protocol_id stringclasses 263
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NCT02603835 | 10.8 | Monitor Responsibilities | 10.8 Monitor Responsibilities TherOx personnel or its designees will perform study monitoring. The monitoring process begins with the site initiation activities and continues, in general, until the study close-out visit. While study monitoring normally involves a personal visit to the investigational site, some monitor... | [] |
NCT02603835 | 10.8.1 | Obligations / Qualifications of Study Monitors | 10.8.1 Obligations / Qualifications of Study Monitors Qualified study monitors will oversee the progress of the clinical investigation in accordance with 21 CFR Part 52.29. Monitoring procedures and monitor qualifications (i.e., curriculum vitae, training) will be retained by the CRO. A monitoring log will be maintaine... | [] |
NCT02603835 | 10.8.2 | Periodic Monitoring Visit Activities | 10.8.2 Periodic Monitoring Visit Activities TherOx or their designee is responsible for assuring throughout the clinical investigation through periodic monitoring visits and personal contact that the investigator's obligations, as set forth in applicable regulations, are being fulfilled and that the facilities used in ... | [] |
NCT02603835 | 10.8.3 | Study Close-Out Activities | 10.8.3 Study Close-Out Activities When the study has been completed or terminated, the Monitor should assure that all site closeout activities have been addressed. These activities are documented in more detail in the clinical procedure for study close out. | [] |
NCT02603835 | 10.8.4 | Documentation of Monitoring Visits and Communications | 10.8.4 Documentation of Monitoring Visits and Communications The monitor will complete a written report for each site visit documenting the visit date, site personnel meeting, activities undertaken and a record of the findings, conclusions, and actions undertaken or recommended to correct deficiencies. Accordingly, mon... | [] |
NCT02603835 | 10.9 | Contract Research Organization Responsibilities | 10.9 Contract Research Organization Responsibilities The CRO for the IC-HOT clinical study is the Experien Group. The CRO will perform the below noted activities: - 1. Site Initiation (jointly with TherOx) - 2. Clinical Monitoring - 3. Data base development - 4. Data review - 5. Data query and data clarification resolu... | [] |
NCT02603835 | 10.10 | Records and Reports | 10.10 Records and Reports | [] |
NCT02603835 | 10.10.1 | Required Data | 10.10.1 Required Data All required clinical data for this study will be collected on standardized Case Report Forms (CRFs). A set of draft CRFs can be found in Appendix A. Source and other administrative records will be maintained for a minimum of two (2) years after the latter of either the completion of the investiga... | [] |
NCT02603835 | 10.10.2 | Data Submission | 10.10.2 Data Submission All data MUST be sent to the CRO, Experien Group, according to the following schedule: Table 3. Data Submission Schedule | Form | Submission Time | |-----------------------------------------------------------|------------------------------| | Notification Form | Within 24 Hours of Procedure | | ... | [] |
NCT02603835 | 10.10.3 | Investigator Reports | 10.10.3 Investigator Reports The investigator for each study center is responsible for the generation of the following reports according to the schedule of Table 4. Table 4. Reports Required from Clinical Investigators | Type of Report | Prepared by Investigator For: | Time Constraints of Notification | |--------------... | [] |
NCT02603835 | 10.11 | Investigational Site Termination | 10.11 Investigational Site Termination TherOx reserves the right to terminate an Investigational Site for any of the following reasons: - 1. Failure to secure Informed Consent from a patient or legal guardian representative prior to enrolling the patient into this study. - 2. Repeated protocol violations. - 3. Repeated... | [] |
NCT02603835 | 10.12 | Study Committees | 10.12 Study Committees | [] |
NCT02603835 | 10.12.1 | Executive Committee | 10.12.1 Executive Committee The Executive Committee will review and approve the final trial design and protocol issued to the clinical sites. This committee is responsible for reviewing the final trial results and determining the methods of presentation and publication. The Executive Committee will also have discretion... | [] |
