protocol_id stringclasses 263
values | section_number stringlengths 1 12 | title stringlengths 1 1.88k | content stringlengths 0 866k | merged_titles listlengths 0 491 |
|---|---|---|---|---|
NCT03343626 | 14.3 | Quality Assurance Audits and Regulatory Agency Inspections | 14.3 Quality Assurance Audits and Regulatory Agency Inspections The trial site also may be subject to quality assurance audits by the sponsor or designees. In this circumstance, the sponsor-designated auditor will contact the site in advance to arrange an auditing visit. The auditor may ask to visit the facilities wher... | [] |
NCT03343626 | 15.0 | ETHICAL ASPECTS OF THE TRIAL | 15.0 ETHICAL ASPECTS OF THE TRIAL This trial will be conducted with the highest respect for the individual participants (ie, subjects) according to the protocol, the ethical principles that have their origin in the Declaration of Helsinki (1), and ICH E6 (2). Each investigator will conduct the trial according to applic... | [] |
NCT03343626 | 15.1 | IRB and/or IEC Approval | 15.1 IRB and/or IEC Approval IRBs and IECs must be constituted according to the applicable requirements of each participating region. The sponsor or designee will require documentation noting all names and titles of members who make up the respective IRB or IEC. If any member of the IRB or IEC has direct participation ... | [] |
NCT03343626 | 15.2 | Subject Information, Informed Consent and Subject Authorization | 15.2 Subject Information, Informed Consent and Subject Authorization Written consent documents will embody the elements of informed consent as described in the Declaration of Helsinki (1) and ICH E6 (2) and will be in accordance with all applicable laws and regulations. The ICF, subject authorization form (if applicabl... | [] |
NCT03343626 | 15.3 | Subject Confidentiality | 15.3 Subject Confidentiality The sponsor and designees affirm and uphold the principle of the subject's right to protection against invasion of privacy. Throughout this trial, a subject's source data will only be linked to the sponsor's clinical trial database or documentation via a unique identification number. As per... | [] |
NCT03343626 | 15.4 | Publication, Disclosure, and Clinical Trial Registration Policy | 15.4 Publication, Disclosure, and Clinical Trial Registration Policy | [] |
NCT03343626 | 15.4.1 | Publication and Disclosure | 15.4.1 Publication and Disclosure The results of this trial are expected to be published in a scientific journal. It is anticipated that clinical and laboratory co-investigators will participate in authorship. The order of authorship and choice of journal will be proposed by the sponsor to the principal investigator(s)... | [] |
NCT03343626 | 15.4.2 | Clinical Trial Registration | 15.4.2 Clinical Trial Registration In order to ensure that information on clinical trials reaches the public in a timely manner and to comply with applicable law, regulation and guidance, the sponsor will, at a minimum register all clinical trials conducted in subjects that it sponsors anywhere in the world on Clinical... | [] |
NCT03343626 | 15.4.3 | Clinical Trial Results Disclosure | 15.4.3 Clinical Trial Results Disclosure The sponsor will post the results of this clinical trial, regardless of outcome, on ClinicalTrials.gov or other publicly accessible websites, as required by applicable laws and/or regulations. regulatio Trial completion corresponds to the date on which the final subject was exam... | [] |
NCT03343626 | 15.5 | Insurance and Compensation for Injury | 15.5 Insurance and Compensation for Injury Each subject in the trial must be insured in accordance with the regulations applicable to the site where the subject is participating. If a local underwriter is required, then the sponsor or sponsor's designee will obtain clinical trial insurance against the risk of injury to... | [] |
NCT03343626 | 16.0 | REFERENCES | 16.0 REFERENCES - 1. WMA. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. Jama. 2013;310(20):2191-4. Epub 2013/10/22. - 2. ICH. Harmonised Tripartite Guideline E6(R1) Guideline for Good Clinical Practice. Step 4. June 1996. 1996 [27 January 2017]; Ava... | [
"Appendix A Responsibilities of the Investigator",
"Appendix B Elements of the Subject Informed Consent Form",
"Appendix C Investigator Consent to Use of Personal Information",
"Appendix D CDC Websites",
"Appendix E FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventiv... |
NCT03345836 | 1.0 | Title Page | 1.0 Title Page
Clinical Study Protocol M14-431 A Multicenter, Randomized, Double-Blind, Placebo-Controlled Induction Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects with Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or are Intolerant to Biologic Therapy
Incorp... | [
"Clinical Study Protocol M14-431",
