Clinical trial NCT03407482
Conditions: Lupus Erythematosus, Systemic
Sponsor: Genentech, Inc.
Start date: 2018-01-09; Completion date: 2019-11-20
Enrollment: 160 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Detailed description:

Arms: arm 1: Participants previously enrolled in the parent GA30044 Study, now received GDC-0853 (200mg) orally twice daily (BID).
Interventions: intervention 1: GDC-0853
Intervention descriptions: intervention 1: Participants received GDC-0853 at a dose of 200mg, as per the dosing schedule described above.

Protocol documents:
Prot_SAP_000.pdf: 
 
Official Title: A Phase II, Open-Label Extension Study of Patients Previously 
Enrolled in Study GA30044 to Evaluate the Long-Term Safety and 
Efficacy of GDC-0853 in Patients With Moderate to Severe Active 
Systemic Lupus Erythematosus 
NCT Number: NCT03407482 
Document Date: Protocol Version 1: 20-June-2017 
 
 


FINAL PROTOCOL APPROVAL 
 
CONFIDENTIAL 
The information contained in this document, especially any unpublished data, is the property of 
Genentech, Inc. (or under its control) and therefore is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable Ethics Committee 
or Institutional Review Board.  It is understood that this information will not be disclosed to others 
without written authorization from Genentech except to the extent necessary to obtain informed 
consent from persons to whom the drug may be administered. 
 
GDC-0853—Genentech, Inc. 
Protocol GA30066, Version 1  
PROTOCOL 
TITLE: 
A PHASE II, OPEN-LABEL EXTENSION STUDY OF 
PATIENTS PREVIOUSLY ENROLLED IN STUDY 
GA30044 TO EVALUATE THE LONG-TERM 
SAFETY AND EFFICACY OF GDC-0853 IN 
PATIENTS WITH MODERATE TO SEVERE ACTIVE 
SYSTEMIC LUPUS ERYTHEMATOSUS 
PROTOCOL NUMBER: GA30066 
VERSION NUMBER: 
1 
EUDRACT NUMBER: 
2017-001764-37 
IND NUMBER: 
130011 
TEST PRODUCT: 
GDC-0853 (RO7010939) 
MEDICAL MONITOR: 
, M.D. 
SPONSOR: 
Genentech, Inc. 
DATE FINAL: 
See electronic date stamp below 
 
20-Jun-2017 20:24:16
Title
Approver's Name
Company Signatory (Clinical)
Date and Time (UTC)


GDC-0853—Genentech, Inc. 
2/ Protocol GA30066, Version 1  
 
TABLE OF CONTENTS 
PROTOCOL ACCEPTANCE FORM .................................................................. 10 
PROTOCOL SYNOPSIS .................................................................................... 11 
1. 
BACKGROUND .......................................................................................... 20 
1.1 
Background on Systemic Lupus (rythematosus .................... 20 
1.2 
Background on Bruton’s Tyrosine Kinase and 
GDC-0853 ............................................................................. 21 
1.2.1 
Bruton’s Tyrosine Kinase ....................................................... 21 
1.2.2 
Nonclinical Experience with GDC-0853 ................................. 21 
1.2.3 
Clinical Experience with GDC-0853 ....................................... 23 
1.3 
Study Rationale and Benefit–Risk Assessment ..................... 24 
1.3.1 
Primary Nonclinical Toxicity Findings .................................... 25 
1.3.2 
Potential Risks for Clinical Toxicities ..................................... 26 
1.3.2.1 
Infections ............................................................................... 27 
1.3.2.2 
Vaccinations .......................................................................... 27 
1.3.2.3 
Bleeding ................................................................................. 27 
1.3.2.4 
Cytopenias ............................................................................. 27 
1.3.2.5 
Gastrointestinal Effects .......................................................... 28 
1.3.2.6 
Hepatotoxicity ........................................................................ 28 
1.3.2.7 
Cardiovascular Effects ........................................................... 28 
1.3.2.8 
Vascular Inflammation ........................................................... 29 
1.3.2.9 
Malignancy ............................................................................ 29 
2. 
OBJECTIVES AND ENDPOINTS ............................................................... 29 
3. 
STUDY DESIGN ......................................................................................... 30 
3.1 
Description of the Study......................................................... 30 
3.1.1 
Internal Monitoring Committee and Scientific 
Oversight Committee ............................................................. 32 
3.2 
End of Study and Length of Study ......................................... 32 
3.3 
Rationale for Study Design .................................................... 33 
3.3.1 
Rationale for GDC-0853 Dose and Schedule ........................ 33 
3.3.2 
Rationale for Open-Label Design .......................................... 34 


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3/ Protocol GA30066, Version 1  
3.3.3 
Rationale for PK Sample Collection Schedule ....................... 34 
3.3.4 
Rationale for Other Study Design Elements .......................... 34 
3.3.4.1 
Efficacy Measurements ......................................................... 34 
3.3.4.2 
Corticosteroid Taper .............................................................. 35 
3.3.4.3 
Additional Clinical Outcomes Assessments ........................... 35 
3.3.4.4 
Concomitant Medication Rationale ........................................ 35 
4. 
MATERIALS AND METHODS .................................................................... 36 
4.1 
Patients .................................................................................. 36 
4.1.1 
Inclusion Criteria .................................................................... 36 
4.1.2 
Exclusion Criteria ................................................................... 37 
4.2 
Study Treatment .................................................................... 39 
4.2.1 
Formulation, Packaging, and Handling .................................. 39 
4.2.2 
Dosage, Administration, and Compliance .............................. 39 
4.2.2.1 
GDC-0853 Dose and Administration ..................................... 39 
4.2.2.2 
GDC-0853 Compliance.......................................................... 40 
4.2.2.3 
Background Standard of Care Therapy ................................. 40 
4.2.2.4 
Background Standard of Care Therapy 
Compliance ............................................................................ 43 
4.2.3 
Investigational Medicinal Product Accountability ................... 43 
4.2.4 
Continued Access to GDC-0853 ........................................... 43 
4.3 
Concomitant Therapy, Prohibited Food, and 
Additional Restrictions ........................................................... 44 
4.3.1 
Permitted Therapy ................................................................. 44 
4.3.1.1 
Antimalarials .......................................................................... 45 
4.3.1.2 
Mycophenolate Mofetil/Mycophenolic Acid ............................ 45 
4.3.1.3 
Azathioprine ........................................................................... 45 
4.3.1.4 
Methotrexate .......................................................................... 45 
4.3.1.5 
Non-Steroidal Anti-,nflammatory Drugs ................................. 45 
4.3.1.6 
ACE Inhibitors and ARBs....................................................... 45 
4.3.1.7 
Dietary Supplements ............................................................. 45 
4.3.1.8 
Acid Reducing Agents ........................................................... 46 
4.3.2 
Prohibited Therapy ................................................................ 46 
4.3.2.1 
Live or Attenuated Vaccinations ............................................ 47 


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4/ Protocol GA30066, Version 1  
4.3.2.2 
CYP3A Inhibition ................................................................... 47 
4.3.3 
Prohibited Food ..................................................................... 48 
4.3.4 
Additional Restrictions ........................................................... 48 
4.4 
Study Assessments ............................................................... 48 
4.4.1 
Informed Consent Forms and Screening Log ........................ 48 
4.4.2 
Physical Examinations ........................................................... 49 
4.4.3 
Vital Signs .............................................................................. 49 
4.4.4 
Tuberculin Purified Protein Derivative Skin Test .................... 49 
4.4.5 
SLE Disease Activity Assessments ....................................... 49 
4.4.5.1 
BILAG-2004 Index ................................................................. 50 
4.4.5.2 
SLEDAI-2K and SELENA-SLEDAI Flare Index ..................... 50 
4.4.5.3 
Glucocorticoid Toxicity Change Index ................................... 51 
4.4.5.4 
SLICC/ACR Damage Index for Systemic Lupus 
Erythematosus ....................................................................... 51 
4.4.5.5 
Cutaneous Lupus Erythematosus Disease Area 
and Severity Index (CLASI) ................................................... 51 
4.4.5.6 
Physician’s Global Assessment (PGA) .................................. 51 
4.4.5.7 
Patient’s Global Assessment ................................................. 51 
4.4.6 
Systemic Lupus Erythematosus Responder Index 
(SRI) ...................................................................................... 52 
4.4.6.1 
Optional Photography ............................................................ 52 
4.4.7 
Laboratory, Biomarker, and Other Biological 
Samples ................................................................................. 52 
4.4.8 
Electrocardiograms ................................................................ 54 
4.4.9 
Patient-Reported Outcomes .................................................. 55 
4.4.10 
Samples for Research Biosample Repository ....................... 55 
4.4.10.1 
Overview of the Research Biosample Repository .................. 55 
4.4.10.2 
Approval by the Institutional Review Board or 
Ethics Committee .................................................................. 56 
4.4.10.3 
Sample Collection .................................................................. 56 
4.4.10.4 
Confidentiality ........................................................................ 56 
4.4.10.5 
Consent to Participate in the Research 
Biosample Repository ............................................................ 57 
4.4.10.6 
Withdrawal from the Research Biosample 
Repository ............................................................................. 57 


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5/ Protocol GA30066, Version 1  
4.4.10.7 
Monitoring and Oversight ....................................................... 57 
4.5 
Treatment, Patient, Study, and Site 
Discontinuation ...................................................................... 58 
4.5.1 
Study Treatment Discontinuation ........................................... 58 
4.5.2 
Patient Discontinuation from Study ........................................ 59 
4.5.3 
Study Discontinuation ............................................................ 59 
4.5.4 
Site Discontinuation ............................................................... 60 
5. 
ASSESSMENT OF SAFETY ....................................................................... 60 
5.1 
Safety Plan ............................................................................ 60 
5.1.1 
Safety Plan for Potential Risks Associated with 
GDC-0853 ............................................................................. 60 
5.1.1.1 
Infections ............................................................................... 60 
5.1.1.2 
Vaccinations .......................................................................... 61 
5.1.1.3 
Bleeding ................................................................................. 62 
5.1.1.4 
Cytopenias ............................................................................. 63 
5.1.1.5 
Gastrointestinal Effects .......................................................... 64 
5.1.1.6 
Hepatotoxicity ........................................................................ 64 
5.1.1.7 
Cardiovascular Effects ........................................................... 65 
5.1.1.8 
Vascular Inflammation ........................................................... 65 
5.1.1.9 
Malignancy ............................................................................ 66 
5.1.2 
Management of Study Treatment in Patients Who 
Experience Specific Adverse Events ..................................... 66 
5.2 
Safety Parameters and Definitions ........................................ 70 
5.2.1 
Adverse Events ..................................................................... 71 
5.2.2 
Serious Adverse Events (Immediately Reportable 
to the Sponsor) ...................................................................... 71 
5.2.3 
Adverse Events of Special Interest (Immediately 
Reportable to the Sponsor) .................................................... 72 
5.3 
Methods and Timing for Capturing and 
Assessing Safety Parameters ................................................ 72 
5.3.1 
Adverse Event Reporting Period ........................................... 73 
5.3.2 
Eliciting Adverse Event Information ....................................... 73 
5.3.3 
Assessment of Severity of Adverse Events ........................... 73 
5.3.4 
Assessment of Causality of Adverse Events ......................... 74 


