Systemic Lupus Erythematosus
Conditions
Brief summary
This is a study to evaluate the safety and efficacy of GDC-0853 in combination with standard of care therapy in participants with moderate to severe active systemic lupus erythematosus (SLE).
Interventions
DRUGGDC-0853
Participants received GDC-0853 at dosages of 150 or 200mg as per the dosing schedules described above.
DRUGPlacebo
Participants received matching placebo to GDC-0853 at dosages of 150 and 200mg as per the dosing schedules described above.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Fulfillment of SLE classification criteria according to either American College of Rheumatology (ACR) or Systemic Lupus International Collaborating Clinics (SLICC) criteria at any time prior to or at screening * At least one serologic marker of SLE at screening as follows: positive antinuclear antibody (ANA) test by immunofluorescent assay with titer \>/= 1:80; or positive anti-double-stranded DNA (anti-dsDNA) antibodies; or positive anti-Smith antibody * At both screening and Day 1, moderate to severe active SLE, defined as meeting all of the following unless indicated otherwise: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥ 8 (at screening only) with clinical SLEDAI-2K score \>/= 4.0 (at both screening and Day 1), Physician's Global Assessment \>/= 1.0 (out of 3), and currently receiving at least one standard oral treatment for SLE * If on oral corticosteroids (OCS), the dose must be \</= 40 mg/day prednisone (or equivalent) * Stable doses of anti-malarial or immunosuppressive therapies * Participants must be willing to avoid pregnancy
Exclusion criteria
* Proteinuria \> 3.5 g/24 h or equivalent using urine protein-to-creatinine ratio (uPCR) in a first morning void urine sample * Active proliferative lupus nephritis (as assessed by the investigator) or histological evidence of active Class III or Class IV lupus nephritis on renal biopsy performed in the 6 months prior to screening (or during the screening period) * History of having required hemodialysis or high dose corticosteroids (\>100 mg/d) prednisone or equivalent) for the management of lupus renal disease within 90 days of Day 1 * Neuropsychiatric or central nervous system lupus manifestations * Serum creatinine \> 2.5 mg/dL, or estimated glomerular-filtration rate \< 30 milliliter per minute (mL/min) or on chronic renal replacement therapy * History of receiving a solid organ transplant * Evidence of active, latent, or inadequately treated infection with Mycobacterium tuberculosis (TB) * Significant and uncontrolled medical disease within the 12 weeks prior to screening in any organ system (e.g., cardiac, neurologic, pulmonary, renal, hepatic, endocrine, metabolic, gastrointestinal, or psychiatric) not related to SLE, which, in the investigator's or Sponsor's opinion, would preclude study participation * History of cancer, including hematological malignancy and solid tumors, within 10 years of screening * Need for systemic anticoagulation with warfarin, other oral or injectable anticoagulants, or anti-platelet agents * Evidence of chronic and/or active hepatitis B or C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Systemic Lupus Erythematosus Responder Index (SRI)-4 Response at Week 48 | Week 48 | The Systemic Lupus Erythematosus Responder Index (SRI)-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SRI-4 Response at Week 24 With a Sustained Reduction of OCS Dose to < 10 mg/Day and </= Day 1 Dose During Week 12 Through Week 24 | Week 24 | The SRI-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity. OCS tapering requires a sustained reduction of OCS from Week 12 through Week 24 \[less than 10 milligram per day (mg/day) and less or equal to the dose received on Day 1\]. |
| SRI-4 Response at Week 24 | Week 24 | The SRI-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity. |
| SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels | Week 48 | The SRI-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity. The Plasmablast Signature (PB) is a Bruton's Tyrosine Kinase (BTK)-dependent blood RNA signature comprised of three genes (IgJ, MZB1 and TXNDC5). Q1/2/3/4 = Quartile 1/2/3/4. |
| SRI-4 Response With a Sustained Reduction of OCS Dose to ≤ 10 mg/Day and ≤ Day 1 Dose During Week 36 Through 48 in Patients With High vs. Low Plasmablast Signature Levels | Week 48 | The SRI-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity. The Plasmablast Signature (PB) is a Bruton's Tyrosine Kinase (BTK)-dependent blood RNA signature comprised of three genes (IgJ, MZB1 and TXNDC5). Q1/2/3/4 = Quartile 1/2/3/4. |