NCT02614794 | 1 | GLOSSARY AND TERMS | 1 GLOSSARY AND TERMS | 1 | GLOSSARY AND TERMS | |----------|--------------------------------------------------------------------| | 5FU | 5-fluorouracil | | ADL | activities of daily living | | AE | adverse event | | ALT/SGPT | alanine aminotransferase/serum glutamic-pyruvate transaminase | | ANC | absolute neutrophil ... | [] |
NCT02614794 | 2 | PROTOCOL SYNOPSIS | 2 PROTOCOL SYNOPSIS Protocol Number: ONT-380-206 Version: Version 12, 30-Jul-2021 Phase: 2 Product Name: Tucatinib Sponsor: Seagen Inc. 21823 30th Drive SE Bothell, WA 98021
Protocol Title Phase 2 Randomized, Double-Blinded, Controlled Study of Tucatinib vs. Placebo in Combination with Capecitabine and Trastuzumab in ... | [
"Protocol Title",
"Double-blind Phase Study Objectives",
"Double-blind Phase Primary Objective",
"Double-blind Phase Secondary Objectives",
"Double-blind Phase Safety Objective",
"Double-blind Phase Pharmacokinetic Objective",
"Double-blind Phase Exploratory Objectives",
"Double-blind Phase Endpoints"... |
NCT02614794 | 3 | BACKGROUND AND RATIONALE | 3 BACKGROUND AND RATIONALE | [] |
NCT02614794 | 3.1 | HER2+ Breast Cancer | 3.1 HER2+ Breast Cancer Breast cancer is the most common form of cancer in women worldwide (Bray 2017), and the second leading cause of cancer-related death in the United States (U.S. Cancer Statistics Working Group 2010).Approximately 20% of breast cancers overexpress the human epidermal growth factor receptor 2 (HER2... | [] |
NCT02614794 | 3.1.1 | Brain Metastases in HER2+ Breast Cancer | 3.1.1 Brain Metastases in HER2+ Breast Cancer Perhaps the greatest unmet medical need in the post-trastuzumab era is treatment and prevention of brain metastases. Recent data suggest that the incidence of first relapse occurring in the brain is increasing in patients who have received trastuzumab-based adjuvant therapy... | [] |
NCT02614794 | 3.2 | Tucatinib | 3.2 Tucatinib | [] |
NCT02614794 | 3.2.1 | Product Description and Mechanism of Action | 3.2.1 Product Description and Mechanism of Action Tucatinib is an orally available, reversible HER2 small molecule tyrosine kinase inhibitor that is being developed as a novel treatment for HER2+ breast cancer. One of the key features of tucatinib is its potency and selectivity for HER2 compared to the closely related ... | [] |
NCT02614794 | 3.2.2 | Nonclinical Studies | 3.2.2 Nonclinical Studies A detailed description of nonclinical studies can be found in the Investigator's Brochure (IB). | [] |
NCT02614794 | 3.2.3 | Clinical Studies | 3.2.3 Clinical Studies See the IB for current data on all tucatinib studies. | [] |
NCT02614794 | 3.2.4 | Tucatinib in the Treatment of Brain Metastases | 3.2.4 Tucatinib in the Treatment of Brain Metastases Both Study ONT-380-004 (tucatinib + T-DM1) and Study ONT-380-005 (tucatinib + capecitabine, trastuzumab or capecitabine and trastuzumab) have enrolled patients with either previously treated stable brain metastases, untreated brain metastases, or previously treated a... | [] |
NCT02614794 | 3.3 | Potential Risks, Benefits and Rationale for the Combination of Tucatinib with Capecitabine and Trastuzumab in a Phase 2 Study | 3.3 Potential Risks, Benefits and Rationale for the Combination of Tucatinib with Capecitabine and Trastuzumab in a Phase 2 Study Overall, tucatinib has been associated with an acceptable safety profile and has demonstrated both single-agent and combination anti-tumor activity, including in patients with progression af... | [] |
NCT02614794 | 3.3.1 | Trastuzumab | 3.3.1 Trastuzumab Trastuzumab is a humanized anti-HER2 antibody that binds to subdomain IV of the HER2 extracellular domain and exerts its antitumor effects by blocking HER2 cleavage, stimulating antibody-dependent, cell-mediated cytotoxicity and inhibiting ligandindependent HER2-mediated mitogenic signaling (Arteaga 2... | [] |
NCT02614794 | 3.3.2 | Capecitabine | 3.3.2 Capecitabine Capecitabine is a prodrug of fluorouracil. It undergoes hydrolysis in the liver and tissues to form fluorouracil which is the active moiety. Fluorouracil is a fluorinated pyrimidine antimetabolite that inhibits thymidylate synthetase, blocking the methylation of deoxyuridylic acid to thymidylic acid,... | [] |
