protocol_id stringclasses 263
values | section_number stringlengths 1 12 | title stringlengths 1 1.88k | content stringlengths 0 866k | merged_titles listlengths 0 491 |
|---|---|---|---|---|
NCT03940573 | 5.1 | Benefits | *5.1 Benefits*
The benefits of using the Eclipse System are that it is a self-managed, non-surgical device that may help a woman to control their accidental bowel leakage symptoms. It is possible that the Eclipse System may not provide any direct benefit to subjects in this research study. The information collected in... | [] |
NCT03940573 | 5.2 | Risks | *5.2 Risks*
The main risk to being in this research study is a risk of sharing protected (personal) health information (PHI), and the potential breach of confidentiality. | [] |
NCT03940573 | 5.3 | Other Risks of the Device | *5.3 Other Risks of the Device*
The Eclipse System Patient Guide directs patients to report any of the following to their doctor if they occur:
- Foul odor or excessive vaginal discharge
- Difficulty urinating or defecating
- Significant bleeding not associated with menstruation
- New onset or worsening pelvic pain o... | [
"Warnings"
] |
NCT03940573 | 6 | Revision Record | | Document | Revision | Section amendment and rationale |
|----------|----------|---------------------------------|
| Protocol | A | Initial draft | | [] |
NCT03971422 | 1 | PROTOCOL SUMMARY | [] | |
NCT03971422 | 1.1 | Synopsis |
| Protocol Title: | ... | [
"Protocol Title:",
"Short Title:",
"Rationale:",
"Objectives and Endpoints",
"Secondary",
"Overall Design",
"Number of Participants",
"Treatment Groups and Duration"
] |
NCT03971422 | 1.2 | Schema | A schematic diagram of the study is provided in [Figure](#page-20-1) 1-1.
Figure 1-1: Study Schematic
IVIg=intravenous immunoglobulin G; OLE=open-label extension; PEX=plasma exchange; Rozimab=rozanolixizumab
The sample size for Stage 1 of the study is (approximately study participants ... | [] |
NCT03971422 | 1.3 | Schedule of Activities | | Clinical Study ProtocolRozanolixizumab | | | | | | | | | | | thereof.23 Feb 2021MG0003variations | | | | |
|----------------------... | [] |
NCT03971422 | 1.4 | Schedule of Activities (sub-study) | | Procedure | | Tre... | [] |
NCT03971422 | 2 | INTRODUCTION | Rozanolixizumab is a humanized IgG4 monoclonal antibody that is being developed as an inhibitor of the activity of the FcRn for IgG.
By blocking the activity of FcRn, rozanolixizumab accelerates the catabolism of IgG antibodies, including IgG pathogenic autoantibodies. The aim is to reduce the concentration of pathoge... | [] |
NCT03971422 | 2.1 | Study Rationale | Myasthenia gravis is a serious, sometimes life-threatening, debilitating condition associated with numerous symptoms including muscular weakness and fatigue. The major pathophysiology leading to MG is the abnormal production of IgG autoantibodies directed toward nicotinic AChR or MuSK protein. Most available treatments... | [] |
NCT03971422 | 2.2 | Background | To date, rozanolixizumab has been administered to human study participants in the following clinical studies: UP0018, MG0002, TP0001, TP0003, TP0006, CIDP01, CIDP04 and UP0060. UP0018 is a completed first-in-human study (FIH), and MG0002 is a completed Phase 2 study in study participants with generalized MG; and TP0001... | [] |
NCT03971422 | 2.3 | Benefit/Risk Assessment | Generalized myasthenia gravis (gMG) is a rare, debilitating, chronic autoimmune disease driven by, in large part, IgG autoantibodies that target neuromuscular junctions (NMJs). Most current treatment approaches are not targeted treatments to the specific underlying pathology of IgG
autoantibody formation. Rather, they... | [] |
NCT03971422 | 3 | OBJECTIVES AND ENDPOINTS | Table 3-1: Study Objectives and Endpoints
| | such as PEX, or intravenous administration of immunoglobulins at a healthcare facility. ... | [
"Secondary"
] |
NCT03971422 | 4 | STUDY DESIGN | [] | |
NCT03971422 | 4.1 | Overall Design | This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, 3-arm, repeat dose study evaluating the efficacy and safety of two doses of rozanolixizumab and matching placebo in patients with generalized MG who experience moderate to severe symptoms (Myasthenia Gravis Foundation of America [MGFA II-IVa]... | [] |
NCT03971422 | 4.2 | Scientific Rationale for Study Design | MG0003 is designed to evaluate the efficacy, safety, and tolerability of rozanolixizumab given in dose exposures at or in study participants with MG. The previously conducted FIH study, UP0018, provided the safety, tolerability, and PK information for multiple dose exposures of administered as iv or sc infusion over in... | [] |
NCT03971422 | 4.3 | Justification for Dose | The selection of fixed unit dosing is introduced as part of future development plans to support patient self-injection with a medical device in a home setting. Dose stratified on weight tiers have been defined to replicate PD effects throughout the weight range that is similar to weightbased (mg/kg) dosing. The propose... | [] |
NCT03971422 | 4.4 | End of Study definition | A study participant is considered to have completed the study if he/she has completed all phases of the study including the Observation Period. Study participants will have an EOS Visit performed 8 weeks after the last dose of study medication, or upon discontinuation of the study.