| SRI-4 Response at Week 48 With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to Less Than (<)10 Milligrams Per Day (mg/Day) and Less Than or Equal to (</=) Day 1 Dose During Week 36 Through Week 48 | Week 48 | The SRI-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity. OCS tapering requires a sustained reduction of OCS from Week 36 through Week 48 \[less than 10 milligram per day (mg/day) and less or equal to the dose received on Day 1\]. |
| BILAG-based Composite Lupus Assessment (BICLA) Response at Week 24 and 48 | Week 24, 48 | The BICLA is a composite index that is defined as follows: \[1\] At least one gradation of improvement in baseline BILAG scores in all body systems with moderate or severe disease activity at entry (e.g., all A (severe disease) scores falling to B (moderate), C (mild), or D (no activity) and all B scores falling to C or D; \[2\] No new BILAG A or more than one new BILAG B scores; \[3\] No worsening of total SLEDAI-2K score from baseline; \[4\] No significant deterioration (=\<10%) in physician's global assessment and \[5\] No treatment failure (initiation of non-protocol treatment). |
| Percentage of Participants With Adverse Events (AEs) | Baseline up to 8 weeks after the last dose of study drug (up to Week 56). | An Adverse Event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. |
| Plasma Concentrations of Fenebrutinib at Specified Timepoints | Baseline (Pre-dose), Week 24 (Pre-dose and Post-dose) and Week 48 (Pre-dose) | The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received. Descriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below. |
| SRI-6 Response at Week 24 and 48 | Week 24, 48 | The Systemic Lupus Erythematosus Responder Index (SRI)-6 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥6 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity. |
Countries
Argentina, Brazil, Bulgaria, Chile, Colombia, Germany, Mexico, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 69 centers in 12 countries.
Pre-assignment details
An overall total of 616 participants were screened into the study, of which 356 participants were screen failures. 260 participants (Intent-To-Treat/ITT population) were randomized into the study, of which 1 participant did not receive any study treatment meaning that the Safety population consisted of 259 participants.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received matching placebo to GDC-0853 orally starting on Day 1 and ending at Week 48, in combination with background standard of care therapy. | 86 |
| GDC-0853 (150mg) QD Participants received GDC-0853 (150mg) orally once daily (QD) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy. | 87 |
| GDC-0853 (200mg) BID Participants received GDC-0853 (200mg) orally twice daily (BID) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy. | 87 |
| Total | 260 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 6 | 9 |
| Overall Study | Death | 2 | 0 | 0 |
| Overall Study | Lack of Efficacy | 2 | 3 | 3 |
| Overall Study | Lost to Follow-up | 0 | 1 | 2 |
| Overall Study | Non-Compliance With Contraceptive Method | 1 | 0 | 0 |
| Overall Study | Non-Compliance With Study Drug | 1 | 1 | 2 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Pregnancy | 1 | 2 | 0 |
| Overall Study | Randomised in Error | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 8 | 7 | 5 |
Baseline characteristics
| Characteristic | GDC-0853 (150mg) QD | Total | GDC-0853 (200mg) BID | Placebo |
|---|---|---|---|---|
| Age, Continuous | 43.3 Years STANDARD_DEVIATION 12.4 | 41.3 Years STANDARD_DEVIATION 11.6 | 40.4 Years STANDARD_DEVIATION 10.6 | 40.2 Years STANDARD_DEVIATION 11.5 |
| Race/Ethnicity, Customized American Indian or Alaska native | 8 Participants | 36 Participants | 17 Participants | 11 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 10 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 15 Participants | 39 Participants | 13 Participants | 11 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 61 Participants | 176 Participants | 61 Participants | 54 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 5 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 25 Participants | 83 Participants | 26 Participants | 32 Participants |
| Race/Ethnicity, Customized Not Stated | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 62 Participants | 170 Participants | 52 Participants | 56 Participants |
| Sex: Female, Male Female | 82 Participants | 251 Participants | 84 Participants | 85 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 3 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 84 | 1 / 87 | 0 / 88 |
| other Total, other adverse events | 42 / 84 | 54 / 87 | 51 / 88 |
| serious Total, serious adverse events | 9 / 84 | 4 / 87 | 12 / 88 |
Outcome results
Primary
Systemic Lupus Erythematosus Responder Index (SRI)-4 Response at Week 48
The Systemic Lupus Erythematosus Responder Index (SRI)-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity.