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6/ Protocol GA30066, Version 1  
5.3.5 
Procedures for Recording Adverse Events ............................ 75 
5.3.5.1 
Diagnosis versus Signs and Symptoms................................. 75 
5.3.5.2 
Adverse Events That Are Secondary to Other 
Events.................................................................................... 75 
5.3.5.3 
Persistent or Recurrent Adverse Events ................................ 76 
5.3.5.4 
Abnormal Laboratory Values ................................................. 76 
5.3.5.5 
Abnormal Vital Sign Values ................................................... 77 
5.3.5.6 
Abnormal Liver Function Tests .............................................. 78 
5.3.5.7 
Deaths ................................................................................... 78 
5.3.5.8 
Preexisting Medical Conditions .............................................. 78 
5.3.5.9 
Lack of Efficacy or Worsening of Lupus................................. 79 
5.3.5.10 
Hospitalization or Prolonged Hospitalization .......................... 79 
5.3.5.11 
Adverse Events Associated with an Overdose or 
Error in Drug Administration .................................................. 79 
5.3.5.12 
Patient-Reported Outcome Data ........................................... 80 
5.4 
Immediate Reporting Requirements from 
Investigator to Sponsor .......................................................... 80 
5.4.1 
Emergency Medical Contacts ................................................ 80 
5.4.2 
Reporting Requirements for Serious Adverse 
Events and Adverse Events of Special Interest ..................... 81 
5.4.2.1 
Events That Occur prior to Study Drug Initiation .................... 81 
5.4.2.2 
Events That Occur after Study Drug Initiation ........................ 81 
5.4.3 
Reporting Requirements for Pregnancies .............................. 81 
5.4.3.1 
Pregnancies in Female Patients ............................................ 81 
5.4.3.2 
Pregnancies in Female Partners of Male Patients ................. 82 
5.4.3.3 
Congenital Anomalies/Birth Defects and 
Abortions ............................................................................... 82 
5.5 
Follow-Up of Patients after Adverse Events .......................... 82 
5.5.1 
Investigator Follow-Up ........................................................... 82 
5.5.2 
Sponsor Follow-Up ................................................................ 83 
5.6 
Adverse Events That Occur after the Adverse 
Event Reporting Period.......................................................... 83 
5.7 
Expedited Reporting to Health Authorities, 
Investigators, Institutional Review Boards, and 
Ethics Committees ................................................................. 83 


GDC-0853—Genentech, Inc. 
7/ Protocol GA30066, Version 1  
6. 
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN ....................... 84 
6.1 
Determination of Sample Size ............................................... 84 
6.2 
Summaries of Conduct of Study ............................................ 84 
6.3 
Summaries of Demogaphic and Baseline 
Characteristics ....................................................................... 84 
6.4 
Safety Analyses ..................................................................... 84 
6.5 
Efficacy Analyses .................................................................. 84 
6.6 
Pharmacokinetic Analyses ..................................................... 85 
6.7 
Interim Analysis ..................................................................... 85 
7. 
DATA COLLECTION AND MANAGEMENT ............................................... 85 
7.1 
Data Quality Assurance ......................................................... 85 
7.2 
Electronic Case Report Forms ............................................... 86 
7.3 
Source Data Documentation .................................................. 86 
7.4 
Use of Computerized Systems .............................................. 86 
7.5 
Retention of Records ............................................................. 87 
8. 
ETHICAL CONSIDERATIONS .................................................................... 87 
8.1 
Compliance with Laws and Regulations ................................ 87 
8.2 
Informed Consent .................................................................. 87 
8.3 
Institutional Review Board or Ethics Committee .................... 88 
8.4 
Confidentiality ........................................................................ 89 
8.5 
Financial Disclosure .............................................................. 89 
9. 
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION ..................................................................................... 90 
9.1 
Study Documentation ............................................................ 90 
9.2 
Protocol Deviations ................................................................ 90 
9.3 
Site Inspections ..................................................................... 90 
9.4 
Administrative Structure ......................................................... 90 
9.5 
Publication of Data and Protection of Trade 
Secrets .................................................................................. 90 
9.6 
Protocol Amendments ........................................................... 91 
10. REFERENCES ........................................................................................... 92 
 


GDC-0853—Genentech, Inc. 
8/ Protocol GA30066, Version 1  
 
LIST OF TABLES 
Table 1 
Objectives and Corresponding Endpoints ................................... 29 
Table 2 
Permitted Dose Ranges for Immunosuppressant and 
Antimalarial Medications ............................................................. 44 
Table 3 
Guidelines for Management of GDC-0853 in Patients Who 
Experience Specific Adverse Events .......................................... 67 
Table 4 
Adverse Event Severity Grading Scale for Events Not 
Specifically Listed in NCI CTCAE ............................................... 74 
Table 5 
Causal Attribution Guidance ....................................................... 75 
 
 
LIST OF FIGURES 
Figure 1 
Study Schema ............................................................................. 32 
 
 
LIST OF APPENDICES 
 
Appendix 1 
Schedule of Activities ................................................. 96 
Appendix 2 
Types and Doses of Standard Oral 
Treatments for Systemic Lupus 
Erythematosus Permitted in Study ........................... 101 
Appendix 3 
Glucocorticoid Toxicity Change Index ...................... 102 
Appendix 4 
Suggested Prednisone Taper Schedule 
Achieving  10 mg/day by 12 Weeks ....................... 109 
Appendix 5 
Childbearing Potential, Pregnancy 
Testing, and Contraception ...................................... 110 
Appendix 6 
Bottle and Label Configuration for 
GDC-0853 Administration ........................................ 112 
Appendix 7 
Concomitant Medications  (Including 
Foods and Herbal Products) .................................... 113 
Appendix 8 
Systemic Lupus International 
Collaborating Clinics/American College 
of Rheumatology Damage Index for 
Systemic Lupus Erythematosus ............................... 115 
Appendix 9 
BILAG-2004 Index Glossary .................................... 119 
Appendix 10 
Systemic Lupus Erythematosus 
Disease Activity Index 2000  (SLEDAI-
2K) ........................................................................... 138 
Appendix 11 
SELENA-SLEDAI Flare Index (SFI) ......................... 150 


GDC-0853—Genentech, Inc. 
9/ Protocol GA30066, Version 1  
Appendix 12 
Cutaneous Lupus Erythematosus 
Disease Area and Severity Index 
(CLASI) .................................................................... 151 
Appendix 13 
Physician’s Global Assessment ............................... 154 
Appendix 14 
Patient’s Global Assessment ................................... 156 
Appendix 15 
Concomitant Medications (Including 
Foods and Herbal Products) .................................... 157 


 
GDC-0853—Genentech, Inc. 
10/ Protocol GA30066, Version 1  
PROTOCOL ACCEPTANCE FORM 
TITLE: 
A PHASE II, OPEN-LABEL EXTENSION STUDY OF 
PATIENTS PREVIOUSLY ENROLLED IN STUDY 
GA30044 TO EVALUATE THE LONG-TERM 
SAFETY AND EFFICACY OF GDC-0853 IN 
PATIENTS WITH MODERATE TO SEVERE ACTIVE 
SYSTEMIC LUPUS ERYTHEMATOSUS 
PROTOCOL NUMBER: GA30066 
VERSION NUMBER: 
1 
EUDRACT NUMBER: 
2017-001764-37 
IND NUMBER: 
130011 
TEST PRODUCT: 
GDC-0853 (RO7010939) 
MEDICAL MONITOR: 
, M.D. 
SPONSOR: 
Genentech, Inc. 
 
I agree to conduct the study in accordance with the current protocol. 
 
 
 
Principal Investigator’s Name  (print) 
 
 
 
 
 
Principal Investigator’s Signature 
 
Date 
Please retain the signed original of this form for your study files.  Please return a copy to 
the contact provided to the investigator at study start. 
 
 






 
GDC-0853—Genentech, Inc. 
13/ Protocol GA30066, Version 1  
are encouraged to call the Medical Monitor before discontinuing GDC-0853.  If GDC-0853 
dosing is reduced or interrupted during the OLE, it may be resumed or increased back to 
baseline if permitted by the Medical Monitor, based on the clinical context.  
Patients should be encouraged to remain stable on their background therapies 
(e.g., antimalarials, immunosuppressants), but they will be allowed to change doses, 
discontinue, and/or switch to other permitted immunosuppressant therapies during the OLE if 
clinically indicated.  Certain doses and combinations of immunosuppressants are not allowed 
with GDC-0853.  Patients requiring escape therapy may switch to or add certain other permitted 
therapies (IV or oral corticosteroids [OCSs], or permitted immunosuppressants while continuing 
GDC-0853.  If any prohibited medications are used, GDC-0853 must be discontinued.  
Patients who enter the OLE study on prednisone > 10 mg/day or equivalent OCS should be 
encouraged to taper their OCS, with the goal of achieving an OCS dose of  10 mg/day 
prednisone or equivalent.   
Number of Patients 
Up to approximately 240 patients from Study GA30044 can be enrolled in this study. 
Target Population 
Inclusion Criteria 
Patients must meet the following criteria for study entry: 
• 
Signed Informed Consent Form  
• 
Age 18−76 years, inclusive, at time of signing Informed Consent Form 
• 
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  
• 
Women of childbearing potential must have a negative urine pregnancy test at baseline  
A serum pregnancy test is needed on Day 1 only if the urine pregnancy test is positive. 
• 
For women of childbearing potential (including those who have had a tubal ligation):  
Agreement to remain abstinent (refrain from heterosexual intercourse) or use a 
contraceptive method with a failure rate of  1% per year during the treatment period and for 
at least 60 days after the last dose of study drug.  
A woman is considered to be of childbearing potential if she is postmenarcheal, has 
not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no 
identified cause other than menopause), and has not undergone surgical sterilization 
(removal of ovaries and/or uterus). 
Examples of contraceptive methods with a failure rate of  1% per year include 
bilateral tubal ligation, male sterilization, established proper use of hormonal 
contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and 
copper intrauterine devices.  Women using estrogen-containing hormonal 
contraceptives as a method of contraception must also use a barrier, such as a male 
condom, in conjunction with the hormonal contraceptives. 
The reliability of sexual abstinence should be evaluated in relation to the duration of 
the clinical trial and the preferred and usual lifestyle of the patient.  Periodic abstinence 
(e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal 
are not acceptable methods of contraception. 
• 
For men:  agreement to remain abstinent (refrain from heterosexual intercourse) or use 
contraceptive measures, and agreement to refrain from donating sperm, as defined below  
Men with female partners of childbearing potential (including those who have had a 
tubal ligation) must remain abstinent or use a condom plus an additional contraceptive 
method that together result in a failure rate of  1% per year during the treatment 
period and for at least 120 days (4 months) after the last dose of study treatment.  Men 
must refrain from donating sperm during this same period. 