NCT02614794 | 3.3.3 | Double-blind Phase Study Rationale | 3.3.3 Double-blind Phase Study Rationale Despite the marked improvements in PFS and OS with the introduction of new agents for the treatment of HER2+ breast cancer, patients with unresectable locally advanced or metastatic breast cancer are not cured with currently available therapy and represent an ongoing medical nee... | [] |
NCT02614794 | 3.3.4 | Unblinded Phase Study Rationale | 3.3.4 Unblinded Phase Study Rationale Previously, the study sponsor, Seagen, performed the per-protocol primary analysis of this trial. At the time of the primary analysis, the trial met the primary endpoint of progression-free survival (PFS), showing that the addition of tucatinib was superior to trastuzumab and capec... | [] |
NCT02614794 | 4 | STUDY OBJECTIVES | 4 STUDY OBJECTIVES | [] |
NCT02614794 | 4.1 | Double-blind Phase | 4.1 Double-blind Phase | [] |
NCT02614794 | 4.1.1 | Primary Objective | 4.1.1 Primary Objective • To assess the effect of tucatinib vs. placebo in combination with capecitabine and trastuzumab on PFS per RECIST 1.1 based on blinded independent central review (BICR) | [] |
NCT02614794 | 4.1.2 | Secondary Objectives | 4.1.2 Secondary Objectives - To assess the effect of tucatinib vs. placebo in combination with capecitabine and trastuzumab in patients with brain metastases at baseline, defined as patients with a history of brain metastases, current brain metastases, or equivocal brain lesions at baseline, using RECIST 1.1 based on (... | [] |
NCT02614794 | 4.1.2.1 | Safety Objective | 4.1.2.1 Safety Objective • To assess the safety and tolerability of tucatinib in combination with capecitabine and trastuzumab | [] |
NCT02614794 | 4.1.2.2 | Pharmacokinetic Objective | 4.1.2.2 Pharmacokinetic Objective • To evaluate the pharmacokinetics of tucatinib and metabolite ONT-993 when administered in combination with capecitabine and trastuzumab | [] |
NCT02614794 | 4.1.3 | Exploratory Objectives | 4.1.3 Exploratory Objectives - To assess the effect of tucatinib vs. placebo in combination with capecitabine and trastuzumab using RANO-BM based on BICR in patients with brain metastases at baseline - To identify potential biomarkers of response, including human epidermal growth factor receptor 2 (HER2) mutations and ... | [] |
NCT02614794 | 4.2 | Unblinded Phase | 4.2 Unblinded Phase - To assess the safety and tolerability of tucatinib in combination with capecitabine and trastuzumab - To assess PFS per RECIST 1.1 by investigator - To assess OS | [] |
NCT02614794 | 5 | STUDY DESIGN | 5 STUDY DESIGN | [] |
NCT02614794 | 5.1 | Overview of Study Design | 5.1 Overview of Study Design Figure 5-1 Double-blind Study Schematic  a Treatment will continue until unacceptable toxicity, disease progression, withdrawal of consent, or study closure. Patients with CNS progression may undergo local therapy to CNS lesions and continue on study treatment with ap... | [] |
NCT02614794 | 5.1.1 | Double-blind Phase | 5.1.1 Double-blind Phase In this phase, the study is a randomized, international, multi-center, double-blind study of tucatinib or placebo in combination with capecitabine and trastuzumab in patients with unresectable locally advanced or metastatic HER2+ breast cancer who have had prior treatment with trastuzumab, pert... | [
"Tumor Response Assessments",
"Safety Assessments",
"Pharmacokinetics and Biomarker Assessments",
"HEOR and QoL"
] |
NCT02614794 | 5.1.2 | Unblinded Phase | 5.1.2 Unblinded Phase Based on the positive results of the per-protocol primary analysis of this trial, the Sponsor decided to unblind this trial and offer tucatinib to patients on the control arm. Protocol Version 11 established a new Unblinded Phase of the study, and presented study procedures for these 2 distinct ph... | [
"Treatments Administered in the Unblinded Phase",
"Screening for Crossover Criteria",
"Tumor Response Assessments",
"Safety Assessments",
"Assessments after Treatment Discontinuation"
] |
