Systemic Lupus Erythematosus
Conditions
Brief summary
The purpose of this study is to determine the ability of XmAb5871 to maintain Systemic Lupus Erythematosus (SLE) disease activity improvement achieved by a brief course of disease-suppressing steroid therapy
Interventions
BIOLOGICALXmAb5871
BIOLOGICALPlacebo to match XmAb5871
Sponsors
PPD Development, LP
ICON plc
Xencor, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized (1:1, no stratification), Double-Blinded, Placebo-Controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients with a diagnosis of SLE as defined by the ACR criteria * Patients have a history of a (+) ANA, (+) ENA or a (+) anti-dsDNA serology documented within one year prior to randomization * Investigator has assessed the patient and in their judgment, the SLE disease activity is not organ threatening * Both investigator and patient agree that it is acceptable to discontinue their current immunosuppressant SLE medications and receive a brief course of IM steroid therapy * If patients are on oral steroids, they must be on the equivalent of ≤15 mg/day of prednisone to enter screening, and must be able to taper to ≤10 mg/day by randomization
Exclusion criteria
* History or evidence of a clinically unstable/uncontrolled disorder, condition or disease, other than SLE that, in the opinion of the investigator would pose a risk to patient safety or interfere with the study evaluation, procedures or completion * Patients who have organ threatening manifestations of SLE including active Class 3 or 4 lupus nephritis requiring induction or maintenance therapy or any other disorder for which stopping SLE therapy is contraindicated * Active CNS lupus such as seizures or psychosis that in the opinion of the investigator would preclude participation * Unstable hemolytic anemia or thrombocytopenia * Patient is pregnant or breast feeding, or planning to become pregnant while participating in the study * Use of any biologic therapy (including belimumab) within 6 months of randomization, or prior exposure to a monoclonal antibody directed to CD20 (such as rituximab) within 12 months of randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Without Loss of Systemic Lupus Erythematosus Disease Activity Improvement on Day 225 | Day 225 | Landmark proportion of patients without loss of systemic lupus erythematosus disease activity improvement on Day 225 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Without Loss of Systemic Lupus Erythematosus Disease Activity Improvement on Day 169 | Day 169 | Landmark proportion of patients without loss of systemic lupus erythematosus disease activity improvement on Day 169 |
| Time to Loss of Systemic Lupus Erythematosus Disease Activity Improvement Achieved by a Short Period of IM Steroid Therapy in SLE Patients | From the date of randomization until the date of loss of Systemic Lupus Erythematosus Disease Activity Improvement, or the date of the final efficacy assessment, up to 239 days. | Loss of improvement was defined as worsening of disease activity that in the opinion of the principal investigator requires a change in treatment (exclusive of a decrease in oral steroids) AND one of: 1. SELENA- SLEDAI increase of \>=4 points from maximal improvement OR 2. Worsening of at least 1 BILAG A or B score OR 3. New BILAG A or B score. |
Countries
United States
Participant flow
Recruitment details
First informed consent date: 16FEB2016 First randomization date: 07MAR2016 Last informed consent date: 09NOV2017 Last randomization date: 07DEC2017
Pre-assignment details
After obtaining informed consent, IM depomedrol was administered and screening studies were performed over the 2-4 week screening period. Immunosuppressive therapy must have been stopped or tapered off by randomization on Day 1. Patients who did not meet the disease activity improvement criteria during the screening period were not randomized.