The EOS is defined as the date of th... | [] |
NCT03971422 | 5 | STUDY POPULATION | [] | |
NCT03971422 | 5.1 | Inclusion Criteria | Study participants are eligible to be included in the study only if all of the following criteria apply:
1. Study participant must be ≥18 years of age, at the time of signing the informed consent.
- 2. Study participant has documented diagnosis of gMG at Visit 1, based on study participant's history and supported by ... | [
"Age",
"Type of participant and disease characteristics",
"Weight",
"Sex",
"Informed consent"
] |
NCT03971422 | 5.2 | Exclusion Criteria | Unless otherwise stated, each criterion is applicable to at Visit 1. Study participants are excluded from the study if any of the following criteria apply:
- 1. Study participant has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the study participan... | [
"Medical conditions",
"Prior/Concomitant therapy",
"Table 5-1: Treatment-free Period for Exclusionary Immunosuppressants, Biologics, and Other Therapies Prior to Baseline (Visit 2)",
"Prior/Concurrent clinical study experience",
"Diagnostic assessments",
"Other exclusions"
] |
NCT03971422 | 5.3 | Lifestyle Restrictions | There are no lifestyle restrictions during the study unless deemed to interfere with compliance with the protocol as deemed by the investigator.
The use of medicinal cannabidiols and medicinal marijuana (prescribed by a physician) is permitted. | [] |
NCT03971422 | 5.4 | Screen Failures | Screen failures are defined as study participants who consent to participate in the clinical study but are not subsequently randomly assigned to study treatment. A minimal set of screen failure information is required to ensure transparent reporting of screen failure study participants to meet the Consolidated Standard... | [] |
NCT03971422 | 6 | STUDY TREATMENTS | [] | |
NCT03971422 | 6.1 | Treatments Administered | | Study Treatment Name: ... | [] |
NCT03971422 | 6.2 | Preparation, Handling, Storage, and Accountability requirements | The Investigator or designee must confirm appropriate temperature conditions have been maintained during transit for all study treatment received and any discrepancies are reported and resolved before use of the study treatment.
Confidential Page 45 of 188
Only participants enrolled in the study may receive study tre... | [] |
NCT03971422 | 6.2.1 | Drug accountability | A Drug Accountability form will be used to record study medication dispensing and return information on a by-participant basis and will serve as source documentation during the course of the study. Details of any study medication lost, damaged (due to breakage or wastage), not used, partially used, disposed of at the s... | [] |
NCT03971422 | 6.3 | Measures to Minimize Bias: Randomization and Blinding | An interactive response technology (IRT) will be used for assigning eligible study participants to a treatment regimen (as applicable) based on a predetermined production randomization and/or packaging schedule provided by UCB (or designee). The randomization schedule will be produced by the IRT vendor. The IRT will ge... | [] |
NCT03971422 | 6.3.1 | Procedures for maintaining and breaking the treatment blind | [] | |
NCT03971422 | 6.3.1.1 | Maintenance of study treatment blind | All study participant treatment details, rozanolixizumab treatment arm, planned dose, or placebo will be allocated and maintained by the IRT system.