NCT02614794 | 5.1.3 | Continuation on Study Treatment After CNS-Only Progression | 5.1.3 Continuation on Study Treatment After CNS-Only Progression For patients in both the Double-blind and Unblinded Phases, patients may continue study treatment for clinical benefit after a PFS event in brain with medical monitor approval. If a patient is found to have radiographic progressive disease per RECIST 1.1 ... | [] |
NCT02614794 | 5.2 | Rationale for the Study Design | 5.2 Rationale for the Study Design | [] |
NCT02614794 | 5.2.1 | Rationale for the Patient Population | 5.2.1 Rationale for the Patient Population Eligible patients for this study are those with progressive, unresectable locally advanced or metastatic HER2+ breast cancer who have had prior treatment with trastuzumab, pertuzumab, and T-DM1 (Freedman 2012; Cardoso 2014; Giordano 2014; Ramakrishna 2014).There is currently n... | [] |
NCT02614794 | 5.2.2 | Rationale for the Dose and Regimen | 5.2.2 Rationale for the Dose and Regimen All patients will receive a treatment backbone of capecitabine and trastuzumab, a combination recommended in current treatment guidelines in this patient population for whom no single standard of care therapy exists. In the CEREBEL study, patients treated with the combination of... | [] |
NCT02614794 | 5.2.2.1 | Rationale for Regimen in Patients with Brain Metastases | 5.2.2.1 Rationale for Regimen in Patients with Brain Metastases Patients with brain metastases have frequently been excluded from trials with systemic cancer therapies due to difficulties in imaging assessment in the brain and a lack of flexibility with regard to treatment discordant responses in CNS and non-CNS locati... | [] |
NCT02614794 | 5.2.3 | Rationale for Efficacy Assessments | 5.2.3 Rationale for Efficacy Assessments Efficacy will be assessed looking at all sites of disease using RECIST 1.1 (Eisenhauer 2009). The primary endpoint will be PFS, as assessed per BICR RECIST 1.1. The two key secondary endpoints, PFS in patients with baseline brain metastases assessed centrally using RECIST 1.1 an... | [] |
NCT02614794 | 5.2.3.1 | Rationale for CNS Efficacy Assessments | 5.2.3.1 Rationale for CNS Efficacy Assessments Contrast MRI of the brain will be performed at baseline for all patients. This is being performed to more thoroughly evaluate the activity of tucatinib in brain by establishing a baseline in all patients, even those with asymptomatic unsuspected brain metastases. Contrast ... | [] |
NCT02614794 | 5.2.4 | Rationale for PK Assessment Plan | 5.2.4 Rationale for PK Assessment Plan Pharmacokinetic assessments of trough levels of tucatinib and metabolite drug levels will be performed on Day 1 of Cycles 2-6 prior to administration of tucatinib or placebo, and peak level on Day 1 of Cycle 3 within 1–4 h after administration of tucatinib or placebo. Patients wil... | [] |
NCT02614794 | 5.2.5 | Rationale for Health Economics Assessments | 5.2.5 Rationale for Health Economics Assessments Health-related quality of life is an important outcome from both clinical and economic perspectives. A substantial body of literature supports the validity and reliability of the health questionnaire EQ-5D-5L instrument for assessing quality of life in a health economic ... | [] |
NCT02614794 | 5.2.6 | Rationale for Exploratory Endpoints | 5.2.6 Rationale for Exploratory Endpoints | [] |
NCT02614794 | 5.2.6.1 | Biomarker Assessments | 5.2.6.1 Biomarker Assessments Biomarker assessments may include the confirmation of HER2 status by ISH or FISH, and an exploratory assessment of HER2 mutations or other mutations as potential biomarkers of response. HER2 status will be verified by central laboratory analysis using ASCO/CAP guidelines. Next generation D... | [] |
NCT02614794 | 5.3 | Double-blind Phase Endpoints | 5.3 Double-blind Phase Endpoints | [] |
NCT02614794 | 5.3.1 | Double-blind Phase Primary Endpoint | 5.3.1 Double-blind Phase Primary Endpoint • PFS, defined as the time from randomization to documented disease progression (as determined by BICR per RECIST 1.1), or death from any cause, whichever occurs first | [] |
NCT02614794 | 5.3.2 | Double-blind Phase Secondary Endpoints | 5.3.2 Double-blind Phase Secondary Endpoints
