Clinical trial NCT02908100: A Study of the Safety and Efficacy of GDC-0853 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus
Official title: A Phase II, Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of GDC-0853 in Patients With Moderate to Severe Active Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2016-09-20
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Systemic Lupus Erythematosus Responder Index (SRI)-4 Response at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: 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
timeFrame: Week 48
measure: 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
timeFrame: Week 24
measure: SRI-4 Response at Week 24
timeFrame: Week 24
measure: SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels
timeFrame: Week 48
measure: 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
timeFrame: Week 48
measure: SRI-6 Response at Week 24 and 48
timeFrame: Week 24, 48
measure: BILAG-based Composite Lupus Assessment (BICLA) Response at Week 24 and 48
timeFrame: Week 24, 48
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline up to 8 weeks after the last dose of study drug (up to Week 56).
measure: Plasma Concentrations of Fenebrutinib at Specified Timepoints
timeFrame: Baseline (Pre-dose), Week 24 (Pre-dose and Post-dose) and Week 48 (Pre-dose)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Alamitos
country: United States
facility: Valerius Medical Group & Research Ctr of Greater Long Beach
state: California
city: Boca Raton
country: United States
facility: RASF-Clinical Research Center
state: Florida
city: Brandon
country: United States
facility: Bay Area Arthritis and Osteoporosis
state: Florida
city: Orlando
country: United States
facility: Omega Research Consultants
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida
state: Florida
city: Idaho Falls
country: United States
facility: Institute of Arthritis Research
state: Idaho
city: Wichita
country: United States
facility: Via Christi Research, a division of Via Christi Hospitals Wichita, Inc.
state: Kansas
city: Baton Rouge
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Monroe
country: United States
facility: The Arthritis & Diabetes Clinic, Inc.; Research
state: Louisiana
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials
state: New Mexico
city: Canton
country: United States
facility: Saint Lawrence Health System
state: New York
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: Raleigh
country: United States
facility: Shanahan Rheumatology & Immunology, PLLC
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Clinical Trials Management Office
state: Ohio
city: Austin
country: United States
facility: Tekton Research Inc
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research
state: Texas
city: San Marcos
country: United States
facility: Arthritis Clinic Of Central Texas
state: Texas
city: Buenos Aires
country: Argentina
facility: Organizacion Medica de Investigacion
city: Buenos Aires
country: Argentina
facility: APRILLUS
city: La Plata
country: Argentina
facility: Hospital Italiano de La Plata
city: San Juan
country: Argentina
facility: CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
city: San Miguel
country: Argentina
facility: Centro Medico Privado de Reumatologia; Reumathology
city: Vitoria
country: Brazil
facility: CEDOES - Diagnóstico e Pesquisa
state: ES
city: Goiânia
country: Brazil
facility: CIP - Centro Internacional de Pesquisa X; Pesquisa Clinica
state: GO
city: Belo Horizonte
country: Brazil
facility: Hospital das Clinicas - UFMG
state: MG
city: Juiz de Fora
country: Brazil
facility: CMiP - Centro Mineiro de Pesquisa*X*
state: MG
city: Curitiba
country: Brazil
facility: Edumed - Educação e Saúde SA
state: PR
city: Porto Alegre
country: Brazil
facility: Hospital Moinhos de Vento
state: RS
city: Porto Alegre
country: Brazil
facility: Centro de Pesquisas em Diabetes - CPD
state: RS
city: Itajai
country: Brazil
facility: Clinica de Neoplasias Litoral
state: SC
city: Santo Andre
country: Brazil
facility: Faculdade de Medicina do ABC - FMABC
state: SP
city: Santo Andre
country: Brazil
facility: Hospital Estadual Mario Covas
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Abreu Sodré - AACD
state: SP
city: Plovdiv
country: Bulgaria
facility: MHAT Plovdiv
city: Ruse
country: Bulgaria
facility: Medical Center "Teodora", EOOD
city: Sofia
country: Bulgaria
facility: Medical Center Excelsior OOD
city: Sofia
country: Bulgaria
facility: UMHAT "Sv. Ivan Rilski", EAD
city: Sofia
country: Bulgaria
facility: MC "Synexus - Sofia", EOOD
city: Stara Zagora
country: Bulgaria
facility: Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
city: Providencia
country: Chile
facility: CTR Estudios SPA
city: Santiago
country: Chile
facility: Dermacross
city: Santiago
country: Chile
facility: Centro de Estudios Reumatológicos
city: Santiago
country: Chile
facility: SOMEAL
city: Santiago
country: Chile
facility: Biomedica
city: Armenia
country: Colombia
facility: CEQUIN - Fundación Cardiomet Eje Cafetero
city: Barranquilla
country: Colombia
facility: Centro Integral de Reumatologia del Caribe SAS CIRCARIBE SAS
city: Barranquilla
country: Colombia
facility: Centro de Reumatologia y Ortopedia
city: Bucaramanga
country: Colombia
facility: Medicity S.A.S.
city: Bucaramanga
country: Colombia
facility: Servimed S.A.S.
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe
city: Berlin
country: Germany
facility: Charite Research Organisation GmbH; Phase - I Unit of Hematology and Oncology
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea St.Mary's Hospital
city: Torreon
country: Mexico
facility: Centro de Investigacion Alberto Bazzoni S.A. de C.V.
state: Coahuila
city: Mérida
country: Mexico
facility: Unidad de Atencion Medica e Investigacion en Salud S.C.
state: Yucatan
city: Cuernavaca
country: Mexico
facility: Consultorio Particular del Dr. Miguel Cortes Hernandez
city: Mexico
country: Mexico
facility: Hospital Angeles Lindavista
city: Saltillo
country: Mexico
facility: Hospital Universitario de Saltillo
city: San Luis Potosi
country: Mexico
facility: Hospital Central Dr Ignacio Morones Prieto
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
state: LA Coruña
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Valladolid
country: Spain
facility: Hospital Clinico Universitario de Valladolid; Servicio de Reumatologia
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: Guy's Hospital; Louise Coote Lupus Unit
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.