 
GDC-0853—Genentech, Inc. 
14/ Protocol GA30066, Version 1  
Men with pregnant female partners must remain abstinent or use a condom during the 
treatment period and for at least 28 days after the last dose of study treatment to avoid 
exposing the embryo. 
The reliability of sexual abstinence should be evaluated in relation to the duration of 
the clinical trial and the preferred and usual lifestyle of the patient.  Periodic abstinence 
(e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal 
are not acceptable methods of contraception. 
 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from study entry: 
• 
Met protocol-defined treatment-stopping criteria during Study GA30044 
• 
An adverse event in Study GA30044 that required permanent discontinuation of study drug 
• 
During Study GA30044, treatment with any therapy that is prohibited in this study   
• 
In the opinion of the investigator, any new (since initially enrolling in the Phase II 
Study GA30044), significant, uncontrolled comorbidity or new clinical manifestation (related 
to SLE or not) that 1) requires medications not allowed in this protocol or 2) could put the 
patient at undue risk from a safety perspective   
If the Principal Investigator has questions related to exclusion, he or she should consult 
the Medical Monitor.  
• 
Pregnant or breastfeeding, or intending to become pregnant during the study or within 60 
days after the last dose of study drug 
• 
Any uncontrolled or clinically significant laboratory abnormality that would affect safety, 
interpretation of study data, or the patient’s participation in the study in the opinion of the 
investigator in consultation with the Medical Monitor 
• 
Any major episode of infection requiring hospitalization or treatment with IV antibiotics 
within the last 4 weeks of Study GA30044  
• 
Evidence of active, latent, or inadequately treated infection with Mycobacterium tuberculosis 
(TB) as defined as follows: 
– 
A positive QuantiFERON−TB Gold (QFT) or T-SPOT TB test or a Mantoux purified 
protein derivative (PPD) skin test (performed per Centers for Disease Control and 
Prevention [CDC] guidelines using 5 tuberculin units per 0.1 mL) result of ≥ 5 mm of 
induration, performed at the Week 44 visit of Study GA30044 or later, prior to entry into 
Study GA30066 
– 
Patients with a history of bacillus Calmette-Guérin vaccination should be screened 
using the QFT test only.  
– 
A positive QFT test should be considered a positive diagnostic TB test. 
– 
If initial QFT is indeterminate, perform a confirmatory test with either QFT or T-SPOT.  
The Principal Investigator may consult with the Medical Monitor to discuss selection of 
confirmatory test based on the patient’s disease status and baseline 
immunosuppression.  
– 
An indeterminate QFT test followed by a negative QFT or negative T-SPOT test should 
be considered a negative diagnostic TB test. 
– 
An indeterminate QFT test followed by an indeterminate QFT test or borderline or 
positive T-SPOT test should be considered a positive diagnostic TB test. 
• 
Patients who experienced a de novo or reactivated serious viral infection, such as hepatitis 
B virus or hepatitis C virus (HCV) during Study GA30044  
Positive hepatitis B surface antigen (HBsAg) or hepatitis C serology (regardless of 
treatment status) or positive hepatitis B core antibody (HBcAb) (tested at Week 44 of 
Study GA30044 or later, prior to entry into Study GA30066) are exclusionary. 


 
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15/ Protocol GA30066, Version 1  
• 
Patients who developed a malignancy (with the exception of non-serious local and 
resectable basal or squamous cell carcinoma of the skin) during the Phase II 
Study GA30044 
• 
12-lead ECG at the Week 48 visit of Study GA30044 that demonstrates clinically relevant 
abnormalities that may affect patient safety or interpretation of study results, including the 
following:  
QTcF > 440 msec demonstrated by at least two ECGs > 30 minutes apart 
• 
Current treatment with medications that are well known to prolong the QT interval at 
doses that have a clinically meaningful effect on QT, as determined by the investigator 
The investigator may contact the Sponsor for confirmation if needed.  The investigator 
may reference the CredibleMeds Web site: 
https://www.crediblemeds.org/pdftemp/pdf/CompositeList.pdf. 
• 
Estimated glomerular-filtration rate (based on the 4-variable Modification of Diet in Renal 
Disease equation) < 30 mL/min or on chronic renal replacement therapy 
• 
Laboratory values from the Week 44 visit of Study GA30044 (which may be repeated once 
at a later unscheduled visit, if necessary) that meet the following criteria:  
– 
AST or ALT > 1.5 × ULN (unless due to known autoimmune hepatitis) 
– 
Total bilirubin > 1.2 ULN 
– 
Amylase or lipase > 2 × ULN 
– 
Hemoglobin < 7 g/dL 
– 
ANC < 1.5 × 109/L 
– 
Absolute lymphocyte count (ALC) < 0.5 × 109/L 
– 
Platelet count < 50,000/μL 
End of Study 
The end of this study is defined as the date when the last patient, last visit occurs.  The end of 
the study is expected to occur 56 weeks after the last patient is enrolled. 
Length of Study 
The maximum time in the study for a patient is 56 weeks, including treatment for 48 weeks and 
an 8-week safety follow-up period after the last dose of GDC-0853.  The total length of the study, 
from enrollment of the first patient to the end of the study, is expected to be approximately 
3.5 years. 
Investigational Medicinal Products 
Test Product (Investigational Drug) 
The investigational medicinal product (IMP) for this study is GDC-0853 50-mg tablets. 
Non-Investigational Medicinal Products 
Corticosteroids 
Patients who enter the OLE study on prednisone > 10 mg/day or equivalent OCS should be 
encouraged to taper their OCS, with the goal of achieving an OCS dose of < 10 mg/day 
prednisone or equivalent.   
Burst Treatment 
In the case of increased disease activity, the patient will have the opportunity to receive burst 
treatment (defined as an increase or new dose of oral prednisone or equivalent), in addition to 
the study treatment.  The patient should return to the clinic, either at a scheduled study visit or 
unscheduled flare visit, to be evaluated and to receive an increase or new dose of oral 
prednisone as follows: 
• 
A burst is defined as an increase or new dose of oral prednisone up to 40 mg/day (or 
equivalent). 
 


 
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Escape Therapy 
If an increase in immunosuppressive therapy (referred to as “escape therapy”) is deemed 
medically necessary due to increased SLE disease activity, the patient will be given escape 
therapy, which will be recorded on the Immunosuppressant Review and/or Corticosteroid 
Medication eCRFs.  Patients receiving the following escape therapies, after informing the 
Medical Monitor, will be allowed to remain on study drug but will be considered a 
protocol-defined “non-responder” in the secondary efficacy analysis:   
• 
IV steroids  
• 
OCS doses exceeding the limits described in the study 
New or increased doses of an immunosuppressant medication up to the maximum allowed in 
the study. 
Statistical Methods 
Primary Analysis 
The analyses will include all patients who received at least one dose of the study drug during 
this OLE study.  Safety will be analyzed based on reported/documented adverse events 
including AESIs, and changes in laboratory results, ECGs, physical findings, and vital signs. 
Determination of Sample Size   
No formal sample size calculations were performed for this OLE study. The maximum number 
of patients eligible for enrollment is approximately 240 (i.e., all patients enrolled in Study 
GA30044). 
 
 


 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
ACE 
angiotensin converting enzyme 
AESI 
adverse event of special interest 
ALC 
absolute lymphocyte count 
ARB 
angiotensin receptor blocker 
ARC 
American College of Rheumatology 
AUC0-24 
area under the concentration−time curve from time 0 to 24 hours 
BCR 
B-cell receptor 
BID 
twice a day 
BILAG 
British Isles Lupus Assessment Group 
BTK 
Bruton’s tyrosine kinase 
Cmax 
maximum concentration observed 
CDC 
Centers for Disease Control and Prevention 
CIA 
collagen-induced arthritis 
CLASI 
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLAE 
dose-limiting adverse event 
EC 
Ethics Committee 
eCRF 
electronic Case Report Form 
EDC 
electronic data capture 
ESR 
erythrocyte sedimentation rate 
EULAR 
European League Against Rheumatism 
FcγR 
Fc gamma receptor 
GGT 
gamma-glutamyl transpeptidase 
GI 
gastrointestinal  
GTCI 
Glucocorticoid Toxicity Change Index 
H2RA 
H2-receptor antagonist 
HbA1c 
glycosylated hemoglobin 
HBcAb 
hepatitis B core antibody 
HBsAg 
hepatitis B surface antigen 
HCV 
hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act 
 
 
ICH 
International Council for Harmonisation 
IFN 
interferon 
IL 
interleukin 
IMC 
Internal Monitoring Committee 