Time frame: Week 48
Population: The Intent-To-Treat (ITT) population was defined as all randomized participants regardless of whether they received any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Systemic Lupus Erythematosus Responder Index (SRI)-4 Response at Week 48 | 44.2 Percentage of Participants |
| GDC-0853 (150mg) QD | Systemic Lupus Erythematosus Responder Index (SRI)-4 Response at Week 48 | 50.6 Percentage of Participants |
| GDC-0853 (200mg) BID | Systemic Lupus Erythematosus Responder Index (SRI)-4 Response at Week 48 | 51.7 Percentage of Participants |
p-value: 0.37395% CI: [-8.5, 21.2]Cochran-Mantel-Haenszel
p-value: 0.33995% CI: [-7.3, 22.4]Cochran-Mantel-Haenszel
Secondary
BILAG-based Composite Lupus Assessment (BICLA) Response at Week 24 and 48
The BICLA is a composite index that is defined as follows: \[1\] At least one gradation of improvement in baseline BILAG scores in all body systems with moderate or severe disease activity at entry (e.g., all A (severe disease) scores falling to B (moderate), C (mild), or D (no activity) and all B scores falling to C or D; \[2\] No new BILAG A or more than one new BILAG B scores; \[3\] No worsening of total SLEDAI-2K score from baseline; \[4\] No significant deterioration (=\<10%) in physician's global assessment and \[5\] No treatment failure (initiation of non-protocol treatment).
Time frame: Week 24, 48
Population: The BICLA-evaluable population was defined as all all ITT participants who had at least one body system with moderate or severe disease activity at baseline as determined by BILAG-2004, i.e., at least one BILAG domain was scored as A or B at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | BILAG-based Composite Lupus Assessment (BICLA) Response at Week 24 and 48 | Week 24 | 47.5 Percentage of Participants |
| Placebo | BILAG-based Composite Lupus Assessment (BICLA) Response at Week 24 and 48 | Week 48 | 41.2 Percentage of Participants |
| GDC-0853 (150mg) QD | BILAG-based Composite Lupus Assessment (BICLA) Response at Week 24 and 48 | Week 24 | 45.9 Percentage of Participants |
| GDC-0853 (150mg) QD | BILAG-based Composite Lupus Assessment (BICLA) Response at Week 24 and 48 | Week 48 | 52.9 Percentage of Participants |
| GDC-0853 (200mg) BID | BILAG-based Composite Lupus Assessment (BICLA) Response at Week 24 and 48 | Week 24 | 44.6 Percentage of Participants |
| GDC-0853 (200mg) BID | BILAG-based Composite Lupus Assessment (BICLA) Response at Week 24 and 48 | Week 48 | 42.2 Percentage of Participants |
Comparison: Week 24p-value: 0.93695% CI: [-16.8, 13.6]Cochran-Mantel-Haenszel
Comparison: Week 24p-value: 0.68395% CI: [-18.2, 12.4]Cochran-Mantel-Haenszel
Comparison: Week 48p-value: 0.08695% CI: [-3.4, 26.8]Cochran-Mantel-Haenszel
Comparison: Week 48p-value: 0.87995% CI: [-14.2, 16.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Adverse Events (AEs)
An Adverse Event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: Baseline up to 8 weeks after the last dose of study drug (up to Week 56).
