A Phase II Study of M2951 in SLE

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Brief Summary
M2951 is an investigational drug under evaluation for treatment of autoimmune and inflammatory disorders. The purpose of the study was to assess the Safety and Efficacy of M2951 in participants with Systemic Lupus Erythematosus (SLE).
Brief Title
A Phase II Study of M2951 in SLE
Categories
Infectious Disease
Lung
Completion Date
Completion Date Type
Actual
Conditions
Systemic Lupus Erythematosus
Eligibility Criteria
Inclusion Criteria:

* Eligible male and female participants, aged 18 to 75 years
* Must have diagnosis of SLE with either the Systemic Lupus International Collaborating Clinics (SLICC) criteria for SLE, or at least four of the 11 American College of Rheumatology (ACR) classification criteria for SLE, of at least six months duration prior to Screening
* SLEDAI-2K total score greater than or equal to (\>=) 6 (including clinical SLEDAI greater than or equal to (\>=) 4) at Screening Visit
* And be positive for anti-double-stranded Deoxyribonucleic Acid (DNA) and/or anti-nuclear antibody (ANA greater than or equal to (\>=) 1:80) and/or anti-Smith (anti-Sm) antibody at the time of Screening
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Participants are not eligible for this study if they have active, clinically significant interstitial lung disease or pulmonary arterial hypertension
* Proteinuria (urine protein to creatinine ratio \[UPCR\] \> 4 mg/mg)
* Acutely worsened renal function
* Central nervous system SLE
* Or within two weeks prior to Screening or during Screening: use of oral corticosteroids greater than (\>) 30 mg daily prednisone equivalent
* Use of injectable corticosteroids, or change in dose of corticosteroids.
* Other protocol defined exclusion criteria could apply
Inclusion Criteria
Inclusion Criteria:

* Eligible male and female participants, aged 18 to 75 years
* Must have diagnosis of SLE with either the Systemic Lupus International Collaborating Clinics (SLICC) criteria for SLE, or at least four of the 11 American College of Rheumatology (ACR) classification criteria for SLE, of at least six months duration prior to Screening
* SLEDAI-2K total score greater than or equal to (\>=) 6 (including clinical SLEDAI greater than or equal to (\>=) 4) at Screening Visit
* And be positive for anti-double-stranded Deoxyribonucleic Acid (DNA) and/or anti-nuclear antibody (ANA greater than or equal to (\>=) 1:80) and/or anti-Smith (anti-Sm) antibody at the time of Screening
* Other protocol defined inclusion criteria could apply

Gender
All
Gender Based
false
Keywords
Systemic Lupus Erythematosus
M2951
Placebo
Dose response
Oral Corticosteroids
Safety
Efficacy
Autoimmune And Inflammatory Disorders
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
75 Years
Minimum Age
18 Years
NCT Id
NCT02975336
Org Class
Industry
Org Full Name
EMD Serono
Org Study Id
MS200527-0018
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase II, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study To Evaluate the Safety and Efficacy of M2951 in Subjects With SLE
Primary Outcomes
Outcome Description
SRI-4 response was defined as greater than or equal to (\>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score, no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and no treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to Systemic Lupus Erythematosus (SLE) divided into 9 organ systems. For each organ system A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale =from 0(very well) to 100(very poor).
Outcome Measure
DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Week 52
Outcome Time Frame
Week 52
Outcome Description
SRI-6 response was defined as \>= 6-point reduction in SLEDAI-2K total score, no new BILAG A and no more than 1 new BILAG B domain score and no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system :A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale =from 0(very well) to 100(very poor).
Outcome Measure
DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6) at Week 52
Outcome Time Frame
Week 52
Outcome Description
Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in participant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs: events between first dose of study drug that were absent before treatment/that worsened relative to pre-treatment state up to 56 weeks. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with TEAEs and serious TEAEs were reported.
Outcome Measure
DBPC Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Outcome Time Frame
Baseline up to Week 56
Outcome Description
Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs by severity were reported.
Outcome Measure
DBPC Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Outcome Time Frame
Baseline up to Week 56
Outcome Description
Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate, respiratory rate, weight and height. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in vital signs were reported.
Outcome Measure
DBPC Period: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Outcome Time Frame
Baseline up to Week 56
Outcome Description
12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.
Outcome Measure
DBPC Period: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings
Outcome Time Frame
Baseline up to Week 56
Outcome Description
Laboratory investigation included hematology, biochemistry, urinalysis and coagulation. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in laboratory parameters were reported.