 
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Abbreviation 
Definition 
IMP 
investigational medicinal product 
IND 
Investigational New Drug (application) 
IRB 
Institutional Review Board 
IxRS 
interactive voice or Web-based response system 
MAD 
multiple-ascending dose 
MCH 
mean corpuscular hemoglobin 
NCI 
National Cancer Institute 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse 
Events 
NOAEL 
no observed adverse effect level 
NSAID 
nonsteroidal anti-inflammatory drug 
NZB 
New Zealand Black 
NZW 
New Zealand White 
OCS 
oral corticosteroid 
OLE 
open-label extension 
PD 
pharmacodynamic 
PGA 
Physician’s Global Assessment 
PK 
pharmacokinetic 
PPD 
purified protein derivative 
PPI 
proton pump inhibitor 
PRO 
patient-reported outcome 
QTc 
corrected QT interval 
QTcF 
QT interval corrected using Fridericia’s formula 
QFT 
QuantiFERON®−TB Gold 
QD 
once a day, daily 
RA 
rheumatoid arthritis 
RBR 
Research Biosample Repository 
SAD 
single-ascending dose 
SELENA 
Safety of Estrogens in Lupus Erythematosus National Assessment 
SFI 
SELENA-SLEDAI Flare Index 
SLE 
systemic lupus erythematosus   
SLEDAI 
SLE Disease Activity Index 
SLEDAI-2K 
SLE Disease Activity Index 2000 
SLICC 
Systemic Lupus International Collaborating Clinics 
SOC 
standard of care 
SRI 
SLE Responder Index 
TB 
tuberculosis 


 
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Abbreviation 
Definition 
TLR 
toll-like receptor 
TNF-α 
tumor necrosis factor-alpha 
ULN 
upper limit of normal 
VAS 
visual analogue scale 
WGS 
whole genome sequencing 
XLA 
X-linked agammaglobulinemia 


 
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1. 
BACKGROUND 
1.1 
BACKGROUND ON SYSTEMIC LUPUS ERYTHEMATOSUS 
Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease that occurs 
primarily in women of childbearing age.  It is characterized by multisystem involvement 
and immunological abnormalities, and much of the tissue damage is thought to occur 
through autoantibody formation and immune complex deposition.  The disease is 
heterogeneous in its clinical presentation, course, and prognosis.  However, most 
patients present with joint involvement, skin rashes, mouth ulcers, Raynaud’s 
phenomenon, and/or severe fatigue.  Inflammation of pericardial and pleural tissues may 
also be present.  The most serious manifestations include central nervous system and 
renal involvement, which correlate with poor outcomes that include temporary or 
permanent disability or death.  Typically, the disease follows a relapsing-remitting course 
with intermittent periods of disease activity (flare) interspersed with periods of relative 
quiescence. 
The incidence and prevalence of SLE varies with sex, race, and ethnicity.  The 
estimated prevalence of SLE ranges between 65 and 155 people per 100,000 
(Walsh et al. 2001; Ward 2004; Naleway et al. 2005; Chakravarty et al. 2007; 
Molina et al. 2007; Sacks et al. 2010; Feldman et al. 2013; Furst et al. 2013; 
Lim et al. 2014).  In adulthood, approximately nine times as many women as men are 
affected.  The disease has a higher incidence and worse outcome among 
African-Americans, Afro-Caribbeans, Hispanics, and Asians compared with Caucasians. 
Medications for the successful treatment of SLE as measured by long-term remission 
are limited, and only one new medication for SLE treatment has been approved in more 
than 50 years (Burness and McCormack 2011).  Analgesics and nonsteroidal 
anti-inflammatory drugs (NSAIDs) provide partial symptomatic relief.  Antimalarial drugs 
are generally well tolerated by patients with SLE and appear to have a beneficial effect 
on the prevention of lupus flares, increasing long-term survival and possibly ameliorating 
certain types of organ damage (Ruiz-Irastorza et al. 2009).  However, these agents are 
generally regarded as having insufficient efficacy for moderate to severe manifestations 
of SLE. 
The mainstays of therapy for more significant manifestations of SLE are corticosteroids 
and off-label use of immunosuppressant drugs (e.g., methotrexate, mycophenolic acid 
[as either mycophenolate mofetil or Myfortic (mycophenolic acid as sodium salt)], 
azathioprine, and cyclophosphamide), which have profound and diverse effects on the 
immune system in patients with lupus (Tunnicliffe et al. 2015).  However, the use of 
these immunosuppressant agents is limited by their safety profiles.  Corticosteroids, for 
example, are effective for many of the manifestations of SLE but have significant 
short- and long-term adverse effects, including infections, osteoporosis, hyperglycemia, 
hypertension, osteonecrosis, cataracts, and hyperlipidemia. 


 
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As a measure of unmet need, the risk of mortality remains elevated for patients with 
lupus.  In the modern era, on the basis of a multisite international cohort of 9500 patients 
with lupus, the standardized mortality ratio was 2.4, with particularly high mortality seen 
with renal disease (Fors Nieves and Izmirly 2016).  The development of new treatments 
for SLE patients with increased efficacy and decreased toxicity remains an important 
and a necessary area of investigation 
1.2 
BACKGROUND ON BRUTON’S TYROSINE KINASE AND 
GDC-0853 
1.2.1 
Bruton’s Tyrosine Kinase 
Discovery of the genetic basis for primary immunodeficiencies has been the source 
of new therapeutic targets in immunomodulatory therapies (Puri et al. 2013; 
Bugatti et al. 2014; Whang and Chang 2014).  In humans, inactivating mutations in the 
gene for Bruton’s tyrosine kinase (BTK), which is located on the X chromosome, can 
result in the development of an immunodeficiency state characterized by a significant 
absence of circulating B cells (Bruton 1952; Tsukada et al. 1993; Vetrie et al. 1993; 
Conley et al. 2005) and very low Ig levels due to a defect in B-cell differentiation at the 
pro- to pre-B cell stage that precludes assembly of the B-cell receptor (BCR) complex 
and Ig gene expression (Reth and Nielsen 2014).  Affected male patients have a primary 
immune deficiency called X-linked agammaglobulinemia (XLA) and are susceptible to 
recurrent infections starting shortly after birth.  Patients with XLA can live relatively 
normal lives on a standard therapy of IV Ig (Kaveri et al. 2011), suggesting that BTK can 
be safely inhibited especially in people with established immune systems. 
BTK is a tyrosine kinase essential for signaling events required for the differentiation and 
activity of B cells during immune system ontology and normal adaptive immune 
responses.  In addition, BTK is required for signaling associated with Fc gamma 
receptor (FcγR), expressed on a variety of myeloid cells.  BTK is activated by 
phosphatidylinositol 3-kinase−dependent plasma membrane recruitment and 
phosphorylation on tyrosine Y551 by the Src-family kinase Lyn.  Autophosphorylation 
and activation also occurs on tyrosine Y223 in a BTK-specific manner.  Once activated, 
BTK induces PLCγ2- and Ca2+-dependent signaling, which leads to the activation of 
NF-κB− and NFAT-dependent pathways leading to cellular activation and differentiation 
(Niiro and Clark 2002).  
The therapeutic potential of BTK inhibitors as anti-cancer agents has been established in 
clinical trials with agents, including ibrutinib, a covalent inhibitor of BTK, which has been 
approved in the United States and Europe for use in patients with mantle-cell lymphoma, 
chronic lymphocytic leukemia, and Waldenstrom macroglobulinemia. 
1.2.2 
Nonclinical Experience with GDC-0853 
GDC-0853 is a highly selective, orally administered, reversible inhibitor of BTK that is 
being developed by Genentech, Inc. as a potential therapeutic for autoimmune diseases, 


 
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including rheumatoid arthritis (RA) and SLE.  GDC-0853 has undergone extensive 
investigation in nonclinical in vitro and in vivo studies to characterize its pharmacological, 
metabolic, and toxicological properties (see the GDC-0853 Investigator’s Brochure). 
In vitro cell-based experiments suggest that antagonism of BTK leads to inhibition of 
BCR-dependent cell proliferation and a reduction of inflammatory cytokine production 
from myeloid cells (including tumor necrosis factor-alpha [TNF-α], interleukin [IL]-1, and 
IL-6) by preventing signaling through the FcγRIII receptor (di Paolo et al. 2011; Liu et al. 
2011).  GDC-0853 effectively blocks BCR- and CD40-mediated activation and 
proliferation of B cells.  BTK in B cells also plays a role in toll-like receptor (TLR) 
4-mediated B-cell proliferation and class switching.  In monocytes, GDC-0853 inhibits 
TLR4- and immune complex-mediated inflammatory cytokine production, including 
TNF-α, which contributes to disease pathogenesis in SLE (Mina-Osorio et al. 2013; 
Bender et al. 2016).  In dendritic cells, BTK contributes to TLR8-mediated cytokine 
production (TNF-α and IL-6) (Sochorová et al. 2007).  In basophils, BTK-dependent 
activation of the Fc epsilon receptor leads to activation and upregulation of CD63.  In 
addition, GDC-0853 has been shown to inhibit the differentiation of human plasmablasts 
into plasma cells in vitro (see the GDC-0853 Investigator’s Brochure).  Patients with 
lupus have multiple abnormalities in the blood, including increased levels of 
plasmablasts (Anolik et al. 2004).  Together, these data suggest that lupus patients with 
elevated levels of plasmablasts might demonstrate a more robust clinical response to 
GDC-0853.  Therefore, an RNA signature biomarker encompassing genes preferentially 
expressed in plasmablasts was developed to detect the presence of elevated 
plasmablasts in the peripheral blood.  In addition, efficacy in patients with high or low 
levels of the plasmablast signature will be compared for potential increased or 
decreased efficacy, respectively (see the GDC-0853 Investigator’s Brochure).  
The efficacy of GDC-0853 has been investigated in inflammatory models of arthritis as 
well as immune-complex mediated renal-injury models similar to the manifestations of 
human SLE.  Arthritis was investigated in female Lewis rats with developing type II 
collagen-induced arthritis (CIA).  GDC-0853 treatment was well tolerated and resulted in 
significant and dose-dependent reduction in ankle swelling.  GDC-0853 was effective at 
significantly reducing anti-rat collagen II IgG antibodies in the serum (obtained on 
Day 16) with daily (QD) doses ≥ 0.25 mg/kg/day.  However, there was no effect of 
GDC-0853 treatment on total anti-rat IgG antibodies in the serum.  Findings from the 
histopathology evaluation were consistent with the clinical findings.  Immune-complex 
mediated inflammation (induced by autoantibodies) and tissue injury is central to the 
pathogenesis and the majority of clinical manifestations of SLE.  GDC-0853 in 
nonclinical studies is a potent inhibitor of these processes.  Studies in interferon 
(IFN)-alpha−accelerated, New Zealand Black (NZB)/New Zealand White (NZW), 
lupus-prone mice have shown that BTK-inhibition resulted in dose-dependent 
improvement in survival (see the GDC-0853 Investigator’s Brochure).  In addition, BTK 
inhibition reduces the development and levels of splenic plasmablasts, a pool of 