Population: The Safety-evaluable population was defined as all participants who received at least one dose of study medication. One participant in the Placebo arm was inadvertently dosed with GDC-0853 for a period of 27 days and was classified as part of the GDC-0853 (200mg) BID arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Adverse Events (AEs) | 76.2 Percentage of Participants |
| GDC-0853 (150mg) QD | Percentage of Participants With Adverse Events (AEs) | 88.5 Percentage of Participants |
| GDC-0853 (200mg) BID | Percentage of Participants With Adverse Events (AEs) | 78.4 Percentage of Participants |
Secondary
Plasma Concentrations of Fenebrutinib at Specified Timepoints
The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received. Descriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.
Time frame: Baseline (Pre-dose), Week 24 (Pre-dose and Post-dose) and Week 48 (Pre-dose)
Population: The PK-evaluable population was defined as all participants who received at least one dose of fenebrutinib (GDC-0853) and had at least 1 evaluable post-dose PK sample. Data presented below is only for participants that were included in the actual analysis with detectable concentrations at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentrations of Fenebrutinib at Specified Timepoints | Week 0 (Pre-dose) | NA ng/mL | — |
| Placebo | Plasma Concentrations of Fenebrutinib at Specified Timepoints | Week 24 (Pre-dose) | 41.9 ng/mL | Standard Deviation 62.4 |
| Placebo | Plasma Concentrations of Fenebrutinib at Specified Timepoints | Week 24 (2hr Post-dose) | 331 ng/mL | Standard Deviation 226 |
| Placebo | Plasma Concentrations of Fenebrutinib at Specified Timepoints | Week 24 (4-6hr Post-dose) | 215 ng/mL | Standard Deviation 131 |
| Placebo | Plasma Concentrations of Fenebrutinib at Specified Timepoints | Week 24 (8-10hr Post-dose) | 120 ng/mL | Standard Deviation 111 |
| Placebo | Plasma Concentrations of Fenebrutinib at Specified Timepoints | Week 48 (Pre-dose) | 25.5 ng/mL | Standard Deviation 28.1 |
| GDC-0853 (150mg) QD | Plasma Concentrations of Fenebrutinib at Specified Timepoints | Week 24 (8-10hr Post-dose) | 233 ng/mL | Standard Deviation 145 |
| GDC-0853 (150mg) QD | Plasma Concentrations of Fenebrutinib at Specified Timepoints | Week 0 (Pre-dose) | NA ng/mL | — |
| GDC-0853 (150mg) QD | Plasma Concentrations of Fenebrutinib at Specified Timepoints | Week 24 (4-6hr Post-dose) | 414 ng/mL | Standard Deviation 187 |
| GDC-0853 (150mg) QD | Plasma Concentrations of Fenebrutinib at Specified Timepoints | Week 24 (Pre-dose) | 180 ng/mL | Standard Deviation 121 |
| GDC-0853 (150mg) QD | Plasma Concentrations of Fenebrutinib at Specified Timepoints | Week 48 (Pre-dose) | 137 ng/mL | Standard Deviation 133 |
| GDC-0853 (150mg) QD | Plasma Concentrations of Fenebrutinib at Specified Timepoints | Week 24 (2hr Post-dose) | 612 ng/mL | Standard Deviation 353 |
Secondary
SRI-4 Response at Week 24
The SRI-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity.
Time frame: Week 24
Population: The Intent-To-Treat (ITT) population was defined as all randomized participants regardless of whether they received any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | SRI-4 Response at Week 24 | 46.5 Percentage of Participants |
| GDC-0853 (150mg) QD | SRI-4 Response at Week 24 | 52.9 Percentage of Participants |
| GDC-0853 (200mg) BID | SRI-4 Response at Week 24 | 52.9 Percentage of Participants |
p-value: 0.4195% CI: [-8.5, 21.2]Cochran-Mantel-Haenszel
p-value: 0.41895% CI: [-8.5, 21.2]Cochran-Mantel-Haenszel
Secondary
SRI-4 Response at Week 24 With a Sustained Reduction of OCS Dose to < 10 mg/Day and </= Day 1 Dose During Week 12 Through Week 24
The SRI-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity. OCS tapering requires a sustained reduction of OCS from Week 12 through Week 24 \[less than 10 milligram per day (mg/day) and less or equal to the dose received on Day 1\].
