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| ID | Type | Description | Link |
|---|---|---|---|
| WA20500 |
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Study was terminated due to an imbalance of serious and opportunistic infections in the ocrelizumab treated patients versus the placebo arm.
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| Name | Class |
|---|---|
| Roche Pharma AG | INDUSTRY |
This is a Phase III, randomized, double-blind, placebo-controlled, multicentre, parallel-group study designed to evaluate the efficacy and safety of ocrelizumab added to SOC (corticosteroid plus one of two immunosuppressant regimens) compared with placebo added to SOC in patients with WHO or ISN Class III or IV lupus nephritis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| OCR 400 mg + SOC | Experimental | Participants received Ocrelizumab 400 mg i.v. infusion on Days 1 and 15, followed by 400 mg i.v. at Week 16 and then every 16 weeks plus SOC regimen. |
|
| OCR 1000 mg + SOC | Experimental | Participants received Ocrelizumab 1000 mg i.v. infusion on Days 1 and 15, followed by 1000 mg i.v. at Week 16 and then every 16 weeks plus SOC regimen. |
|
| Placebo + SOC | Placebo Comparator | Participants received placebo i.v. infusion on Days 1 and 15, followed by placebo infusion at Week 16 and then every 16 weeks plus SOC regimen. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Corticosteroids | Drug | Intravenous and oral repeating dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Achieved Complete Renal Response (CRR) | CRR was defined as: 1. Normal serum creatinine (and with no more than a 25 percent [%] increase from Baseline); 2. Improvement in urinary protein:urinary creatinine ratio to less than or equal to (≤) 0.5. PRR was defined as at least 50 percent (%) reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was greater than (>) 3, a urine protein:urine creatinine ratio of less than (<) 3 needed to be achieved. | Week 48 |
| Percentage of Participants Who Achieved Overall Response | Overall response rate (ORR) equals (=) CRR + PRR. CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from baseline) 2. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50 % reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio is >3, a urine protein:urine creatinine ratio of <3 needs to be achieved. | Week 48 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Achieved a Renal Response (Partial or Complete) by Week 36, and Sustain or Improve This Response Until Week 48 | Weeks 36, 40, 44, and 48 | |
| Time To Complete Renal Response | Time to complete renal response was proposed to be analyzed using a stratified log rank test with race and SOC as stratification factors. Comparisons of ocrelizumab versus placebo were to be expressed as p-values, estimated hazard ratios, adjusted proportions of participants who achieved a complete renal response and their 95% confidence intervals. Kaplan-Meier curves were to be produced. Due to early termination of the study the analyses were not performed. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
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Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).
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Screening was done from Day -14 to Day -1.
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| ID | Title | Description |
|---|---|---|
| FG000 | OCR 400 mg + SOC | Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day. |
| FG001 | OCR 1000 mg + SOC | Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day. |
| FG002 | Placebo + SOC | Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | OCR 400 mg + SOC | Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Who Achieved Complete Renal Response (CRR) | CRR was defined as: 1. Normal serum creatinine (and with no more than a 25 percent [%] increase from Baseline); 2. Improvement in urinary protein:urinary creatinine ratio to less than or equal to (≤) 0.5. PRR was defined as at least 50 percent (%) reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was greater than (>) 3, a urine protein:urine creatinine ratio of less than (<) 3 needed to be achieved. | The primary endpoint was analyzed via an overall response (CRR+PRR) analysis and the separate complete and partial response rates were only summarized descriptively | Posted | Number | Percentage of Participants | Week 48 |
|
Baseline up to 19 months.
