CClinicalTrials.gg
TerminatedNCT03407482Updated Dec 19, 2020Results posted

An Extension Study of GDC-0853 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus

A Phase 2 interventional study of GDC-0853 in Lupus Erythematosus, Systemic, sponsored by Genentech, Inc.. Terminated at 53 sites in 11 countries. Open to participants aged 18 Years to 76 Years. Per ClinicalTrials.gov, last updated 2020-12-19.

Sponsored by Genentech, Inc. · Phase 2, Interventional, and Treatment

Why this study was terminated
The study was ended early due to the lack of efficacy seen in the parent study GA30044.
Phase
Phase 2
Study type
Interventional
Enrollment
160
Allocation
Not applicable
Ages
18 Years to 76 Years
Sex
All
01

Study summary

This Phase II, multicenter, open-label extension (OLE) study will evaluate the long-term safety and efficacy of GDC-0853 in participants with systemic lupus erythematosus (SLE) who have completed Study GA30044 (NCT02908100) up to 48 weeks.

02

Conditions studied

  • Lupus Erythematosus, Systemic
03

Who can participate

Ages eligible
18 Years to 76 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Able to comply with the study protocol, in the investigator's judgment
  • Completion of Study GA30044 up to 48 weeks
  • Acceptable safety and tolerability during Study GA30044 as determined by the investigator

Exclusion criteria

Exclusion Criteria:

  • Met protocol-defined treatment-stopping criteria during Study GA30044
  • An adverse event in Study GA30044 that required permanent discontinuation of study drug
  • In the opinion of the investigator, any new, significant, uncontrolled comorbidity or new clinical manifestation (related to SLE or not) that requires medications not allowed in this protocol; or could put the participant at undue risk from a safety perspective
  • Any uncontrolled or clinically significant laboratory abnormality that would affect safety, interpretation of study data, or the participant's participation in the study in the opinion of the investigator in consultation with the Medical Monitor
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
160 participants (actual)

Study arms

  • Experimental
    GDC-0853 (200mg) BID

    Participants previously enrolled in the parent GA30044 Study, now received GDC-0853 (200mg) orally twice daily (BID).

    Drug: GDC-0853

Interventions

  • DrugGDC-0853

    Participants received GDC-0853 at a dose of 200mg, as per the dosing schedule described above.

05

What researchers measure

Primary outcomes

  1. Percentage of Participants With Adverse Events (AEs)

    An Adverse Event (AE) 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 abnormal laboratory values or abnormal clinical test results), 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.

    Time frame: Baseline up until 8 weeks after the last dose of study drug (up to 56 weeks)

Secondary outcomes

  1. Systemic Lupus Erythematosus Responder-4 Index (SRI-4) up to 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.

    Time frame: Baseline up to Week 48

  2. Area Under the Concentration-Time Curve From Time 0 to Time t (AUC0-t,ss) of GDC-0853 at Steady State

    Population PK model estimated AUC of GDC-0853 From Time 0 to Time t (AUC0-t) at steady-state. AUC was measured in Nanograms (ng) per millilitre(mL)\*hour (hr).

    Time frame: Pre-dose (0 hour [hr]) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56)

  3. Minimum Plasma Concentration of GDC-0853 at Steady State (Ctrough,ss)

    Population PK model estimated minimal plasma concentration (Ctrough) of GDC-0853 at steady-state (ss).

    Time frame: Pre-dose (0 hr) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56)

  4. Plasma Decay Half-Life of GDC-0853 at Steady State (t1/2,ss)

    Population PK model estimated plasma decay half life of GDC-0853 at steady-state.

    Time frame: Pre-dose (0 hr) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56)

  5. Apparent Oral Clearance of GDC-0853 at Steady State (CL/F,ss)

    Population PK model estimated apparent oral clearance of GDC-0853 at steady-state.

    Time frame: Pre-dose (0 hr) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56)

06

Results

Posted Dec 19, 2020
Limitations and caveats
The study was ended early due to the lack of efficacy seen in the parent study GA30044.

Participant flow

The study was conducted at 50 centers in 11 countries.

Participant flow — Overall Study
MilestoneGDC-0853 (200mg) BID
Started160
Completed29
Not completed131
Withdrew: Adverse event12
Withdrew: Disease relapse1
Withdrew: Lost to follow-up1
Withdrew: Non-compliance with study drug1
Withdrew: Pregnancy2
Withdrew: Protocol violation1
Withdrew: Study terminated by sponsor106
Withdrew: Withdrawal by subject6
Withdrew: Data entry error1

Outcome measures

PrimaryPercentage of Participants With Adverse Events (AEs)

An Adverse Event (AE) 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 abnormal laboratory values or abnormal clinical test results), 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.

