protocol_id stringclasses 263
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NCT03853798 | 14 | LIST OF REFERENCES | 14. LIST OF REFERENCES Aizawa S, Kohdera U, Hiramoto M, et al. Ineffective erythropoiesis in the spleen of a patient with pyruvate kinase deficiency. Am J Hematol. 2003;74(1):68-72. doi:10.1002/ajh.10380 Beutler E, Gelbart T. Estimating the prevalence of pyruvate kinase deficiency from the gene frequency in the general... | [] |
NCT03853798 | 15 | APPENDICES | 15. APPENDICES
APPENDIX 1. DEFINITION OF WOMEN OF REPRODUCTIVE POTENTIAL
Definition of Women of Reproductive Potential A woman is considered fertile after menarche and until becoming postmenopausal unless permanently sterile. If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle ca... | [
"APPENDIX 1. DEFINITION OF WOMEN OF REPRODUCTIVE POTENTIAL",
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NCT03977974 | C | o nfi d e nti al I nf or m ati o n | C o nfi d e nti al I nf or m ati o n T h e i nf or m ati o n c o nt ai n e d i n t hi s pr ot o c ol i s c o nfi d e nti al a n d i s i nt e n d e d f or t h e u s e of cli ni c al i n v e sti g at or s. It i s t h e pr o p ert y of Eli Lill y a n d C o m p a n y or it s s u b si di ari e s a n d s h o ul d n ot b e c ... | [
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NCT03977974 | I | ntr o d u cti o n | I ntr o d u cti o n
3. 1 St u d y R ati o n al e St u d y J 2 D M C C V A A is a first i n h u ma n ( FI H) st u d y desi g ne d t o e val uate safet y, t olera bilit y, a n d p har mac o ki net ics ( P K) of or al L Y 3 5 2 6 3 1 8 i n healt h y parti ci pa nt s. L Y 3 5 2 6 3 1 8 is a s mall m o lec ule desi g ne d ... | [
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NCT04002557 | 5.1 | Appendix 2: Template Protocol for non-CTIMPs | 5.1 Appendix 2: Template Protocol for non-CTIMPs
ONSET Optimising Consultation Summaries to Promote Good Health; Views of Adolescents Attending Diabetes Clinic Version 7, 25November2018 MAIN SPONSOR: Imperial College London STUDY COORDINATION CENTRE: University College London Hospital IRAS Project ID: 240163 REC refer... | [
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"Sponsor",
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"1.1 BACKGROUND",
"1.2 RATIONALE FOR CURRENT STUDY",
"2. STUDY OBJECTIVES",
"3. STUDY DESIGN",
"4. PARTICIPANT ENTRY",
"4.1 PRE-REGISTRATION EVALUATIONS",
"4.2... |
NCT04002557 | 5 | ADVERSE EVENTS | 5. ADVERSE EVENTS | [] |
NCT04002557 | 5.1 | DEFINITIONS | 5.1 DEFINITIONS Adverse Event (AE): any untoward medical occurrence in a patient or clinical study subject. Serious Adverse Event (SAE): any untoward and unexpected medical occurrence or effect that: - Results in death - Is life-threatening refers to an event in which the subject was at risk of death at the time of the... | [] |
NCT04002557 | 5.3 | REPORTING PROCEDURES | 5.3 REPORTING PROCEDURES All adverse events should be reported. Depending on the nature of the event the reporting procedures below should be followed. Any questions concerning adverse event reporting should be directed to the Chief Investigator in the first instance. | [] |
NCT04002557 | 5.3.1 | Non serious AEs | 5.3.1 Non serious AEs All such events, whether expected or not, should be recorded. | [] |
NCT04002557 | 5.3.2 | Serious AEs | 5.3.2 Serious AEs An SAE form should be completed and faxed to the Chief Investigator within 24 hours. However, relapse and death due to , and hospitalisations for elective treatment of a pre-existing condition do not need reporting as SAEs. All SAEs should be reported to the where in the opinion of the Chief Investiga... | [] |
NCT04002557 | 6 | ASSESSMENT AND FOLLOW-UP | 6. ASSESSMENT AND FOLLOW-UP We will identify potential participants by accessing UCLH adolescent diabetes clinic clinic schedule. All patients attending an adolescent diabetes outpatient clinic on a particular day will be invited to participate in the study. Every potential participant will receive an invitation pack w... | [] |
NCT04002557 | 7 | DATA ANALYSIS | 7. DATA ANALYSIS We will use constant comparative method for the coding process (Krueger and Casey, 2015). The coding process will consist of reading the transcript and analysing responses to statements given by the study participants one by one. We will examine responses to each statement and code each response accord... | [] |
NCT04002557 | 8 | REGULATORY ISSUES | 8. REGULATORY ISSUES | [] |
NCT04002557 | 8.1 | ETHICS APPROVAL | 8.1 ETHICS APPROVAL The Study Coordination Centre has obtained approval from the North West Haydock Research Ethics Committee (REC) and Health Regulator Authority (HRA). The study must also receive confirmation of capacity and capability from each participating NHS Trust before accepting participants into the study or ... | [] |