The following individuals will receive the randomization code at the start of the study:
- Designated bioanalytical staff analyzing PK samples
- IRT provider
Study site... | [] |
NCT03971422 | 6.3.1.2 | Breaking the treatment blind in an emergency situation | [] | |
NCT03971422 | 6.4 | Treatment Compliance | [] | |
NCT03971422 | 6.5 | Concomitant Medication(s)/Treatment(s) | [] | |
NCT03971422 | 6.5.1 | Permitted concomitant treatments (medications and therapies) | Table 6-1: Permitted Concomitant Treatments
| | | Monitor or equivalent should be consulted prior to unblinding, whenever possible. | In the event of an emergency, it will be possible to determine to which treatment arm and dosethe study participant has been... | [] |
NCT03971422 | 6.5.2 | Prohibited concomitant treatments (medications and therapies) | The following concomitant medications are prohibited during the study:
- All biologics including rituximab
- Cyclophosphamide
- Pimecrolimus
- IPP-201101 (Lupuzor™)
- Immunoadsorption
- Vinca alkaloids (vincristine, vinblastine) PUBLIC COPY
If a study participant needs or takes any prohibited medication or therapy, t... | [] |
NCT03971422 | 6.5.3 | Treatments specific to NMJ interference | Treatments could interfere with the function of the NMJ (and which therefore could impair study participants with MG), such as, but not limited to, include the following medications:
- − botulinum toxin
- − aminoglycoside antibiotics
- − tetracycline antibiotics
- − penicillamine
For a more detailed list please refer... | [
"− magnesium"
] |
NCT03971422 | 6.5.4 | Rescue therapy | Rescue therapy for the study will consist of IVIg or PEX. The study site will supply rescue therapy that will be obtained locally.
Study participants who experience disease worsening (eg, an increase of 2 points on the MG-ADL or 3 points on the QMG scale between two consecutive visits) may be considered for rescue the... | [] |
NCT03971422 | 6.6 | Dose Modification | There is no dose modification allowed in this study. | [] |
NCT03971422 | 6.7 | Treatment after the End of the Study | Study participants who need rescue therapy during the 8-week Observation Period, or complete the Observation Period without rescue therapy, will be invited to enroll into the OLE study. They will be randomized to one of two rozanolixizumab dose arms, equivalent to approximately or . Alternatively, if a study participan... | [] |
NCT03971422 | 7 | DISCONTINUATION OF STUDY MEDICATION AND PARTICIPANT DISCONTINUATION/WITHDRAWAL | [] | |
NCT03971422 | 7.1 | Discontinuation of Study Medication | [] | |
NCT03971422 | 7.1.1 | Liver Chemistry Stopping Criteria | Discontinuation of study treatment for abnormal liver function should be considered by the Investigator when a study participant meets one of the conditions outlined in Figure 7-1 and Figure 7-2, or if the Investigator believes that it is in the best interest of the study participant.
The study participant should foll... | [] |
NCT03971422 | 7.1.2 | QTc Stopping Criteria | If a clinically significant finding is identified (including, but not limited to changes from Baseline in QT interval corrected using Fridericia's formula [QTcF]) after enrollment, the Investigator or qualified designee will determine if the study participant can continue in the study and if any change in participant m... | [] |
NCT03971422 | 7.1.3 | Discontinuation due to other adverse events or medical conditions | Study participants must permanently discontinue rozanolixizumab and move into the Observation Period if any of the following events occur:
- 1. Study participant develops an illness that would interfere with his/her continued exposure to rozanolixizumab.
- 2. Study participant has new onset or recurrent neoplastic dis... | [] |
NCT03971422 | 7.1.4 | Temporary IMP discontinuation | Study participant *must be* TEMPORARILY discontinued from the IMP if any of the following events occur:
1. The study participant develops an event of hypogammaglobulinemia with a serum total IgG of <1g/L irrespective of infection. When the IgG level reaches ≥2g/L, the study participant may be allowed to continue treat... | [] |
NCT03971422 | 7.2 | Participant Discontinuation/Withdrawal from the study | Study participants are free to withdraw from the study at any time, without prejudice to their continued care.