"Incorporating Administrative Changes 1 and 2, and Amendments 1, 2, 3, 4, 5, 6, and 7",
"Confidential Information"
] |
NCT03345836 | 1.1 | Protocol Amendment: Summary of Changes | 1.1 Protocol Amendment: Summary of Changes
Previous Protocol Versions | Protocol | Date | |-------------------------------|-------------------| | Original | 01 June 2017 | | Amendment 1 | 02 October 2017 | | Amendment 2 | 24 January 2018 | | Amendment 2.01 (Canada Only) | 16 May 2018 | | Amendment 2.02 (Hungary Only) ... | [
"Previous Protocol Versions",
"The purpose of this amendment is to:"
] |
NCT03345836 | 1.2 | Synopsis | 1.2 Synopsis | AbbVie Inc. | Protocol Number: M14-431 | |---------------------------------------------------------|---------------------------------------------| | Name of Study Drug: Upadacitinib (ABT-494) | Phase of Development: 3 | | Name of Active Ingredient:Upadacitinib(ABT-494) | Date of Protocol Synopsis: 05Marc... | [
"Methodology (Continued):",
"Part 1",
"Part 2",
"Part 3",
"Methodology (Continued):",
"Methodology (Continued):",
"Concomitant CD-Related Medications (Antibiotics, Aminosalicylates, and/or Methotrexate)",
"Concomitant Corticosteroids",
"Diagnosis and Main Criteria for Inclusion/Exclusion:",
"Main ... |
NCT03345836 | 1.3 | List of Abbreviations and Definition of Terms | 1.3 List of Abbreviations and Definition of Terms
Abbreviations 6-MP 6-mercaptopurine ADL activities of daily living AE adverse event AESI adverse event of special interest ALC absolute lymphocyte count ALT alanine transaminase ANCOVA analysis of covariance ANOVA analysis of variance ANC absolute neutrophil count AP a... | [
"Abbreviations"
] |
NCT03345836 | 3.0 | Introduction | 3.0 Introduction Crohn's disease (CD) encompasses a spectrum of clinical and pathological processes manifested by focal asymmetric, transmural, and occasionally granulomatous inflammation that can affect any segment of the gastrointestinal tract.[1](#page-142-3) The disease can affect persons of any age, and its onset ... | [
"Rationale for Development of a JAK Inhibitor in CD"
] |
NCT03345836 | 3.1 | Differences Statement | 3.1 Differences Statement This study is designed to evaluate the efficacy and safety of upadacitinib 45 mg QD versus placebo in subjects with moderately to severely active CD. The primary difference between Study M14-431 and the prior Phase 2 study of upadacitinib in CD is that this study will test a QD oral formulatio... | [] |
NCT03345836 | 3.2 | Benefits and Risks | 3.2 Benefits and Risks Although conventional and newer treatments such as biologic therapies have improved the standard of care for patients with CD, there remains a significant unmet medical need for patients with inadequate or loss of response to these agents, and efforts are ongoing to develop novel therapies. Clini... | [] |
NCT03345836 | 4.0 | Study Objective | 4.0 Study Objective The objective of Study M14-431 is to evaluate the efficacy and safety of upadacitinib compared to placebo as induction therapy in subjects with moderately and severely active CD. | [] |
NCT03345836 | 5.0 | Investigational Plan | 5.0 Investigational Plan | [] |
NCT03345836 | 5.1 | Overall Study Design and Plan: Description | 5.1 Overall Study Design and Plan: Description Study M14-431 is a Phase 3, randomized, double-blind, placebo-controlled induction study to evaluate the efficacy and safety of upadacitinib, an orally administered JAK1 inhibitor in adult subjects with moderately to severely active CD who have inadequately responded to or... | [
"Part 1",
"Part 2",
"Part 3",
"Screening Period",
"Re-Screen",
"12-Week Induction Period – Part 1 and Part 2",
"12-Week Extended Treatment Period – Part 3",
"Premature Discontinuation of Study (Withdrawal of Informed Consent)",
"Discontinuation of Study Drug and Continuation of Study Participation",... |
NCT03345836 | 5.2 | Selection of Study Population | 5.2 Selection of Study Population It is anticipated that approximately 625 subjects with active moderately to severely active CD will be enrolled at approximately 400 sites worldwide. A subject may be enrolled in this study provided that he/she has met all of the inclusion criteria and none of the exclusion criteria sp... | [] |
NCT03345836 | 5.2.1 | Inclusion Criteria | 5.2.1 Inclusion Criteria - 1. Male or female aged ≥ 18 and ≤ 75 years of age or minimum age of adult consent according to local regulations at Baseline. - 2. Confirmed diagnosis of CD for at least 3 months prior to Baseline. Appropriate documentation of biopsy results consistent with the diagnosis of CD, as determined ... | [] |
NCT03345836 | 5.2.2 | Exclusion Criteria | 5.2.2 Exclusion Criteria A subject will not be eligible for study participation if he/she meets any of the following criteria: 1. Subject with a current diagnosis of ulcerative colitis or indeterminate colitis.