All patients who received any part of an infusion of study drug and provided at least one assessment of safety were included in the safety analysis.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo + SOC | Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Deep vein thrombosis | Vascular disorders | MedDRA 13.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertension | Vascular disorders | MedDRA 13.1 | Non-systematic Assessment |
The study was terminated early due to an imbalance in serious infections in ocrelizumab-treated participants versus placebo-treated participants. Only 139 of the 381 participants randomized completed the 48 week treatment period.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | F. Hoffmann-La Roche Ltd/Genentech Inc. | 1-800-821-8590 | genentech@druginfo.com |
| ID | Term |
|---|---|
| D008181 | Lupus Nephritis |
| D008180 | Lupus Erythematosus, Systemic |
| ID | Term |
|---|---|
| D005921 | Glomerulonephritis |
| D009393 | Nephritis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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| ID | Term |
|---|---|
| D000305 | Adrenal Cortex Hormones |
| D003520 | Cyclophosphamide |
| D009173 | Mycophenolic Acid |
| C533411 | ocrelizumab |
| D001379 | Azathioprine |
| ID | Term |
|---|---|
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
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| Cyclophosphamide | Drug | Cyclophosphamide was administered at a IV dose 500 mg every 2 weeks for up to 6 doses followed by maintenance treatment with azathioprine. |
|
| Mycophenolate Mofetil | Drug | Mycophenolate Mofetil was administered orally at maximum dose of 3 g/day. |
|
| Ocrelizumab | Drug | Ocrelizumab was administed at a dose and as per schedule in arm description |
|
| Placebo | Drug | Placebo was administered as per schedule in arm description |
|
| Azathioprine | Drug | Azathioprine was administered at a dose up to 2 mg/kg/day with a maximum dose of 200 mg. |
|
| Baseline up to Week 48 |
| Area Under the Curve (AUC) of Calculated Glomerular Filtration Rate (cGFR) Between Baseline and Week 48 | The improvement of AUC of cGFR was to be measured between Baseline and Week 48. This was to be analyzed with Analysis of Covariance (ANCOVA) with race and SOC as covariates. | Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48 |
| Percentage of Participants Who Achieved A Reduction In Systemic Lupus Erythematosis Disease Activity Index (SLEDAI) -2K Score | SLEDAI-2K measures disease activity at the visit or within the preceding 10 days. It comprised of 24 descriptors, covering 9 organ systems, and reflects disease activity over the previous 10 days.The total SLEDAI-2K score falls between 0 and 105, with higher scores representing higher disease activity | Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 |
| Time to First Renal Flare In Those Participants Who Demonstrated at Least a Partial Renal Response | Renal flares may be either proteinuric or nephritic as defined below: Proteinuric Flares are defined as follows:In participants who achieve a urine protein:urine creatinine (Upr:Ucr) ≤ 0.5, an increase to Upr:Ucr >1; In participants with an Upr:Ucr >0.5, a doubling of Upr:Ucr (with a minimum increase to Upr:Ucr >2). Nephritic Flare defined as: Increase in serum creatinine of ≥30% from the lowest value achieved in the study accompanied by Increase Upr:Ucr >1 Or New/worsening active urine sediment on two consecutive occasions, in the absence of urinary tract infection or other causes of hematuria. | Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 |
| Percentage of Participants Who Achieved Clinically Meaningful Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF36) From Baseline to Week 48 | The SF36 Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. A score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. The eight sections are: vitality, physical functioning, bodily pain, general health perceptions physical role functioning, emotional role functioning, social role functioning, and mental health. | Baseline and Weeks 1, 12, 24, 36, and 48 |
| Percentage of Participants Who Achieved Clinically Meaningful Improvement in Fatigue Using the Functional Assessment of Chronic Illness Therapy (Facit) Fatigue Questionnaire From Baseline to Week 48 | The FACIT Fatigue Scale is a short, 13-item, easy-to-administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued). | Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 |
| Percentage of Participants Who Achieved Clinically Meaningful Improvement in Pain Using the Modified Brief Pain Inventory Short Form (mBPI-SF) From Baseline to Week 48 | m-BPI-sf is a self-administered 11-point Likert rating scale to rate pain in the past 24 hours. A single item pertains to worst pain in the past 24 hours with a range of 0 (no pain) to 10 (worst imaginable pain). | Baseline and Weeks 1, 12, 24, 36, and 48 |
| Health Care Visits Over the 48-Week Treatment Period | The number of health care visits (including doctor's office visits, Emergency room/ Accident and Emergency [ER/A&E] visits and hospitalizations) over the 48-week treatment period were recorded. | Weeks 1, 24, and 48 |
| Percentage of Participants Who Achieved a CRR or PRR And Who Received A Corticosteroid Dose of <10 Milligrams Per Day (mg/Day) From Week 24 to Week 48 | CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from Baseline) 2. Inactive urinary sediment 3. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50% reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was >3, a urine protein:urine creatinine ratio of <3 needed to be achieved. | Week 48 |
| Percentage of Participants Who Achieved a CRR or PRR And Who Received a Corticosteroid Dose of <5 mg/Day by Week 48 | CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from Baseline) 2. Inactive urinary sediment 3. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50% reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was >3, a urine protein: urine creatinine ratio of <3 needed to be achieved. | Week 48 |