A study participant may also be withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, or administrative reasons.
If the study participant withdraws consent for discl... | [] |
NCT03971422 | 7.3 | Lost to Follow up | A study participant will be considered lost to follow-up if he or she repeatedly fails to return for scheduled visits and is unable to be contacted by the study site. PUBLIC COPY
The following actions must be taken if a participant fails to return to the clinic for a required study visit:
- The site must attempt to c... | [] |
NCT03971422 | 8 | STUDY ASSESSMENTS AND PROCEDURES | Study procedures and their timing are summarized in the Schedule of Activities (Section 1.3).
If needed, the study participant will be allowed to rest before starting any study procedures. Quantitative Myasthenia Gravis scale, MG-C scale, MG-ADL and all other PROs should be administered by the investigator or qualifie... | [] |
NCT03971422 | 8.1 | Efficacy Assessments | [] | |
NCT03971422 | 8.1.1 | MGFA Classification | The Investigator will classify the study participant's MG using the MGFA Clinical Classification (Appendix 12, Section 10.12) (Jaretzki et al, 2000). This is a 5-stage classification (I to V), with a higher class indicating more severe disease. To be eligible for this study, a participant must be graded MGFA CLASS II t... | [] |
NCT03971422 | 8.1.2 | Quantitative Myasthenia Gravis scale | For assessment of the QMG scale, investigators or qualified designee will follow the MGFA's QMG Manual instructions (Appendix 13, Section 10.13). Clinical personnel must complete mandatory training to assess study participants' QMG score (details are provided in the Study Procedures Manual). If not medically appropriat... | [] |
NCT03971422 | 8.1.3 | MG-Composite scale | For assessment of the MG-C scale, the Investigator or qualified designee will examine the study participant to score all items, except for talking, chewing, and swallowing for which the study participant will self-assess. Study participants should not take pyridostigmine (or other AChE inhibitor medication) from midnig... | [] |
NCT03971422 | 8.1.4 | Patient-reported outcomes | Patient-reported outcomes must be completed as per time points mentioned in the Schedule of Activities (Section 1.3). The PROs should be completed prior to any intrusive procedures in a quiet place.
Confidential Page 57 of 188
The PROs should be completed in the following order: MG-ADL, MG Symptoms PRO, PGI-S, PGI-C,... | [] |
NCT03971422 | 8.1.4.1 | MG-Activities of Daily Living | Independently of study visit type (site, home, or virtual), the MG-ADL must be completed by study participants in a quiet place by themselves without the help of a partner or caregiver, before any clinical examination takes place. Study participants should be informed of the importance of this questionnaire and instruc... | [] |
NCT03971422 | 8.1.4.2 | MG Symptoms PRO | The MG Symptoms PRO instrument (Appendix 16, Section 10.16) consists of 42 items across 5 scales: ocular symptoms (items 1-5); bulbar symptoms (items 6-15); respiratory symptoms (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42).
The study participant will be asked to choose t... | [] |
NCT03971422 | 8.1.4.3 | Patient Global Impression of Severity | Patient Global Impression of Severity is a single-state, self-report measure that rates a participant's severity of specific condition (Appendix 17, Section 10.17). The PGI-S is a 5 point scale depicting a participant's rating of overall symptoms ("none," "mild," "moderate," "severe," "very severe,"). | [] |
NCT03971422 | 8.1.4.4 | Patient Global Impression of Change | Patient Global Impression of Change is a single-state, self-report measure that reflects a participant's belief about the efficacy of treatment for a specific condition (Appendix 18, Section 10.18). The PGI-C is a 7-point scale depicting a participant's rating of overall improvement ("very much improved," "much improve... | [] |
NCT03971422 | 8.1.4.5 | EQ-5D-5L | The 5-level EQ-5D (EQ-5D-5L) is designed to improve the instrument's sensitivity and to reduce ceiling effects (Appendix 19, Section 10.19). PUBLIC COPY
The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EuroQol visual analogue scale (EQ VAS).
