Trial Outcomes & Findings for An Extension Study of GDC-0853 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus (NCT NCT03407482)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

160 participants

Primary outcome timeframe

Baseline up until 8 weeks after the last dose of study drug (up to 56 weeks)

Results posted on

2020-12-19

Participant Flow

The study was conducted at 50 centers in 11 countries.

160 participants were enrolled into this OLE study and were included in the ITT and Safety populations.

Participant milestones

Participant milestones
Measure	GDC-0853 (200mg) BID Participants previously enrolled in the parent GA30044 Study, now received GDC-0853 (200mg) orally twice daily (BID).
Overall Study STARTED	160
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	131

Reasons for withdrawal

Reasons for withdrawal
Measure	GDC-0853 (200mg) BID Participants previously enrolled in the parent GA30044 Study, now received GDC-0853 (200mg) orally twice daily (BID).
Overall Study Adverse Event	12
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
Overall Study Data Entry Error	1

Baseline Characteristics

An Extension Study of GDC-0853 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GDC-0853 (200mg) BID n=160 Participants Participants previously enrolled in the parent GA30044 Study, now received GDC-0853 (200mg) orally twice daily (BID).
Age, Continuous	42.8 Years STANDARD_DEVIATION 11.5 • n=5 Participants
Sex: Female, Male Female	155 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	117 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	42 Participants n=5 Participants
Race/Ethnicity, Customized Not Stated	1 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska native	24 Participants n=5 Participants
Race/Ethnicity, Customized Asian	5 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	22 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	5 Participants n=5 Participants
Race/Ethnicity, Customized White	104 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	GDC-0853 (200mg) BID n=160 Participants Participants previously enrolled in the parent GA30044 Study, now received GDC-0853 (200mg) orally twice daily (BID).
Percentage of Participants With Adverse Events (AEs)	64.4 Percentage of Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Population PK model estimated minimal plasma concentration (Ctrough) of GDC-0853 at steady-state (ss).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Population PK model estimated plasma decay half life of GDC-0853 at steady-state.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Population PK model estimated apparent oral clearance of GDC-0853 at steady-state.

Outcome measures

Outcome data not reported

Adverse Events

GDC-0853 (200mg) BID

Serious events: 4 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GDC-0853 (200mg) BID n=160 participants at risk Participants previously enrolled in the parent GA30044 Study, now received GDC-0853 (200mg) orally twice daily (BID).
Infections and infestations CELLULITIS	0.62% 1/160 • Number of events 1 • Baseline up until 8 weeks after the last dose of study drug (up to 56 weeks)
Infections and infestations INFECTIVE TENOSYNOVITIS	0.62% 1/160 • Number of events 1 • Baseline up until 8 weeks after the last dose of study drug (up to 56 weeks)
Infections and infestations URINARY TRACT INFECTION	0.62% 1/160 • Number of events 1 • Baseline up until 8 weeks after the last dose of study drug (up to 56 weeks)
Injury, poisoning and procedural complications LUMBAR VERTEBRAL FRACTURE	0.62% 1/160 • Number of events 1 • Baseline up until 8 weeks after the last dose of study drug (up to 56 weeks)
Musculoskeletal and connective tissue disorders SYSTEMIC LUPUS ERYTHEMATOSUS	0.62% 1/160 • Number of events 1 • Baseline up until 8 weeks after the last dose of study drug (up to 56 weeks)

Other adverse events

Other adverse events
Measure	GDC-0853 (200mg) BID n=160 participants at risk Participants previously enrolled in the parent GA30044 Study, now received GDC-0853 (200mg) orally twice daily (BID).
Gastrointestinal disorders NAUSEA	5.6% 9/160 • Number of events 9 • Baseline up until 8 weeks after the last dose of study drug (up to 56 weeks)
Infections and infestations NASOPHARYNGITIS	8.1% 13/160 • Number of events 14 • Baseline up until 8 weeks after the last dose of study drug (up to 56 weeks)
Infections and infestations URINARY TRACT INFECTION	9.4% 15/160 • Number of events 15 • Baseline up until 8 weeks after the last dose of study drug (up to 56 weeks)

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER