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

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

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).

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Placebo; Drug: GDC-0853

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1015ABO
    • Organizacion Medica de Investigacion
  • Buenos Aires, Argentina, C1194AAO
    • APRILLUS
  • La Plata, Argentina, 1900
    • Hospital Italiano de La Plata
  • San Juan, Argentina, 5400
    • CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
  • San Miguel, Argentina, T4000AXL
    • Centro Medico Privado de Reumatologia; Reumathology
• Brazil
  • ES
    • Vitoria, ES, Brazil, 29055-450
      • CEDOES - Diagnóstico e Pesquisa
  • GO
    • Goiânia, GO, Brazil, 74110-120
      • CIP - Centro Internacional de Pesquisa X; Pesquisa Clinica
  • MG
    • Belo Horizonte, MG, Brazil, 31270-901
      • Hospital das Clinicas - UFMG
    • Juiz de Fora, MG, Brazil, 36010-570
      • CMiP - Centro Mineiro de Pesquisa*X*
  • PR
    • Curitiba, PR, Brazil, 80440-080
      • Edumed - Educacao e Saude SA
  • RS
    • Porto Alegre, RS, Brazil, 90035-001
      • Hospital Moinhos de Vento
    • Porto Alegre, RS, Brazil, 90035-170
      • Centro de Pesquisas em Diabetes - CPD
  • SC
    • Itajai, SC, Brazil, 88301-220
      • Clinica de Neoplasias Litoral
  • SP
    • Santo Andre, SP, Brazil, 09060-650
      • Faculdade de Medicina do ABC - FMABC
    • Santo Andre, SP, Brazil, 09190-610
      • Hospital Estadual Mario Covas
    • Sao Paulo, SP, Brazil, 04023-000
      • Hospital Abreu Sodré - AACD
• Bulgaria
  • Plovdiv, Bulgaria, 4003
    • MHAT Plovdiv
  • Ruse, Bulgaria, 7000
    • Medical Center "Teodora", EOOD
  • Sofia, Bulgaria, 1431
    • UMHAT "Sv. Ivan Rilski", EAD
  • Sofia, Bulgaria, 1000
    • Medical Center Excelsior OOD
  • Sofia, Bulgaria, 1784
    • MC "Synexus - Sofia", EOOD
  • Stara Zagora, Bulgaria, 6000
    • Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
• Chile
  • Providencia, Chile, 7500571
    • CTR Estudios SPA
  • Santiago, Chile, 7501126
    • Centro de Estudios Reumatologicos
  • Santiago, Chile, 66901
    • Dermacross
  • Santiago, Chile
    • Biomedica
  • Santiago, Chile, 7510186
    • SOMEAL
• Colombia
  • Armenia, Colombia, 00000
    • CEQUIN - Fundación Cardiomet Eje Cafetero
  • Barranquilla, Colombia, 00000
    • Centro Integral de Reumatologia del Caribe SAS CIRCARIBE SAS
  • Barranquilla, Colombia, 80020
    • Centro de Reumatologia y Ortopedia
  • Bucaramanga, Colombia, 680003
    • Medicity S.A.S.
  • Bucaramanga, Colombia, 680003
    • Servimed S.A.S.
  • Medellin, Colombia, 050034
    • Hospital Pablo Tobón Uribe
• Germany
  • Berlin, Germany, 12200
    • Charite Research Organisation GmbH; Phase - I Unit of Hematology and Oncology
• Korea, Republic of
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of, 150-713
    • The Catholic University of Korea St.Mary's Hospital
• Mexico
  • Cuernavaca, Mexico, 62290
    • Consultorio Particular del Dr. Miguel Cortes Hernandez
  • Mexico, Mexico, 07760
    • Hospital Angeles Lindavista
  • Saltillo, Mexico, 25000
    • Hospital Universitario de Saltillo
  • San Luis Potosi, Mexico, 78240
    • Hospital Central Dr Ignacio Morones Prieto
  • Coahuila
    • Torreon, Coahuila, Mexico, 27000
      • Centro de Investigacion Alberto Bazzoni S.A. de C.V.
  • Yucatan
    • Mérida, Yucatan, Mexico, 97000
      • Unidad de Atencion Medica e Investigacion en Salud S.C.
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Valladolid, Spain, 47005
    • Hospital Clinico Universitario de Valladolid; Servicio de Reumatologia
  • LA Coruña
    • A Coruña, LA Coruña, Spain, 15006
      • Complejo Hospitalario Universitario A Coruña
• Taiwan
  • Kaohsiung City, Taiwan, 00833
    • Kaohsiung Chang Gung Memorial Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital - Linkou
• United Kingdom
  • London, United Kingdom, NW1 - 2PG
    • University College London Hospital
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital; Louise Coote Lupus Unit
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • Los Alamitos, California, United States, 90720
      • Valerius Medical Group & Research Ctr of Greater Long Beach
  • Florida
    • Boca Raton, Florida, United States, 33486
      • RASF-Clinical Research Center
    • Brandon, Florida, United States, 33511
      • Bay Area Arthritis And Osteoporosis
    • Orlando, Florida, United States, 32810
      • Omega Research Consultants
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Institute of Arthritis Research
  • Kansas
    • Wichita, Kansas, United States, 67208
      • Via Christi Research, a division of Via Christi Hospitals Wichita, Inc.
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Ochsner Clinic Foundation
    • Monroe, Louisiana, United States, 71203
      • The Arthritis & Diabetes Clinic, Inc.; Research
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials
  • New York
    • Canton, New York, United States, 13617
      • Saint Lawrence Health System
    • New York, New York, United States, 10016
      • New York University School of Medicine
  • North Carolina
    • Raleigh, North Carolina, United States, 27617
      • Shanahan Rheumatology & Immunology, PLLC
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Clinical Trials Management Office
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research Inc
    • Houston, Texas, United States, 77089
      • Accurate Clinical Research
    • Houston, Texas, United States, 77058-3675
      • Accurate Clinical Research
    • San Marcos, Texas, United States, 78666
      • Arthritis Clinic of Central Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	Drug: Placebo; Participants received matching placebo to GDC-0853 at dosages of 150 and 200mg as per the dosing schedules described above.
Experimental: 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.	Drug: GDC-0853; Participants received GDC-0853 at dosages of 150 or 200mg as per the dosing schedules described above.; Other Names: RO7010939
Experimental: 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.	Drug: GDC-0853; Participants received GDC-0853 at dosages of 150 or 200mg as per the dosing schedules described above.; Other Names: RO7010939

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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].	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)

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2017
• Primary Completion (Actual): May 28, 2019
• Study Completion (Actual): July 16, 2019

Study Registration Dates

• First Submitted: September 14, 2016
• First Submitted That Met QC Criteria: September 16, 2016
• First Posted (Estimated): September 20, 2016

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: GA30044; 2016-001039-11 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No