Lupus Nephritis
Conditions
Brief summary
The primary objective of the study is to evaluate the long-term safety and tolerability of BIIB023 in participants with lupus nephritis (LN).
Detailed description
This is an extension study for all participants who completed study 211LE201 (NCT01499355) through Week 52 and did not discontinue BIIB023 or placebo. Eligible participants from Study 211LE201 will be followed for up to 108 weeks. Participants who received BIIB023 low dose or high dose in 211LE201 will continue to receive the same dosing in this study (211LE202; NCT01930890) in addition to background therapy. Participants who received placebo in 211LE201 are randomized to receive either BIIB023 low dose or high dose in addition to background therapy.
Interventions
BIOLOGICALBIIB023
DRUGmycophenolate mofetil
titrated to a target daily dose of 2 g (1 g twice daily)
oral corticosteroids (prednisone or equivalent) at a target prednisone dose of 10 mg/day
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to 76 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Subjects who completed Week 52 of Study 211LE201 (NCT01499355) and did not discontinue BIIB023 or placebo study treatment. * Subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 6 months after their last dose of study treatment. Key
Exclusion criteria
* Any significant change in medical history in subjects from Study 211LE201, including laboratory tests or current clinically significant condition that, in the opinion of the Investigator, would have excluded the subjects' participation. The Investigator must re-review the subject's medical fitness for participation and consider any diseases that would preclude treatment under this protocol. * Subjects from Study 211LE201 who discontinued BIIB023 or placebo treatment prior to Week 52 of Study 211LE201. * Female subjects considering becoming pregnant while in the study, currently pregnant, or breast feeding. * Unwillingness or inability to comply with the requirements of the protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the protocol. * Other unspecified reasons that, in the opinion of the Investigator or Biogen, makes the subject unsuitable for enrollment. NOTE: Other Protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Week 108 | AEs with a start date on or after the first dose date in study 211LE202. AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the subject at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed above. |
| Number of Participants Who Discontinued Study Treatment or Withdrew From Study Due to an AE | Up to Week 108 | AEs with a start date on or after the first dose date in study 211LE202. AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the subject at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed above. |
Countries
Argentina, Australia, Belgium, Brazil, Colombia, France, Hong Kong, Hungary, Italy, Malaysia, Mexico, Peru, Philippines, Poland, Russia, South Korea, Spain, Thailand, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo (211LE201) to BIIB023 3 mg/kg (211LE202) Participants who received placebo every 4 weeks (Q4W) plus MMF and oral corticosteroids in 211LE201 and received BIIB023 3 mg/kg IV Q4W plus MMF and oral corticosteroids through Week 100 in 211LE202. | 14 |
| BIIB023 3 mg/kg (211LE201) to BIIB023 3 mg/kg (211LE202) Participants who received BIIB023 3 mg/kg Q4W plus MMF and oral corticosteroids in 211LE201 and received BIIB023 3 mg/kg IV Q4W plus MMF and oral corticosteroids through Week 100 in 211LE202. | 33 |
| Placebo (211LE201) to BIIB023 20 mg/kg (211LE202) Participants who received placebo every 4 weeks (Q4W) plus MMF and oral corticosteroids in 211LE201 and received BIIB023 20 mg/kg IV Q4W plus MMF and oral corticosteroids through Week 100 in 211LE202. | 13 |
| BIIB023 20 mg/kg (211LE201) to BIIB023 20 mg/kg (211LE202) Participants who received BIIB023 20 mg/kg Q4W plus MMF and oral corticosteroids in 211LE201 and received BIIB023 20 mg/kg IV Q4W plus MMF and oral corticosteroids through Week 100 in 211LE202. | 27 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 |
| Overall Study | Consent Withdrawn | 0 | 3 | 0 | 1 |
| Overall Study | Death | 0 | 0 | 0 | 1 |
| Overall Study | Investigator Decision | 0 | 1 | 0 | 0 |
| Overall Study | Study Termination | 14 | 28 | 13 | 25 |
Baseline characteristics
| Characteristic | Placebo (211LE201) to BIIB023 3 mg/kg (211LE202) | BIIB023 3 mg/kg (211LE201) to BIIB023 3 mg/kg (211LE202) | Placebo (211LE201) to BIIB023 20 mg/kg (211LE202) | BIIB023 20 mg/kg (211LE201) to BIIB023 20 mg/kg (211LE202) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 31.3 years STANDARD_DEVIATION 8.96 | 32.6 years STANDARD_DEVIATION 8.93 | 31.5 years STANDARD_DEVIATION 10.06 | 32.2 years STANDARD_DEVIATION 8.23 | 32.1 years STANDARD_DEVIATION 8.76 |
| Age, Customized 18 to 19 years | 0 participants | 0 participants | 1 participants | 1 participants | 2 participants |
| Age, Customized 20 to 29 years | 6 participants | 15 participants | 6 participants | 9 participants | 36 participants |
| Age, Customized 30 to 39 years | 6 participants | 11 participants | 3 participants | 14 participants | 34 participants |
| Age, Customized 40 to 49 years | 2 participants | 6 participants | 2 participants | 1 participants | 11 participants |
| Age, Customized 50 to 55 years | 0 participants | 0 participants | 1 participants | 2 participants | 3 participants |
| Age, Customized > 55 years | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Gender Female | 11 Participants | 29 Participants | 10 Participants | 25 Participants | 75 Participants |
| Gender Male | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 14 | 19 / 33 | 7 / 13 | 13 / 27 |
| serious Total, serious adverse events | 1 / 14 | 7 / 33 | 4 / 13 | 3 / 27 |
Outcome results
Primary
Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs with a start date on or after the first dose date in study 211LE202. AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the subject at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed above.