 
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activated antibody-producing B cells, and systemic inflammation as evidenced by a 
decrease in the type-1 IFN signature in peripheral blood mononuclear cells.   
The GDC-0853 safety profile has been assessed in repeat-dose, general toxicology 
studies (daily oral dosing) ranging from 1 week to 9 months in rats and dogs; in vitro and 
in vivo genetic toxicology studies; in vitro phototoxicity evaluation; in vitro and in vivo 
safety pharmacology studies of the central nervous, respiratory, and cardiovascular 
systems; and embryo-fetal development (Seg II) studies in rats and rabbits.  Overall, 
GDC-0853 was well tolerated for 6 months in rats (up to 104 µM • hr) and 9 months in 
dogs (up to 36 µM • hr).  Notable findings identified in nonclinical toxicology studies 
include vascular inflammation in dogs (≥ 56 µM • hr), hepatotoxicity in dogs (180 µM • hr), 
and a minimal increase in corrected QT (QTc) interval in dogs (7 msec or 3%; 
extrapolated unbound maximum observed concentration [Cmax] of 3.17 µM).  Fetal 
malformations in rats (627 µM • hr) and rabbits (≥ 10.6 µM • hr) warrant the continued use 
of contraception in clinical trials.  On the basis of the nonclinical and clinical safety data 
to date, GDC-0853 is expected to be well tolerated at the doses and duration 
administered in the parent Study GA30044 and the current study (GA30066). 
1.2.3 
Clinical Experience with GDC-0853 
As of 10 May 2017, GDC-0853 or placebo has been administered to 406 subjects (i.e., 
203 healthy subjects, 24 patients with hematological malignancies, 172 patients with RA, 
and 7 patients with SLE) at doses ranging from 0.5 to 600 mg and has been well 
tolerated with no safety signals.  In the single-ascending dose (SAD; GP29318), 
multiple-ascending dose (MAD; GA29347), relative bioavailability (GP29832), and 
oncology (GO29089) studies, GDC-0853 was generally well tolerated with adverse 
events being mostly non-serious, mild, and self-limited and with no dose-limiting adverse 
events (DLAEs) or dose-limiting toxicities.   
In the SAD and MAD healthy volunteer studies, there were no DLAEs, serious adverse 
events, or concerning patterns of adverse events that would preclude further 
development of GDC-0853.  Adverse events in healthy volunteers were all mild and 
included skin reactions (rash, contact dermatitis, and skin irritation from ECG leads; 1 
subject each), nausea (2 subjects), headache, toothache, contusion, and asymptomatic 
bacteriuria (1 subject each).   
In patients with hematological malignancies, the majority of adverse events were 
National Cancer Institute Common Terminology Criteria for Adverse Events (NCI 
CTCAE) Grade 1 or Grade 2 and included fatigue, nausea, diarrhea, headache, 
abdominal pain, dizziness, cough, and thrombocytopenia.  There were 9 serious adverse 
events reported in 5 patients:  abdominal pain, lung infiltration, lung infection and 
pneumonia, febrile neutropenia, gastrointestinal (GI) hemorrhage and upper GI 
hemorrhage, and H1N1 influenza and influenza pneumonia.  There were 2 deaths during 
the study due to complications of confirmed influenza (H1N1 influenza and influenza 
pneumonia).  As of May 2017, 6 patients remain on GDC-0853 (400 mg QD) in 


 
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Study GO29089 with daily dosing lasting up to 23 months (range 18−23, average 
21 months).   
GDC-0853 is also being investigated in two ongoing Phase II trials in RA (blinded, 
placebo-controlled Study GA29350 and open-label extension [OLE] Study GA30067) 
and in SLE (blinded, placebo-controlled Study GA30044).  As of 10 May 2017, 
172 patients with RA had received GDC-0853/placebo in Study GA29350; 53 of these 
patients have entered Study GA30067 and received open-label GDC-0853.  An 
additional 7 patients with SLE have received GDC-0853/placebo in Study GA30044. 
Reported adverse events in the three trials have been mostly non-serious, mild, and 
self-limiting.  In the blinded trials, there has been one reported severe adverse event 
(infection) and two Grade 3 adverse events (elevations in ALT/AST). 
Refer to the GDC-0853 Investigator’s Brochure for additional details on clinical studies. 
1.3 
STUDY RATIONALE AND BENEFIT–RISK ASSESSMENT 
The results from the Phase I studies, nonclinical toxicology studies, and studies in a 
nonclinical model of SLE support further evaluation of GDC-0853 as a potential 
treatment for SLE.  The goal of the parent Phase II study (GA30044) is to evaluate the 
safety and efficacy of GDC-0853 in combination with standard of care (SOC) in patients 
with moderate to severe SLE.  The study tests two dose levels of GDC-0853 in 
comparison with placebo when added to background SOC.  The study was powered to 
detect a meaningful clinical benefit in a composite measure of disease activity across 
multiple organ systems (see Section 3.3.4.1) and includes multiple safety assessments 
and monitoring by an unblinded Internal Monitoring Committee (IMC) and a Scientific 
Oversight Committee.   
This OLE Study GA30066 will evaluate the long-term safety and efficacy of GDC-0853 in 
patients with SLE who have completed the ongoing, blinded Phase II Study GA30044.  
In this study, all patients will receive GDC-0853 starting at a dose of 200 mg twice a day 
(BID) for up to 48 weeks of treatment.  Patients will be allowed to continue and adjust 
their background SOC therapy.  
Inhibition of BTK offers a promising mechanism for the treatment of autoimmune 
diseases, such as RA and SLE (see the GDC-0853 Investigator’s Brochure); however, 
data from clinical studies are lacking.  Humans with a mutation in the XLA gene and who, 
therefore, lack functional BTK from birth, can live relatively normal lives on a standard 
therapy of IV Ig (Kaveri et al. 2011), suggesting that BTK can be safely inhibited, 
especially in people with established immune systems.  GDC-0853 did not deplete IgG 
substantially during short-term treatment of healthy subjects in Phase I studies (see 
GDC-0853 Investigator’s Brochure), but it is not known whether long-term treatment of 
patients will induce depletion.  Therefore, IgG levels will be carefully monitored in this 
study.  Clinical data to date suggest that IgG levels in patients with an established 


 
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immune system may not be significantly depleted, perhaps because BTK inhibitors 
target only the kinase domain and other BTK activities remain intact (Byrd et al. 2013).  
Overall, GDC-0853 has been well tolerated in Phase I healthy subjects and oncology 
studies.  Ongoing clinical studies include Phase II studies in SLE (GA30044), RA 
(GA29350 and GA30067), and chronic spontaneous urticaria (GS39684), as well as 
clinical pharmacology studies in healthy volunteers.  Based on the compelling 
mechanism for BTK inhibition in SLE and the promising results in NZB/NZW lupus-prone 
mice, the benefit−risk ratio for this study is considered appropriate (see the GDC-0853 
Investigator’s Brochure).  The safety profile of GDC-0853 will be further characterized in 
this Phase II study.  A robust safety-monitoring plan that describes the potential risks for 
GDC-0853 and the risk-mitigation strategies to minimize risks for the patients in this trial 
are provided in Section 5.1.   
Clinical experience with GDC-0853 to date has not generated safety concerns that 
would preclude further evaluation in patients with autoimmune diseases (see the 
GDC-0853 Investigator’s Brochure). 
1.3.1 
Primary Nonclinical Toxicity Findings 
The no observed adverse effect levels (NOAELs) determined in the repeat-dose, 
6-month Wistar Han rat (20 mg/kg; 104 µM • hr) and 9-month dog (10 mg/kg; 36 µM • hr) 
studies support multiple-dose exposures in SLE patients at the proposed clinical doses, 
 
.  The primary toxicities identified in 
animals include the following (see Section 1.2.2 and the GDC-0853 Investigator’s 
Brochure for details): 
• 
Vascular inflammation in dogs, characterized by endothelial necrosis, proliferation 
and hypertrophy, vascular/perivascular lymphocyte and macrophage infiltrates, and 
occasional necrosis of the medial smooth-muscle cells were observed in a 4-week 
toxicity study at ≥ 56 µM • hr, and these changes were not completely reversed by 
the end of the 4-week recovery period.  However, in the 9-month toxicity study in 
dogs, no GDC-0853-related vascular inflammation was observed up to the highest 
dose of 10 mg/kg/day (36 µM • hr).  
 
 
• 
Effects on lymphocytes and Igs in rats and dogs were reversible and considered to 
be related to pharmacological activity involving BTK inhibition.  In rats, after 4 weeks 
of dosing, elevated circulating total lymphocyte counts were observed at 
≥ 20 mg/kg/day (≥ 104 µM • hr).  In dogs, after 4 months dosing, decreased 
circulating total lymphocytes were observed at ≥ 10 mg/kg/day (≥ 36 µM • hr).  
Peripheral blood immunophenotyping showed decreased circulating B-cell counts in 
male rats at 20 mg/kg/day and in dogs at ≥ 1 mg/kg/day (≥ 2.1 µM • hr); there were 
no GDC-0853−related effects on total T, helper T, or cytotoxic T cells.  Ig isotyping 
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concentration; mid- and high-dose rats (≥ 17 µM • hr) also had decreased IgM.  
Histopathology in rats and dogs showed a decrease in the number of lymphocytes 
in follicular germinal centers in the spleen, mesenteric and mandibular lymph nodes, 
and/or Peyer's patches.   
• 
Minimal to marked, dose-dependent increases in ALT, AST, and/or bilirubin have 
been observed in rats administered ≥ 6 mg/kg/day (≥ 17 µM • hr).  Hepatotoxicity in 
dogs, consisting of increases in ALT, AST, ALP, gamma-glutamyl transpeptidase 
(GGT), and/or total bilirubin levels correlated with microscopic findings of minimal 
hepatocyte degeneration/disorganization, Kupffer cell hypertrophy/hyperplasia and 
pigment, and perivascular mixed cell infiltrates.  Serum chemistry and 
histopathology findings were observed in the 4-week toxicity study at ≥ 56 µM • hr 
and 180 µM • hr, respectively, and were considered monitorable with liver function 
tests (see Section 1.3.2.6).  The hepatotoxicity findings in dogs were associated 
with moribundity in two high-dose animals.  The NOAEL for these findings was 
considered to be 10 mg/kg (36 µM • hr) in dogs, the most sensitive species, given 
the absence of GDC-0853−related hepatotoxicity at this dose when administered for 
9 months.  These findings were fully reversible and considered monitorable by 
changes in plasma transaminases and bilirubin that occurred at doses lower than 
those producing histopathology findings.  No adverse liver findings were observed in 
the chronic toxicity studies in rats (≤ 104 µM • hr) and dogs (≤ 36 µM • hr).  See 
Section 4 of the GDC-0853 Investigator’s Brochure for further details. 
• 
Fetal malformations were observed in rats (i.e., cleft palate observed at 627 µM • hr) 
and rabbits (i.e., domed-shaped heads with enlarged lateral/third ventricles at 
≥ 10.6 µM • hr).  Thus, highly effective contraception will be mandatory for trial 
participation, and pregnancy monitoring will be performed at least monthly in 
Study GA30044. 
• 
Pancreatic findings observed in rats administered GDC-0853, and other BTK 
inhibitors, were considered to be an on-target, species-specific effect, supported by 
a number of investigative studies (see the GDC-0853 Investigator’s Brochure for 
details).   
 