Outcome Measure
DBPC Period: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Outcome Time Frame
Baseline up to Week 56
Outcome Description
Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 2.
Outcome Measure
DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2
Outcome Time Frame
Week 2
Outcome Description
Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 4.
Outcome Measure
DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 4
Outcome Time Frame
Week 4
Outcome Description
Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 12.
Outcome Measure
DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 12
Outcome Time Frame
Week 12
Outcome Description
Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 24.
Outcome Measure
DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 24
Outcome Time Frame
Week 24
Outcome Description
Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 36.
Outcome Measure
DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 36
Outcome Time Frame
Week 36
Outcome Description
Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 52
Outcome Measure
DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 52
Outcome Time Frame
Week 52
Outcome Description
Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 56
Outcome Measure
DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 56
Outcome Time Frame
Week 56
Outcome Description
Mean total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence activated cell sorting was performed for the analysis of B cell counts.
Outcome Measure
DBPC Period: Mean Absolute Total B Cell Count at Week 4
Outcome Time Frame
Week 4
Outcome Description
Mean absolute total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence activated cell sorting was performed for the analysis of B cell counts.
Outcome Measure
DBPC Period: Mean Absolute Total B Cell Count at Week 24
Outcome Time Frame
Week 24
Outcome Description
Mean absolute total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence activated cell sorting was performed for the analysis of B cell counts.
Outcome Measure
DBPC Period: Mean Absolute Total B Cell Count at Week 52
Outcome Time Frame
Week 52
Outcome Description
Mean absolute total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence activated cell sorting was performed for the analysis of B cell counts.
Outcome Measure
DBPC Period: Mean Absolute Total B Cell Count at Week 56
Outcome Time Frame
Week 56
Outcome Description
Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Outcome Measure
DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2
Outcome Time Frame
Baseline and Week 2
Outcome Description
Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Outcome Measure
DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 4
Outcome Time Frame
Baseline and Week 4
Outcome Description
Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Outcome Measure
DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 12
Outcome Time Frame
Baseline and Week 12
Outcome Description
Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Outcome Measure
DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 24
Outcome Time Frame
Baseline and Week 24
Outcome Description
Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Outcome Measure
DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 36
Outcome Time Frame
Baseline and Week 36
Outcome Description
Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Outcome Measure
DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 52
Outcome Time Frame
Baseline and Week 52
Outcome Description
Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Outcome Measure
DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 56
Outcome Time Frame
Baseline and Week 56
Outcome Description
Change from baseline in Total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.
Outcome Measure
DBPC Period: Change From Baseline in Total B Cell Count at Week 4
Outcome Time Frame
Baseline and Week 4
Outcome Description
Change from baseline in Total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.
Outcome Measure
DBPC Period: Change From Baseline in Total B Cell Count at Week 24
Outcome Time Frame
Baseline and Week 24
Outcome Description
Change from baseline in Total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.
Outcome Measure
DBPC Period: Change From Baseline in Total B Cell Count at Week 52
Outcome Time Frame
Baseline and Week 52
Outcome Description
Change from baseline in Total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.
Outcome Measure
DBPC Period: Change From Baseline in Total B Cell Count at Week 56
Outcome Time Frame
Baseline and Week 56
Secondary Ids
Secondary Id
2016-002950-19
Secondary Outcomes
Outcome Description
BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system based on alphabetic score: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. BILAG evaluated by scoring each of a list of signs and symptoms as: improving (1); same (2); worse (3); new (4); not present (0); not done (ND). Total BILAG score is sum of scores of 9 domains where A=12, B=8, C=1, D=0, and E=0. Total score ranges from 0 to 108 with a higher score indicating greater lupus activity. Time to first severe flare, where a severe flare is defined as at least one BILAG A (Severe disease activity) score in any organ system due to items that are new or worse, compared to the BILAG evaluation at the previous visit, during the 52-Week Treatment. It was measured using Kaplan-Meier (KM) estimates.
Outcome Time Frame
Baseline up to Week 56
Outcome Measure
DBPC Period: Time to First Severe British Isles Lupus Assessment Group (BILAG) A Flare
Outcome Description
SRI-4 response was defined as greater than or equal to (\>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score, no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and no treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to Systemic Lupus Erythematosus (SLE), divided into 9 organ systems. For each organ system A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale =from 0(very well) to 100(very poor).
