Lupus Erythematosus, Systemic
Conditions
Brief summary
This Phase II, multicenter, open-label extension (OLE) study will evaluate the long-term safety and efficacy of GDC-0853 in participants with systemic lupus erythematosus (SLE) who have completed Study GA30044 (NCT02908100) up to 48 weeks.
Interventions
DRUGGDC-0853
Participants received GDC-0853 at a dose of 200mg, as per the dosing schedule described above.
Sponsors
Genentech, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 76 Years
Healthy volunteers
No
Inclusion criteria
* Able to comply with the study protocol, in the investigator's judgment * Completion of Study GA30044 up to 48 weeks * Acceptable safety and tolerability during Study GA30044 as determined by the investigator
Exclusion criteria
* Met protocol-defined treatment-stopping criteria during Study GA30044 * An adverse event in Study GA30044 that required permanent discontinuation of study drug * In the opinion of the investigator, any new, significant, uncontrolled comorbidity or new clinical manifestation (related to SLE or not) that requires medications not allowed in this protocol; or could put the participant at undue risk from a safety perspective * Any uncontrolled or clinically significant laboratory abnormality that would affect safety, interpretation of study data, or the participant's participation in the study in the opinion of the investigator in consultation with the Medical Monitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) | Baseline up until 8 weeks after the last dose of study drug (up to 56 weeks) | An Adverse Event (AE) 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 abnormal laboratory values or abnormal clinical test results), 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systemic Lupus Erythematosus Responder-4 Index (SRI-4) up to Week 48 | Baseline up to 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. |
| Area Under the Concentration-Time Curve From Time 0 to Time t (AUC0-t,ss) of GDC-0853 at Steady State | Pre-dose (0 hour [hr]) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56) | Population PK model estimated AUC of GDC-0853 From Time 0 to Time t (AUC0-t) at steady-state. AUC was measured in Nanograms (ng) per millilitre(mL)\*hour (hr). |
| Minimum Plasma Concentration of GDC-0853 at Steady State (Ctrough,ss) | Pre-dose (0 hr) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56) | Population PK model estimated minimal plasma concentration (Ctrough) of GDC-0853 at steady-state (ss). |
| Plasma Decay Half-Life of GDC-0853 at Steady State (t1/2,ss) | Pre-dose (0 hr) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56) | Population PK model estimated plasma decay half life of GDC-0853 at steady-state. |
| Apparent Oral Clearance of GDC-0853 at Steady State (CL/F,ss) | Pre-dose (0 hr) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56) | Population PK model estimated apparent oral clearance of GDC-0853 at steady-state. |
Countries
Argentina, Brazil, Bulgaria, Chile, Colombia, Mexico, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 50 centers in 11 countries.
Pre-assignment details
160 participants were enrolled into this OLE study and were included in the ITT and Safety populations.
Participants by arm
| Arm | Count |
|---|---|
| GDC-0853 (200mg) BID Participants previously enrolled in the parent GA30044 Study, now received GDC-0853 (200mg) orally twice daily (BID). | 160 |
| Total | 160 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 12 |
| Overall Study | Data Entry Error | 1 |
| Overall Study | Disease Relapse | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Non-Compliance With Study Drug | 1 |
| Overall Study | Pregnancy | 2 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Study Terminated By Sponsor | 106 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | GDC-0853 (200mg) BID |
|---|---|
| Age, Continuous | 42.8 Years STANDARD_DEVIATION 11.5 |
| Race/Ethnicity, Customized American Indian or Alaska native | 24 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 22 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 117 Participants |
| Race/Ethnicity, Customized Multiple | 5 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 42 Participants |
| Race/Ethnicity, Customized Not Stated | 1 Participants |
| Race/Ethnicity, Customized White | 104 Participants |
| Sex: Female, Male Female | 155 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 160 |
| other Total, other adverse events | 31 / 160 |
| serious Total, serious adverse events | 4 / 160 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs)
An Adverse Event (AE) 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 abnormal laboratory values or abnormal clinical test results), 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 until 8 weeks after the last dose of study drug (up to 56 weeks)
Population: The Safety-evaluable population was defined as all participants who received at least one dose of the study drug during this OLE study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GDC-0853 (200mg) BID | Percentage of Participants With Adverse Events (AEs) | 64.4 Percentage of Participants |
Secondary
Apparent Oral Clearance of GDC-0853 at Steady State (CL/F,ss)
Population PK model estimated apparent oral clearance of GDC-0853 at steady-state.
Time frame: Pre-dose (0 hr) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56)
Population: Please note that for this Outcome Measure, incomplete PK data was collected as a result of early termination of the study which meant that data for the (CL/F,ss) parameter could not be generated via the Population PK model.
Secondary
Area Under the Concentration-Time Curve From Time 0 to Time t (AUC0-t,ss) of GDC-0853 at Steady State
Population PK model estimated AUC of GDC-0853 From Time 0 to Time t (AUC0-t) at steady-state. AUC was measured in Nanograms (ng) per millilitre(mL)\*hour (hr).
Time frame: Pre-dose (0 hour [hr]) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56)
Population: Please note that for this Outcome Measure, incomplete PK data was collected as a result of early termination of the study which meant that data for the (AUC0-t,ss) parameter could not be generated via the Population PK model.
Secondary
Minimum Plasma Concentration of GDC-0853 at Steady State (Ctrough,ss)
Population PK model estimated minimal plasma concentration (Ctrough) of GDC-0853 at steady-state (ss).
Time frame: Pre-dose (0 hr) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56)
Population: Please note that for this Outcome Measure, incomplete PK data was collected as a result of early termination of the study which meant that data for the (Ctrough,ss) parameter could not be generated via the Population PK model.
Secondary
Plasma Decay Half-Life of GDC-0853 at Steady State (t1/2,ss)
Population PK model estimated plasma decay half life of GDC-0853 at steady-state.
Time frame: Pre-dose (0 hr) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56)
Population: Please note that for this Outcome Measure, incomplete PK data was collected as a result of early termination of the study which meant that data for the (t1/2,ss) parameter could not be generated via the Population PK model.
Secondary
Systemic Lupus Erythematosus Responder-4 Index (SRI-4) up to 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: Baseline up to Week 48
Population: Please note that for this Outcome Measure, no data was collected at all due to no participants being evaluated at all, as a result of early termination of this study due to fenebrutinib not demonstrating improved efficacy compared to placebo across secondary or exploratory endpoints in the parent study (Study GA30044).