1.3.2 
Potential Risks for Clinical Toxicities 
GDC-0853 is in early clinical development and patient exposure is limited, so the safety 
profile in patients with SLE is unknown.  However, there are several potential risks on 
the basis of the expected mechanism of action of GDC-0853, published literature for 
similar molecules, and nonclinical and clinical studies with GDC-0853.  Several 
measures will be taken to ensure the safety of patients participating in this study based 
on these potential risks (see Section 5.1 for details).  In addition, guidelines for the 
management of study treatment in patients who experience specific adverse events 
have been established (see Section 5.1.2).  Eligibility criteria in this study have been 
designed to exclude patients at higher risk for potential toxicities (see Section 4.1).   


 
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1.3.2.1 
Infections 
GDC-0853 is a targeted immunomodulator, and the degree to which GDC-0853 
antagonism of BTK signaling may suppress immune activity is unknown.  Patients 
participating in this study may be at risk for infections, including opportunistic infections.  
Therefore, the eligibility criteria are intended to protect patient safety and exclude 
patients that may be at a particularly increased risk of infection, including those patients 
with marked baseline lymphopenia.  Total Ig concentrations will also be measured 
regularly throughout the study.  During this study, any serious infection, any infection 
requiring IV antimicrobials, or any opportunistic infection will be considered an adverse 
event of special interest (AESI) and will require expedited reporting to the Sponsor (see 
Section 5.4.2). 
1.3.2.2 
Vaccinations 
The effect of GDC-0853 upon the efficacy of vaccinations is unknown.  It is 
recommended that appropriate vaccinations per European League Against Rheumatism 
(EULAR) recommendations (van Assen et al. 2011) or local guidelines be up to date 
before study participation.  However, as a safety measure, patients will be excluded from 
study participation and will not be dosed with GDC-0853 if they have been vaccinated 
with live, attenuated vaccines (e.g., the intranasal live attenuated influenza vaccines, 
Bacillus Calmette-Guérin virus, and varicella) within 6 weeks before planned dosing in 
Study GA30044.   
1.3.2.3 
Bleeding 
BTK is expressed in platelets and is involved in platelet function via GPVI/Collagen 
receptor signaling and GP1b receptor signaling.  Platelets from patients with XLA 
demonstrate decreased activation in response to submaximal collagen stimulation but 
normal response to thrombin.  However, clinically, there is no reported bleeding 
propensity in XLA patients (Howard et al. 2006).  In the GDC-0853 clinical study 
involving patients with cancer, 2 patients experienced Grade ≥ 3 GI bleeding.  These 
events were not dose related and occurred in patients on NSAIDs/acetylsalicylic acid 
with a history of gastroesophageal or peptic ulcer disease. 
It is unknown if GDC-0853 will increase the risk of bleeding in SLE patients receiving 
antiplatelet or anticoagulant therapies.  Therefore, the eligibility criteria will exclude 
patients at highest risk for GI bleeding.  Patients at high risk for NSAID-related GI injury 
are advised to follow local or recognized guidelines, including concomitant use of proton 
pump inhibitors (PPIs), if indicated.  Any bleeding event of Grade 2 or above is 
considered an AESI with expedited reporting requirements to the Sponsor (see 
Section 5.4.2). 
1.3.2.4 
Cytopenias 
Neutropenia, anemia, and thrombocytopenia have been observed in patients with 
hematologic malignancies who received GDC-0853.  Events have been monitorable and 
clinically manageable without dose discontinuations.  As patients with SLE may have 


 
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cytopenias as a result of their intrinsic SLE disease activity, study eligibility criteria are 
designed to exclude those patients with more marked baseline cytopenias that may 
affect patient safety, and CBCs will be monitored regularly throughout the study. 
1.3.2.5 
Gastrointestinal Effects 
Healthy subjects in the MAD study, GA29347, reported events of mild self-limited 
nausea.  In addition, Grade 1 diarrhea, nausea, and abdominal pain have been reported 
in patients with hematological malignancies treated with GDC-0853; however, the events 
resolved and did not lead to study drug discontinuation.  Patients will be monitored for 
GI side effects throughout this study.   
1.3.2.6 
Hepatotoxicity 
Evidence of hepatobiliary injury was observed in animals administered relatively high 
doses of GDC-0853 in repeat-dose toxicity studies.  In the SAD study, the MAD study for 
14 days in healthy subjects, and a study of hematologic malignancies with daily dosing 
for over 1 year in patients, there have been no adverse events of liver enzyme 
elevations or trends towards elevations in laboratory evaluations.  In Study GA29350, 
there have been 2 cases of Grade 3 elevations in AST and ALT levels in RA patients on 
methotrexate, out of a total of 172 patients (as of data cutoff: 10 May 2017), but as the 
study is still blinded, association with GDC-0853 cannot yet be determined.  For 
inclusion in this study, AST and ALT levels should be no more than 1.5 times the upper 
limit of normal (ULN), and total bilirubin levels should be normal at screening (see 
Section 4.1.1).  Baseline and routine evaluations of AST/ALT and total bilirubin levels will 
be performed throughout the study.  Elevated AST or ALT levels of Grade ≥ 3 (> 5 × ULN) 
or cases of potential drug-induced liver injury that include an elevated ALT or AST level 
in combination with either an elevated bilirubin level or clinical jaundice, as defined by 
Hy’s Law (see Section 5.3.5.6), are AESIs with expedited reporting requirements to the 
Sponsor (see Section 5.4.2).   
1.3.2.7 
Cardiovascular Effects 
GDC-0853 is considered to have a low potential to cause QT interval prolongation or to 
directly affect other cardiovascular parameters at therapeutic exposures.  A minimal 
increase in QTc (7 msec or 3%) interval was noted at 45 mg/kg in the single-dose 
cardiovascular safety pharmacology study in telemetry-instrumented dogs that was not 
considered to be clinically significant/meaningful.  Analysis of ECG data from the SAD 
and MAD studies in healthy subjects did not demonstrate any significant increase in 
either QRS interval or QTcF (QT interval corrected using Fridericia’s formula) intervals.  
Cardiac safety will be evaluated in all patients at baseline and throughout the study with 
routine monitoring of vital signs, including pulse rate and blood pressure, collection of 
ECGs, and reporting of cardiac adverse events.  Patients with high cardiovascular risk 
will be excluded from study participation. 






 
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be approximately 240 patients.  Patients will be assigned the same patient number they 
had in Study GA30044. 
Eligible patients who elect to participate will be enrolled directly into Study GA30066 
after completing 48 weeks of study treatment in Study GA30044 rather than enrolling in 
the safety follow-up period for the blinded study.  Patients will receive open-label 
GDC-0853 at 200 mg BID for 48 weeks, followed by a safety follow-up period of 8 weeks.   
Dose reductions or discontinuations of GDC-0853 will occur, either temporarily or 
permanently, for specific safety reasons (see Section 5.1.2).  Dose reductions may also 
be permitted on the basis of other clinical safety concerns of the investigator, only after 
discussion with the Medical Monitor.  Investigators are encouraged to call the Medical 
Monitor before discontinuing GDC-0853.  If GDC-0853 dosing is reduced or interrupted 
during the OLE, it may be resumed or increased back to baseline if permitted by the 
Medical Monitor, based on the clinical context.  
Patients should be encouraged to remain stable on their background therapies 
(e.g., antimalarials, immunosuppressants), but they will be allowed to change doses, 
discontinue, and/or switch to other permitted immunosuppressant therapies during the 
OLE if clinically indicated (see Section 4.2.2.3.1).  Certain doses and combinations of 
immunosuppressants are not allowed with GDC-0853 (see Section 4.3.2).  Patients 
requiring escape therapy may switch to or add certain other permitted therapies (IV or 
oral corticosteroids [OCSs], or permitted immunosuppressants, see Section 4.1.1) while 
continuing GDC-0853.  If any prohibited medications are used, GDC-0853 must be 
discontinued.  
Patients who enter the OLE study on prednisone > 10 mg/day or equivalent OCS (see 
Appendix 2), should be encouraged to taper their OCS, with the goal of achieving an 
OCS dose of  10 mg/day prednisone or equivalent.   
A schedule of activities is provided in Appendix 1. 


 
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Figure 1 Study Schema 
48-Week Open-Label Treatment
(48 Weeks)
Safety
Follow-Up
(8 weeks)
Week 0 1
12
20
48
56
16
24
4
8
28
32
40
36
44
Primary (Safety)  
GDC-0853 200 mg BID; n ~240
= Site visit
= Endpoint
Arm A
Arm B
Arm C
Blinded Study
GA30044
 
BID = twice a day. 
 