The descriptive system comprises five dime... | [] |
NCT03971422 | 8.1.4.6 | MG Impairment Index | The MGII is a measure of disease severity based on the signs and symptoms of MG patients (Appendix 20, Section 10.20). It was developed using a patient-centered approach and following current guidelines for outcome measure development, incorporating patient input throughout the different development phases (Barnett et ... | [] |
NCT03971422 | 8.1.4.7 | MG-QOL15r | The MG-QOL15r is a brief survey, completed by the study participant, that is designed to assess some aspects of "quality of life" related to MG. The MG-QOL15r was designed to assess the "patient perspective" in the everyday clinic setting or in a clinical study (Appendix 21, Section 10.21).
When completing the 15-item... | [] |
NCT03971422 | 8.2 | Safety Assessments | Planned time points for all safety assessments are provided in the Schedule of Activities (Section 1.3).
Study participants must be observed at site postdose for at least 4 hours following the first 2 infusions, and then 2 hours thereafter for subsequent infusions. | [] |
NCT03971422 | 8.2.1 | Physical examination |
A full physical examination will include, at a minimum, general appearance; ear, nose, and throat; eyes, hair, and skin; and assessments of the cardiovascular, respiratory, GI, neurological, and musculoskeletal systems. Height and weight will be measured and recorded at the Visit 1 (Screening). Body weight will be me... | [
"Full physical examination",
"Brief physical examination"
] |
NCT03971422 | 8.2.2 | Vital signs | Oral, tympanic, or axillary temperature, pulse rate, and blood pressure will be assessed.
Blood pressure (systolic and diastolic), and pulse rate measurements should be preceded by at least 5 minutes of rest for the study participant in a quiet setting without distractions (eg, television, cell phones). All measuremen... | [] |
NCT03971422 | 8.2.3 | Electrocardiograms | Triplicate 12-lead ECG will be obtained as outlined in the Schedule of Activities (Section 1.3) using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Refer to Section 7.1.2 for QTc withdrawal criteria and any additional QTc readings that may be necessary.
All EC... | [] |
NCT03971422 | 8.2.4 | Clinical safety laboratory assessments | See Appendix 2 for the list of clinical laboratory tests to be performed and to the Schedule of Activities (Section 1.3) for the timing and frequency.
The Investigator must review the laboratory report, document this review, and record any clinically relevant changes occurring during the study in the AE section of the... | [] |
NCT03971422 | 8.2.5 | Suicidal risk monitoring | Study participants being treated with rozanolixizumab should be monitored appropriately for suicidal ideation and behavior or any other unusual changes in behavior. Consideration should be given to discontinuing rozanolixizumab in study participants who experience signs of suicidal ideation or behavior.
Families and c... | [] |
NCT03971422 | 8.2.6 | Assessment and management of TB and TB risk factors | Appropriate rigorous precautions are being taken within this protocol to monitor the risk of TB infection in this study (see Section 5.2). Any presumptive diagnosis or diagnosis of a TB infection is a reportable event.
The Investigator should consider all potential sites of infection when assessing for TB during the p... | [
"Physical Examination",
"TB signs and symptoms questionnaire",
"TB assessment by IGRA",
"• Positive IGRA",
"• Indeterminate IGRA",
"TB assessment by chest X-ray",
"Test Conversion",
"Latent TB",
"Active TB or non-tuberculosis mycobacterium infection",
"LTBI, active TB or other NTMB identified duri... |
NCT03971422 | 8.3 | Adverse Events | The definitions of an AE or SAE can be found in Appendix 3 (Section 10.3).
Adverse events can be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally authorized representative).
The Investigator and any designees are responsible for detecting, documenting, and rec... | [] |
NCT03971422 | 8.3.1 | Time period and frequency for collecting AE and SAE information | All SAEs will be collected from the signing of the ICF until the EOS visit at the time points specified in the Schedule of Activities (Section 1.3).
All AEs will be collected from the signing of the ICF until the EOS visit at the time points specified in the Schedule of Activities (Section 1.3).