Efficacy Key Secondary Endpoints - PFS in patients with brain metastases at baseline using RECIST 1.1 based on BICR - OS Other Secondary Endpoints - PFS, defined as the time from randomization to investigator-assessed documented disease progression (per RECIST 1.1), or deat... | [
"Efficacy",
"Safety",
"Pharmacokinetics",
"Heath Economics and Outcomes"
] |
NCT02614794 | 5.3.3 | Double-blind Phase Exploratory Endpoints | 5.3.3 Double-blind Phase Exploratory Endpoints - ORR in brain per RANO-BM as determined by BICR - Duration of response in brain per RANO-BM as determined by BICR - Time to brain progression in patients with brain metastases at baseline per RANO-BM as determined by BICR - Presence of HER2 mutations or other potential bi... | [] |
NCT02614794 | 5.4 | Unblinded Phase Endpoints | 5.4 Unblinded Phase Endpoints - Adverse events (AEs) - Clinical laboratory assessments - Vital signs and other relevant safety variables - Frequency of dose holding, dose reductions, and discontinuations of capecitabine - Frequency of dose holding, dose reductions, and discontinuations of tucatinib - Frequency of dose ... | [] |
NCT02614794 | 5.5 | Study Stopping Rules and Discontinuation Criteria | 5.5 Study Stopping Rules and Discontinuation Criteria Reasons for terminating the study may include but are not limited to the following: - The incidence or severity of AEs in this or other studies indicates a potential health hazard to patients, either through a safety review by the sponsor or an independent safety as... | [] |
NCT02614794 | 5.6 | End of Study | 5.6 End of Study An analysis of OS and PFS conducted approximately 2 years after the last patient was randomized to the study demonstrated that the OS benefit with tucatinib was maintained, and PFS per investigator assessment was consistent with the primary analysis (Curigliano 2021). Moreover, the number of OS events ... | [] |
NCT02614794 | 5.7 | Post-study Care | 5.7 Post-study Care At the time of study closure, patients will revert to physician care. When applicable, the Sponsor will assist with post-trial access to tucatinib. | [] |
NCT02614794 | 5.8 | Minimization of Bias | 5.8 Minimization of Bias | [] |
NCT02614794 | 5.8.1 | Double-blind Phase Randomization | 5.8.1 Double-blind Phase Randomization Patients will be randomized in a 2:1 ratio to receive tucatinib or placebo in combination with capecitabine and trastuzumab by a dynamic hierarchical randomization scheme using an Interactive Response Technology (IRT) system. Randomization will be stratified by the following strat... | [] |
NCT02614794 | 5.8.2 | Double-blind Phase Blinding | 5.8.2 Double-blind Phase Blinding This phase of the study will be double-blinded, and every attempt will be made to maintain the blind throughout the study. The investigator, study center personnel, clinical research organization staff, and sponsor personnel (except for pre-specified Safety personnel) will not have acc... | [] |
NCT02614794 | 5.8.3 | Double-blind Phase Unblinding | 5.8.3 Double-blind Phase Unblinding As per local regulatory reporting requirements, the sponsor Safety Department will unblind the identity of study medication for any unexpected (as per the IB) SAEs that are considered to be related to the blinded study drug (tucatinib/placebo). All other sponsor personnel will remain... | [] |
NCT02614794 | 5.9 | Ethical Considerations | 5.9 Ethical Considerations Despite the advances that have been made, unresectable locally advanced or metastatic HER2+ breast cancer is incurable. The primary goals of treatment remain to extend life and palliate symptoms while preserving quality of life. At present, no single treatment regimen can be considered the gl... | [] |
NCT02614794 | 6 | SELECTION AND WITHDRAWAL OF PATIENTS | 6 SELECTION AND WITHDRAWAL OF PATIENTS | [] |
NCT02614794 | 6.1 | Double-blind Phase Inclusion Criteria | 6.1 Double-blind Phase Inclusion Criteria Patients must meet the following criteria to be eligible for the study: - 1. Have histologically confirmed HER2+ breast carcinoma, with HER2+ defined by ISH or FISH or IHC methodology - a. Tissue blocks or slides must be submitted to confirm HER2 positivity (using ISH or FISH) ... | [] |