3.1.1 
Internal Monitoring Committee and Scientific Oversight 
Committee 
Regular safety reviews for this OLE will be performed by the Sponsor’s IMC in 
combination with the Scientific Oversight Committee as outlined in the IMC-Scientific 
Oversight Committee Agreement.  If necessary, cumulative unblinded data for patients 
remaining in the parent Study GA30044 may also be made available to IMC and 
Scientific Oversight Committee members.  This committee will include a clinical scientist, 
in conjunction with a safety scientist, biostatistician, two external SLE experts who are 
not investigators in this study and statistical programmers from the Sponsor who are not 
members of the Study Management Team.  The committee members will not have direct 
contact with investigational staff or site monitors.  The committee may request that 
additional Sponsor scientists (e.g., clinical pharmacologist, biomarker) participate in data 
analysis.  This committee will review safety data and make recommendations to the 
Sponsor regarding continuation of the study and/or study drug dose modifications.  After 
each meeting, either IMC or the Scientific Oversight Committee will recommend that the 
Sponsor proceed with one of the four following actions:  1) continue the study 
unchanged, 2) discontinue the study for safety reasons, 3) discontinue the study for 
futility (based on analysis of the blinded Study GA30044), or 4) amend the study 
protocol.  For further information, please see the IMC and Scientific Oversight 
Committee Agreement. 
3.2 
END OF STUDY AND LENGTH OF STUDY 
The end of this study is defined as the date when the last patient, last visit occurs.  The 
end of the study is expected to occur 56 weeks after the last patient is enrolled. 
The maximum time in the study for a patient is 56 weeks, including treatment for 
48 weeks and an 8-week safety follow-up period after the last dose of GDC-0853.  The 
total length of the study, from enrollment of the first patient to the end of the study, is 
expected to be approximately 3.5 years. 


 
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3.3 
RATIONALE FOR STUDY DESIGN 
3.3.1 
Rationale for GDC-0853 Dose and Schedule 
The GDC-0853 dose of 200 mg BID is the highest dose under evaluation in 
Study GA30044 and was selected in order to characterize its efficacy, safety, and 
tolerability profile in a larger patient population and for a longer treatment period.  
 
 
 
 
 
 
  
In the event of a safety (e.g., toxicity or intolerance) issue, dose reduction of GDC-0853 
to 200 mg QD or lower for an individual patient is permitted in consultation with the 
Medical Monitor (see Section 5.1.2).  This dose was selected because it is expected to 
reflect what may be a physician-initiated dose reduction in a real-world clinical setting 
(i.e., changing the dosing interval from BID to QD).  
 
 
 
 
   
In healthy subjects receiving GDC-0853 up to 600 mg in the single-dose Study GP29318 
(SAD) and up to 250 mg BID and 500 mg QD for 14 days in the multiple-dose study 
GA29347 (MAD), the safety profile was acceptable and the drug was well tolerated.  No 
maximum tolerated dose was identified, and there were no DLAEs; all adverse events 
were Grade 1 (mild) and transient.  
Data from experiments evaluating the PD effects and anti-inflammatory activity of a tool 
BTK inhibitor compound (GDC-0834) in the rat model of CIA suggest that the amount of 
BTK inhibition anticipated in this study may be sufficient to achieve meaningful 
anti-inflammatory activity.  These studies suggest that 70% BTK inhibition, as measured 
by phospho-BTK inhibition, is required for half-maximal activity (Liu et al. 2011).  
However, it is not known whether BTK inhibition in the rat CIA model accurately predicts 
efficacy in human RA.  
Dose levels in this study are anticipated to result in exposures below 36 µM • hr (mean 
AUC0-24), which is the NOAEL from nonclinical toxicology studies.  The NOAEL 
(36 µM • hr) was defined in the 9-month dog study by vasculitis at higher doses 
(≥ 56 µM • hr). For further details, see the GDC-0853 Investigator’s Brochure. 
 
 
 




 
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studies, is accepted by health authorities to measure reduction in SLE disease activity, 
and is a composite measure that includes the SLE Disease Activity Index 2000 
(SLEDAI-2K), British Isles Lupus Assessment Group 2004 (BILAG-2004), and 
Physician’s Global Assessment (PGA).  SRI responses have been detected at 
timepoints as early as 12 weeks in prior clinical trials; however, therapeutic benefit is 
often measured at 24 weeks with maximal benefit seen as late as 48−52 weeks 
post-treatment intervention (Burness and McCormack 2011; Navarra et al. 2011; 
Furie et al. 2015; Khamashta et al. 2016).  
Several other clinically meaningful and exploratory aspects of SLE disease activity will 
be evaluated, using the Cutaneous Lupus Erythematosus Disease Area and Severity 
Index (CLASI), SELENA-SLEDAI Flare Index (SFI), and patient-reported outcome (PRO) 
measures (i.e., Patient’s Global Assessment).  Each of these measures has been well 
established and validated in previous studies. 
3.3.4.2 
Corticosteroid Taper 
There is a substantial unmet need for effective corticosteroid-sparing treatments for SLE, 
and this study will assess the corticosteroid sparing potential of GDC-0853.  Chronic 
corticosteroid use has many adverse short- and long-term consequences, so reducing 
corticosteroid doses in patients with SLE will decrease the incidence of short- and 
long-term comorbidities and potential adverse events, including in patients in this trial.  
The Glucocorticoid Toxicity Change Index (GTCI) (Miloslavsky et al. 2017) will be used 
to determine the potential of GDC-0853 to reduce steroid-induced systemic side effects 
(see Appendix 3).  In addition, unrestricted use of corticosteroids in SLE clinical trials 
can confound safety and efficacy measurements and decrease the ability to detect the 
biologic activity/efficacy of the experimental drug (Reddy et al. 2013).  Although the 
investigators can adjust steroids per their discretion based on SLE disease activity to 
best determine the safety and efficacy of GDC-0853, corticosteroids should be tapered 
as tolerated during the OLE, with a goal of < 10 mg/day prednisone or equivalent.   
3.3.4.3 
Additional Clinical Outcomes Assessments 
PRO and clinician-reported outcome data will be collected to more fully characterize the 
clinical profile of GDC-0853.  
3.3.4.4 
Concomitant Medication Rationale 
Patients in this study will continue on their background SOC therapy in order to ensure 
that all patients receive effective therapy for SLE.  Open-label study drug GDC-0853 will 
be administered to determine if GDC-0853 improves clinical response and/or reduces 
the need for systemic steroids in combination with SOC.  The eligibility criteria exclude 
patients on certain SLE therapies in order to reduce the risk for potential toxicities.  
Patients should be encouraged to remain stable on their background therapies 
(e.g., antimalarials, immunosuppressants), but they will be allowed to change doses, 
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OLE if clinically indicated (see Section 4.2.2.3.1).  Certain doses and combinations of 
immunosuppressants are not allowed with GDC-0853 (see Section 4.3.2). 
For guidance on concomitant medications that are unrelated to background SOC 
therapy, please refer to Section 4.3.  
4. 
MATERIALS AND METHODS  
4.1 
PATIENTS 
Up to approximately 240 patients from Study GA30044 can be enrolled in this study. 
4.1.1 
Inclusion Criteria 
Patients must meet the following criteria for study entry: 
• 
Signed Informed Consent Form (see Section 4.4.1) 
• 
Age 18−76 years, inclusive, at time of signing Informed Consent Form 
• 
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  
• 
Women of childbearing potential must have a negative urine pregnancy test at 
baseline  
A serum pregnancy test is needed on Day 1 only if the urine pregnancy test is 
positive. 
• 
For women of childbearing potential (including those who have had a tubal ligation):  
Agreement to remain abstinent (refrain from heterosexual intercourse) or use a 
contraceptive method with a failure rate of  1% per year during the treatment period 
and for at least 60 days after the last dose of study drug.  
A woman is considered to be of childbearing potential if she is postmenarcheal, 
has not reached a postmenopausal state (≥ 12 continuous months of 
amenorrhea with no identified cause other than menopause), and has not 
undergone surgical sterilization (removal of ovaries and/or uterus). 
Examples of contraceptive methods with a failure rate of  1% per year include 
bilateral tubal ligation, male sterilization, established proper use of hormonal 
contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, 
and copper intrauterine devices.  Women using estrogen-containing hormonal 
contraceptives as a method of contraception must also use a barrier, such as a 
male condom, in conjunction with the hormonal contraceptives. 
The reliability of sexual abstinence should be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the patient.  
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation 
methods) and withdrawal are not acceptable methods of contraception. 


 
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• 
For men:  agreement to remain abstinent (refrain from heterosexual intercourse) or 
use contraceptive measures, and agreement to refrain from donating sperm, as 
defined below (also see Appendix 5) 
Men with female partners of childbearing potential (including those who have 
had a tubal ligation) must remain abstinent or use a condom plus an additional 
contraceptive method that together result in a failure rate of  1% per year 
during the treatment period and for at least 120 days (4 months) after the last 
dose of study treatment.  Men must refrain from donating sperm during this 
same period. 
Men with pregnant female partners must remain abstinent or use a condom 
during the treatment period and for at least 28 days after the last dose of study 
treatment to avoid exposing the embryo. 
The reliability of sexual abstinence should be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the patient.  
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation 
methods) and withdrawal are not acceptable methods of contraception. 
 
4.1.2 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from study entry: 
• 
Met protocol-defined treatment-stopping criteria during Study GA30044 
• 
An adverse event in Study GA30044 that required permanent discontinuation of 
study drug 
• 
During Study GA30044, treatment with any therapy that is prohibited in this study 
(see Section 4.3.2)  
• 
In the opinion of the investigator, any new (since initially enrolling in the Phase II 
Study GA30044), significant, uncontrolled comorbidity or new clinical manifestation 
(related to SLE or not) that 1) requires medications not allowed in this protocol (see 
Section 4.3.2) or 2) could put the patient at undue risk from a safety perspective   
If the Principal Investigator has questions related to exclusion, he or she should 
consult the Medical Monitor.  
• 
Pregnant or breastfeeding, or intending to become pregnant during the study or 
within 60 days after the last dose of study drug 
• 
Any uncontrolled or clinically significant laboratory abnormality that would affect 
safety, interpretation of study data, or the patient’s participation in the study in the 
opinion of the investigator in consultation with the Medical Monitor 
• 
Any major episode of infection requiring hospitalization or treatment with IV 
antibiotics within the last 4 weeks of Study GA30044  
• 
Evidence of active, latent, or inadequately treated infection with Mycobacterium 
tuberculosis (TB) as defined as follows: 
– 
A positive QuantiFERON−TB Gold (QFT) or T-SPOT TB test or a Mantoux 
purified protein derivative (PPD) skin test (performed per Centers for Disease 