Concomitant Medications and Treatments - 2. Subject on CD-related antibiotics who: - has not been on stable ... | [
"Concomitant Medications and Treatments",
"Medications and Treatments During the Screening Period",
"Prior Medications and Treatments",
"CD Related",
"Safety"
] |
NCT03345836 | 5.2.3 | Prior and Concomitant Therapy | 5.2.3 Prior and Concomitant Therapy | [] |
NCT03345836 | 5.2.3.1 | Prior Therapy | 5.2.3.1 Prior Therapy Any medication or vaccine (including over-the-counter or prescription medicines, vitamins and/or herbal supplements) that the subject is receiving at the time of screening, and/or receives during the study, must be recorded along with the reason for use, date(s) of administration including start a... | [] |
NCT03345836 | 5.2.3.2 | Concomitant Therapy | 5.2.3.2 Concomitant Therapy Changes in all concomitant medications will be assessed at each study visit from Baseline through Week 12/PD and during Weeks 12 to 24/PD visits for subjects who participate in the Part 3. Any changes will be documented in the source documents and captured on the appropriate eCRF page. | [] |
NCT03345836 | 5.2.3.2.1 | Concomitant CD-Related Medications (Antibiotics, Aminosalicylates, and/or Methotrexate) | 5.2.3.2.1 Concomitant CD-Related Medications (Antibiotics, Aminosalicylates, and/or Methotrexate) All subjects receiving a stable dose of CD-related antibiotics, aminosalicylates, or MTX at Baseline should maintain their concomitant treatments, without dose changes through the end of the study. Initiating and/or changi... | [] |
NCT03345836 | 5.2.3.2.2 | Concomitant Corticosteroids | 5.2.3.2.2 Concomitant Corticosteroids Subjects who enter the study on oral corticosteroids are not allowed to change the corticosteroid dose during the first 4 weeks of the induction treatment period. Doses of corticosteroids may be decreased during the first 4 weeks only in the event of moderateto-severe treatment rel... | [] |
NCT03345836 | 5.2.3.3 | Prohibited Therapy | 5.2.3.3 Prohibited Therapy
Biologic Therapies Subjects must have discontinued any biologic therapy prior to the first dose of study drug as specified in the washout procedures in Exclusion Criterion 15, Section [5.2.2](#page-44-1). For all other biologic therapies, contact the AbbVie TA MD for the washout period requi... | [
"Biologic Therapies",
"Strong CYP3A Inhibitors or Inducers",
"Traditional Chinese Medicine",
"Investigational Drugs",
"Vaccines",
"Other medications prohibited during the study:"
] |
NCT03345836 | 5.2.4 | Contraception Recommendations | 5.2.4 Contraception Recommendations
Contraception Recommendation for Females A woman who is postmenopausal or permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy) is not considered to be a woman of childbearing potential and is not required to follow contraception recommenda... | [
"Contraception Recommendation for Females"
] |
NCT03345836 | 5.3 | Efficacy, Pharmacokinetic, Pharmacodynamic, Exploratory Research, and Safety Assessments/Variables | 5.3 Efficacy, Pharmacokinetic, Pharmacodynamic, Exploratory Research, and Safety Assessments/Variables Study procedures will be performed as summarized in Section [5.3.1.1](#page-58-3). All subjects must meet the study selection criteria outlined in Section [5.2.1](#page-42-2) and Section [5.2.2](#page-44-1) in order t... | [] |
NCT03345836 | 5.3.1 | Efficacy and Safety Measurements Assessed and Flow Chart | 5.3.1 Efficacy and Safety Measurements Assessed and Flow Chart Study procedures described are listed in the following section of this protocol and are summarized in tabular format in [Appendix](#page-149-1) C. | [] |
NCT03345836 | 5.3.1.1 | Study Procedures | 5.3.1.1 Study Procedures The study procedures outlined in [Appendix](#page-149-1) C are discussed in detail in this section, with the exception of optional exploratory research (discussed in Section [5.3.1.2\)](#page-84-1), drug concentration measurements (discussed in Section [5.3.2\)](#page-85-1), the collection of p... | [
"Informed Consent",
"Inclusion/Exclusion Criteria",
"Medical and Surgical History",
"TB Testing/TB Prophylaxis",
"TB Test",
"TB Prophylaxis",
"Chest X-Ray",
"12-Lead Electrocardiogram (ECG)",
"Height and Weight",
"Vital Signs",
"Physical Examination",
"Pregnancy Test",
"Hepatitis Screen",
... |