NCT02614794 | 6.2 | Double-blind Phase Exclusion Criteria | 6.2 Double-blind Phase Exclusion Criteria Patients will be excluded from the study for any of the following reasons: - 1. Have previously been treated with: - a. lapatinib within 12 months of starting study treatment (except in cases where lapatinib was given for ≤ 21 days and was discontinued for reasons other than di... | [] |
NCT02614794 | 6.3 | Unblinded Phase Crossover Criteria | 6.3 Unblinded Phase Crossover Criteria | [] |
NCT02614794 | 6.3.1 | Crossover Inclusion Criteria | 6.3.1 Crossover Inclusion Criteria Patients who were randomized to the control arm (placebo + trastuzumab + capecitabine) must meet the inclusion criteria below at the time of crossover screening to be eligible to crossover to the experimental arm. Prior scans and imaging may be used for crossover inclusion/exclusion c... | [] |
NCT02614794 | 15 | Previously treated brain metastases | 15. Previously treated brain metastases - a. Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy in the opinion of the investigator - ... | [
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"6.4 Criteria for Discontinuation of Study Treatment",
"7 TREATMENTS ADMINISTERED",
"7.1 Standard of Care Treatment",
"7.1.1 Capecitabine",
"7.1.1.1 Risks Associated with Capecitabine",
"7.1.2 Trastuzumab",
"Intravenous",
"Subcutaneous",
"Biosimilar",
"Gener... |
NCT02704364 | 1 | SYNOPSIS | 1 SYNOPSIS | | 'NGM Protocol 15-0106 | |-----------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|... | [] |
NCT02704364 | 2 | INTRODUCTION | 2 INTRODUCTION | [] |
NCT02704364 | 2.1 | BACKGROUND | 2.1 BACKGROUND | [] |
NCT02704364 | 2.1.1 | Primary Sclerosing Cholangitis (PSC) | 2.1.1 Primary Sclerosing Cholangitis (PSC) PSC is a chronic cholestatic liver disease that is characterized by diffuse inflammation and fibrosis of the bile ducts (Chapman et al. 2010). The intra and/or extrahepatic bile ducts can be affected; ongoing destruction often leads to cholestasis, advanced fibrosis, liver cir... | [] |
NCT02704364 | 2.1.2 | Treatment of PSC | 2.1.2 Treatment of PSC Currently, the primary therapy for PSC is endoscopic or radiologic dilatation or stenting of bile-duct strictures targeted at reducing or halting progression of the disease (Kaya et al. 2001; Lindor et al. 2015). Although there is no established or approved pharmacologic therapy for PSC, ursodeox... | [] |
NCT02704364 | 2.1.3 | Therapeutic Rationale for NGM282 in PSC | 2.1.3 Therapeutic Rationale for NGM282 in PSC Fibroblast growth factor 19 (FGF19) is a naturally occurring protein selectively expressed and secreted in the gastrointestinal tract. FGF19 functions as an ileal hormone that directly regulates the classic pathway of hydrophobic ("toxic") bile acid synthesis by altering th... | [] |
NCT02704364 | 2.2 | NONCLINICAL STUDIES | 2.2 NONCLINICAL STUDIES NGM has completed a series of in vitro and in vivo nonclinical studies supportive of the clinical development of NGM282 in patients with PSC. Please refer to the Investigator's Brochure (IB) for additional information on these studies. | [] |
NCT02704364 | 2.2.1 | Nonclinical Safety Assessment | 2.2.1 Nonclinical Safety Assessment The nonclinical safety of NGM282 has been assessed in general toxicity studies in CD-1 mice and cynomolgus monkeys for up to 26 weeks of treatment and in embryo–fetal toxicity studies in CD-1 mice and New Zealand White rabbits. NGM282 was pharmacologically active in the mouse and mon... | [] |
NCT02704364 | 2.3 | CLINICAL STUDIES | 2.3 CLINICAL STUDIES NGM has conducted a Phase 1 clinical trial in normal volunteers as well as Phase 2a and 2b trials in PBC patients. These studies are supportive of the clinical development of NGM282 in patients with PSC. Please refer to the IB for additional detailed information on these studies. | [] |
NCT02704364 | 2.4 | RATIONALE FOR DOSE SELECTION OF NGM282 FOR PSC | 2.4 RATIONALE FOR DOSE SELECTION OF NGM282 FOR PSC The doses selected for the Phase 2 trial in PSC are supported by both the nonclinical and clinical data generated to date. The dose range for the first-in-human Phase 1 clinical trial (0.1–30 mg) was based on a broad approach to dose calculation considering the pharmac... | [] |
NCT02704364 | 3 | STUDY OBJECTIVES | 3 STUDY OBJECTIVES
Primary Objective: Evaluate the treatment effect of NGM282 as measured by the mean change in ALP from Baseline to Week 12 in patients with PSC.