| Average Corticosteroid Burden Measured by AUC of the Cumulative Corticosteroid Dose Between 16 and 48 Weeks | AUC is the area under the curve (mathematically known as definite integral) in a plot of concentration of drug in blood plasma against time. AUC was to be used to determine the average corticosteroid burden. | Weeks 16, 20, 24, 28, 32, 36, 40, 44, and 48 |
| Percentage of Participants Who Stopped Immunosuppressants After Week 48 | The number of participants who stopped immunosuppressants were to be determined by survey. | Week 48 |
| Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit | CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. CD19+ cells were measured as cells per microliter (cells/uL). | Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32 |
| Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) | CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. 0 represents 0% of participants. | Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32 |
| Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit | CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. n = number of participants analyzed at the specified visit. 0 represents 0% of participants. | Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32 |
| Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit | CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. \ | Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32 |
| Percentage of Participants Achieving a Major Clinical Response or a Partial Clinical Response | A major clinical response was defined as British Isles Lupus Assessment Group (BILAG) C scores or better at Week 24 without developing any new A or two new B scores up to Week 24 and maintenance of this response without developing a moderate or severe flare between Week 24 and Week 48. A partial clinical response was defined as BILAG C scores or better at Week 24 and maintaining this response without developing a flare for 16 consecutive weeks. The BILAG is an organ-specific 86-question assessment based on the principle of the doctor's intent to treat, which requires an assessment of improved (1), the same (2), worse (3), or new (4) over the last month. Within each organ system, multiple manifestations and laboratory tests are combined into a single score for that organ. The resulting scores for each organ can be A through E, where A is very active disease, B is moderate activity, C is mild stable disease, D is resolved activity, and E indicates the organ was never involved. | Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 |
| Adverse event, serious fatal |
|
| Adverse Event |
|
| Withdrawal by Subject |
|
| Administrative reasons |
|
| BG001 | OCR 1000 mg + SOC | Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day. |
| BG002 | Placebo + SOC | Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day. |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | OCR 1000 mg + SOC | Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day. |
| OG002 | Placebo + SOC | Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day. |
|
|
| Primary | Percentage of Participants Who Achieved Overall Response | Overall response rate (ORR) equals (=) CRR + PRR. CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from baseline) 2. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50 % reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio is >3, a urine protein:urine creatinine ratio of <3 needs to be achieved. | The primary endpoint was analyzed via an overall response (CRR+PRR) analysis and the separate complete and partial response rates were only summarized descriptively | Posted | Number | 95% Confidence Interval | Percentage of Participants | Week 48 |
|
|
|
| Secondary | Percentage of Participants Who Achieved a Renal Response (Partial or Complete) by Week 36, and Sustain or Improve This Response Until Week 48 | Efficacy date were summarized in the primary endpoints and due to early study termination the protocol was modified to transition the participants into the safety follow-up period. Additional efficacy outcome measures were not analyzed and study results focus on the full summary of safety data. | Posted | Weeks 36, 40, 44, and 48 |
|
|
| Secondary | Time To Complete Renal Response | Time to complete renal response was proposed to be analyzed using a stratified log rank test with race and SOC as stratification factors. Comparisons of ocrelizumab versus placebo were to be expressed as p-values, estimated hazard ratios, adjusted proportions of participants who achieved a complete renal response and their 95% confidence intervals. Kaplan-Meier curves were to be produced. Due to early termination of the study the analyses were not performed. | Efficacy date were summarized in the primary endpoints and due to early study termination the protocol was modified to transition the participants into the safety follow-up period. Additional efficacy outcome measures were not analyzed and study results focus on the full summary of safety data. | Posted | Baseline up to Week 48 |
|
|
| Secondary | Area Under the Curve (AUC) of Calculated Glomerular Filtration Rate (cGFR) Between Baseline and Week 48 | The improvement of AUC of cGFR was to be measured between Baseline and Week 48. This was to be analyzed with Analysis of Covariance (ANCOVA) with race and SOC as covariates. | Due to the early termination and unblinding of the study, no data was collected for this endpoint and analysis was not performed. | Posted | Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48 |
|
|