Time frame:
Baseline up until 8 weeks after the last dose of study drug (up to 56 weeks)
Reported as:
Number · Percentage of Participants
Percentage of Participants With Adverse Events (AEs)
Percentage of ParticipantsGDC-0853 (200mg) BID
Percentage of Participants With Adverse Events (AEs)64.4
SecondarySystemic Lupus Erythematosus Responder-4 Index (SRI-4) up to 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.

Time frame:
Baseline up to Week 48

No measurements were reported for this outcome.

SecondaryArea Under the Concentration-Time Curve From Time 0 to Time t (AUC0-t,ss) of GDC-0853 at Steady State

Population PK model estimated AUC of GDC-0853 From Time 0 to Time t (AUC0-t) at steady-state. AUC was measured in Nanograms (ng) per millilitre(mL)\*hour (hr).

Time frame:
Pre-dose (0 hour [hr]) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56)

No measurements were reported for this outcome.

SecondaryMinimum Plasma Concentration of GDC-0853 at Steady State (Ctrough,ss)

Population PK model estimated minimal plasma concentration (Ctrough) of GDC-0853 at steady-state (ss).

Time frame:
Pre-dose (0 hr) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56)

No measurements were reported for this outcome.

SecondaryPlasma Decay Half-Life of GDC-0853 at Steady State (t1/2,ss)

Population PK model estimated plasma decay half life of GDC-0853 at steady-state.

Time frame:
Pre-dose (0 hr) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56)

No measurements were reported for this outcome.

SecondaryApparent Oral Clearance of GDC-0853 at Steady State (CL/F,ss)

Population PK model estimated apparent oral clearance of GDC-0853 at steady-state.

Time frame:
Pre-dose (0 hr) at Weeks 0, 24, 48, at unscheduled or flare or early termination visit (up to Week 56)

No measurements were reported for this outcome.

Adverse events

Collected over Baseline up until 8 weeks after the last dose of study drug (up to 56 weeks). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
GDC-0853 (200mg) BID0/160 (0%)4/160 (2.5%)31/160 (19.4%)
Most frequent serious events
Most frequent serious events
EventGDC-0853 (200mg) BID
CELLULITISInfections and infestations1/160
INFECTIVE TENOSYNOVITISInfections and infestations1/160
URINARY TRACT INFECTIONInfections and infestations1/160
LUMBAR VERTEBRAL FRACTUREInjury, poisoning and procedural complications1/160
SYSTEMIC LUPUS ERYTHEMATOSUSMusculoskeletal and connective tissue disorders1/160
Most frequent other events
Most frequent other events
EventGDC-0853 (200mg) BID
URINARY TRACT INFECTIONInfections and infestations15/160
NASOPHARYNGITISInfections and infestations13/160
NAUSEAGastrointestinal disorders9/160

Baseline characteristics

Age, Continuous
Age, Continuous(Years)GDC-0853 (200mg) BID
Mean42.8 ± 11.5
Sex: Female, Male
Sex: Female, Male(Participants)GDC-0853 (200mg) BID
Female155
Male5
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)GDC-0853 (200mg) BID
Hispanic or Latino117
Not Hispanic or Latino42
Not Stated1
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)GDC-0853 (200mg) BID
American Indian or Alaska native24
Asian5
Black or African American22
Multiple5
White104
07

