study as outlined in this protocol in accordance with ICH E6(R2) and all applicable guidelines and regulations. | [] |
NCT02991144 | 12.6 | Adverse Events and Study Report Requirements | 12.6 Adverse Events and Study Report Requirements By participating in this study, the investigator agrees to submit reports of SAEs according to the time line and method outlined in the protocol. In addition, the investigator agrees to submit annual reports to the study site IRB/IEC/IBC as appropriate. | [] |
NCT02991144 | 12.7 | Investigator's Final Report | 12.7 Investigator's Final Report Upon completion of the study, the investigator, where applicable, should inform the institution; the investigator/institution should provide the IRB/IEC/IBC with a summary of the study's outcome and the sponsor and regulatory authority(ies) with any reports required. | [] |
NCT02991144 | 12.8 | Record Retention | 12.8 Record Retention Essential documents should be retained until at least 2 years after the last approval of a marketing application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of clinical dev... | [] |
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