Time frame: Up to Week 108
Population: The safety population was defined as all participants who received at least 1 dose of study treatment (3 or 20 mg/kg BIIB023 in Study 211LE202).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious event related to dose-blinded treatment | 0 participants |
| Placebo (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious event | 1 participants |
| Placebo (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Fatal event | 0 participants |
| Placebo (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Event related to dose-blinded treatment | 1 participants |
| Placebo (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Severe event | 0 participants |
| Placebo (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Moderate or severe event | 2 participants |
| Placebo (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious event related to MMF | 0 participants |
| Placebo (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Event related to MMF | 2 participants |
| Placebo (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any event | 4 participants |
| BIIB023 3 mg/kg (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Event related to MMF | 8 participants |
| BIIB023 3 mg/kg (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious event related to dose-blinded treatment | 2 participants |
| BIIB023 3 mg/kg (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious event | 7 participants |
| BIIB023 3 mg/kg (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Moderate or severe event | 12 participants |
| BIIB023 3 mg/kg (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any event | 23 participants |
| BIIB023 3 mg/kg (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Severe event | 4 participants |
| BIIB023 3 mg/kg (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Fatal event | 0 participants |
| BIIB023 3 mg/kg (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious event related to MMF | 3 participants |
| BIIB023 3 mg/kg (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Event related to dose-blinded treatment | 5 participants |
| Placebo (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Event related to MMF | 2 participants |
| Placebo (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any event | 7 participants |
| Placebo (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Moderate or severe event | 3 participants |
| Placebo (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Severe event | 1 participants |
| Placebo (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Event related to dose-blinded treatment | 1 participants |
| Placebo (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious event | 4 participants |
| Placebo (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious event related to dose-blinded treatment | 1 participants |
| Placebo (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious event related to MMF | 1 participants |
| Placebo (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Fatal event | 0 participants |
| BIIB023 20 mg/kg (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious event related to dose-blinded treatment | 1 participants |
| BIIB023 20 mg/kg (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Event related to dose-blinded treatment | 4 participants |
| BIIB023 20 mg/kg (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Severe event | 3 participants |
| BIIB023 20 mg/kg (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Fatal event | 1 participants |
| BIIB023 20 mg/kg (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious event related to MMF | 2 participants |
| BIIB023 20 mg/kg (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Moderate or severe event | 6 participants |
| BIIB023 20 mg/kg (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious event | 3 participants |
| BIIB023 20 mg/kg (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Event related to MMF | 9 participants |
| BIIB023 20 mg/kg (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any event | 19 participants |
Primary
Number of Participants Who Discontinued Study Treatment or Withdrew From Study Due to an AE
AEs with a start date on or after the first dose date in study 211LE202. AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the subject at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed above.
Time frame: Up to Week 108
Population: The safety population was defined as all participants who received at least 1 dose of study treatment (3 or 20 mg/kg BIIB023 in Study 211LE202).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Who Discontinued Study Treatment or Withdrew From Study Due to an AE | Discontinued treatment due to an AE | 0 participants |
| Placebo (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Who Discontinued Study Treatment or Withdrew From Study Due to an AE | Withdrew from study due to an AE | 0 participants |
| BIIB023 3 mg/kg (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Who Discontinued Study Treatment or Withdrew From Study Due to an AE | Withdrew from study due to an AE | 2 participants |
| BIIB023 3 mg/kg (211LE201) to BIIB023 3 mg/kg (211LE202) | Number of Participants Who Discontinued Study Treatment or Withdrew From Study Due to an AE | Discontinued treatment due to an AE | 0 participants |
| Placebo (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Who Discontinued Study Treatment or Withdrew From Study Due to an AE | Discontinued treatment due to an AE | 0 participants |
| Placebo (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Who Discontinued Study Treatment or Withdrew From Study Due to an AE | Withdrew from study due to an AE | 0 participants |
| BIIB023 20 mg/kg (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Who Discontinued Study Treatment or Withdrew From Study Due to an AE | Discontinued treatment due to an AE | 0 participants |
| BIIB023 20 mg/kg (211LE201) to BIIB023 20 mg/kg (211LE202) | Number of Participants Who Discontinued Study Treatment or Withdrew From Study Due to an AE | Withdrew from study due to an AE | 1 participants |