NCT04002557 | 8.2 | CONSENT | 8.2 CONSENT Consent to enter the study must be sought from each participant only after a full explanation has been given, an information leaflet offered and time allowed for consideration. Signed participant consent should be obtained. The right of the participant to refuse to participate without giving reasons must be... | [] |
NCT04002557 | 8.3 | CONFIDENTIALITY | 8.3 CONFIDENTIALITY The Chief Investigator will preserve the confidentiality of participants taking part in the study and is registered under the Data Protection Act. | [] |
NCT04002557 | 8.4 | INDEMNITY | 8.4 INDEMNITY Imperial College London holds negligent harm and non-negligent harm insurance policies which apply to this study. | [] |
NCT04002557 | 8.5 | SPONSOR | 8.5 SPONSOR Imperial College London will act as the main Sponsor for this study. Delegated responsibilities will be assigned to the NHS trusts taking part in this study. | [] |
NCT04002557 | 8.6 | FUNDING | 8.6 FUNDING Funding is not available for this study | [] |
NCT04002557 | 8.7 | AUDITS | 8.7 AUDITS The study may be subject to inspection and audit by Imperial College London under their remit as sponsor and other regulatory bodies to ensure adherence to GCP and the UK Policy Framework for Health and Social Care Research. | [] |
NCT04002557 | 9 | STUDY MANAGEMENT | 9. STUDY MANAGEMENT The day-to-day management of the study will be co-ordinated through UCLH. | [] |
NCT04002557 | 10 | PUBLICATION POLICY | 10. PUBLICATION POLICY The study registration and publication will be supported by The Imperial Open Access Fund and will be available in fully open access journals only. | [] |
NCT04002557 | 11 | REFERENCES | 11. REFERENCES Bartle, D. (2004). Copies of clinic letters to the family. Archives of Disease in Childhood, 89(11), pp.1032-1033. Baxter, S., Farrell, K., Brown, C., Clarke, J. and Davies, H. (2008). Where have all the copy letters gone? A review of current practice in professional–patient correspondence. Patient Educa... | [
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"Appendix 1 – Focus group discussion schedule",
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NCT04004273 | 1 | AMENDMENT HISTORY | 1. AMENDMENT HISTORY Protocol version 1 – 1/5/2018 Protocol version 2 – 14/11/2018 Protocol version 3 – 19/02/2020 Protocol version 4 – 20/05/2020 Protocol version 5 – 09/09/2020 Protocol version 6 – 23/09/2021 | AmendmentNo. | ProtocolVersion | Dateissued | Author(s) ofchanges | Details of Changes made | |------------... | [] |
NCT04004273 | 2 | KEY STUDY CONTACTS | 2. KEY STUDY CONTACTS | Chief Investigator | Dr James King | | | |--------------------|-------------------------------------------------------|--|--| | | Lecturer in Exercise Physiology | | | | | School of Sport, Exercise & Health Sciences | | | | | Loughborough University | | | | | Loughborough | | | | | Leicestershir... | [] |
NCT04004273 | 3 | STUDY SUMMARY | 3. STUDY SUMMARY | Full study title | The Impact of Type 2 Diabetes and Exercise on Liver FatQuality | | | |------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------... | [] |
NCT04004273 | 4 | FUNDING AND SUPPORT IN KIND | 4. FUNDING AND SUPPORT IN KIND | FUNDER(S) | FINANCIAL AND NON-FINANCIALSUPPORT GIVEN | |---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------... | [] |
NCT04004273 | 5 | ABBREVIATIONS | 5. ABBREVIATIONS AE Adverse event AR Adverse reaction BMI Body Mass Index BRC NIHR Biomedical Research Centre CI Chief Investigator CRF Case Report Form CRN Clinical Research Network CRO Contract Research Organisation CT Clinical Trials EC Ethics Committee (see REC) GCP Good Clinical Practice GP General Practitioner 1 ... | [] |
NCT04004273 | 6 | PEER REVIEW | 6. PEER REVIEW The research outlined in this protocol document has been peer reviewed by four independent experts in the research field during the Diabetes UK grant award process (competitive funding process). Within this process, the chief investigator was required to amend or rebut reviewer's comments and the final p... | [] |
NCT04004273 | 7 | BACKGROUND AND RATIONALE | 7. BACKGROUND AND RATIONALE Non-alcoholic fatty liver disease (NAFLD) is often described as the hepatic manifestation of the metabolic syndrome and is defined as the excessive accumulation of fat within the liver (hepatic steatosis) in individuals who do not consume excessive alcohol or possess viral hepatic pathology ... | [] |
NCT04004273 | 8 | OBJECTIVES | 8. OBJECTIVES
Co-primary objectives To determine: a) whether differences exist in the liver saturated fat index between obese men with NAFLD, with versus without, T2DM; b) the impact of six weeks exercise training on these outcomes in obese men with NAFLD and T2DM/prediabetes.