NCT03345836 | 5.3.1.2 | Collection and Handling of Optional Samples for Exploratory Research | 5.3.1.2 Collection and Handling of Optional Samples for Exploratory Research Subjects will have the option to provide samples for exploratory research. Subjects may still participate in the main study even if they decide not to participate in this optional exploratory research. The procedures for obtaining and document... | [] |
NCT03345836 | 5.3.1.2.1 | Optional Samples for Histology Exploratory Research | 5.3.1.2.1 Optional Samples for Histology Exploratory Research Optional intestinal biopsy samples for histopathology and biological investigations, including but not limited to, transcriptomic analyses and immunohistochemistry may be evaluated in approximately 200 subjects (intestinal biopsy substudy). Samples will be c... | [] |
NCT03345836 | 5.3.2 | Drug Concentration Measurements | 5.3.2 Drug Concentration Measurements | [] |
NCT03345836 | 5.3.2.1 | Collection of Samples for Analysis | 5.3.2.1 Collection of Samples for Analysis Blood samples for assay of upadacitinib will be collected at each visit beginning at Week 2. On the Week 4 visit day, if possible, subjects should take the oral study drug dose at the clinic after collecting the PK blood sample, except if the subjects regularly take the study ... | [] |
NCT03345836 | 5.3.2.2 | Handling/Processing of Samples | 5.3.2.2 Handling/Processing of Samples Detailed instructions for the handling and processing of plasma and serum samples will be provided by the central laboratory. The plasma samples will be shipped to the central laboratory. Upadacitinib plasma concentration will be determined at AbbVie. Instructions for the preparat... | [] |
NCT03345836 | 5.3.2.3 | Disposition of Samples | 5.3.2.3 Disposition of Samples The frozen plasma samples for upadacitinib assays and samples for biologics testing will be packed in dry ice sufficient to last during transportation and shipped from the study site to the central laboratory according to instructions in the central laboratory Lab Manual. An inventory of ... | [] |
NCT03345836 | 5.3.2.4 | Measurement Methods | 5.3.2.4 Measurement Methods Plasma concentrations of upadacitinib will be determined under the supervision of the Drug Analysis Department at AbbVie using validated liquid chromatography/mass spectrometry methods. Any additional metabolite(s) may be analyzed using non-validated methods. Serum levels of biologics will b... | [] |
NCT03345836 | 5.3.3 | Efficacy Variables | 5.3.3 Efficacy Variables The following endpoint definitions apply to the efficacy variables described below: - Clinical remission per PROs: average daily very soft or liquid SF ≤ 2.8 AND average daily AP score ≤ 1.0 and both not greater than Baseline - Clinical remission per CDAI: CDAI 1 in any individual variable, as ... | [] |
NCT03345836 | 5.3.3.1 | Part 1 Primary Variables | 5.3.3.1 Part 1 Primary Variables The co-primary and ranked secondary endpoints will be analyzed separately for EU/EMA and US/FDA regulatory purposes. The endpoints are specified separately for each set of analyses. Co-primary endpoints for EU/EMA regulatory purposes: - 1. Proportion of subjects with clinical remission ... | [] |
NCT03345836 | 5.3.3.2 | Part 1 Secondary Variables | 5.3.3.2 Part 1 Secondary Variables | [] |
NCT03345836 | 5.3.3.2.1 | Ranked Secondary Variables | 5.3.3.2.1 Ranked Secondary Variables The ranked secondary endpoints for EU/EMA regulatory purposes are as follows: - 1. Proportion of subjects with clinical remission per CDAI (CDAI < 150) at Week 12 - 2. Proportion of subjects with clinical remission per PROs at Week 4 - 3. Proportion of subjects with endoscopic remis... | [] |
NCT03345836 | 5.3.3.2.2 | Additional Efficacy Variables | 5.3.3.2.2 Additional Efficacy Variables Non-ranked endpoints are as follows: - Proportion of subjects: - with clinical remission per PROs over time - with clinical remission per CDAI (CDAI 50% from Baseline of the induction study or endoscopic remission at Week 12, as scored by central reviewer - with SES-CD ≤ 2 at Wee... | [] |
NCT03345836 | 5.3.3.3 | Part 2 Variables | 5.3.3.3 Part 2 Variables Same efficacy endpoints as those listed in Part 1 (Section [5.3.3.1](#page-87-2) and Section [5.3.3.2\)](#page-88-2) are considered for Part 2 of the study. All the Part 2 efficacy endpoints are considered additional endpoints and ranking of the endpoints is not applicable for Part 2. | [] |