Study locations

53 sites
  • Valerius Medical Group
    Los Alamitos, California 90720, United States
  • RASF-Clinical Research Center
    Boca Raton, Florida 33486, United States
  • Bay Area Arthritis and Osteoporosis
    Brandon, Florida 33511, United States
  • Clinical Research of West Florida
    Clearwater, Florida 33765, United States
  • Institute of Arthritis Research
    Idaho Falls, Idaho 83404, United States
  • Ochsner Clinic Foundation
    Baton Rouge, Louisiana 70809, United States
  • Shanahan Rheumatology & Immunology, PLLC
    Raleigh, North Carolina 27617, United States
  • Tekton Research Inc
    Austin, Texas 78745, United States
  • Accurate Clinical Research
    Houston, Texas 77058-3675, United States
  • Accurate Clinical Research
    Houston, Texas 77089, United States
  • Arthritis Clinic Of Central Texas
    San Marcos, Texas 78666, United States
  • APRILLUS
    Buenos Aires, C1194AAO, Argentina
  • Hospital Italiano de La Plata
    La Plata, 1900, Argentina
  • CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
    San Juan, 5400, Argentina
  • Centro Médico Privado de Reumatología
    San Miguel de Tucuman, T4000AXL, Argentina
  • CIP - Centro Internacional de Pesquisa
    Goiania, GO 74110-120, Brazil
  • Centro Mineiro de Pesquisa - CMIP
    Juiz de Fora, MG 36036-330, Brazil
  • Edumed - Educação e Saúde SA
    Curitiba, PR 80440-080, Brazil
  • Centro de Pesquisas em Diabetes - CPD
    Porto Alegre, RS 90035-170, Brazil
  • Clinica de Neoplasias Litoral
    Itajai, SC 88301-220, Brazil
  • Faculdade de Medicina do ABC - FMABC
    Santo Andre, SP 09060-650, Brazil
  • Centro Multidisciplinar de Estudos Clínicos - CEMEC*X*
    Santo Andre, SP 09190-510, Brazil
  • Centro de Pesquisas Clinicas; CPCLIN
    Sao Paulo, SP 01228-200, Brazil
  • Hospital Abreu Sodré - AACD
    Sao Paulo, SP 04023-000, Brazil
  • MHAT Plovdiv
    Plovdiv, 4003, Bulgaria
  • Medical Center "Teodora", EOOD
    Ruse, 7000, Bulgaria
  • Medical Center Excelsior OOD
    Sofia, 1000, Bulgaria
  • UMHAT "Sv. Ivan Rilski", EAD
    Sofia, 1431, Bulgaria
  • MC "Synexus - Sofia", EOOD
    Sofia, 1784, Bulgaria
  • Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
    Stara Zagora, 6000, Bulgaria
  • CTR Estudios SPA
    Providencia, 7500571, Chile
  • Dermacross
    Santiago, 66901, Chile
  • Centro de Estudios Reumatologi
    Santiago, 7501126, Chile
  • Biomedica
    Santiago, Chile
  • Centro Integral de Reumatologia del Caribe SAS CIRCARIBE SAS
    Barranquilla, 00000, Colombia
  • Centro de Investigacion Medico Asistencial S.A.S
    Barranquilla, 80020, Colombia
  • Medicity S.A.S.
    Bucaramanga, 680003, Colombia
  • Servimed S.A.S.
    Bucaramanga, 680003, Colombia
  • Hospital Pablo Tobon Uribe
    Medellin, 050034, Colombia
  • Konkuk University Medical Center
    Seoul, 05030, Korea, Republic of
  • Centro de Investigacion Alberto Bazzoni S.A. de C.V.
    Torreon, Coahuila 27000, Mexico
  • Unidad de Atencion Medica e Investigacion en Salud S.C.
    Mérida, Yucatan 97000, Mexico
  • Hospital Angeles Lindavista
    Mexico, 07760, Mexico
  • Hospital Universitario de Saltillo
    Saltillo, 25000, Mexico
  • Hospital Central Dr. Ignacio Morones Prieto
    San Luis Potosi S.l.p., 78240, Mexico
  • Fundación Profesor Novoa Santos
    A Coruna, LA Coruña 15006, Spain
  • Hospital Universitari Vall d'Hebron
    Barcelona, 08035, Spain
  • Hospital General Universitario Gregorio Marañon
    Madrid, 28007, Spain
  • Hospital Clinico Universitario Valladolid
    Valladolid, 47005, Spain
  • Hospital Universitario Rio Hortega
    Valladolid, 47012, Spain
  • Kaohsiung Chang Gung Memorial Hospital
    Kaohsiung City, 00833, Taiwan
  • National Taiwan University Hospital
    Taipei, 10002, Taiwan
  • Guy's Hospital; Louise Coote Lupus Unit
    London, SE1 9RT, United Kingdom
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Jun 20, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

09

Registry details

Key details

Study ID
NCT03407482
Lead sponsor
Genentech, Inc.
Responsible party
Sponsor
First posted
Jan 23, 2018
Start date
Jan 9, 2018
Primary completion
Nov 20, 2019
Completion
Nov 20, 2019
Results posted
Dec 19, 2020
Last update
Dec 19, 2020

Study contacts

Clinical Trials
study director · Hoffmann-La Roche

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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