Systemic Lupus Erythematosus
Conditions
Keywords
SLE
Brief summary
This is a Phase III, randomized, double blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of ocrelizumab compared to placebo when combined with a single stable background immunosuppressive medication and a corticosteroid regimen in patients with moderately to severely active systemic lupus erythematosus, who do not have moderate to severe glomerulonephritis.
Interventions
DRUGPrednisone
Oral repeating dose
DRUGImmunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate)
Oral repeating dose
DRUGMethylprednisolone
Intravenous repeating dose
DRUGOcrelizumab
Intravenous repeating dose
DRUGPlacebo
Intravenous repeating dose
Sponsors
Roche Pharma AG
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 16 years or above at the time of screening * Diagnosis of SLE * Active disease at screening
Exclusion criteria
* Presence of active moderate to severe glomerulonephritis * Currently active retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia * Lack of peripheral venous access * Pregnancy or breast feeding mothers * History of severe allergic or anaphylactic reactions to humanized, chimeric or murine monoclonal antibodies or i.v. immunoglobulin * Known severe chronic pulmonary disease * Evidence of significant or uncontrolled concomitant diseases in any organ system not related to SLE, which, in the investigator's opinion, would impair patient participation * Concomitant condition which has required treatment with systemic corticosteroid (excluding topical or inhaled) at any time in the 52 weeks prior to screening * Known HIV or chronic active Hepatitis B or chronic active Hepatitis C infection * Known active infection of any kind (but excluding fungal infection of nail beds or oral thrush which has resolved before Day 1) within 30 days prior to Day 1. In addition, any major episode of infection requiring hospitalization or treatment with intravenous anti-infectives in the 30 days prior to Day 1 or oral anti-infectives in the 14 days prior to Day 1 * History of serious recurrent or chronic infection * History of cancer (except basal cell carcinoma of the skin that has been excised and cured) * History of alcohol or drug abuse in the 52 weeks prior to screening * Major surgery in the 4 weeks prior to screening excluding diagnostic surgery * Previous treatment with CAMPATH-1H * Previous treatment with a BAFF directed treatment in the 12 months prior to screening * Previous treatment with a B-cell targeted therapy other than one directed at BAFF * Treatment with any investigational agent, other than those above, in the 28 days prior to screening or five half-lives of the investigational drug (whichever is longer) * Receipt of any live vaccine in the 6 weeks prior to Day 1 * Intolerance or contraindication to oral or i.v. corticosteroids * Treatment with a second immunosuppressive or immunomodulatory drug in the 8 weeks prior to Day 1 * Prednisone dose of ≥ 0.7 mg/kg/day (or equivalent) for \> 7 of the previous 30 days prior to screening * Treatment with cyclophosphamide or a calcineurin inhibitor in the 12 weeks prior to screening * Positive hepatitis BsAg or hepatitis C serology. Patients who are HBsAg negative but HBcAb positive may be enrolled with a negative DNA test
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Major Clinical Response (MCR) | Week 48 |
| Number of Participants With Partial Clinical Response (PCR) | Week 48 |
| Number of Non-responders (NR) | Week 48 |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants Achieved A MCR At Week 48, Who Did Not Experience A Flare Before Week 96 | Week 48 to Week 96 |
| Change in SF-36 Subscale And Summary Scores From Baseline At Week 48 | Baseline, Week 48 |
| Change In FACIT-Fatigue Assessment From Baseline To Week 48 | Baseline, Week 48 |
| Change From Baseline In Pain Quality And Impact Of Pain On Daily Function Measured By The Brief Pain Inventory Short Form At Week 48 | Baseline, Week 48 |
| Time to First Moderate to Severe Flare | Week 48 to Week 96 |
| Number of Participants With Adverse Events | Up to 2.5 years |
| Number of Participants Who Achieved a BILAG Score of C or Better at Week 24. | Week 24 |
| Time Adjusted Mean SLEDAI-2K Score | Week 48 |
| Annualized Flare Rate | Week 48 to Week 96 |
| The EQ-5D Single Index Utility Score At Week 48 | Baseline, Week 48 |
| Number of Participants Who Achieved A Major Or Partial Clinical Response At Week 48 (PCR Plus MCR Proportion), Who Did Not Experience A Flare Before Week 96 | Week 48 to Week 96 |
| Number of Participants Who Achieved A MCR At Week 48, Who Did Not Experience A Flare Before Week 72 | Week 48 to Week 72 |
Participant flow
Recruitment details
A maximum screening window of 14 days was allowed.