| Secondary | Percentage of Participants Who Achieved A Reduction In Systemic Lupus Erythematosis Disease Activity Index (SLEDAI) -2K Score | SLEDAI-2K measures disease activity at the visit or within the preceding 10 days. It comprised of 24 descriptors, covering 9 organ systems, and reflects disease activity over the previous 10 days.The total SLEDAI-2K score falls between 0 and 105, with higher scores representing higher disease activity | Due to the early termination and unblinding of the study, no data was collected for this endpoint and analysis was not performed. | Posted | Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 |
|
|
| Secondary | Time to First Renal Flare In Those Participants Who Demonstrated at Least a Partial Renal Response | Renal flares may be either proteinuric or nephritic as defined below: Proteinuric Flares are defined as follows:In participants who achieve a urine protein:urine creatinine (Upr:Ucr) ≤ 0.5, an increase to Upr:Ucr >1; In participants with an Upr:Ucr >0.5, a doubling of Upr:Ucr (with a minimum increase to Upr:Ucr >2). Nephritic Flare defined as: Increase in serum creatinine of ≥30% from the lowest value achieved in the study accompanied by Increase Upr:Ucr >1 Or New/worsening active urine sediment on two consecutive occasions, in the absence of urinary tract infection or other causes of hematuria. | Efficacy date were summarized in the primary endpoints and due to early study termination the protocol was modified to transition the participants into the safety follow-up period. Additional efficacy outcome measures were not analyzed and study results focus on the full summary of safety data. | Posted | Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 |
|
|
| Secondary | Percentage of Participants Who Achieved Clinically Meaningful Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF36) From Baseline to Week 48 | The SF36 Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. A score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. The eight sections are: vitality, physical functioning, bodily pain, general health perceptions physical role functioning, emotional role functioning, social role functioning, and mental health. | Due to the early termination and unblinding of the study, no data was collected for this endpoint and analysis was not performed. | Posted | Baseline and Weeks 1, 12, 24, 36, and 48 |
|
|
| Secondary | Percentage of Participants Who Achieved Clinically Meaningful Improvement in Fatigue Using the Functional Assessment of Chronic Illness Therapy (Facit) Fatigue Questionnaire From Baseline to Week 48 | The FACIT Fatigue Scale is a short, 13-item, easy-to-administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued). | Due to the early termination and unblinding of the study, no data was collected for this endpoint and analysis was not performed. | Posted | Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 |
|
|
| Secondary | Percentage of Participants Who Achieved Clinically Meaningful Improvement in Pain Using the Modified Brief Pain Inventory Short Form (mBPI-SF) From Baseline to Week 48 | m-BPI-sf is a self-administered 11-point Likert rating scale to rate pain in the past 24 hours. A single item pertains to worst pain in the past 24 hours with a range of 0 (no pain) to 10 (worst imaginable pain). | Due to the early termination and unblinding of the study, no data was collected for this endpoint and analysis was not performed. | Posted | Baseline and Weeks 1, 12, 24, 36, and 48 |
|
|
| Secondary | Health Care Visits Over the 48-Week Treatment Period | The number of health care visits (including doctor's office visits, Emergency room/ Accident and Emergency [ER/A&E] visits and hospitalizations) over the 48-week treatment period were recorded. | Due to the early termination and unblinding of the study, no data was collected for this endpoint and analysis was not performed. | Posted | Weeks 1, 24, and 48 |
|
|
| Secondary | Percentage of Participants Who Achieved a CRR or PRR And Who Received A Corticosteroid Dose of <10 Milligrams Per Day (mg/Day) From Week 24 to Week 48 | CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from Baseline) 2. Inactive urinary sediment 3. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50% reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was >3, a urine protein:urine creatinine ratio of <3 needed to be achieved. | Efficacy date were summarized in the primary endpoints and due to early study termination the protocol was modified to transition the participants into the safety follow-up period. Additional efficacy outcome measures were not analyzed and study results focus on the full summary of safety data. | Posted | Week 48 |
|
|
| Secondary | Percentage of Participants Who Achieved a CRR or PRR And Who Received a Corticosteroid Dose of <5 mg/Day by Week 48 | CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from Baseline) 2. Inactive urinary sediment 3. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50% reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was >3, a urine protein: urine creatinine ratio of <3 needed to be achieved. | Efficacy date were summarized in the primary endpoints and due to early study termination the protocol was modified to transition the participants into the safety follow-up period. Additional efficacy outcome measures were not analyzed and study results focus on the full summary of safety data. | Posted | Week 48 |
|
|
| Secondary | Average Corticosteroid Burden Measured by AUC of the Cumulative Corticosteroid Dose Between 16 and 48 Weeks | AUC is the area under the curve (mathematically known as definite integral) in a plot of concentration of drug in blood plasma against time. AUC was to be used to determine the average corticosteroid burden. | Due to the early termination and unblinding of the study, no data was collected for this endpoint and analysis was not performed. | Posted | Weeks 16, 20, 24, 28, 32, 36, 40, 44, and 48 |
