Clinical Trial Results:
A Phase II, Open-Label Extension Study of Patients Previously Enrolled in Study GA30044 to Evaluate the Long-Term Safety and Efficacy of GDC-0853 in Patients With Moderate to Severe Active Systemic Lupus Erythematosus
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Summary
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EudraCT number |
2017-001764-37 |
Trial protocol |
GB ES PT BG |
Global end of trial date |
20 Nov 2019
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Results information
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Results version number |
v2(current) |
This version publication date |
06 Jan 2021
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First version publication date |
05 Nov 2020
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GA30066
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03407482 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH4070
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Public contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Nov 2019
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Nov 2019
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To evaluate the long-term safety and efficacy of GDC-0853
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Protection of trial subjects |
All study subjects were required to read and sign an Informed Consent Form.
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Background therapy |
All Subjects were on immunosuppressants, antimalarials and/or corticosteroids. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Jan 2018
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
2 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 18
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Country: Number of subjects enrolled |
Bulgaria: 8
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Country: Number of subjects enrolled |
Brazil: 41
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Country: Number of subjects enrolled |
Chile: 28
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Country: Number of subjects enrolled |
Colombia: 25
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Country: Number of subjects enrolled |
Spain: 5
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Country: Number of subjects enrolled |
United Kingdom: 1
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Country: Number of subjects enrolled |
Korea, Republic of: 1
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Country: Number of subjects enrolled |
Mexico: 12
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Country: Number of subjects enrolled |
Taiwan: 3
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Country: Number of subjects enrolled |
United States: 18
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Worldwide total number of subjects |
160
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EEA total number of subjects |
14
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
154
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From 65 to 84 years |
6
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 50 centers in 11 countries. | ||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
160 subjects were enrolled into this OLE study and were included in the ITT and Safety populations. | ||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||
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Arms
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Arm title
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GDC-0853 (200mg) BID | ||||||||||||||||||||||||||
Arm description |
Subjects previously enrolled in the parent GA30044 Study, now received GDC-0853 (200mg) orally twice daily (BID). | ||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||
Investigational medicinal product name |
GDC-0853
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Investigational medicinal product code |
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Other name |
fenebrutinib
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
GDC-0853 was administered orally twice daily (BID) at a dose of 200mg.
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Baseline characteristics reporting groups
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Reporting group title |
GDC-0853 (200mg) BID
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Reporting group description |
Subjects previously enrolled in the parent GA30044 Study, now received GDC-0853 (200mg) orally twice daily (BID). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
GDC-0853 (200mg) BID
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Reporting group description |
Subjects previously enrolled in the parent GA30044 Study, now received GDC-0853 (200mg) orally twice daily (BID). | ||
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End point title |
Percentage of Subjects With Adverse Events (AEs) [1] | ||||||||
End point description |
An Adverse Event (AE) is any untoward medical occurrence in a subject 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.
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End point type |
Primary
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End point timeframe |
Baseline up until 8 weeks after the last dose of study drug (up to 56 weeks)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were performed, as this study has only 1 arm. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Systemic Lupus Erythematosus Responder-4 Index (SRI-4) up to Week 48 | ||||||
End point description |
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. No data was collected at all due to no subjects being evaluated at all, because 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).
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 48
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| Notes [2] - Not evaluated due to early termination. |
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| No statistical analyses for this end point | |||||||
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End point title |
Area Under the Concentration-Time Curve From Time 0 to Time t (AUC0-t,ss) of GDC-0853 at Steady State | ||||||||
End point description |
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). 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.
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End point type |
Secondary
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End point timeframe |
Pre-dose (0 hour [hr]) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56)
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| Notes [3] - Not evaluated due to early termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Minimum Plasma Concentration of GDC-0853 at Steady State (Ctrough,ss) | ||||||||
End point description |
Population PK model estimated minimal plasma concentration (Ctrough) of GDC-0853 at steady-state (ss). 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.
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End point type |
Secondary
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End point timeframe |
Pre-dose (0 hr) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56)
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| Notes [4] - Not evaluated due to early termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Plasma Decay Half-Life of GDC-0853 at Steady State (t1/2,ss) | ||||||||
End point description |
Population PK model estimated plasma decay half life of GDC-0853 at steady-state. 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.
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End point type |
Secondary
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End point timeframe |
Pre-dose (0 hr) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56)
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| Notes [5] - Not evaluated due to early termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Apparent Oral Clearance of GDC-0853 at Steady State (CL/F,ss) | ||||||||
End point description |
Population PK model estimated apparent oral clearance of GDC-0853 at steady-state. 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.
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End point type |
Secondary
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End point timeframe |
Pre-dose (0 hr) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56)
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| Notes [6] - Not evaluated due to early termination. |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up until 8 weeks after the last dose of study drug (up to 56 weeks)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.1
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Reporting groups
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Reporting group title |
GDC-0853 (200mg) BID
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Reporting group description |
Subjects previously enrolled in the parent GA30044 Study, now received GDC-0853 (200mg) orally twice daily (BID). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The study was ended early due to the lack of efficacy seen in the parent study GA30044. | |||