Secondary Objectives: - Assess the safety and tolerability of NGM282 in patients with PSC with 12 weeks of treatment. - Evaluate the percentage change from... | [
"Primary Objective:",
"Secondary Objectives:",
"Exploratory PD Objectives:"
] |
NCT02704364 | 4 | STUDY DESIGN | 4 STUDY DESIGN This is a multiple-center, randomized, double-blind, placebo-controlled, parallel-group study of NGM282 when administered for 12 weeks as a daily subcutaneous (SC) injection in patients with PSC. Approximately 60 subjects will be randomized across approximately 40–45 sites worldwide. Patients will sign t... | [] |
NCT02704364 | 4.1 | STUDY STOPPING CRITERIA | 4.1 STUDY STOPPING CRITERIA The entire study may be discontinued at the discretion of the Sponsor based on the occurrence of the following: - Adverse events (AEs) with respect to their nature, frequency, severity, and/or duration - Medical or ethical reasons affecting the continued performance of the study - Difficulti... | [] |
NCT02704364 | 5 | SUBJECT SELECTION | 5 SUBJECT SELECTION | [] |
NCT02704364 | 5.1 | INCLUSION CRITERIA | 5.1 INCLUSION CRITERIA Patients who meet the following criteria may be included in the study: - 1. Males and females between 18 and 75 years of age inclusive who are able to comprehend instructions and follow the study procedures, and are willing to sign an Informed Consent Form (ICF). - 2. Confirmed diagnosis of PSC b... | [
"OR"
] |
NCT02704364 | 5.2 | EXCLUSION CRITERIA | 5.2 EXCLUSION CRITERIA Any of the following will exclude potential subjects from the study: 1. Clinically significant acute or chronic liver disease of an etiology other than PSC. 27 May 2016 Page 25 of 71 - a. Patients with stable treated overlapping PSC and autoimmune hepatitis (AIH) will be allowed to enroll into th... | [] |
NCT02704364 | 5.3 | DISCONTINUATION OF STUDY TREATMENT IN AN INDIVIDUAL SUBJECT | 5.3 DISCONTINUATION OF STUDY TREATMENT IN AN INDIVIDUAL SUBJECT Study treatment will be discontinued if any of the following CTCAE categories or abnormal elevations in liver function tests occurs on-treatment: - Any Grade 3 TEAE related to study drug - Any Grade 4 or higher TEAE - Elevation of ALT and total bilirubin >... | [] |
NCT02704364 | 5.4 | DISCONTINUATION OF SUBJECTS FROM STUDY PARTICIPATION | 5.4 DISCONTINUATION OF SUBJECTS FROM STUDY PARTICIPATION Patients will be informed that they are free to withdraw from the study at any time and for any reason. The Principal Investigator (PI) may remove a subject from the study if, in the PI's opinion, it is not in the best interest of the subject to continue the stud... | [] |
NCT02704364 | 5.5 | SCHEDULE OF STUDY PROCEDURES | 5.5 SCHEDULE OF STUDY PROCEDURES The Schedule of Study Procedures is shown in Table 5.5-1. The visits should occur as close to the intended dates as possible. However, there is an acceptable ± 3-day window for individual scheduled visits. Subjects attending any visits out of windows from Day 1 to Week 12/Early Withdraw... | [] |
NCT02704364 | 5.6 | STUDY VISIT PROCEDURES | 5.6 STUDY VISIT PROCEDURES | [] |
NCT02704364 | 5.6.1 | Day –42 to Day –1 (Screening) Procedures | 5.6.1 Day –42 to Day –1 (Screening) Procedures Patients will report to this visit fasted for 10 hours with only water allowed. The following screening procedures will be performed for all potential subjects at a visit (or visits) conducted within 42 days prior to dosing: - Obtain informed consent. - Collect demographic... | [] |
NCT02704364 | 5.6.2 | Day 1 Procedures | 5.6.2 Day 1 Procedures Subjects will report to this visit fasted for 10 hours with only water allowed. The following procedures will be performed at the Day 1 Visit:
