Lupus Nephritis
Conditions
Keywords
nephritis, atacicept
Brief summary
The purpose of this study is to learn whether atacicept treatment leads to improvement in kidney function in subjects with active lupus nephritis in combination with mycophenolate mofetil (MMF) and corticosteroids. The study was sponsored by Merck Serono International; operational oversight was provided by ZymoGenetics.
Interventions
DRUGAtacicept
Atacicept will be administered at a dose of 150 milligram (mg) subcutaneously (SC) twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks.
DRUGMycophenolate mofetil
MMF will be administered orally with a starting dose of 500 mg twice daily for 1 week, will be increased to 1000 mg twice daily for 1 week, then it will be adjusted to 1500 mg or lower twice daily as per investigator's discretion.
DRUGPlacebo
Placebo will be administered at a dose of 150 mg SC twice weekly for 4 weeks followed by 150 mg SC once weekly for 48 weeks.
DRUGCorticosteroids
High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever is less will be administered for 4 Weeks and will be tapered to 7.5 to 10 mg/day up to Week 12.
Sponsors
ZymoGenetics
EMD Serono
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
* Diagnosis of systemic lupus erythematosus (SLE) satisfying at least 4 out of the 11 American College of Rheumatology (ACR) criteria (Appendix B) * Renal biopsy performed consistent with active International Society of Nephrology/Renal Pathology Society (ISN/PRS) class III or IV lupus nephritis
Exclusion criteria
* Estimated glomerular filtration rate (GFR) less than or equal to (\<=) 30 milliliter per minute (mL/min) per 1.73 square meter (m\^2) * Active central nervous system SLE deemed to be severe or progressive and/or associated with significant cognitive impairment * Any treatment with MMF, azathioprine, or cyclophosphamide within the last 6 months, or known hypersensitivity to MMF or atacicept. * Any prior treatment with abatacept, rituximab, belimumab, or other B cell modulating agents.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Confirmed Complete Renal Response (CRR), Partial Response, and Non-response | At Week 52 | Complete renal response (CRR): from baseline, a return to within 10% of normal for renal function (assessed by calculated glomerular filtration rate \[GFR\]), improvement in proteinuria (urine protein/creatinine ratio \<0.5) & resolution of hematuria. Partial response (PR): from baseline, a \<= 10% worsening in renal function ( by calculated GFR); 50% improvement in proteinuria (assessed by urine protein/creatinine ratio) & resolution of hematuria, Non-response (NR): Neither criteria for CR or PR was met. Subjects were also deemed NR if they had treatment failure, regardless of CR or PR status. Subjects cannot be treatment failures. A response of CRR was confirmed if the Week 52 value is CRRand if the Week 48 value is CRR and at least 4 weeks apart from Week 52 /if the Week 48 value was missing/ less than 4 weeks from Week 52, then the Week 56 response must be CRR - if the Week 52 value was missing, then Week 48 and Week 56 must be CRR. |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Normalization of Renal Function | At Week 52 |
| Number of Participants With New Lupus Flares | At Week 52 |
Countries
Czechia, Malaysia, Singapore, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atacicept Plus Mycophenolate Mofetil Plus Corticosteroids Atacicept was administered SC at a loading dose of 150 mg twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks. MMF was administered orally with a starting dose of 500 mg twice daily for 1 week, increased to 1000 mg twice daily for 1 week, then adjusted to 1500 mg or lower twice daily as per investigator's discretion. High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever was less was administered for 4 Weeks and tapered to 7.5 to 10 mg/day up to Week 12. | 4 |
| Placebo Plus Mycophenolate Mofetil Plus Corticosteroids Placebo was administered SC at a loading dose of 150 mg twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks. MMF was administered orally with a starting dose of 500 mg twice daily for 1 week, increased to 1000 mg twice daily for 1 week, then adjusted to 1500 mg or lower twice daily as per investigator's discretion. High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever was less was administered for 4 Weeks and tapered to 7.5 to 10 mg/day up to Week 12. | 2 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Other | 1 | 1 |
Baseline characteristics
| Characteristic | Atacicept Plus Mycophenolate Mofetil Plus Corticosteroids | Placebo Plus Mycophenolate Mofetil Plus Corticosteroids | Total |
|---|---|---|---|
| Age, Continuous | 36.8 years STANDARD_DEVIATION 11.3 | 36.0 years STANDARD_DEVIATION 25.5 | 36.5 years STANDARD_DEVIATION 14.4 |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 1 / 2 |
| serious Total, serious adverse events | 3 / 4 | 0 / 2 |
Outcome results
Primary
Percentage of Participants With Confirmed Complete Renal Response (CRR), Partial Response, and Non-response
Complete renal response (CRR): from baseline, a return to within 10% of normal for renal function (assessed by calculated glomerular filtration rate \[GFR\]), improvement in proteinuria (urine protein/creatinine ratio \<0.5) & resolution of hematuria. Partial response (PR): from baseline, a \<= 10% worsening in renal function ( by calculated GFR); 50% improvement in proteinuria (assessed by urine protein/creatinine ratio) & resolution of hematuria, Non-response (NR): Neither criteria for CR or PR was met. Subjects were also deemed NR if they had treatment failure, regardless of CR or PR status. Subjects cannot be treatment failures. A response of CRR was confirmed if the Week 52 value is CRRand if the Week 48 value is CRR and at least 4 weeks apart from Week 52 /if the Week 48 value was missing/ less than 4 weeks from Week 52, then the Week 56 response must be CRR - if the Week 52 value was missing, then Week 48 and Week 56 must be CRR.
Time frame: At Week 52
Population: Due to early termination of the study caused by unanticipated safety issues, the outcome measure was not assessed.
Secondary
Number of Participants With New Lupus Flares
Time frame: At Week 52
Population: Due to early termination of the study caused by unanticipated safety issues, the outcome measure was not assessed.
Secondary
Percentage of Participants With Normalization of Renal Function
Time frame: At Week 52
Population: Due to early termination of the study caused by unanticipated safety issues, the outcome measure was not assessed.