Secondary objectives - To characterise p... | [
"Co-primary objectives",
"Secondary objectives"
] |
NCT04004273 | 9 | STUDY DESIGN | 9. STUDY DESIGN
Summary of trial design This study consists of two parts: a cross-sectional component (Part A) and a randomised controlled trial (RCT) (Part B). All participants will complete Part A (non-diabetic obese men with NAFLD and obese men with NAFLD & T2DM/prediabetes); however, only one of the two study grou... | [
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NCT04004273 | 10 | TRIAL PARTICIPANTS | 10. TRIAL PARTICIPANTS
Overall description of trial participants The participants we are seeking to recruit are inactive and obese men, with clinically elevated liver fat, with or without T2DM/prediabetes. The inclusion and exclusion criteria can be found overleaf.
Recruitment strategy Recruitment will target individ... | [
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"Additional criteria for participants wi... |
NCT04004273 | 11 | STUDY PROCEDURES | 11. STUDY PROCEDURES
Verbal eligibility check Prior to commencing the study, participants will be contacted via telephone and an initial verbal eligibility check will take place (approx. 30 min conversation). Following this, potentially eligible participants will be invited to visit the Sir Peter Mansfield Imaging Cen... | [
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"Anthropometry, blood pressure and finger prick blood test",
"Magnetic resonance imaging (MRI)",
"Familiarisation with weighed food records and physical... |
NCT04004273 | 12 | TREATMENT OF TRIALPARTICIPANTS | 12. TREATMENT OF TRIALPARTICIPANTS
Overview of procedures This study will consist of two parts (A and B) and will include two discrete groups of participants. - 1. Obese men with NAFLD will complete Part A only - 2. Obese men with NAFLD and T2DM/prediabetes will complete Part A andB Table 1 provides an overview of the... | [
"Overview of procedures",
"Exercise training",
"Remuneration and expenses"
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NCT04004273 | 13 | SAFETY REPORTING | 13. SAFETY REPORTING
Definitions
Adverse Event (AE) An AE or adverse experience is: Any untoward medical occurrence in a patient or clinical investigation participants, which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (inclu... | [
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NCT04004273 | 14 | STATISTICS | 14. STATISTICS
Description of statistical methods Descriptive statistics will be calculated to outline the characteristics of the study sample. Normality of data will be assessed using histograms and box plots, while further analysis of skewness and kurtosis will be conducted if normality is not clear from the histogr... | [
"Description of statistical methods",
"The Number of Participants",
"Procedure for dealing with missing and spurious data"
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NCT04004273 | 15 | DIRECT ACCESS TO SOURCE DATA / DOCUMENTS | 15. DIRECT ACCESS TO SOURCE DATA / DOCUMENTS Beyond the study team, direct access will be granted to authorised representatives from the sponsor, host institution and the regulatory authorities to permit trial-related monitoring, audits and inspections. | [] |
NCT04004273 | 16 | QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES | 16. QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES Loughborough University as sponsor operate a risk-based audit programme to which this study will be subject. The research team will be responsible for all elements of study management on an on-going basis. A documented monitoring log and audit trail will be maintaine... | [] |
NCT04004273 | 17 | CODE OF PRACTICE AND REGULATIONS | 17. CODE OF PRACTICE AND REGULATIONS
Ethics Approval from Loughborough University (sponsor), a Local Research Ethics Committee (REC), the Health Research Authority (HRA), University of Nottingham, University Hospitals of Leicester NHS Trust R&D and Nottingham University Hospitals Trust R & D will be sought prior to th... | [