Time frame: Week 24
Population: The Intent-To-Treat (ITT) population was defined as all randomized participants regardless of whether they received any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | SRI-4 Response at Week 24 With a Sustained Reduction of OCS Dose to < 10 mg/Day and </= Day 1 Dose During Week 12 Through Week 24 | 43.0 Percentage of Participants |
| GDC-0853 (150mg) QD | SRI-4 Response at Week 24 With a Sustained Reduction of OCS Dose to < 10 mg/Day and </= Day 1 Dose During Week 12 Through Week 24 | 47.1 Percentage of Participants |
| GDC-0853 (200mg) BID | SRI-4 Response at Week 24 With a Sustained Reduction of OCS Dose to < 10 mg/Day and </= Day 1 Dose During Week 12 Through Week 24 | 47.1 Percentage of Participants |
p-value: 0.61495% CI: [-10.7, 18.9]Cochran-Mantel-Haenszel
p-value: 0.60795% CI: [-10.7, 18.9]Cochran-Mantel-Haenszel
Secondary
SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels
The SRI-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity. The Plasmablast Signature (PB) is a Bruton's Tyrosine Kinase (BTK)-dependent blood RNA signature comprised of three genes (IgJ, MZB1 and TXNDC5). Q1/2/3/4 = Quartile 1/2/3/4.
Time frame: Week 48
Population: The Intent-To-Treat (ITT) population was defined as all randomized participants regardless of whether they received any study drug. Data presented below is only for participants that were included in the actual analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q1 | 37.5 Percentage of Participants |
| Placebo | SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q2 | 54.5 Percentage of Participants |
| Placebo | SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q3 | 36.8 Percentage of Participants |
| Placebo | SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q4 | 50.0 Percentage of Participants |
| GDC-0853 (150mg) QD | SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q4 | 42.9 Percentage of Participants |
| GDC-0853 (150mg) QD | SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q1 | 52.4 Percentage of Participants |
| GDC-0853 (150mg) QD | SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q3 | 52.4 Percentage of Participants |
| GDC-0853 (150mg) QD | SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q2 | 54.2 Percentage of Participants |
| GDC-0853 (200mg) BID | SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q4 | 47.8 Percentage of Participants |
| GDC-0853 (200mg) BID | SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q2 | 63.2 Percentage of Participants |
| GDC-0853 (200mg) BID | SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q3 | 52.0 Percentage of Participants |
| GDC-0853 (200mg) BID | SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q1 | 45.0 Percentage of Participants |
Comparison: Plasmablast Signature Level Q1p-value: 0.37895% CI: [-14, 43.7]Cochran-Mantel-Haenszel
Comparison: Plasmablast Signature Level Q1p-value: 0.73295% CI: [-21.7, 36.7]Cochran-Mantel-Haenszel
Comparison: Plasmablast Signature Level Q2p-value: 0.595% CI: [-29.2, 28.4]Cochran-Mantel-Haenszel
Comparison: Plasmablast Signature Level Q2p-value: 0.23495% CI: [-21.4, 38.7]Cochran-Mantel-Haenszel
Comparison: Plasmablast Signature Level Q3p-value: 0.36495% CI: [-14.9, 46]Cochran-Mantel-Haenszel
Comparison: Plasmablast Signature Level Q3p-value: 0.13495% CI: [-14.1, 44.4]Cochran-Mantel-Haenszel
Comparison: Plasmablast Signature Level Q4p-value: 0.8395% CI: [-37.6, 23.3]Cochran-Mantel-Haenszel
Comparison: Plasmablast Signature Level Q4p-value: 0.96395% CI: [-32.1, 27.8]Cochran-Mantel-Haenszel
Secondary
SRI-4 Response at Week 48 With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to Less Than (<)10 Milligrams Per Day (mg/Day) and Less Than or Equal to (</=) Day 1 Dose During Week 36 Through Week 48
The SRI-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity. OCS tapering requires a sustained reduction of OCS from Week 36 through Week 48 \[less than 10 milligram per day (mg/day) and less or equal to the dose received on Day 1\].