All SAEs will be reco... | [] |
NCT03971422 | 8.3.2 | Method of detecting AEs and SAEs | Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and non-leading verbal questioning of the participant is the preferred method to inquire about AE occurrences. | [] |
NCT03971422 | 8.3.3 | Follow-up of AEs and SAEs | After the initial AE/SAE report, the Investigator is required to proactively follow each participant at subsequent visits/contacts. All AEs and SAEs, (and non-serious AEs of special interest and adverse events of special monitoring [AESM], as defined in Section 8.3.6 and Section 8.3.7, respectively), will be followed u... | [] |
NCT03971422 | 8.3.4 | Regulatory reporting requirements for SAEs | Prompt notification (24 hrs) by the Investigator to the sponsor of an SAE is essential so that legal obligations and ethical responsibilities towards the safety of participants and the safety of a study treatment under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regu... | [] |
NCT03971422 | 8.3.5 | Pregnancy | Details of all pregnancies in female participants and, if indicated, female partners of male participants will be collected after the start of study treatment and until 3 months after the last dose. PUBLIC COPY
If a pregnancy is reported, the Investigator must immediately inform the sponsor within 24 hours of learning... | [] |
NCT03971422 | 8.3.6 | Adverse events of special interest | An AE of special interest (AESI) is any AE that a regulatory authority has mandated be reported on an expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the administration of a UCB product/compound. An AESI should be immediately reported within 24 hrs to UCB. Potential Hy's Law, d... | [] |
NCT03971422 | 8.3.7 | Adverse events of special monitoring | For rozanolixizumab, AESM that require immediate reporting (within 24 hrs regardless of seriousness) to UCB are:
- Severe headache
- Severe GI disorders (ie, abdominal pain, diarrhea, vomiting)
- Opportunistic infection
In case of severe headache or serious headache (regardless of severity), the headache questionnair... | [] |
NCT03971422 | 8.3.8 | Treatment-emergent adverse events | Treatment-emergent AEs are defined as AEs starting after the time of first IMP administration up to and including 8 weeks after the final dose. PUBLIC COPY | [] |
NCT03971422 | 8.4 | Safety Signal Detection | Selected data from this study will be reviewed periodically to detect as early as possible any safety concern(s) related to the study medication so that investigators, clinical study participants, regulatory authorities, and IRBs/IECs will be informed appropriately and as early as possible.
In addition, an unblinded I... | [] |
NCT03971422 | 8.5 | Treatment of Overdose | Any dose increase of 10% or greater from the assigned dose for each administered dose of IMP per week should be considered an overdose, irrespective of the weight tier band. Overdose events
Confidential Page 67 of 188
are only considered AEs or SAEs if there are associated clinical signs and symptoms or if the act of... | [] |
NCT03971422 | 8.6 | Pharmacokinetics and Anti-drug Antibodies | Whole blood samples will be collected for measurement of plasma concentrations of rozanolixizumab and ADA as specified in the Schedule of Activities (Section 1.3). Additional PK samples will be collected (Section 1.4) at selected sites for study participants who have consented to participate in the sub-study. Blood sam... | [] |
NCT03971422 | 8.7 | Pharmacodynamics | Venous blood samples will be collected at timepoints specified in the Schedule of Activities (Section 1.3) for measurement of:
• Serum IgG and IgG sub-classes concentrations
• Serum MG-specific autoantibodies (anti-MuSK/anti-AChR) levels (all subsequent testing will be limited to the positive antibody)
For all immun... | [] |
NCT03971422 | 8.8 | Genetics | Genetics are not evaluated in this study. | [] |
NCT03971422 | 8.9 | Biomarkers | Collection of samples for exploratory biomarker research is also part of this study. Blood samples for biomarker research are required and will be collected from all study participants in this study as specified in the Schedule of Activities (Section 1.3). Exploratory samples are collected predose. Additional explorato... | [] |
NCT03971422 | 8.9.1 | Immunology | Blood samples for immunological testing are required and will be collected from all study participants in this study as specified in the Schedule of Activities (Section 1.3) for measurement of:
- IgA, IgE, IgM
- Serum complement (C3, C4) and serum cytokines
- Plasma complement (C3a, C5a)
- Tetanus toxoid IgG
Samples ... | [] |
NCT03971422 | 8.10 | Medical Resource Utilization and Health Economics | Medical Resource Utilization and Health Economics parameters will not be measured for this study. | [] |
NCT03971422 | 9 | STATISTICAL CONSIDERATIONS | A description of statistical methods follows and will be described in more detail in the Statistical Analysis Plan (SAP).