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NCT04004273 | 18 | DATA HANDLING AND RECORD KEEPING | 18. DATA HANDLING AND RECORD KEEPING All data collected will be kept strictly confidential and in accordance with the Data Protection Act 1998. The research staff will ensure that the participants' anonymity is maintained. On all study-specific documents, other than the signed consent form and enrolment log, the partic... | [] |
NCT04004273 | 19 | STUDY GOVERNANCE | 19. STUDY GOVERNANCE PPI Involvement Group: the NIHR Leicester BRC has an established diabetes PPI group who frequently provide support for research projects led by researchers within the Diabetes Research Centre (University of Leicester) and Loughborough University (School of Sport, Exercise and Health Sciences). Memb... | [
"Trial steering committee (TSC)",
"Data safety monitoring committee",
"Access to the final study dataset"
] |
NCT04004273 | 20 | FINANCE AND INSURANCE | 20. FINANCE AND INSURANCE This research will be funded by Diabetes UK (Early Career Small Grant – Dr James King) and the NIHR Nottingham and Leicester BRCs. All costs due to be incurred within this research project are detailed below. Please note that this study will additionally be supported by the established infrast... | [] |
NCT04004273 | 21 | PUBLICATION / DISSEMINATION POLICY | 21. PUBLICATION / DISSEMINATION POLICY At the end of this study the data will be tabulated and analysed statistically. These data will then be written up within a final report that will be submitted by the Chief Investigator to the primary study sponsor (Diabetes UK) within six months of study completion. Within one ye... | [] |
NCT04004273 | 22 | REFERENCES | 22. REFERENCES - 1. Buzzetti E, Pinzani M, Tsochatzis EA (2016) The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 65(8): 1038-1048. - 2. Younossi ZM, Blissett D, Blissett R, Henry L, Stepanova M, Younossi Y, Racila A, Hunt S, Beckerman R (2016) The economic and clinical burden of n... | [] |
NCT04016779 | 11 | Males must: | 11. Males must: - a. Use 2 methods of contraception in combination if his female partner is of childbearing potential; this combination of contraceptive methods must be used from the Baseline Visit to ≥ 1 month after the last dose of SM, or - b. Have been surgically sterilized prior to the Screening Visit.
Exclusion C... | [
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"Phase 3 Studies",
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"Adolescents (12 to 17 years of age)",
"1.3 Study Rationale",
"2 ST... |
NCT04016779 | 33.2 | Inclusion Criteria | 33.2 Inclusion Criteria - 1. Is male or female, aged 18 to 40 IU/L) or permanently sterilized (e.g., bilateral tubal ligation, hysterectomy, bilateral oophorectomy for 6 months minimum prior to screening).
11. Males must: - a. Use 2 methods of contraception in combination if his female partner is of childbearing poten... | [
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"4.4 Blinding",
"4.5 Stu... |
NCT04067518 | A | Phase 2 Clinical Study of SHP674 in Patients with Newly Diagnosed, Untreated Acute Lymphoblastic Leukemia | A Phase 2 Clinical Study of SHP674 in Patients with Newly Diagnosed, Untreated Acute Lymphoblastic Leukemia Protocol No.: SHP674-201 (Referred to internally at Servier as CL1-95014-001) Edition: 1.5 Date: 22 January, 2021 Investigational product (test drug): SHP674 (Referred to internally at Servier as S095014) Phase o... | [
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"List of Parameters (Hematology, Chemistry, Urinalysis, Vital Signs, ECG, and Genetic Testing)",
"Study participation period",
"Time points for investigational product administra... |
NCT04067518 | I | Study Title | I Study Title A Phase 2 Clinical Study of SHP674 in Patients with Newly Diagnosed, Untreated Acute Lymphoblastic Leukemia
II Study Objectives and Endpoints
Study Objectives
Part 1 - Primary objective - To assess the tolerability and safety of a single dose of SHP674 in subjects with newly diagnosed, untreated acute ... | [
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NCT04067518 | V | Inclusion Criteria | V Inclusion Criteria Subjects who are enrolled in the study must meet all of the following criteria: - 1) For Part 1, personally provided informed assent or written informed consent. If informed assent is obtained from a subject, written informed consent should be obtained from a legally acceptable representative. For ... | [