Time frame: Week 48
Population: The Intent-To-Treat (ITT) population was defined as all randomized participants regardless of whether they received any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | SRI-4 Response at Week 48 With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to Less Than (<)10 Milligrams Per Day (mg/Day) and Less Than or Equal to (</=) Day 1 Dose During Week 36 Through Week 48 | 41.9 Percentage of Participants |
| GDC-0853 (150mg) QD | SRI-4 Response at Week 48 With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to Less Than (<)10 Milligrams Per Day (mg/Day) and Less Than or Equal to (</=) Day 1 Dose During Week 36 Through Week 48 | 50.6 Percentage of Participants |
| GDC-0853 (200mg) BID | SRI-4 Response at Week 48 With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to Less Than (<)10 Milligrams Per Day (mg/Day) and Less Than or Equal to (</=) Day 1 Dose During Week 36 Through Week 48 | 44.8 Percentage of Participants |
p-value: 0.22395% CI: [-6.1, 23.5]Cochran-Mantel-Haenszel
p-value: 0.73795% CI: [-11.8, 17.7]Cochran-Mantel-Haenszel
Secondary
SRI-4 Response With a Sustained Reduction of OCS Dose to ≤ 10 mg/Day and ≤ Day 1 Dose During Week 36 Through 48 in Patients With High vs. Low Plasmablast Signature Levels
The SRI-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity. The Plasmablast Signature (PB) is a Bruton's Tyrosine Kinase (BTK)-dependent blood RNA signature comprised of three genes (IgJ, MZB1 and TXNDC5). Q1/2/3/4 = Quartile 1/2/3/4.
Time frame: Week 48
Population: The Intent-To-Treat (ITT) population was defined as all randomized participants regardless of whether they received any study drug. Data presented below is only for participants that were included in the actual analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | SRI-4 Response With a Sustained Reduction of OCS Dose to ≤ 10 mg/Day and ≤ Day 1 Dose During Week 36 Through 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q1 | 33.3 Percentage of Participants |
| Placebo | SRI-4 Response With a Sustained Reduction of OCS Dose to ≤ 10 mg/Day and ≤ Day 1 Dose During Week 36 Through 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q2 | 54.5 Percentage of Participants |
| Placebo | SRI-4 Response With a Sustained Reduction of OCS Dose to ≤ 10 mg/Day and ≤ Day 1 Dose During Week 36 Through 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q3 | 36.8 Percentage of Participants |
| Placebo | SRI-4 Response With a Sustained Reduction of OCS Dose to ≤ 10 mg/Day and ≤ Day 1 Dose During Week 36 Through 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q4 | 45.0 Percentage of Participants |
| GDC-0853 (150mg) QD | SRI-4 Response With a Sustained Reduction of OCS Dose to ≤ 10 mg/Day and ≤ Day 1 Dose During Week 36 Through 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q4 | 42.9 Percentage of Participants |
| GDC-0853 (150mg) QD | SRI-4 Response With a Sustained Reduction of OCS Dose to ≤ 10 mg/Day and ≤ Day 1 Dose During Week 36 Through 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q1 | 52.4 Percentage of Participants |
| GDC-0853 (150mg) QD | SRI-4 Response With a Sustained Reduction of OCS Dose to ≤ 10 mg/Day and ≤ Day 1 Dose During Week 36 Through 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q3 | 52.4 Percentage of Participants |
