A Study of the Safety and Efficacy of GDC-0853 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus
- Registration Number
- NCT02908100
- Lead Sponsor
- Genentech, Inc.
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 260
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description GDC-0853 (150mg) QD GDC-0853 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. Placebo 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. GDC-0853 (200mg) BID GDC-0853 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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 \[less than 10 milligram per day (mg/day) and less or equal to the dose received on Day 1\].
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.
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.
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).
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.
Trial Locations
- Locations (69)
Institute of Arthritis Research
🇺🇸Idaho Falls, Idaho, United States
Valerius Medical Group & Research Ctr of Greater Long Beach
🇺🇸Los Alamitos, California, United States
RASF-Clinical Research Center
🇺🇸Boca Raton, Florida, United States
Arthritis Clinic Of Central Texas
🇺🇸San Marcos, Texas, United States
Hospital Abreu Sodré - AACD
🇧🇷Sao Paulo, SP, Brazil
Albuquerque Clinical Trials
🇺🇸Albuquerque, New Mexico, United States
CEDOES - Diagnóstico e Pesquisa
🇧🇷Vitoria, ES, Brazil
APRILLUS
🇦🇷Buenos Aires, Argentina
CIP - Centro Internacional de Pesquisa X; Pesquisa Clinica
🇧🇷Goiânia, GO, Brazil
Bay Area Arthritis and Osteoporosis
🇺🇸Brandon, Florida, United States
Centro Medico Privado de Reumatologia; Reumathology
🇦🇷San Miguel, Argentina
CMiP - Centro Mineiro de Pesquisa*X*
🇧🇷Juiz de Fora, MG, Brazil
Shanahan Rheumatology & Immunology, PLLC
🇺🇸Raleigh, North Carolina, United States
Clinica de Neoplasias Litoral
🇧🇷Itajai, SC, Brazil
Hospital Clinico Universitario de Valladolid; Servicio de Reumatologia
🇪🇸Valladolid, Spain
Edumed - Educação e Saúde SA
🇧🇷Curitiba, PR, Brazil
Organizacion Medica de Investigacion
🇦🇷Buenos Aires, Argentina
Charite Research Organisation GmbH; Phase - I Unit of Hematology and Oncology
🇩🇪Berlin, Germany
The Catholic University of Korea St.Mary's Hospital
🇰🇷Seoul, Korea, Republic of
The Arthritis & Diabetes Clinic, Inc.; Research
🇺🇸Monroe, Louisiana, United States
Hospital das Clinicas - UFMG
🇧🇷Belo Horizonte, MG, Brazil
New York University School of Medicine
🇺🇸New York, New York, United States
Centro de Estudios Reumatológicos
🇨🇱Santiago, Chile
Complejo Hospitalario Universitario A Coruña
🇪🇸A Coruña, LA Coruña, Spain
Konkuk University Medical Center
🇰🇷Seoul, Korea, Republic of
Dermacross
🇨🇱Santiago, Chile
Servimed S.A.S.
🇨🇴Bucaramanga, Colombia
Guy's Hospital; Louise Coote Lupus Unit
🇬🇧London, United Kingdom
Hospital Estadual Mario Covas
🇧🇷Santo Andre, SP, Brazil
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Saint Lawrence Health System
🇺🇸Canton, New York, United States
Hospital Italiano de La Plata
🇦🇷La Plata, Argentina
CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
🇦🇷San Juan, Argentina
UMHAT "Sv. Ivan Rilski", EAD
🇧🇬Sofia, Bulgaria
Centro de Investigacion Alberto Bazzoni S.A. de C.V.
🇲🇽Torreon, Coahuila, Mexico
Hospital Central Dr Ignacio Morones Prieto
🇲🇽San Luis Potosi, Mexico
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Chang Gung Memorial Hospital - Linkou
🇨🇳Taoyuan, Taiwan
Ochsner Clinic Foundation
🇺🇸Baton Rouge, Louisiana, United States
Hospital Moinhos de Vento
🇧🇷Porto Alegre, RS, Brazil
Centro de Pesquisas em Diabetes - CPD
🇧🇷Porto Alegre, RS, Brazil
Faculdade de Medicina do ABC - FMABC
🇧🇷Santo Andre, SP, Brazil
Medical Center Excelsior OOD
🇧🇬Sofia, Bulgaria
Biomedica
🇨🇱Santiago, Chile
CEQUIN - Fundación Cardiomet Eje Cafetero
🇨🇴Armenia, Colombia
Hospital Universitario de Saltillo
🇲🇽Saltillo, Mexico
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Clinical Research of West Florida
🇺🇸Tampa, Florida, United States
Ohio State University Clinical Trials Management Office
🇺🇸Columbus, Ohio, United States
Accurate Clinical Research
🇺🇸Houston, Texas, United States
University College London Hospital
🇬🇧London, United Kingdom
MHAT Plovdiv
🇧🇬Plovdiv, Bulgaria
Centro Integral de Reumatologia del Caribe SAS CIRCARIBE SAS
🇨🇴Barranquilla, Colombia
Unidad de Atencion Medica e Investigacion en Salud S.C.
🇲🇽Mérida, Yucatan, Mexico
MC "Synexus - Sofia", EOOD
🇧🇬Sofia, Bulgaria
Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
🇧🇬Stara Zagora, Bulgaria
Centro de Reumatologia y Ortopedia
🇨🇴Barranquilla, Colombia
Medicity S.A.S.
🇨🇴Bucaramanga, Colombia
Hospital Pablo Tobon Uribe
🇨🇴Medellin, Colombia
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
CTR Estudios SPA
🇨🇱Providencia, Chile
SOMEAL
🇨🇱Santiago, Chile
Medical Center "Teodora", EOOD
🇧🇬Ruse, Bulgaria
Consultorio Particular del Dr. Miguel Cortes Hernandez
🇲🇽Cuernavaca, Mexico
Hospital Angeles Lindavista
🇲🇽Mexico, Mexico
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung City, Taiwan
Omega Research Consultants
🇺🇸Orlando, Florida, United States
Tekton Research Inc
🇺🇸Austin, Texas, United States
Via Christi Research, a division of Via Christi Hospitals Wichita, Inc.
🇺🇸Wichita, Kansas, United States