"\\ Note:",
"VI Exclusion Criteria",
"VII Target Sample Size",
"VIII Investigational Products"
] |
NCT04067518 | X | Planned Study Period | X Planned Study Period May, 2019 to December, 2022 A snapshot of data will be taken for analysis of all available endpoints after all subjects completed remission induction therapy. The clinical study report (CSR) will be based on the data from the period of remission induction phase. Additional safety, PK and survival... | [
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"1.1 Background",
"1.2 Positioning of L-asparaginase Preparations in the Treatment of ALL",
"1.3 SHP674",
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"1.4 Nonclinical Study Results",
"1.5 Clinical Study Results",
"1.5.1 Outline of Foreign Clinical Studies",
... |
NCT04074330 | 1.0 | ADMINISTRATIVE INFORMATION | 1.0 ADMINISTRATIVE INFORMATION | [] |
NCT04074330 | 1.1 | Contacts | 1.1 Contacts A separate contact information list will be provided to each site. Serious adverse event (SAE) and pregnancy reporting information is presented in Section 10.0, as is information on reporting product complaints. Takeda Development Center-sponsored investigators per individual country requirements will be p... | [] |
NCT04074330 | 1.3 | Protocol Amendment 8 Summary of Changes and Rationale for Amendment | 1.3 Protocol Amendment 8 Summary of Changes and Rationale for Amendment This section describes the changes to the protocol incorporating Amendment 8. The primary reason for this amendment was to expand Phase 2 enrollment in Cohorts B and C in order to evaluate two dose levels, 120 mg and 60 mg QW. This will add an addi... | [
"INVESTIGATOR AGREEMENT"
] |
NCT04074330 | 2.0 | STUDY SUMMARY | 2.0 STUDY SUMMARY | Name of Sponsor(s): Takeda Development Center | Compound: | |--------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------| | Americas, Inc. (TDC Americas) | TAK-98... | [
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"Phase 2:",
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"Main Criteria for Exclusion:",
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NCT04074330 | 3.0 | STUDY REFERENCE INFORMATION | 3.0 STUDY REFERENCE INFORMATION | [] |
NCT04074330 | 3.1 | Study-Related Responsibilities | 3.1 Study-Related Responsibilities The sponsor will perform all study-related activities with the exception of those identified in the clinical supplier list in the study manual. The identified vendors will perform specific study-related activities either in full or in partnership with the sponsor. | [] |
NCT04074330 | 3.2 | Principal Investigator | 3.2 Principal Investigator Takeda will select a signatory coordinating investigator from the investigators who participate in the study. Selection criteria for this investigator will include significant knowledge of the study protocol, the study medication, their expertise in the therapeutic area and the conduct of cli... | [] |
NCT04074330 | 3.3 | List of Abbreviations | 3.3 List of Abbreviations ADCC antibody-dependent cell-mediated cytotoxicity ADCP antibody-dependent cell-mediated phagocytosis AE adverse event ANC absolute neutrophil count aNHL aggressive Non-Hodgkin Lymphoma ASCT autologous stem-cell transplant ASTCT American Society for Transplantation and Cellular Therapy AUC0-∞ ... | [
"Study No. TAK-981-1501 Page 25 of 163",
"Protocol Incorporating Amendment No. 8 20 May 2022"
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NCT04074330 | 3.4 | Corporate Identification | 3.4 Corporate Identification TDC Japan Takeda Development Center Japan TDC Asia Takeda Development Center Asia, Pte Ltd TDC Europe Takeda Development Centre Europe Ltd TDC Americas Takeda Development Center Americas, Inc. TDC TDC Japan, TDC Asia, TDC Europe and/or TDC Americas, as applicable Takeda Millennium Pharmaceu... | [] |
NCT04074330 | 4.0 | INTRODUCTION | 4.0 INTRODUCTION | [] |
NCT04074330 | 4.1 | Non-Hodgkin Lymphoma | 4.1 Non-Hodgkin Lymphoma Non-Hodgkin lymphoma (NHL) is among the most common cancers in the United States and Europe with more than 70,000 and 93,000 new cases diagnosed every year, respectively (Ferlay et al. 2018; Siegel et al. 2018). NHL is a heterogeneous group of malignancies with varying clinical characteristics ... | [] |