|
|
| Secondary | Percentage of Participants Who Stopped Immunosuppressants After Week 48 | The number of participants who stopped immunosuppressants were to be determined by survey. | Due to the early termination and unblinding of the study, no data was collected for this endpoint and analysis was not performed. | Posted | Week 48 |
|
|
| Secondary | Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit | CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. CD19+ cells were measured as cells per microliter (cells/uL). | N = number of participants analyzed at the specified visit | Posted | Mean | Standard Deviation | Cells/uL | Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32 |
|
|
|
| Secondary | Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) | CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. 0 represents 0% of participants. | N = number of participants analyzed at the specified visit | Posted | Number | Percentage of Participants | Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32 |
|
|
|
| Secondary | Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit | CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. n = number of participants analyzed at the specified visit. 0 represents 0% of participants. | N = number of participants analyzed at the specified visit | Posted | Number | Percentage of Participants | Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32 |
|
|
|
| Secondary | Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit | CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. \ | N = number of participants analyzed at the specified visit | Posted | Number | Percentage of Participants | Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32 |
|
|
|
| Secondary | Percentage of Participants Achieving a Major Clinical Response or a Partial Clinical Response | A major clinical response was defined as British Isles Lupus Assessment Group (BILAG) C scores or better at Week 24 without developing any new A or two new B scores up to Week 24 and maintenance of this response without developing a moderate or severe flare between Week 24 and Week 48. A partial clinical response was defined as BILAG C scores or better at Week 24 and maintaining this response without developing a flare for 16 consecutive weeks. The BILAG is an organ-specific 86-question assessment based on the principle of the doctor's intent to treat, which requires an assessment of improved (1), the same (2), worse (3), or new (4) over the last month. Within each organ system, multiple manifestations and laboratory tests are combined into a single score for that organ. The resulting scores for each organ can be A through E, where A is very active disease, B is moderate activity, C is mild stable disease, D is resolved activity, and E indicates the organ was never involved. | Efficacy date were summarized in the primary endpoints and due to early study termination the protocol was modified to transition the participants into the safety follow-up period. Additional efficacy outcome measures were not analyzed and study results focus on the full summary of safety data. | Posted | Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 |
|
|
| 6 |
| 125 |
| 36 |
| 125 |
| 96 |
| 125 |
| EG001 | OCR 1000 mg + SOC | Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day. | 6 | 127 | 38 | 127 | 91 | 127 |
| EG002 | OCR 400 mg + SOC | Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day. | 3 | 126 | 53 | 126 | 101 | 126 |
| Hypertension | Vascular disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Malignant hypertension | Vascular disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Acute myeloid leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.1 | Non-systematic Assessment |
|
| Anogenital warts | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.1 | Non-systematic Assessment |
|
| Cervix carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.1 | Non-systematic Assessment |
|
| Gastric cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.1 | Non-systematic Assessment |
|
| Rectal adenoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.1 | Non-systematic Assessment |
|
| Renal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.1 | Non-systematic Assessment |
|
| Abortion missed | Pregnancy, puerperium and perinatal conditions | MedDRA 13.1 | Non-systematic Assessment |
|
| Gestational hypertension | Pregnancy, puerperium and perinatal conditions | MedDRA 13.1 | Non-systematic Assessment |
|
| Adverse drug reaction | General disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Generalised oedema | General disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Polyserositis | General disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Suicide attempt | Psychiatric disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Amenorrhoea | Reproductive system and breast disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Cervical dysplasia | Reproductive system and breast disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Ovarian cyst | Reproductive system and breast disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Ovarian mass | Reproductive system and breast disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 13.1 | Non-systematic Assessment |
|
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA 13.1 | Non-systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 13.1 | Non-systematic Assessment |
|
| Blood creatine increased | Investigations | MedDRA 13.1 | Non-systematic Assessment |
|
| Weight increased | Investigations | MedDRA 13.1 | Non-systematic Assessment |
|