Participants by arm
| Arm | Count |
|---|---|
| XmAb5871 XmAb5871 administered by IV infusion for up to a total of 16 infusions | 52 |
| Placebo Placebo to match XmA5871 administered by IV infusion for up to a total of 16 infusions | 52 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 2 |
| Overall Study | Completed Study Under Original Protocol | 0 | 1 |
| Overall Study | Lack of Response | 0 | 1 |
| Overall Study | Loss of Improvement per Protocol | 14 | 25 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | No Documented Disease Improvement | 0 | 1 |
| Overall Study | Non-Compliance With Study Drug | 0 | 3 |
| Overall Study | Refused infusion (no study treatment) | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | XmAb5871 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 45.5 years | 45.0 years | 43.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 10 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 94 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 26 Participants | 51 Participants | 25 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 44 Participants | 25 Participants |
| Region of Enrollment United States | 52 participants | 104 participants | 52 participants |
| Sex: Female, Male Female | 50 Participants | 99 Participants | 49 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 3 Participants |
| SLEDAI Total Score at Screening--Efficacy Evaluable Population | 8.0 units on a scale | 10.0 units on a scale | 10.0 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 52 |
| other Total, other adverse events | 41 / 52 | 28 / 52 |
| serious Total, serious adverse events | 7 / 52 | 4 / 52 |
Outcome results
Primary
Percentage of Patients Without Loss of Systemic Lupus Erythematosus Disease Activity Improvement on Day 225
Landmark proportion of patients without loss of systemic lupus erythematosus disease activity improvement on Day 225
Time frame: Day 225
Population: Efficacy Evaluable Population: All patients who:~* Complete study through Day 225 assessments~* Discontinue due to reaching the protocol specified LOI endpoint (and have not missed 2 or more consecutive doses prior to the LOI visit)~* Discontinue due to drug-related adverse event (nonresponder)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| XmAb5871 | Percentage of Patients Without Loss of Systemic Lupus Erythematosus Disease Activity Improvement on Day 225 | 21 Participants |
| Placebo | Percentage of Patients Without Loss of Systemic Lupus Erythematosus Disease Activity Improvement on Day 225 | 12 Participants |
p-value: 0.18395% CI: [-6.6, 32.6]Barnard's Unconditional Exact Test P-val
Secondary
Percentage of Patients Without Loss of Systemic Lupus Erythematosus Disease Activity Improvement on Day 169
Landmark proportion of patients without loss of systemic lupus erythematosus disease activity improvement on Day 169
Time frame: Day 169
Population: Efficacy Evaluable Population: All patients who:~* Complete study through Day 225 assessments~* Discontinue due to reaching the protocol specified LOI endpoint (and have not missed 2 or more consecutive doses prior to the LOI visit)~* Discontinue due to drug-related adverse event (nonresponder)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| XmAb5871 | Percentage of Patients Without Loss of Systemic Lupus Erythematosus Disease Activity Improvement on Day 169 | 29 Participants |
| Placebo | Percentage of Patients Without Loss of Systemic Lupus Erythematosus Disease Activity Improvement on Day 169 | 17 Participants |
p-value: 0.107595% CI: [-3.7, 37.3]Barnard's Unconditional Exact Test P-val
Secondary
Time to Loss of Systemic Lupus Erythematosus Disease Activity Improvement Achieved by a Short Period of IM Steroid Therapy in SLE Patients
Loss of improvement was defined as worsening of disease activity that in the opinion of the principal investigator requires a change in treatment (exclusive of a decrease in oral steroids) AND one of: 1. SELENA- SLEDAI increase of \>=4 points from maximal improvement OR 2. Worsening of at least 1 BILAG A or B score OR 3. New BILAG A or B score.
Time frame: From the date of randomization until the date of loss of Systemic Lupus Erythematosus Disease Activity Improvement, or the date of the final efficacy assessment, up to 239 days.
Population: Efficacy Evaluable Population: All patients who:~* Complete study through Day 225 assessments~* Discontinue due to reaching the protocol specified LOI endpoint (and have not missed 2 or more consecutive doses prior to the LOI visit)~* Discontinue due to drug-related adverse event (nonresponder)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| XmAb5871 | Time to Loss of Systemic Lupus Erythematosus Disease Activity Improvement Achieved by a Short Period of IM Steroid Therapy in SLE Patients | 230 days |
| Placebo | Time to Loss of Systemic Lupus Erythematosus Disease Activity Improvement Achieved by a Short Period of IM Steroid Therapy in SLE Patients | 131 days |
p-value: 0.025295% CI: [0.3, 0.92]Log Rank