Outcome Time Frame
Week 52
Outcome Measure
DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Week 52 in Serologically Active (SA) Subgroup
Outcome Description
SRI-6 response was defined as \>= 6-point reduction in SLEDAI-2K total score, no new BILAG A and no more than 1 new BILAG B domain score and no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system :A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale = from 0(very well) to 100(very poor).
Outcome Time Frame
Week 52
Outcome Measure
DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6) at Week 52 in Serologically Active Subgroup
Outcome Description
BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system based on alphabetic score: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. BILAG evaluated by scoring each of a list of signs and symptoms as: improving (1); same (2); worse (3); new (4); not present (0); not done (ND). Total BILAG score is sum of scores of 9 domains where A=12, B=8, C=1, D=0, and E=0. Total score ranges from 0 to 108 with a higher score indicating greater lupus activity. A Moderate to Severe (BILAG A or 2B) flare is defined as at least one BILAG A (severe disease activity) grade or two BILAG B (moderate disease activity) grade in any organ system due to items that are new or worse, compared to the BILAG evaluation at the previous visit, during the 52 week treatment. It was measured using Kaplan-Meier (KM) estimates.
Outcome Time Frame
Baseline up to Week 56
Outcome Measure
DBPC Period: Time to First British Isles Lupus Assessment Group (BILAG) A or 2B Moderate to Severe Flare
Outcome Description
A participant has a flare-free status if no flare has been reported during the 52-week treatment period. Participants who discontinued treatment prior to Week 52, without having a flare are counted as not being flare free at Week 52. A flare was defined as either 1 or more new BILAG-2004 A (severe disease activity) or 2 or more new BILAG-2004 B (moderate disease activity) items compared to the previous visit. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system based on alphabetic score: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected.
Outcome Time Frame
up to Week 52
Outcome Measure
DBPC Period: Number of Participants With British Isles Lupus Assessment Group (BILAG) 2004 Flare-Free Status During the 52-Week Treatment Period
Outcome Description
A flare was defined as either 1 or more new BILAG-2004 A (severe disease activity) or 2 or more new BILAG-2004 B (moderate disease activity) items compared to the previous visit. The occurrence of a new flare was checked for each available visit versus the previous available visit up to Week 52. If no new flares occurred, the number of flares was set to 0. Otherwise all flares were counted leading to the maximum number of flares of 13. The annualized flare rate was calculated as the number of flares divided by the flare exposure time in days multiplied with 365.25 (1 year). The flare exposure time is the time up to Week 52 (date of BILAG-2004 assessment at Week 52) or up to the date of last available BILAG 2004 assessment.
Outcome Time Frame
Baseline up to Week 52
Outcome Measure
DBPC Period: Annualized Flare Rate
Outcome Description
Low disease activity is defined as SLEDAI-2K score \<=2. SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms at the time of assessment or during the previous 30 days. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms).
Outcome Time Frame
Week 52
Outcome Measure
DBPC Period: Number of Participants With Low Disease Activity Status, Defined by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score of Less Than or Equal (<= ) 2 at Week 52
Outcome Description
Low disease activity is defined as SLEDAI-2K score \<=2. SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms at the time of assessment or during the previous 30 days. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms). Clinical SLEDAI-2K score is equal to the SLEDAI-2K score from electronic case report form (eCRF) excluding the components 'Increased Deoxyribonucleic acid (DNA) Binding' and 'Low Complement'.
Outcome Time Frame
Week 52
Outcome Measure
DBPC Period: Number of Participants With Low Disease Activity Status, Defined by Clinical Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score of Less Than or Equal (<= ) 2 at Week 52
Outcome Description
SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms at the time of assessment or during the previous 30 days. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms).
Outcome Time Frame
Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Outcome Measure
DBPC Period: Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Outcome Description
CLASI is an validated measurement instrument for lupus erythematosus developed for use in clinical studies that consists of separate scores for the activity of the disease (CLASI-A). The CLASI activity score is calculated on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. The CLASI activity score ranges from 0-70, with higher scores indicating more severe skin disease. Severity categories based on the CLASI activity score are as follows: mild (0-9), moderate (10-20), and severe (21-70).