Pre-assignment details
During the screening period, participants received oral prednisone after the physician's evaluation and scoring of a BILAG questionnaire.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo infusions were administered on Days 1 and 15, followed by placebo infusion at Week 16 and then every 16 weeks | 10 |
| Ocrelizumab 400 mg Ocrelizumab was administered at a dose 400 mg i.v. on Days 1 and 15, followed by 400 mg i.v. at Week 16 and then every 16 weeks | 11 |
| Ocrelizumab 1000 mg Ocrelizumab was administered i.v. at a dose on Days 1 and 15, followed by 1000 mg i.v. at Week 16 and then every 16 weeks | 12 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative | 4 | 0 | 8 |
| Overall Study | Death | 0 | 2 | 0 |
| Overall Study | Did not cooperate | 1 | 0 | 1 |
| Overall Study | Fail to return | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 4 | 0 |
Baseline characteristics
| Characteristic | Placebo | Ocrelizumab 400 mg | Ocrelizumab 1000 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 41.0 Years STANDARD_DEVIATION 13.82 | 40.2 Years STANDARD_DEVIATION 8.8 | 36.3 Years STANDARD_DEVIATION 11.31 | 39.0 Years STANDARD_DEVIATION 11.24 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 2 Participants | 4 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 9 Participants | 8 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 1 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 8 Participants | 7 Participants | 20 Participants |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 10 Participants | 30 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 10 | 10 / 11 | 8 / 12 |
| serious Total, serious adverse events | 0 / 10 | 6 / 11 | 3 / 12 |
Outcome results
Primary
Number of Non-responders (NR)
Time frame: Week 48
Population: Evaluation of the primary and some secondary endpoints was to occur at Week 48 with further analyses conducted at Week 96. However, following the early termination of the study, the analysis of the primary and secondary endpoints were not conducted
Primary
Number of Participants With Major Clinical Response (MCR)
Time frame: Week 48
Population: Evaluation of the primary and some secondary endpoints was to occur at Week 48 with further analyses conducted at Week 96. However, following the early termination of the study, the analysis of the primary and secondary endpoints were not conducted.
Primary
Number of Participants With Partial Clinical Response (PCR)
Time frame: Week 48
Population: Evaluation of the primary and some secondary endpoints was to occur at Week 48 with further analyses conducted at Week 96. However, following the early termination of the study, the analysis of the primary and secondary endpoints were not conducted
Secondary
Annualized Flare Rate
Time frame: Week 48 to Week 96
Population: Evaluation of the primary and some secondary endpoints was to occur at Week 48 with further analyses conducted at Week 96. However, following the early termination of the study, the analysis of the primary and secondary endpoints were not conducted
Secondary
Change From Baseline In Pain Quality And Impact Of Pain On Daily Function Measured By The Brief Pain Inventory Short Form At Week 48
Time frame: Baseline, Week 48
Population: Evaluation of the primary and some secondary endpoints was to occur at Week 48 with further analyses conducted at Week 96. However, following the early termination of the study, the analysis of the primary and secondary endpoints were not conducted
Secondary
Change In FACIT-Fatigue Assessment From Baseline To Week 48
Time frame: Baseline, Week 48
Population: Evaluation of the primary and some secondary endpoints was to occur at Week 48 with further analyses conducted at Week 96. However, following the early termination of the study, the analysis of the primary and secondary endpoints were not conducted
Secondary
Change in SF-36 Subscale And Summary Scores From Baseline At Week 48
Time frame: Baseline, Week 48
Population: Evaluation of the primary and some secondary endpoints was to occur at Week 48 with further analyses conducted at Week 96. However, following the early termination of the study, the analysis of the primary and secondary endpoints were not conducted
Secondary
Number of Participants Achieved A MCR At Week 48, Who Did Not Experience A Flare Before Week 96
Time frame: Week 48 to Week 96
Population: Evaluation of the primary and some secondary endpoints was to occur at Week 48 with further analyses conducted at Week 96. However, following the early termination of the study, the analysis of the primary and secondary endpoints were not conducted
Secondary
Number of Participants Who Achieved a BILAG Score of C or Better at Week 24.
Time frame: Week 24
Population: Evaluation of the primary and some secondary endpoints was to occur at Week 48 with further analyses conducted at Week 96. However, following the early termination of the study, the analysis of the primary and secondary endpoints were not conducted
Secondary
Number of Participants Who Achieved A Major Or Partial Clinical Response At Week 48 (PCR Plus MCR Proportion), Who Did Not Experience A Flare Before Week 96
Time frame: Week 48 to Week 96
Population: Evaluation of the primary and some secondary endpoints was to occur at Week 48 with further analyses conducted at Week 96. However, following the early termination of the study, the analysis of the primary and secondary endpoints were not conducted
Secondary
Number of Participants Who Achieved A MCR At Week 48, Who Did Not Experience A Flare Before Week 72
Time frame: Week 48 to Week 72
Population: Evaluation of the primary and some secondary endpoints was to occur at Week 48 with further analyses conducted at Week 96. However, following the early termination of the study, the analysis of the primary and secondary endpoints were not conducted
Secondary
Number of Participants With Adverse Events
Time frame: Up to 2.5 years
Population: Evaluation of the primary and some secondary endpoints was to occur at Week 48 with further analyses conducted at Week 96. However, following the early termination of the study, the analysis of the primary and secondary endpoints were not conducted
Secondary
The EQ-5D Single Index Utility Score At Week 48
Time frame: Baseline, Week 48
Population: Evaluation of the primary and some secondary endpoints was to occur at Week 48 with further analyses conducted at Week 96. However, following the early termination of the study, the analysis of the primary and secondary endpoints were not conducted
Secondary
Time Adjusted Mean SLEDAI-2K Score
Time frame: Week 48
Population: Evaluation of the primary and some secondary endpoints was to occur at Week 48 with further analyses conducted at Week 96. However, following the early termination of the study, the analysis of the primary and secondary endpoints were not conducted
Secondary
Time to First Moderate to Severe Flare
Time frame: Week 48 to Week 96
Population: Evaluation of the primary and some secondary endpoints was to occur at Week 48 with further analyses conducted at Week 96. However, following the early termination of the study, the analysis of the primary and secondary endpoints were not conducted