NCT04074330 | 4.1.1 | Follicular Lymphoma | 4.1.1 Follicular Lymphoma Indolent NHL (iNHL) represents 40% of all NHL subtypes, with FL occurring with the greatest frequency (Harris et al. 1999). iNHL presents with a broad spectrum of disease characteristics. Patients with FL often experience a chronic relapsing and remitting disease course and are exposed to seve... | [] |
NCT04074330 | 4.1.2 | Diffuse Large B-Cell Lymphoma | 4.1.2 Diffuse Large B-Cell Lymphoma Aggressive non-Hodgkin Lymphoma (aNHL) accounts for approximately 30% to 40% of all NHL (The Non-Hodgkin's Lymphoma Classification Project 1997) and DLBCL is the most common histological subtype (Beham-Schmid 2017). Combination chemotherapy with the addition of rituximab is standard ... | [] |
NCT04074330 | 4.2 | TAK-981 | 4.2 TAK-981 TAK-981 is a first in class small molecule inhibitor of small ubiquitin-like modifier (SUMO)ylation. | [] |
NCT04074330 | 4.2.1 | Protein SUMOylation Biology in Cancer | 4.2.1 Protein SUMOylation Biology in Cancer SUMOylation is a post-translational modification that attaches a SUMO protein to protein substrates, regulating their activity, subcellular localization and stability (Geiss-Friedlander and Melchior 2007). There are 3 functional mammalian paralogues of the SUMO proteins, smal... | [] |
NCT04074330 | 4.2.2 | Nonclinical Pharmacology | 4.2.2 Nonclinical Pharmacology Biochemical assays demonstrated that TAK-981 is a mechanism-based inhibitor of SUMO-activating enzyme that potently inhibits enzyme activity by forming a covalent adduct with SUMO. Strong selectivity for SUMO-activating enzyme was observed over the other closely related ubiquitin-activati... | [] |
NCT04074330 | 4.2.4 | Nonclinical Toxicology | 4.2.4 Nonclinical Toxicology The nonclinical toxicology profile of TAK-981 has been fully characterized in a comprehensive toxicology program that included single- and repeat-dose studies in rats and dogs. Repeat daily dosing resulted in unacceptable toxicity due to multiorgan failure in rats and fever (increased body ... | [] |
NCT04074330 | 4.2.5 | Clinical Experience | 4.2.5 Clinical Experience TAK-981 is currently being evaluated in this ongoing Phase 1/2 clinical efficacy and safety study of the combination with rituximab in patients with relapsed/refractory indolent or aggressive CD20+ NHLs (Study TAK-981-1501), in the ongoing first-in-human (FIH) Phase 1/2 study in patients with ... | [] |
NCT04074330 | 4.3 | Rituximab | 4.3 Rituximab Rituximab is a chimeric murine/human immunoglobulin (Ig) G1 kappa monoclonal antibody that targets CD20. Its mechanisms of actions are thought to be ADCC, complement-dependent cytotoxicity, and induction of apoptosis and ADCP after binding to the CD20 antigen on the cell surface. The biological effect is ... | [] |
NCT04074330 | 4.4 | Rationale for the Proposed Study | 4.4 Rationale for the Proposed Study One approach to enhancing the efficacy of rituximab is the addition of other agents that could potentiate its activity. There is strong nonclinical evidence demonstrating that TAK-981 can synergize with rituximab to eliminate CD20+ NHL cells (Section 4.2.2). TAK-981 has been shown t... | [] |
NCT04074330 | 4.4.1 | Rationale for the Starting Dose and Schedule | 4.4.1 Rationale for the Starting Dose and Schedule | [] |
NCT04074330 | 4.4.1.1 | TAK-981 | 4.4.1.1 TAK-981 TAK-981 has been extensively characterized in preclinical studies (Sections 4.2.2 and 4.2.3) and is currently being evaluated as a single agent in the FIH study TAK-981-1002. The starting dose for the FIH study was based on minimum anticipated biological effect level with 3 mg of TAK-981 administered IV... | [
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"Effects in Renal Pelvis",
"IRRs and Potential for CRS",
"Injection Site Reactions",
"Reproductive and Development Toxicity",
"Genotoxicity"
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NCT04074330 | 4.5.2 | Potential Effects of Rituximab | 4.5.2 Potential Effects of Rituximab Rituximab toxicities are generally associated with B cell depletion, infusion reactions, and/or tumor lysis syndrome (TLS). For detailed information regarding the safety of rituximab administration please refer to the United States Food and Drug Administration (FDA)-approved package... | [] |