Outcome Time Frame
Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Outcome Measure
DBPC Period: Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Outcome Description
BICLA response defined as participants meeting following criteria: \[1\] At least one gradation of improvement in baseline BILAG scores in all body systems with moderate or severe disease activity at entry (example: all A (severe disease) scores falling to B (moderate), C (mild), or D (no activity) and all B scores falling to C or D; \[2\] No new BILAG A or more than one new BILAG B scores; \[3\] No worsening of total SLEDAI-2K score from baseline; \[4\] No significant deterioration (=\<10%) in physician's global assessment and \[5\] No treatment failure (initiation of non-protocol treatment).
Outcome Time Frame
Week 52
Outcome Measure
DBPC Period: Number of Participants With Response Based on BILAG-Based Composite Lupus Assessment (BICLA) at Week 52
Outcome Description
BILAG 2004 disease activity Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system based on alphabetic score: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. BILAG evaluated by scoring each of a list of signs and symptoms as: improving (1); same (2); worse (3); new (4); not present (0); not done (ND). Total BILAG score is sum of scores of 9 domains where A=12, B=8, C=1, D=0, and E=0. Total score ranges from 0 to 108 with a higher score indicating greater lupus activity.
Outcome Time Frame
Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Outcome Measure
DBPC Period: Change From Baseline in British Isles Lupus Assessment Group (BILAG)-2004 Score at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Outcome Description
The Physician's Global Assessment of Disease Activity was recorded using the 100 millimeter horizontal Visual Analog Scale (VAS). Physician rated participant's disease activity on a scale ranged from 0-100 millimeter (mm), where 0 indicated no disease activity and 100 represented maximum disease activity.
Outcome Time Frame
Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Outcome Measure
DBPC Period: Change From Baseline in Physician's Global Assessment (PGA) Score at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Outcome Description
The 36-Item Short-Form Health Survey (SF-36) was a standardized survey evaluating 8 aspects of functional health and well-being. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) was based primarily on physical functioning, role-physical, bodily pain, and general health scales and mental component summary (MCS) encompasses vitality, social functioning, role-emotional, and mental health scales. Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0 - 100 (100 = highest level of mental functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100 = highest level of physical functioning).
Outcome Time Frame
Baseline, Week 4, 8, 12, 16, 24, 32, 40 and 52
Outcome Measure
DBPC Period: Change From Baseline in Study 36-Item Short Form Health Survey Version 2 (SF-36v2) Physical Component Summary Score and Mental Component Summary Scores at Week 4, 8, 12, 16, 24, 32, 40 and 52
Outcome Description
The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L profile defines health in terms of mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each dimension has five levels: 1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, and 5: extreme problems. Responses were used to generate a weighted summary index (EQ-5D index), which ranges from 0 (dead) to 1.00 (perfect health). A higher score indicates better health and positive changes from baseline indicate improvement of health.
Outcome Time Frame
Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52
Outcome Measure
DBPC Period: Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire at Week 4, 8, 12, 16, 24, 32, 40 and 52
Outcome Description
The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L profile defines health in terms of mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each dimension has five levels: 1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, and 5: extreme problems. The responses were used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 was the worst health you can imagine and 100 was the best health you can imagine.
Outcome Time Frame
Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52
Outcome Measure
DBPC Period: Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Visual Analog Scale (VAS) at Week 4, 8, 12, 16, 24, 32, 40 and 52
Outcome Description
The Lupus QoL assessment is a 34 item questionnaire across 8 domains that is designed to find out how systemic lupus erythematosus (SLE) affects a participant's life. Domains include physical health, pain, planning, intimate relationships, burden to others, emotional health, body image, and fatigue. Participants indicate their responses on a 5-point Likert response format, where 4=never, 3=occasionally, 2= a good bit of the time, 1=most of the time, and 0=worst of the time. Summary scores can be calculated for all 8 domains. A LupusQoL score for each domain was reported on a 0 to 100 scale, with greater values indicating better health related QoL.
Outcome Time Frame
Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52
Outcome Measure
DBPC Period: Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score at Week 4, 8, 12, 16, 24, 32, 40 and 52
Outcome Description
The PGIC is a self-rated scale that asks the participant to describe the change in activity limitations, symptoms, emotions, and overall quality of life (QoL) related to the participants painful condition on the following scale: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse) and 7 (very much worse). Number of participants in the PGIC categories of any improvement (that is PGIC scale score 1, 2 or 3), no change (that is PGIC scale score 4) and any worsening (that is PGIC scale score 5, 6 or 7) are reported.
Outcome Time Frame
Week 4, 8, 12, 16, 24, 32, 40, and 52
Outcome Measure
DBPC Period: Number of Participants With Patient Global Impression of Change (PGIC) Scale Score of Any Improvement, no Change and Any Worsening
Outcome Description
The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assess self reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status.