The statistical design of this study involves two stages, with an interim analysis at the end of Stage 1. | [] |
NCT03971422 | 9.1 | Definition of Analysis Sets | - Enrolled Set: All study participants who have signed the informed consent.
- Randomized Set (RS): All enrolled study participants who were randomized.
- Safety Set (SS): All randomized study participants who received at least one dose of IMP. Analysis of this set will be according to the treatment the study participa... | [] |
NCT03971422 | 9.2 | General Statistical Considerations | Statistical evaluation will be performed by the sponsor or designee and supervised by the Exploratory Statistics Department of UCB. Data will be summarized as follows:
• Summarized by dose levels of rozanolixizumab or placebo
All analyses will be performed using Statistical Analysis System (SAS®) version 9.3 or later... | [] |
NCT03971422 | 9.3 | Estimands | The primary efficacy analysis will evaluate the 'hypothetical' estimand in anti-AChR or anti-MuSK autoantibody-positive participants with generalized MG who experience moderate to severe symptoms and are being considered for additional treatment such as IVIg or PEX, where the main intercurrent events are the use of res... | [] |
NCT03971422 | 9.4 | Planned Efficacy/Outcome Analyses | [] | |
NCT03971422 | 9.4.1 | Analysis of the primary efficacy endpoint | The formal testing strategy proposed is a flexible combination test based on the inverse normal method (Lehmacher and Wassmer, 1999) with equal weighting of Stage 1 (up to the formal interim analysis) and Stage 2 (post-interim analysis) data. Confirmatory testing of single hypotheses is based on a closed-testing proced... | [] |
NCT03971422 | 9.4.2 | Analysis of secondary and other efficacy endpoints | All continuous secondary efficacy variables will be analyzed using the combination testing strategy and model defined for the primary analysis. The binary secondary efficacy variable of MG-ADL responder (≥2.0 points improvement from Baseline) at Day 43 (Visit 10) will be analyzed using logistic regression, including a ... | [] |
NCT03971422 | 9.5 | Planned Safety and other Analyses | [] | |
NCT03971422 | 9.5.1 | Safety analyses | The frequency and severity of all TEAEs will be presented for each treatment group separately by System Organ Class, high level term, and preferred term (Medical Dictionary for Regulatory Activities [MedDRA]® ). The data will be displayed as number of study participants experiencing the TEAE, percentage of study partic... | [] |
NCT03971422 | 9.5.2 | Other analyses | [] | |
NCT03971422 | 9.5.2.1 | Pharmacokinetic analyses | The PK-PPS dataset will be used. Pharmacokinetic variables of rozanolixizumab like AUC (area under the curve), Cmax (maximum concentration) cannot be derived, since blood sampling will be performed at 1 time point post-dosing per visit only. Thus, PK is restricted to concentration data. In addition to the general descr... | [] |
NCT03971422 | 9.5.2.2 | Anti-drug antibodies analyses | A tiered ADA approach will be used for the study. Anti-drug antibody assessment will involve Screening (above or below the cutpoint) of all samples for ADA, followed by a confirmatory assessment (confirmed or not confirmed positive) leading to an anti-rozanolixizumab antibody positive or negative assessment for each sa... | [] |
NCT03971422 | 9.6 | Handling of protocol deviations | Important protocol deviations are identified as part of the data cleaning process in the Data Cleaning Plan (DCP). Ongoing data cleaning meetings will be held throughout the duration of the study. Objectives of these meetings include to review and update (if necessary) the important protocol deviations in the DCP. Furt... | [] |
NCT03971422 | 9.7 | Handling of dropouts or missing data | All imputation of missing or partial dates for safety assessments, as well as handling missing efficacy data (where applicable), will be detailed in the SAP. | [] |
NCT03971422 | 9.8 | Planned interim analysis and data monitoring | [] |
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