NCT03345836 | 5.3.3.4 | Part 3 Variables | 5.3.3.4 Part 3 Variables - Proportion of subjects: - with clinical remission per PROs over time - with clinical remission per CDAI (CDAI 50% from Baseline of the induction study or endoscopic remission at Week 24, as scored by central reviewer - with SES-CD ≤ 2 at Week 24 - with SES-CD ulcerated surface subscore of 0 a... | [
"● Change from Baseline in:",
"● Time to:"
] |
NCT03345836 | 5.3.4 | Safety Variables | 5.3.4 Safety Variables Safety analyses will be performed on all subjects who receive at least one dose of study drug. Incidence of AEs, changes in vital signs, physical examination results, and clinical laboratory data will be assessed throughout the study. | [] |
NCT03345836 | 5.3.5 | Pharmacokinetic Variables | 5.3.5 Pharmacokinetic Variables Plasma upadacitinib concentrations will be obtained at the times indicated in [Appendix](#page-149-1) C. A non-linear mixed-effects modeling approach will be used to estimate the population central values and the empirical Bayesian estimates of the individual values of upadacitinib oral ... | [] |
NCT03345836 | 5.3.6 | Optional Exploratory Research Variables | 5.3.6 Optional Exploratory Research Variables Optional samples may be collected to conduct exploratory investigations into known and novel biomarkers. The types of biomarkers to be analyzed may include, but are not limited to, nucleic acids, proteins, lipids or metabolites. The samples may be analyzed as part of a mult... | [] |
NCT03345836 | 5.4 | Removal of Subjects from Therapy or Assessment | 5.4 Removal of Subjects from Therapy or Assessment | [] |
NCT03345836 | 5.4.1 | Discontinuation of Individual Subjects | 5.4.1 Discontinuation of Individual Subjects Subjects can request to be discontinued from participating in the study at any time for any reason including but not limited to disease progression or lack of response to treatment. The investigator may discontinue any subject's participation for any reason, including but no... | [
"Lost to Follow-Up"
] |
NCT03345836 | 5.4.2 | Discontinuation of Entire Study | 5.4.2 Discontinuation of Entire Study AbbVie may terminate this study prematurely, either in its entirety or at any study site, for reasonable cause provided that written notice is submitted in advance of the intended termination. The investigator may also terminate the study at his/her site for reasonable cause, after... | [] |
NCT03345836 | 5.5 | Treatments | 5.5 Treatments | [] |
NCT03345836 | 5.5.1 | Treatments Administered | 5.5.1 Treatments Administered Study drug will be taken orally QD, beginning on Day 1 (Baseline), and should be taken at approximately the same time each day. The study drug can be taken with or without food. Subjects will continue their stable background CD therapy, if allowed per protocol. AbbVie will not supply any b... | [] |
NCT03345836 | 5.5.2 | Identity of Investigational Product | 5.5.2 Identity of Investigational Product The individual study drug information is presented in [Table](#page-99-4) 4. Table 4. Identity of Investigational Product | Investigational Product | Dosage Form | Strength | Route ofAdministration | |-------------------------|--------------------|----------|-------------------... | [] |
NCT03345836 | 5.5.2.1 | Packaging and Labeling | 5.5.2.1 Packaging and Labeling Upadacitinib and matching placebo will be packaged in bottles with quantities sufficient to accommodate study design. Each kit label will contain a unique kit number. This kit number is assigned to a subject via interactive response technology (IRT) and encodes the appropriate study drug ... | [] |
NCT03345836 | 5.5.2.2 | Storage and Disposition of Study Drug(s) | 5.5.2.2 Storage and Disposition of Study Drug(s) Study drugs must be stored at controlled room temperature (15° to 25°C/59° to 77°F). The investigational products are for investigational use only and are to be used only  within the context of this study. The study drug supplied for this study m... | [] |
NCT03345836 | 5.5.3 | Method of Assigning Subjects to Treatment Groups | 5.5.3 Method of Assigning Subjects to Treatment Groups All subjects will be assigned a unique identification number by the IRT at the Screening visit and will keep the same unique subject identification number throughout the study. Subjects who meet all of the inclusion criteria and none of the exclusion criteria defin... | [] |
