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

Systemic Lupus Erythematosus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02908100
• Other study ID #: GA30044
• Secondary ID: 2016-001039-11
• Status: Completed
• Phase: Phase 2
• Start date: January 19, 2017
• Est. completion date: July 16, 2019

Study information

• Verified date: May 2024
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 260
• Est. completion date: July 16, 2019
• Est. primary completion date: May 28, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Chile,  Colombia,  Germany,  Korea, Republic of,  Mexico,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Week 48
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].	Week 48
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].	Week 24
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.	Week 24
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.	Week 48
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.	Week 48
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.	Week 24, 48
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).	Week 24, 48
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.	Baseline up to 8 weeks after the last dose of study drug (up to Week 56).
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.	Baseline (Pre-dose), Week 24 (Pre-dose and Post-dose) and Week 48 (Pre-dose)