Pre-dose: - Reassess inclusion/exclusion criteria. - Measure body weight. - Conduct physical examination. - Obtain 12-lead ECG (after subject has been su... | [
"Pre-dose:",
"In-clinic dosing:",
"Before clinic discharge:"
] |
NCT02704364 | 5.6.3 | Week 1 Procedures | 5.6.3 Week 1 Procedures Subjects will report to this visit fasted for 10 hours with only water allowed and undosed. The following procedures will be performed at the Week 1 visit:
Pre-dose: - Measure vital signs (including temperature, respiratory rate, and seated blood pressure and pulse). - Assess for concomitant me... | [
"Pre-dose:",
"Dosing:"
] |
NCT02704364 | 5.6.4 | Week 2 Procedures | 5.6.4 Week 2 Procedures Subjects will report to this visit fasted for 10 hours with only water allowed and undosed. The following procedures will be performed at the Week 2 visit:
Pre-dose: - Conduct physical examination. - Measure vital signs (including temperature, respiratory rate, and seated blood pressure and pul... | [
"Pre-dose:",
"Dosing:",
"Discharge (20 minutes after dosing):"
] |
NCT02704364 | 5.6.5 | Week 4 Procedures | 5.6.5 Week 4 Procedures Subjects will report to this visit fasted for 10 hours with only water allowed and undosed. The following procedures will be performed at the Week 4 visit:
Pre-dose: - Conduct physical examination. - Measure body weight. - Measure vital signs (including temperature, respiratory rate, and seated... | [
"Pre-dose:",
"Dosing:"
] |
NCT02704364 | 5.6.6 | Week 8 Procedures | 5.6.6 Week 8 Procedures Subjects will report to this visit fasted for 10 hours with only water allowed and undosed. The following procedures will be performed at the Week 8 visit:
Pre-dose: - Conduct physical exam. - Measure body weight. - Measure vital signs (including temperature, respiratory rate, and seated blood ... | [
"Pre-dose:",
"Dosing:",
"Discharge (20 minutes after dosing):"
] |
NCT02704364 | 5.6.7 | Week 12 (End of Treatment)/Early Withdrawal Procedures | 5.6.7 Week 12 (End of Treatment)/Early Withdrawal Procedures Subjects will report to this visit fasted for 10 hours with only water allowed and undosed. The following procedures will be performed at the Week 12/Early Withdrawal Visit:
Pre-dose: - Measure body weight. - Conduct physical examination. - Obtain 12-lead EC... | [
"Pre-dose:",
"Dosing:",
"Discharge:"
] |
NCT02704364 | 5.6.8 | Week 16 (End of Study) Procedures | 5.6.8 Week 16 (End of Study) Procedures This visit will be performed 4 weeks after last dose of study medication. Subjects will report to this visit fasted for 10 hours with only water allowed. The following procedures will be performed at the Week 16 visit: - Measure body weight. - Conduct physical examination. - Obta... | [] |
NCT02704364 | 5.7 | CONCOMITANT MEDICATIONS | 5.7 CONCOMITANT MEDICATIONS Any medication taken within 4 weeks prior to Screening and during the study period, as well as the reason for use, will be recorded in the source documents and the eCRFs. Subjects should refrain from the use of any new prescription medications or products or change in the dose or frequency o... | [
"In addition:"
] |
NCT02704364 | 5.8 | DIET AND ACTIVITY CONTROL | 5.8 DIET AND ACTIVITY CONTROL Subjects should maintain their normal level of physical activity, diet, and lifestyle throughout the entire study (i.e., will not begin a new exercise program or participate in any unusually strenuous physical exertion). 27 May 2016 Page 40 of 71 | [] |
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