Outcome Time Frame
Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52
Outcome Measure
DBPC Period: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 4, 8, 12, 16, 24, 32, 40 and 52
Outcome Description
BILAG A or 2B flare is defined as at least one BILAG A grade or two BILAG B grade in any organ system due to items that are new or worse, compared to the BILAG evaluation at the previous visit, during the 52 week treatment period. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to systemic lupus erythematosus (SLE), divided into 9 organ systems. For each organ system based on alphabetic score: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected.
Outcome Time Frame
Baseline and Week 52
Outcome Measure
DBPC Period: Number of Participants With Change From Baseline in Prednisone Equivalent Corticosteroid (CS) Dose by >=25% to a Dose of <=7.5 Milligram Per Day (mg/Day), With no BILAG A or 2B Flare in Disease Activity at Week 52
Outcome Description
Change From Baseline in Prednisone-equivalent CS Daily Dose at Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 were reported.
Outcome Time Frame
Baseline, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Outcome Measure
DBPC Period: Change From Baseline to Week 52 in Prednisone Equivalent Corticosteroid (CS) Daily Dose at at Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Outcome Description
Number of Participants With Reduction From Baseline in Prednisone-equivalent Corticosteroid (CS) Daily Dose by \> 0 to 25%, \>25% to 50%, \>50% to 100% or an Increase at Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 were reported.
Outcome Time Frame
Baseline, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Outcome Measure
DBPC Period: Number of Participants With Reduction From Baseline in Prednisone Equivalent Corticosteroid (CS) Daily Dose by > 0 to 25%, >25% to 50%, >50% to 100% or an Increase at Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Outcome Description
Cumulative Prednisone-equivalent Corticosteroid (CS) Dose was calculated at Week 52.
Outcome Time Frame
Week 52
Outcome Measure
DBPC Period: Cumulative Prednisone Equivalent Corticosteroid (CS) Dose at Week 52
Outcome Description
SRI-4 response was defined as greater than or equal to (\>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score, no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and no treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to Systemic Lupus Erythematosus (SLE), divided into 9 organ systems. For each organ system A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale =from 0(very well) to 100(very poor).
Outcome Time Frame
Week 52
Outcome Measure
DBPC Period: Number of Participants With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to 7.5 mg Prednisone Equivalent Per Day or Less With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Week 52
Outcome Description
SRI-6 response was defined as \>= 6-point reduction in SLEDAI-2K total score, no new BILAG A and no more than 1 new BILAG B domain score and no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system :A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale =from 0(very well) to 100(very poor).
Outcome Time Frame
Week 52
Outcome Measure
DBPC Period: Number of Participants With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to 7.5 mg Prednisone Equivalent Per Day or Less With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6) at Week 52
Outcome Description
SRI-4 response was defined as greater than or equal to (\>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score, no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and no treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to Systemic Lupus Erythematosus (SLE), divided into 9 organ systems. For each organ system A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale = from very well(0)-very poor(100).
Outcome Time Frame
Week 52
Outcome Measure
DBPC Period: Number of Participants With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to 7.5 mg Prednisone Equivalent Per Day or Less With Response Based on SRI-4 at Week 52 in Serologically Active Subgroup
Outcome Description
Lupus low disease activity state will be measured as: SLEDAI-2K \<= 4; No activity in any major organ systems (renal, central nervous system, cardiopulmonary, vasculitis, fever); No new features of disease activity compared with the previous assessment; Prednisone-equivalent \<= 7.5 milligram per day; Unchanged background immunosuppressive therapy.
Outcome Time Frame
Week 52
Outcome Measure
DBPC Period: Number of Participants With Lupus Low Disease Activity State (LLDAS) at Week 52
See Also Links
Url
Trial Awareness and Transparency website
Url
US Medical Information website, Medical Resources
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
75
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Chaim Putterman
Investigator Email
chaim.putterman@einsteinmed.org
Investigator Phone
718-430-4266
Categories Mesh Debug
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
MeSH Terms
LUPUS ERYTHEMATOSUS, SYSTEMIC
CONNECTIVE TISSUE DISEASES
SKIN AND CONNECTIVE TISSUE DISEASES
AUTOIMMUNE DISEASES
IMMUNE SYSTEM DISEASES
COUNTERFEIT DRUGS
EVOBRUTINIB
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS