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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-001039-11 | EudraCT Number |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | 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. |
|
| GDC-0853 (150mg) QD | Experimental | 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. |
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| GDC-0853 (200mg) BID | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GDC-0853 | Drug | Participants received GDC-0853 at dosages of 150 or 200mg as per the dosing schedules described above. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Week 48 |
| Measure | Description | Time Frame |
|---|---|---|
| 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]. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294 | United States | ||
| Valerius Medical Group & Research Ctr of Greater Long Beach |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34042314 | Derived | Isenberg D, Furie R, Jones NS, Guibord P, Galanter J, Lee C, McGregor A, Toth B, Rae J, Hwang O, Desai R, Lokku A, Ramamoorthi N, Hackney JA, Miranda P, de Souza VA, Jaller-Raad JJ, Maura Fernandes A, Garcia Salinas R, Chinn LW, Townsend MJ, Morimoto AM, Tuckwell K. Efficacy, Safety, and Pharmacodynamic Effects of the Bruton's Tyrosine Kinase Inhibitor Fenebrutinib (GDC-0853) in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis Rheumatol. 2021 Oct;73(10):1835-1846. doi: 10.1002/art.41811. Epub 2021 Aug 24. |
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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.
The study was conducted at 69 centers in 12 countries.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | GDC-0853 (150mg) QD |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 9, 2018 |
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| Placebo | Drug | Participants received matching placebo to GDC-0853 at dosages of 150 and 200mg as per the dosing schedules described above. |
|
| Week 48 |
| 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]. | Week 24 |
| 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. | Week 24 |
| 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. | Week 48 |
| 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. | Week 48 |
| 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. | Week 24, 48 |
| 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). | Week 24, 48 |
| 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. | Baseline up to 8 weeks after the last dose of study drug (up to Week 56). |
| 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. | Baseline (Pre-dose), Week 24 (Pre-dose and Post-dose) and Week 48 (Pre-dose) |
| Los Alamitos |
| California |
| 90720 |
| United States |
| RASF-Clinical Research Center | Boca Raton | Florida | 33486 | United States |
| Bay Area Arthritis and Osteoporosis | Brandon | Florida | 33511 | United States |
| Omega Research Consultants | Orlando | Florida | 32810 | United States |
| Clinical Research of West Florida | Tampa | Florida | 33603 | United States |
| Institute of Arthritis Research | Idaho Falls | Idaho | 83404 | United States |
| Via Christi Research, a division of Via Christi Hospitals Wichita, Inc. | Wichita | Kansas | 67208 | United States |
| Ochsner Clinic Foundation | Baton Rouge | Louisiana | 70809 | United States |
| The Arthritis & Diabetes Clinic, Inc.; Research | Monroe | Louisiana | 71203 | United States |
| Albuquerque Clinical Trials | Albuquerque | New Mexico | 87102 | United States |
| Saint Lawrence Health System | Canton | New York | 13617 | United States |
| New York University School of Medicine | New York | New York | 10016 | United States |
| Shanahan Rheumatology & Immunology, PLLC | Raleigh | North Carolina | 27617 | United States |
| Ohio State University Clinical Trials Management Office | Columbus | Ohio | 43210 | United States |
| Tekton Research Inc | Austin | Texas | 78745 | United States |
| Accurate Clinical Research | Houston | Texas | 77058-3675 | United States |
| Accurate Clinical Research | Houston | Texas | 77089 | United States |
| Arthritis Clinic Of Central Texas | San Marcos | Texas | 78666 | United States |
| Organizacion Medica de Investigacion | Buenos Aires | C1015ABO | Argentina |
| APRILLUS | Buenos Aires | C1194AAO | Argentina |
| Hospital Italiano de La Plata | La Plata | 1900 | Argentina |
| CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica | San Juan | 5400 | Argentina |
| Centro Medico Privado de Reumatologia; Reumathology | San Miguel | T4000AXL | Argentina |
| CEDOES - Diagnóstico e Pesquisa | Vitória | Espírito Santo | 29055-450 | Brazil |
| CIP - Centro Internacional de Pesquisa X; Pesquisa Clinica | Goiânia | Goiás | 74110-120 | Brazil |
| Hospital das Clinicas - UFMG | Belo Horizonte | Minas Gerais | 31270-901 | Brazil |
| CMiP - Centro Mineiro de Pesquisa*X* | Juiz de Fora | Minas Gerais | 36010-570 | Brazil |
| Edumed - Educação e Saúde SA | Curitiba | Paraná | 80440-080 | Brazil |
| Hospital Moinhos de Vento | Porto Alegre | Rio Grande do Sul | 90035-001 | Brazil |
| Centro de Pesquisas em Diabetes - CPD | Porto Alegre | Rio Grande do Sul | 90035-170 | Brazil |
| Clinica de Neoplasias Litoral | Itajaí | Santa Catarina | 88301-220 | Brazil |
| Faculdade de Medicina do ABC - FMABC | Santo André | São Paulo | 09060-650 | Brazil |
| Hospital Estadual Mario Covas | Santo André | São Paulo | 09190-610 | Brazil |
| Hospital Abreu Sodré - AACD | São Paulo | São Paulo | 04023-000 | Brazil |
| MHAT Plovdiv | Plovdiv | 4003 | Bulgaria |
| Medical Center "Teodora", EOOD | Rousse | 7000 | Bulgaria |
| Medical Center Excelsior OOD | Sofia | 1000 | Bulgaria |
| UMHAT "Sv. Ivan Rilski", EAD | Sofia | 1431 | Bulgaria |
| MC "Synexus - Sofia", EOOD | Sofia | 1784 | Bulgaria |
| Medical Center "Nov Rehabilitatsionen Tsentar", EOOD | Stara Zagora | 6000 | Bulgaria |
| CTR Estudios SPA | Providencia | 7500571 | Chile |
| Dermacross | Santiago | 66901 | Chile |
| Centro de Estudios Reumatológicos | Santiago | 7501126 | Chile |
| SOMEAL | Santiago | 7510186 | Chile |
| Biomedica | Santiago | Chile |
| CEQUIN - Fundación Cardiomet Eje Cafetero | Armenia | 00000 | Colombia |
| Centro Integral de Reumatologia del Caribe SAS CIRCARIBE SAS | Barranquilla | 00000 | Colombia |
| Centro de Reumatologia y Ortopedia | Barranquilla | 80020 | Colombia |
| Medicity S.A.S. | Bucaramanga | 680003 | Colombia |
| Servimed S.A.S. | Bucaramanga | 680003 | Colombia |
| Hospital Pablo Tobon Uribe | Medellín | 050034 | Colombia |
| Charite Research Organisation GmbH; Phase - I Unit of Hematology and Oncology | Berlin | 12200 | Germany |
| Centro de Investigacion Alberto Bazzoni S.A. de C.V. | Torreón | Coahuila | 27000 | Mexico |
| Unidad de Atencion Medica e Investigacion en Salud S.C. | Mérida | Yucatán | 97000 | Mexico |
| Consultorio Particular del Dr. Miguel Cortes Hernandez | Cuernavaca | 62290 | Mexico |
| Hospital Angeles Lindavista | México | 07760 | Mexico |
| Hospital Universitario de Saltillo | Saltillo | 25000 | Mexico |
| Hospital Central Dr Ignacio Morones Prieto | San Luis Potosí City | 78240 | Mexico |
| Konkuk University Medical Center | Seoul | 05030 | South Korea |
| The Catholic University of Korea St.Mary's Hospital | Seoul | 150-713 | South Korea |
| Complejo Hospitalario Universitario A Coruña | A Coruña | LA Coruña | 15006 | Spain |
| Hospital Universitari Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital General Universitario Gregorio Marañon | Madrid | 28007 | Spain |
| Hospital Clinico Universitario de Valladolid; Servicio de Reumatologia | Valladolid | 47005 | Spain |
| Kaohsiung Chang Gung Memorial Hospital | Kaohsiung City | 00833 | Taiwan |
| National Taiwan University Hospital | Taipei | 10002 | Taiwan |
| Chang Gung Memorial Hospital - Linkou | Taoyuan | 333 | Taiwan |
| University College London Hospital | London | NW1 - 2PG | United Kingdom |
| Guy's Hospital; Louise Coote Lupus Unit | London | SE1 9RT | United Kingdom |
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.
| FG002 | 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. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Ethnicity | Number | Participants |
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| Race/Ethnicity, Customized | Race | Number | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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. | The Intent-To-Treat (ITT) population was defined as all randomized participants regardless of whether they received any study drug. | Posted | Number | Percentage of Participants | Week 48 |
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| 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]. | The Intent-To-Treat (ITT) population was defined as all randomized participants regardless of whether they received any study drug. | Posted | Number | Percentage of Participants | Week 48 |
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| 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]. | The Intent-To-Treat (ITT) population was defined as all randomized participants regardless of whether they received any study drug. | Posted | Number | Percentage of Participants | Week 24 |
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| 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. | The Intent-To-Treat (ITT) population was defined as all randomized participants regardless of whether they received any study drug. | Posted | Number | Percentage of Participants | Week 24 |
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| 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. | 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. | Posted | Number | Percentage of Participants | Week 48 |
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| 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. | 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. | Posted | Number | Percentage of Participants | Week 48 |
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| 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. | The Intent-To-Treat (ITT) population was defined as all randomized participants regardless of whether they received any study drug. | Posted | Number | Percentage of Participants | Week 24, 48 |
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| 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). | 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. | Posted | Number | Percentage of Participants | Week 24, 48 |
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| 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. | 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. | Posted | Number | Percentage of Participants | Baseline up to 8 weeks after the last dose of study drug (up to Week 56). |
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| 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. | 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. | Posted | Mean | Standard Deviation | ng/mL | Baseline (Pre-dose), Week 24 (Pre-dose and Post-dose) and Week 48 (Pre-dose) |
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Baseline up to 8 weeks after the last dose of study drug (up to Week 56).
The Safety 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. AEs that were entered into the database at the time of the database lock were included in the AE analysis.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 2 | 84 | 9 | 84 | 42 | 84 |
| EG001 | 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. | 1 | 87 | 4 | 87 | 54 | 87 |
| EG002 | 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. | 0 | 88 | 12 | 88 | 51 | 88 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| LEUKOCYTOSIS | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| THROMBOCYTOPENIA | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| CONGESTIVE CARDIOMYOPATHY | Cardiac disorders | MedDRA 22.0 | Systematic Assessment |
| |
| MYOCARDITIS | Cardiac disorders | MedDRA 22.0 | Systematic Assessment |
| |
| MULTIPLE ORGAN DYSFUNCTION SYNDROME | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| PYREXIA | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| EPSTEIN-BARR VIRUS INFECTION | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| GASTROENTERITIS BACTERIAL | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| INFECTED SKIN ULCER | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| OSTEOMYELITIS CHRONIC | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| PNEUMONIA | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| PULMONARY TUBERCULOSIS | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| PYELONEPHRITIS | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| SEPTIC SHOCK | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| URINARY TRACT INFECTION | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| ANKLE FRACTURE | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
| |
| ALANINE AMINOTRANSFERASE INCREASED | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| ASPARTATE AMINOTRANSFERASE INCREASED | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| CHEST WALL HAEMATOMA | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| MUSCULAR WEAKNESS | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| SYSTEMIC LUPUS ERYTHEMATOSUS | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| CERVIX CARCINOMA STAGE 0 | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.0 | Systematic Assessment |
| |
| SALIVARY GLAND NEOPLASM | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.0 | Systematic Assessment |
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| SYNCOPE | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| ABORTION SPONTANEOUS | Pregnancy, puerperium and perinatal conditions | MedDRA 22.0 | Systematic Assessment |
| |
| DEPRESSION | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
| |
| RENAL COLIC | Renal and urinary disorders | MedDRA 22.0 | Systematic Assessment |
| |
| RENAL IMPAIRMENT | Renal and urinary disorders | MedDRA 22.0 | Systematic Assessment |
| |
| ACUTE RESPIRATORY FAILURE | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| PULMONARY OEDEMA | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| RESPIRATORY FAILURE | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| SKIN ULCER | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| ABORTION INDUCED | Surgical and medical procedures | MedDRA 22.0 | Systematic Assessment |
| |
| DEEP VEIN THROMBOSIS | Vascular disorders | MedDRA 22.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| LYMPHOPENIA | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| NEUTROPENIA | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| ABDOMINAL PAIN UPPER | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| DIARRHOEA | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| NAUSEA | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| BRONCHITIS | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| GASTROENTERITIS | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| INFLUENZA | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| NASOPHARYNGITIS | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| SINUSITIS | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| URINARY TRACT INFECTION | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| HEADACHE | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| RASH | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800 821-8590 | genentech@druginfo.com |
| May 22, 2020 |
| Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D008180 | Lupus Erythematosus, Systemic |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000619415 | fenebrutinib |
Not provided
Not provided
Not provided
| Male |
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| Not Hispanic or Latino |
|
| Not Stated |
|
| Asian |
|
| Black or African American |
|
| Multiple |
|
| White |
|
| Absolute Difference |
| 7.5 |
| 2-Sided |
| 95 |
| -7.3 |
| 22.4 |
| Superiority |
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.
| OG002 | 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. |
|
|
|
| OG002 | 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. |
|
|
|
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. |
|
|
|
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.
| OG002 | 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. |
|
|
|
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. |
| OG002 | 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. |
|
|
|
| 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. |
|
|
|
| OG002 |
| 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. |
|
|
|
| OG002 |
| 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. |
|
|
| Participants |
|
|