| GDC-0853 (150mg) QD | SRI-4 Response With a Sustained Reduction of OCS Dose to ≤ 10 mg/Day and ≤ Day 1 Dose During Week 36 Through 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q2 | 54.2 Percentage of Participants |
| GDC-0853 (200mg) BID | SRI-4 Response With a Sustained Reduction of OCS Dose to ≤ 10 mg/Day and ≤ Day 1 Dose During Week 36 Through 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q4 | 39.1 Percentage of Participants |
| GDC-0853 (200mg) BID | SRI-4 Response With a Sustained Reduction of OCS Dose to ≤ 10 mg/Day and ≤ Day 1 Dose During Week 36 Through 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q2 | 57.9 Percentage of Participants |
| GDC-0853 (200mg) BID | SRI-4 Response With a Sustained Reduction of OCS Dose to ≤ 10 mg/Day and ≤ Day 1 Dose During Week 36 Through 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q3 | 44.0 Percentage of Participants |
| GDC-0853 (200mg) BID | SRI-4 Response With a Sustained Reduction of OCS Dose to ≤ 10 mg/Day and ≤ Day 1 Dose During Week 36 Through 48 in Patients With High vs. Low Plasmablast Signature Levels | Plasmablast Signature Level Q1 | 40.0 Percentage of Participants |
Comparison: Plasmablast Signature Level Q1p-value: 0.18995% CI: [-9.4, 47.5]Cochran-Mantel-Haenszel
Comparison: Plasmablast Signature Level Q1p-value: 0.90995% CI: [-21.9, 35.2]Cochran-Mantel-Haenszel
Comparison: Plasmablast Signature Level Q2p-value: 0.595% CI: [-29.2, 28.4]Cochran-Mantel-Haenszel
Comparison: Plasmablast Signature Level Q2p-value: 0.23495% CI: [-27.1, 33.8]Cochran-Mantel-Haenszel
Comparison: Plasmablast Signature Level Q3p-value: 0.36495% CI: [-14.9, 46]Cochran-Mantel-Haenszel
Comparison: Plasmablast Signature Level Q3p-value: 0.3195% CI: [-22, 36.3]Cochran-Mantel-Haenszel
Comparison: Plasmablast Signature Level Q4p-value: 0.92295% CI: [-32.5, 28.2]Cochran-Mantel-Haenszel
Comparison: Plasmablast Signature Level Q4p-value: 0.70195% CI: [-35.4, 23.7]Cochran-Mantel-Haenszel
Secondary
SRI-6 Response at Week 24 and 48
The Systemic Lupus Erythematosus Responder Index (SRI)-6 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥6 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity.
Time frame: Week 24, 48
Population: The Intent-To-Treat (ITT) population was defined as all randomized participants regardless of whether they received any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | SRI-6 Response at Week 24 and 48 | Week 24 | 31.4 Percentage of Participants |
| Placebo | SRI-6 Response at Week 24 and 48 | Week 48 | 27.9 Percentage of Participants |
| GDC-0853 (150mg) QD | SRI-6 Response at Week 24 and 48 | Week 24 | 34.5 Percentage of Participants |
| GDC-0853 (150mg) QD | SRI-6 Response at Week 24 and 48 | Week 48 | 39.1 Percentage of Participants |
| GDC-0853 (200mg) BID | SRI-6 Response at Week 24 and 48 | Week 24 | 33.3 Percentage of Participants |
| GDC-0853 (200mg) BID | SRI-6 Response at Week 24 and 48 | Week 48 | 35.6 Percentage of Participants |
Comparison: Week 24p-value: 0.69295% CI: [-10.9, 17.1]Cochran-Mantel-Haenszel
Comparison: Week 24p-value: 0.87195% CI: [-12, 15.9]Cochran-Mantel-Haenszel
Comparison: Week 48p-value: 0.10595% CI: [-2.8, 25.1]Cochran-Mantel-Haenszel
Comparison: Week 48p-value: 0.28695% CI: [-6.1, 21.6]Cochran-Mantel-Haenszel