A Study of the Safety and Efficacy of GDC-0853 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus

NCT02908100 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: GA300442016-001039-11
• Study Type: interventional
• Target: 260
• Locations: 12 countries
• Sites: 70

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).

Conditions

Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (9)

• 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

• 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

• SRI-4 Response at Week 24

  Week 24

• SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels

  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

  Week 48

Study Arms (3)

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.

Drug: Placebo

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.

Drug: GDC-0853

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.

Drug: GDC-0853

Interventions

GDC-0853 DRUG

Participants received GDC-0853 at dosages of 150 or 200mg as per the dosing schedules described above.

Also known as: RO7010939

GDC-0853 (150mg) QD; GDC-0853 (200mg) BID

Placebo DRUG

Participants received matching placebo to GDC-0853 at dosages of 150 and 200mg as per the dosing schedules described above.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (70)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Valerius Medical Group & Research Ctr of Greater Long Beach

Los Alamitos, California, 90720, United States

Location

RASF-Clinical Research Center

Boca Raton, Florida, 33486, United States

Location

Bay Area Arthritis and Osteoporosis

Brandon, Florida, 33511, United States

Location

Omega Research Consultants

Orlando, Florida, 32810, United States

Location

Clinical Research of West Florida

Tampa, Florida, 33603, United States

Location

Institute of Arthritis Research

Idaho Falls, Idaho, 83404, United States

Location

Via Christi Research, a division of Via Christi Hospitals Wichita, Inc.

Wichita, Kansas, 67208, United States

Location

Ochsner Clinic Foundation

Baton Rouge, Louisiana, 70809, United States

Location

The Arthritis & Diabetes Clinic, Inc.; Research

Monroe, Louisiana, 71203, United States

Location

Albuquerque Clinical Trials

Albuquerque, New Mexico, 87102, United States

Location

Saint Lawrence Health System

Canton, New York, 13617, United States

Location

New York University School of Medicine

New York, New York, 10016, United States

Location

Shanahan Rheumatology & Immunology, PLLC

Raleigh, North Carolina, 27617, United States

Location

Ohio State University Clinical Trials Management Office

Columbus, Ohio, 43210, United States

Location

Tekton Research Inc

Austin, Texas, 78745, United States

Location

Accurate Clinical Research

Houston, Texas, 77058-3675, United States

Location

Accurate Clinical Research

Houston, Texas, 77089, United States

Location

Arthritis Clinic Of Central Texas

San Marcos, Texas, 78666, United States

Location

Organizacion Medica de Investigacion

Buenos Aires, C1015ABO, Argentina

Location

APRILLUS

Buenos Aires, C1194AAO, Argentina

Location

Hospital Italiano de La Plata

La Plata, 1900, Argentina

Location

CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica

San Juan, 5400, Argentina

Location

Centro Medico Privado de Reumatologia; Reumathology

San Miguel, T4000AXL, Argentina

Location

CEDOES - Diagnóstico e Pesquisa

Vitória, Espírito Santo, 29055-450, Brazil

Location

CIP - Centro Internacional de Pesquisa X; Pesquisa Clinica

Goiânia, Goiás, 74110-120, Brazil

Location

Hospital das Clinicas - UFMG

Belo Horizonte, Minas Gerais, 31270-901, Brazil

Location

CMiP - Centro Mineiro de Pesquisa*X*

Juiz de Fora, Minas Gerais, 36010-570, Brazil

Location

Edumed - Educação e Saúde SA

Curitiba, Paraná, 80440-080, Brazil

Location

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, 90035-001, Brazil

Location

Centro de Pesquisas em Diabetes - CPD

Porto Alegre, Rio Grande do Sul, 90035-170, Brazil

Location

Clinica de Neoplasias Litoral

Itajaí, Santa Catarina, 88301-220, Brazil

Location

Faculdade de Medicina do ABC - FMABC

Santo André, São Paulo, 09060-650, Brazil

Location

Hospital Estadual Mario Covas

Santo André, São Paulo, 09190-610, Brazil

Location

Hospital Abreu Sodré - AACD

São Paulo, São Paulo, 04023-000, Brazil

Location

MHAT Plovdiv

Plovdiv, 4003, Bulgaria

Location

Medical Center "Teodora", EOOD

Rousse, 7000, Bulgaria

Location

Medical Center Excelsior OOD

Sofia, 1000, Bulgaria

Location

UMHAT "Sv. Ivan Rilski", EAD

Sofia, 1431, Bulgaria

Location

MC "Synexus - Sofia", EOOD

Sofia, 1784, Bulgaria

Location

Medical Center "Nov Rehabilitatsionen Tsentar", EOOD

Stara Zagora, 6000, Bulgaria

Location

CTR Estudios SPA

Providencia, 7500571, Chile

Location

Dermacross

Santiago, 66901, Chile

Location

Centro de Estudios Reumatológicos

Santiago, 7501126, Chile

Location

SOMEAL

Santiago, 7510186, Chile

Location

Biomedica

Santiago, Chile

Location

CEQUIN - Fundación Cardiomet Eje Cafetero

Armenia, 00000, Colombia

Location

Centro Integral de Reumatologia del Caribe SAS CIRCARIBE SAS

Barranquilla, 00000, Colombia

Location

Centro de Reumatologia y Ortopedia

Barranquilla, 80020, Colombia

Location

Medicity S.A.S.

Bucaramanga, 680003, Colombia

Location

Servimed S.A.S.

Bucaramanga, 680003, Colombia

Location

Hospital Pablo Tobon Uribe

Medellín, 050034, Colombia

Location

Charite Research Organisation GmbH; Phase - I Unit of Hematology and Oncology

Berlin, 12200, Germany

Location

Centro de Investigacion Alberto Bazzoni S.A. de C.V.

Torreón, Coahuila, 27000, Mexico

Location

Unidad de Atencion Medica e Investigacion en Salud S.C.

Mérida, Yucatán, 97000, Mexico

Location

Consultorio Particular del Dr. Miguel Cortes Hernandez

Cuernavaca, 62290, Mexico

Location

Hospital Angeles Lindavista

México, 07760, Mexico

Location

Hospital Universitario de Saltillo

Saltillo, 25000, Mexico

Location

Hospital Central Dr Ignacio Morones Prieto

San Luis Potosí City, 78240, Mexico

Location

Konkuk University Medical Center

Seoul, 05030, South Korea

Location

The Catholic University of Korea St.Mary's Hospital

Seoul, 150-713, South Korea

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, LA Coruña, 15006, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Clinico Universitario de Valladolid; Servicio de Reumatologia

Valladolid, 47005, Spain

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 00833, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Chang Gung Memorial Hospital - Linkou

Taoyuan District, 333, Taiwan

Location

University College London Hospital

London, NW1 - 2PG, United Kingdom

Location

Guy's Hospital; Louise Coote Lupus Unit

London, SE1 9RT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34042314 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

fenebrutinib

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2016
• First Posted: September 20, 2016
• Study Start: January 19, 2017
• Primary Completion: May 28, 2019
• Study Completion: July 16, 2019
• Last Updated: May 8, 2024
• Results First Posted: July 7, 2020

Record last verified: 2024-05

Locations

BR (11); TW (3); ME (6); GB (2); DE (1); CO (6); AR (5); KR (2); ES (4); BU (6); US (19); CL (5)