NCT04074330 | 4.5.3 | TAK-981 in Combination with Rituximab | 4.5.3 TAK-981 in Combination with Rituximab Nonclinical toxicology studies with the combination of TAK-981 and rituximab, or other anti-CD-20 agents, were not conducted and are not warranted per ICH S9 (ich.org/products/guidelines/safety/article/safety-guidelines.html). Compared to TAK-981 alone, synergistic toxicity, ... | [] |
NCT04074330 | 4.5.4 | Coronavirus Disease 2019 Pandemic | 4.5.4 Coronavirus Disease 2019 Pandemic The coronavirus disease 2019 (COVID-19) pandemic has affected health care and specifically cancer care broadly across the globe. Based on current knowledge, the benefit/risk assessment for patient participation in this study remains favorable. The benefit/risk considerations for ... | [] |
NCT04074330 | 5.0 | STUDY OBJECTIVES AND ENDPOINTS | 5.0 STUDY OBJECTIVES AND ENDPOINTS | [] |
NCT04074330 | 5.1 | Objectives | 5.1 Objectives | [] |
NCT04074330 | 5.1.1 | Primary Objectives | 5.1.1 Primary Objectives The primary objectives are:
Phase 1: - To determine the safety and tolerability of TAK-981 in combination with rituximab in patients with r/r NHL. - To establish the RP2D of TAK-981 in combination with rituximab.
Phase 2: To evaluate the efficacy of TAK-981 in combination with rituximab in se... | [
"Phase 1:",
"Phase 2:"
] |
NCT04074330 | 5.1.2 | Secondary Objectives | 5.1.2 Secondary Objectives The secondary objectives are: To characterize the PK profile of TAK-981 in combination with rituximab.
Phase 1: - To determine the MTD and/or PAD of TAK-981 when administered in combination with rituximab. For non-commercial use only - To assess the preliminary antitumor activity of TAK-981-... | [
"Phase 1:",
"Phase 2:",
"Phase 2:"
] |
NCT04074330 | 5.2.2 | Secondary Endpoints | 5.2.2 Secondary Endpoints The secondary endpoints for this study are: - PK parameters after the first dose of TAK-981 on C1D1 and Cycle 1, Day 8 (C1D8) (data permitting): - Cmax. - Time of first occurrence of Cmax (tmax). - Area under the plasma concentration-time curve from time 0 to time t (AUC0-t). - AUC0-∞. - Termi... | [
"Phase 1:",
"Phase 2:"
] |
NCT04074330 | 5.2.3 | Additional/Exploratory Endpoints | 5.2.3 Additional/Exploratory Endpoints 5.2.3.1 Exploratory Endpoints (Global Study; Not Applicable to Patients Enrolled in China)    study or study drugs occurs. Treatment may be continued beyond disease progression, with sponsor approval, if, in ... | [] |
NCT04074330 | 6.2 | Phase 1 Study Design | 6.2 Phase 1 Study Design The dose-finding, dose-escalation part of the study will enroll patients with aNHL (mantle cell lymphoma patients are also allowed) and iNHL. Patients will be treated in cohorts with increasing doses of TAK-981 administered IV as a 1-hour infusion on Days 1 and 8 followed by a fixed dose of rit... | [] |
NCT04074330 | 6.3 | Phase 2 Study Design | 6.3 Phase 2 Study Design The Phase 2 part of the study uses a non-randomized, open-label, uncontrolled, parallel arm design that will enroll 1 cohort of patients with FL and another 2 cohorts of patients with DLBCL, one with patients that have relapsed after a chimeric antigen receptor T-cell therapy (CAR-T) that has b... | [
"Figure 6.c TAK-981-1501 Study Schematic of Phase 1 and Phase 2"
] |
NCT04074330 | 6.5 | Duration of Study | 6.5 Duration of Study | [] |
NCT04074330 | 6.5.1 | Duration of an Individual Patient's Study Participation | 6.5.1 Duration of an Individual Patient's Study Participation Patient participation will include screening, treatment, and follow-up. Screening will last up to 28 days before the first dose of study drug, during which the patient's eligibility and baseline characteristics will be determined. Treatment with TAK-981 with... | [] |
NCT04074330 | 6.5.2 | End of Study/Study Completion Definition and Planned Reporting | 6.5.2 End of Study/Study Completion Definition and Planned Reporting The final data cutoff for the clinical study report will be conducted after all patients have been discontinued from treatment or transferred to a long-term safety study, a single-patient investigational new drug application, or a similar program (Sec... | [] |