NCT03345836 | 5.5.4 | Selection and Timing of Dose for Each Subject | 5.5.4 Selection and Timing of Dose for Each Subject Subjects should take study drug as outlined in Section [5.5.1.](#page-98-2) On dosing days that occur on study visit days, subjects should follow the regular dosing schedule (refer to Section [5.3.2.1](#page-85-2) regarding Week 4 visit). Each subject's dosing schedul... | [] |
NCT03345836 | 5.5.5 | Blinding | 5.5.5 Blinding All AbbVie personnel with direct oversight of the conduct and management of the trial (with the exception of AbbVie Drug Supply Management Team), the investigator, study site personnel, and the subject will remain blinded to each subject's treatment throughout the study and until that data is locked and ... | [] |
NCT03345836 | 5.5.5.1 | Blinding of Investigational Product | 5.5.5.1 Blinding of Investigational Product In order to maintain the blind, the upadacitinib tablets and placebo tablets provided for the study will be identical in appearance.  | [] |
NCT03345836 | 5.5.5.2 | Blinding of Data for Data Monitoring Committee (DMC) | 5.5.5.2 Blinding of Data for Data Monitoring Committee (DMC) An external DMC comprised of persons independent of AbbVie and with relevant expertise in their field will review unblinded safety data from the ongoing study. The primary responsibility of the DMC will be to protect the safety of the subjects participating i... | [] |
NCT03345836 | 5.5.6 | Treatment Compliance | 5.5.6 Treatment Compliance The investigator or his/her designated and qualified representatives will administer/dispense study drug only to subjects enrolled in the study in accordance with the protocol. The study drug must not be used for reasons other than that described in the protocol. Subjects will be instructed t... | [] |
NCT03345836 | 5.5.7 | Drug Accountability | 5.5.7 Drug Accountability The investigator or his/her representative will verify that study drug supplies are received intact and in the correct amounts. This will be documented by signing and dating the Proof of Receipt or similar document and by registering the arrival of drug through the IRT. The original Proof of R... | [] |
NCT03345836 | 5.6 | Discussion and Justification of Study Design | 5.6 Discussion and Justification of Study Design | [] |
NCT03345836 | 5.6.1 | Discussion of Study Design and Choice of Control Groups | 5.6.1 Discussion of Study Design and Choice of Control Groups Upadacitinib is a novel, orally administered JAK1 inhibitor being developed for the treatment of adult patients with inflammatory diseases and may provide improved clinical benefit to CD patients. The proposed study is a Phase 3, randomized, double-blind, pl... | [] |
NCT03345836 | 5.6.2 | Appropriateness of Measurements | 5.6.2 Appropriateness of Measurements Standard statistical, clinical, and laboratory procedures will be utilized in this study. All efficacy measurements in this study are standard for assessing disease activity in subjects with CD. All clinical and laboratory procedures in this study are standard and generally accepte... | [] |
NCT03345836 | 5.6.3 | Suitability of Subject Population | 5.6.3 Suitability of Subject Population Adult male and female subjects between 18 to 75 years of age (or minimum age of adult consent according to local regulations) with moderately to severely active CD, who meet all of the inclusion criteria and none of the exclusion criteria, are eligible for enrollment in this stud... | [] |
NCT03345836 | 5.6.4 | Selection of Doses in the Study | 5.6.4 Selection of Doses in the Study This study will evaluate one induction dose of upadacitinib (45 mg QD) ([Figure](#page-34-1) 1). The selection of this dose was informed by the analysis of the 16-week safety, efficacy and exposure-response data of Phase 2 CD Study M13-740, which evaluated 5 induction doses of upad... | [] |
NCT03345836 | 6.0 | Complaints | 6.0 Complaints A Complaint is any written, electronic, or oral communication that alleges deficiencies related to the physical characteristics, identity, quality, purity, potency, durability, reliability, safety, effectiveness, or performance of a product/device after it is released for distribution. Complaints associa... | [] |
NCT03345836 | 6.1 | Medical Complaints | 6.1 Medical Complaints The investigator will monitor each subject for clinical and laboratory evidence of AEs on a routine basis throughout the study. The investigator will assess and record any AE in  detail including the date of onset, event diagnosis (if known) or sign/symptom, severity, tim... | [] |