| Acute myocardial infarction | Cardiac disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Cardiac failure | Cardiac disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Cardiac failure congestive | Cardiac disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Cardio-respiratory arrest | Cardiac disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Myocardial infarction | Cardiac disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Pleuropericarditis | Cardiac disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Stress cardiomyopathy | Cardiac disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Agranulocytosis | Blood and lymphatic system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Anaemia of chronic disease | Blood and lymphatic system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Antiphospholipid syndrome | Blood and lymphatic system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Cerebral haemorrhage | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Cerebral infarction | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Cerebrovascular disorder | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Ischaemic stroke | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Lupus encephalitis | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Vasculitis cerebral | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Enteritis | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Rectal ulcer | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Lupus nephritis | Renal and urinary disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Nephritis | Renal and urinary disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Nephrotic syndrome | Renal and urinary disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Renal disorder | Renal and urinary disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Renal failure chronic | Renal and urinary disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Tubulointerstitial nephritis | Renal and urinary disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Urinary bladder haemorrhage | Renal and urinary disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Hepatitis | Hepatobiliary disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Muscle contracture | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Systemic lupus erythematosus | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Abscess | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Abscess limb | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Appendicitis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Arthritis bacterial | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Bacterial sepsis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Bronchopneumonia | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Enteritis infectious | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Erysipelas | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Gastrointestinal infection | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| H1N1 influenza | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Haematoma infection | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Herpes virus infection | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Herpes zoster disseminated | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Impetigo | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Infection | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Laryngitis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Legionella infection | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Neurocryptococcosis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Neutropenic infection | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Neutropenic sepsis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Pneumocystis jirovecii pneumonia | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Pneumonia cytomegaloviral | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Pseudomembranous colitis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Pyelonephritis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Pyoderma | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Salmonella bacteraemia | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Salmonella sepsis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Staphylococcal bacteraemia | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Strongyloidiasis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Tuberculosis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Urosepsis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 13.1 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Dyslipidaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D013872 | Thionucleosides |
| D013457 | Sulfur Compounds |
| D015122 | Mercaptopurine |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
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| Day 15 Pre-infusion |
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| Week 16 Pre-infusion |
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| Week 32 Post-infusion |
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| Day 15 |
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| Week 4 |
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| Week 16 |
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| Week 32 |
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| Week 48 |
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| Day 1 Pre-infusion |
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| Day 1 Post-infusion |
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| Day 15 Pre-infusion |
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| Day 15 Post-infusion |
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| Week 16 Pre-infusion |
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| Week 16 Post-infusion |
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| Week 32 Pre-infusion |
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| Week 32 Post-infusion |
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