NCT04074330 | 6.5.3 | Timeframes for Primary and Secondary Endpoints to Support Disclosures | 6.5.3 Timeframes for Primary and Secondary Endpoints to Support Disclosures Refer to Table 6.a for disclosures information for all primary and secondary endpoints. Table 6.a Primary and Secondary Endpoints for Disclosures | Endpoint | Definition | Maximum Time Frame | |--------------------------------------------------... | [] |
NCT04074330 | 6.5.4 | Total Study Duration | 6.5.4 Total Study Duration It is anticipated that this study will last for approximately 72 months. | [] |
NCT04074330 | 6.5.5 | Poststudy Access | 6.5.5 Poststudy Access Subjects who have met the primary (and secondary) endpoints of the study and, in the opinion of the investigator and confirmed by the sponsor, experienced a clinically important benefit from TAK-981 in combination with rituximab may continue to receive TAK-981 or the combination in an extension p... | [
"Duration of Poststudy Access"
] |
NCT04074330 | 7.0 | STUDY POPULATION | 7.0 STUDY POPULATION | [] |
NCT04074330 | 7.1 | Inclusion Criteria | 7.1 Inclusion Criteria Each patient must meet all the following inclusion criteria to be enrolled in the study: - 1. Adults ≥18 years old. - 2. Patient populations: - a) For Phase 1 Dose Escalation: - aNHL including mantle cell lymphoma and DLBCL histologies such as transformed DLBCL from low-grade lymphoma (follicular... | [] |
NCT04074330 | 7.2 | Exclusion Criteria | 7.2 Exclusion Criteria Patients meeting any of the following exclusion criteria are not to be enrolled in the study: - 1. CNS lymphoma; active brain or leptomeningeal metastases, as indicated by positive cytology from lumbar puncture or CT scan/magnetic resonance imaging (MRI). - 2. Hypersensitivity to TAK-981, rituxim... | [] |
NCT04074330 | 8.0 | STUDY DRUG | 8.0 STUDY DRUG | [] |
NCT04074330 | 8.1 | Study Drug Administration | 8.1 Study Drug Administration All protocol-specific criteria for administration of study drug must be met and documented before drug administration. Study drug will be administered only to eligible patients under the supervision of the investigator or identified subinvestigator(s). All patients will receive TAK-981 and... | [] |
NCT04074330 | 8.1.1 | Rituximab | 8.1.1 Rituximab Rituximab is available as single-use vials of 100 mg/10 mL and 500 mg/50 mL of drug substance (refer to Appendix I) (Rituxan (rituximab) Injection for Intravenous Use 2019). The dose of rituximab will be calculated based on actual weight at enrollment. The total doses of rituximab throughout therapy sho... | [] |
NCT04074330 | 8.2 | Definitions of DLT for Phase 1 Only | 8.2 Definitions of DLT for Phase 1 Only Toxicity will be evaluated according to the NCI CTCAE, Version 5.0; except CRS, which will be graded according to ASTCT Consensus Grading for CRS (Lee et al. 2019). During the Phase 1 part of the study, a DLT will be defined as any of the following AEs that occur during Cycle 1 u... | [] |
NCT04074330 | 8.3 | Definition of DLT-Evaluable Patients for Phase 1 Only | 8.3 Definition of DLT-Evaluable Patients for Phase 1 Only Patients assigned to a particular dose cohort in Phase 1 are considered evaluable for assessment of a DLT if either of the following criteria are met during the DLT assessment period: - The patient experienced a DLT at any time after initiation of the first infu... | [] |
NCT04074330 | 8.4 | Definition of PAD | 8.4 Definition of PAD The PAD of TAK-981 is defined as the dose at which there is evidence of pharmacodynamic effects (which may include the induction of cytokines/chemokines or type 1 IFN signature in blood, or evidence of activation of immune cells or antitumor activity). The PAD can be defined retrospectively once M... | [] |
NCT04074330 | 8.5 | Dose-Escalation Rules for Phase 1 Only | 8.5 Dose-Escalation Rules for Phase 1 Only In the Phase 1 portion of the study, only TAK-981 will be escalated. Rituximab is administered at a fixed dose of 375 mg/m2 for each scheduled infusion. The following dose levels of TAK-981 are considered a priori:10, 15, 25, 40, 60, 90, 120, and 160 mg. Evaluation of intermed... | [] |
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