NCT03345836 | 6.1.1 | Definitions | 6.1.1 Definitions | [] |
NCT03345836 | 6.1.1.1 | Adverse Event | 6.1.1.1 Adverse Event An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal ... | [] |
NCT03345836 | 6.1.1.2 | Serious Adverse Events | 6.1.1.2 Serious Adverse Events If an AE meets any of the following criteria, it is to be reported to AbbVie as a serious adverse event (SAE) within 24 hours of the site being made aware of the SAE. | Death of Subject | An event that results in the death of a subject. | | |-----------------------------------------------... | [] |
NCT03345836 | 6.1.1.3 | Adverse Events of Special Interest | 6.1.1.3 Adverse Events of Special Interest The following AEs of special interest will be monitored during the study (see detailed toxicity management in Section [6.1.7\)](#page-117-1): - Serious infections; - Opportunistic infections; - Herpes zoster; - Active TB; - Malignancy (all types); - Adjudicated gastrointestina... | [] |
NCT03345836 | 6.1.2 | Adverse Event Severity | 6.1.2 Adverse Event Severity When criteria are available, events should be graded as described in the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, which can be accessed at: http://ctep.cancer.gov/protocolDevelopment/electronic\applications/ctc.htm#ctc\40. If no gr... | [] |
NCT03345836 | 6.1.3 | Relationship to Study Drug | 6.1.3 Relationship to Study Drug The investigator will use the following definitions to assess the relationship of the AE to the use of study drug: Reasonable Possibility After consideration of factors including timing of the event, biologic plausibility, clinical judgment, and potential alternative causes, there is su... | [] |
NCT03345836 | 6.1.4 | Adverse Event Collection Period | 6.1.4 Adverse Event Collection Period All AEs reported from the time of study drug administration until 30 days following discontinuation of study drug administration have elapsed will be collected, whether solicited or spontaneously reported by the subject. Subjects who discontinue study drug treatment but continue to... | [] |
NCT03345836 | 6.1.5 | Adverse Event Reporting | 6.1.5 Adverse Event Reporting In the event of an SAE, whether associated with study drug or not, the investigator will notify Clinical Pharmacovigilance within 24 hours of the site being made aware of the SAE by entering the SAE data into the EDC system. SAEs that occur prior to the site having access to the RAVE® syst... | [
"Email: PPDINDPharmacovigilance@abbvie.com"
] |
NCT03345836 | 6.1.6 | Pregnancy | 6.1.6 Pregnancy Pregnancy in a study subject must be reported to AbbVie within 1 working day of the site becoming aware of the pregnancy. Subjects who become pregnant during the study must be discontinued from study drug (Section [5.4.1\)](#page-96-2).  Information regarding a pregnancy occurre... | [] |
NCT03345836 | 6.1.7 | Toxicity Management | 6.1.7 Toxicity Management The toxicity management of the AEs including AEs of special interest consists of safety monitoring (review of AEs on an ongoing basis, and periodical/ad hoc review of safety issues by a safety DMC), interruption of study drug dosing with appropriate clinical management if applicable, and disco... | [
"[Table](#page-119-1) 5. Specific Toxicity Management Guidelines for Abnormal Laboratory Values (Continued)"
] |
NCT03345836 | 6.1.8 | Data Monitoring Committee (DMC) | 6.1.8 Data Monitoring Committee (DMC) An external, independent DMC will be responsible for monitoring unblinded safety data and alerting AbbVie to possible safety concerns related to the conduct of the study. See Section [5.5.5.2](#page-104-0) for details. | [] |
NCT03345836 | 6.1.9 | Cardiovascular Adjudication Committee (CAC) | 6.1.9 Cardiovascular Adjudication Committee (CAC) An independent committee of physician experts in cardiac adjudication will be utilized to assess cardiovascular AEs and embolic and thrombotic events (non-cardiac, non-CNS) in a blinded manner as defined by the CAC charter. The events that are adjudicated and the adjudi... | [] |
NCT03345836 | 6.2 | Product Complaint | 6.2 Product Complaint | [] |
NCT03345836 | 6.2.1 | Definition | 6.2.1 Definition A Product Complaint is any Complaint (see Section [6.0](#page-108-2) for the definition) related to the drug component of the product. For a product this may include, but is not limited to, damaged/broken product or packaging, product appearance whose color/markings do not match the labeling, labeling ... | [] |
NCT03345836 | 6.2.2 | Reporting | 6.2.2 Reporting Product Complaints concerning the investigational product must be reported to the Sponsor within 24 hours of the study site's knowledge of the event via the Product Complaint form. Product Complaints occurring during the study will be followed-up to a satisfactory conclusion. All follow-up information i... | [] |
NCT03345836 | 8.0 | Statistical Methods and Determination of Sample Size | 8.0 Statistical Methods and Determination of Sample Size | [] |
NCT03345836 | 8.1 | Statistical and Analytical Plans | 8.1 Statistical and Analytical Plans The objective of the statistical analysis of Study M14-431 is to evaluate the efficacy and safety of an upadacitinib 45-mg QD induction dose versus placebo in subjects with moderately and severely active CD. The extent of missing data due to COVID-19 will be monitored and appropriat... | [] |
NCT03345836 | 8.1.1 | Datasets for Analysis | 8.1.1 Datasets for Analysis | [] |
NCT03345836 | 8.1.1.1 | Intent to Treat Analysis Set | 8.1.1.1 Intent to Treat Analysis Set The intent-to-treat (ITT) analysis set includes all randomized subjects who have received at least one dose of study drug in the double-blind induction period from Part 1. The ITT subjects will be analyzed as randomized. The ITT set is the primary population for efficacy analysis. A... | [] |
NCT03345836 | 8.1.1.2 | Safety Analysis Set | 8.1.1.2 Safety Analysis Set The safety analysis set consists of all subjects who received at least one dose of the study drug. Similarly, safety analysis set (Part 1), safety analysis set (Part 2), and safety analysis set (Part 3) consist of subjects who received at least one dose of the study drug, enrolled in Part 1,... | [] |
NCT03345836 | 8.1.2 | Definition of Missing Data Imputation | 8.1.2 Definition of Missing Data Imputation Missing data will be imputed using one or more of the following methods: Non-Responder Imputation (NRI): The NRI approach is used for binary efficacy variables. These variables can take values of 'Achieved' or 'Not Achieved' or may be missing for any reason including disconti... | [] |
NCT03345836 | 8.1.3 | Subject Disposition | 8.1.3 Subject Disposition The number and percentage of subjects who are enrolled, randomized, and received at least one dose of study drug, the number of subjects who completed the study and the number of subjects who prematurely discontinued and the reason for premature discontinuation will be summarized by treatment ... | [] |
NCT03345836 | 8.1.4 | Demographics and Baseline Characteristics | 8.1.4 Demographics and Baseline Characteristics Demographics and baseline characteristics of the study subjects will be summarized using descriptive statistics. Summary statistics for continuous variables will include the number of observations, mean, standard deviation, median, and range for each treatment group. For ... | [] |
NCT03345836 | 8.1.5 | Prior and Concomitant Medications | 8.1.5 Prior and Concomitant Medications Prior therapy and medications will include all therapies and medications administered prior to the date of the first dose of study drug. Prior therapy and medication will be summarized for the ITT analysis set. No statistical test will be performed. Concomitant medications will b... | [] |
NCT03345836 | 8.1.6 | Efficacy Analysis | 8.1.6 Efficacy Analysis The co-primary and ranked secondary endpoints will be analyzed separately for EU/EMA and US/FDA regulatory purposes; these endpoints are specified in Section [5.3.3](#page-87-0) separately for each set of analyses. | [] |
NCT03345836 | 8.1.6.1 | Primary Efficacy Variables | 8.1.6.1 Primary Efficacy Variables The co-primary endpoints are the proportion of subjects with clinical remission per PROs (EU/EMA) and per CDAI (US/FDA) at Week 12 and proportion of subjects with endoscopic response at Week 12 for the ITT population in Part 1. The comparison between treatment groups on the co-primary... | [] |
NCT03345836 | 8.1.6.2 | Secondary Efficacy Variables | 8.1.6.2 Secondary Efficacy Variables A multiple testing procedure will be used to provide strong control of the type 1 error rate at alpha = 0.05 (2-sided) across analyses with respect to the co-primary endpoints, and ranked secondary endpoints as specified in Section [5.3.3](#page-87-0). Specifically, testing will uti... | [] |
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