 
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Control and Prevention [CDC] guidelines using 5 tuberculin units per 0.1 mL) 
result of ≥ 5 mm of induration, performed at the Week 44 visit of 
Study GA30044 or later, prior to entry into Study GA30066 
– 
Patients with a history of bacillus Calmette-Guérin vaccination should be 
screened using the QFT test only.  
– 
A positive QFT test should be considered a positive diagnostic TB test. 
– 
If initial QFT is indeterminate, perform a confirmatory test with either QFT or 
T-SPOT.  The Principal Investigator may consult with the Medical Monitor to 
discuss selection of confirmatory test based on the patient’s disease status and 
baseline immunosuppression.  
– 
An indeterminate QFT test followed by a negative QFT or negative T-SPOT 
test should be considered a negative diagnostic TB test. 
– 
An indeterminate QFT test followed by an indeterminate QFT test or borderline 
or positive T-SPOT test should be considered a positive diagnostic TB test. 
• 
Patients who experienced a de novo or reactivated serious viral infection, such as 
hepatitis B virus or hepatitis C virus (HCV) during Study GA30044  
Positive hepatitis B surface antigen (HBsAg) or hepatitis C serology (regardless 
of treatment status) or positive hepatitis B core antibody (HBcAb) (tested at 
Week 44 of Study GA30044 or later, prior to entry into Study GA30066) are 
exclusionary. 
• 
Patients who developed a malignancy (with the exception of non-serious local and 
resectable basal or squamous cell carcinoma of the skin) during the Phase II 
Study GA30044 
• 
12-lead ECG at the Week 48 visit of Study GA30044 that demonstrates clinically 
relevant abnormalities that may affect patient safety or interpretation of study results, 
including the following:  
QTcF > 440 msec demonstrated by at least two ECGs > 30 minutes apart 
• 
Current treatment with medications that are well known to prolong the QT interval at 
doses that have a clinically meaningful effect on QT, as determined by 
the investigator 
The investigator may contact the Sponsor for confirmation if needed.  The 
investigator may reference the CredibleMeds Web site: 
https://www.crediblemeds.org/pdftemp/pdf/CompositeList.pdf. 
• 
Estimated glomerular-filtration rate (based on the 4-variable Modification of Diet in 
Renal Disease equation)  30 mL/min or on chronic renal replacement therapy 
• 
Laboratory values from the Week 44 visit of Study GA30044 (which may be 
repeated once at a later unscheduled visit, if necessary) that meet the following 
criteria:  
– 
AST or ALT > 1.5 × ULN (unless due to known autoimmune hepatitis) 
– 
Total bilirubin > 1.2 ULN 


 
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– 
Amylase or lipase > 2 × ULN 
– 
Hemoglobin  7 g/dL 
– 
ANC  1.5 × 109/L 
– 
Absolute lymphocyte count (ALC)  0.5 × 109/L 
– 
Platelet count  50,000/µL 
 
4.2 
STUDY TREATMENT  
The investigational medicinal product (IMP) for this study is GDC-0853. 
4.2.1 
Formulation, Packaging, and Handling 
GDC-0853 will be provided by the Sponsor as 50-mg dose strength tablets.    
Tablets will be supplied in bottles, which will be appropriately labeled for this study.  
GDC-0853 tablets should be stored between 2°C (35.6°F) and 8°C (46.4°F). 
For information on the formulation and handling of GDC-0853, see the GDC-0853 
Investigator’s Brochure. 
4.2.2 
Dosage, Administration, and Compliance 
4.2.2.1 
GDC-0853 Dose and Administration 
The GDC-0853 dose regimen is oral 200 mg BID.  Patients will receive GDC-0853 
approximately every 12 hours for approximately 48 weeks.  The first open-label dose of 
GDC-0853 should be the a.m. dose (taken in clinic) during the Week 48 visit of the 
GA30044 study (which is Day 1 of Study GA30066).  Patients should be directed to take 
one dose (a total of 4 tablets) BID (total of 8 tablets each day).  On clinic visit days when 
PK assessments are performed (Day 1 and Week 24), patients should be instructed that 
GDC-0853 will be administered in the clinic. 
In general, a dosing window of  ± 2 hours is acceptable.  If a dose is taken more than 
2 hours late or is missed altogether, the patient should resume normal dosing with the 
next scheduled dose.  Patients should record on the bottle the dose that was missed and 
notify study staff of any missed doses.  Doses that are vomited will be considered 
missed doses.  
A dose reduction of GDC-0853 for specific safety events is permitted (see Table 3).  For 
a potential dose reduction for other adverse events not listed in the table, please consult 
the Medical Monitor.  If dose reduction is indicated, the dose of GDC-0853 may be 
reduced from 200 mg BID to 200 mg QD or lower (in consultation with the Medical 
Monitor).  If the adverse event resolves and the patient has increased lupus disease 
activity, it is up to the discretion of the investigator in consultation with the Medical 
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Guidelines for dose reduction and treatment interruption or discontinuation are provided 
in Section 5.1.2. 
GDC-0853 will be orally administered and may be taken with or without food except for 
the instances (see Appendix 1) where the dose of oral study drug is to be administered 
at the clinic visit while fasting (≥ 4 hours prior to the clinic visit).  The dates and times of 
the most recent prior meal, last dose of GDC-0853 (prior to clinic visit), and timing of 
GDC-0853 administration in clinic should be recorded at clinic visits with PK and/or 
fasting lipid assessments.  In addition, any use of PPIs, H2-receptor antagonists (H2RAs), 
and/or short-acting antacids (e.g., Maalox®, Pepto-Bismol®, Rolaids®) should be 
recorded as concomitant medications, including time and date of last administration prior 
to the PK clinic visits.  Administration of GDC-0853 should be staggered with 
short-acting antacid use (i.e., GDC-0853 should be taken 2 hours before or 2 hours after 
the short-acting antacid). 
At study visits, sufficient GDC-0853 tablets will be dispensed to complete dosing until the 
next scheduled visit.  When GDC-0853 is administered at the site, it will be administered 
under supervision of study personnel, and the amount of GDC-0853 dispensed must be 
recorded. 
4.2.2.2 
GDC-0853 Compliance 
The following measure will be taken to assess patient compliance with study drug:  
Patients will be directed to bring any used and unused bottles to each visit.   
Sites will be responsible for prepopulating the dates on the dosing label (that should be 
affixed to the bottle) for when patients are scheduled to take study drug.  Under the 
corresponding dates listed, the patients will record the times (a.m. or p.m.) that they take 
each dose on the affixed label.  Refer to Appendix 6 for the bottle and label configuration.  
The number of tablets issued minus the number of tablets returned will be used to 
calculate the number of tablets taken and compliance.   
Compliance will be documented on the source record.   
Any overdose or incorrect administration of study drug should be noted on the Study 
Drug Administration electronic Case Report Form (eCRF).  Adverse events associated 
with an overdose or incorrect administration of study drug should be recorded on the 
Adverse Event eCRF.  If compliance is ≤ 80%, the investigator or designee is to counsel 
the patient and ensure steps are taken to improve compliance. 
4.2.2.3 
Background Standard of Care Therapy 
4.2.2.3.1 
Immunosuppressant Therapy 
Patients should be encouraged to remain stable on their background therapies 
(e.g., antimalarials, immunosuppressants), but they will be allowed to change doses, 
discontinue, and/or switch to other permitted immunosuppressant therapies during the 


 
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OLE if clinically indicated (see Section 4.3.1).  Certain doses and combinations of 
immunosuppressants are not allowed with GDC-0853 (see Section 4.3.2).  
If dose modification (increase or decrease) of an immunosuppressant is required 
because of increased clinical disease activity or toxicity, this must be recorded as an 
adverse event on the Adverse Event eCRF, and the dose modification must be recorded 
in the Immunosuppressant Review eCRF.   
Any overdose or incorrect administration of an immunosuppressant should be noted on 
the Immunosuppressant Review eCRF.  Adverse events associated with an overdose or 
incorrect administration of an immunosuppressant should be recorded on the 
Adverse Event eCRF. 
4.2.2.3.2 
Corticosteroid  
Patients who enter the OLE study on prednisone > 10 mg/day or equivalent OCS (see 
Appendix 2) should be encouraged to taper their OCS, with the goal of achieving an 
OCS dose of  10 mg/day prednisone or equivalent.  All steroid changes should be 
captured on the OCS diary (see Section 4.2.2.4). 
Any change in steroid dose must be recorded on the Corticosteroid Medication eCRF.  
It is recommended that all patients receiving corticosteroids should receive appropriate 
supportive therapy to help prevent steroid-induced osteoporosis (e.g., calcium, vitamin D 
supplements, bisphosphonates) as per local guidelines and physician preference.  
Pneumocystis jiroveci pneumonia prophylaxis is also recommended to be used as per 
local SOC. 
4.2.2.3.3 
Burst Treatment 
In the case of increased disease activity, the patient will have the opportunity to receive 
burst treatment (defined as an increase or new dose of oral prednisone or equivalent), in 
addition to the study treatment.  The patient should return to the clinic, either at a 
scheduled study visit or unscheduled flare visit, to be evaluated and to receive an 
increase or new dose of oral prednisone as follows: 
• 
A burst is defined as an increase or new dose of oral prednisone up to 40 mg/day 
(or equivalent, see Appendix 2). 
 
When using corticosteroids as a burst treatment, the investigator may temporarily 
increase the dose of corticosteroids, and then the investigator should attempt to taper 
the patient back down to his or her previous corticosteroid dose, ideally within 2 weeks.  
Patients will continue to receive their designated dose of study treatment (see 
Section 3.1) during the burst treatment.  The previous corticosteroid dose is defined as 
the dose of corticosteroids taken prior to the burst.  If the patient was not previously on 
corticosteroids, the investigator should attempt to taper the patient back off 
corticosteroids completely.  If the patient was on a corticosteroid-tapering schedule at 


 
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the time of the burst treatment, the investigator will revise the tapering schedule as 
necessary to attempt to meet the target OCS dose ( 10 mg/day).  
Any changes in steroid doses will be recorded in the Corticosteroid Medication eCRF. 
Patients may receive corticosteroids for emergent illness other than SLE (e.g., trauma, 
asthma) or if clinically warranted to prevent adrenal crisis (e.g., prior to surgery).  If 
possible, the additional corticosteroid treatment in these cases should last no more than 
7 days.  After resolution of the acute emergent illness, the patient should resume his or 
her standard OCS dose and taper regimen. 
Any dose of steroid higher than the maximum burst levels above or any necessity for 
additional burst treatments for increased SLE-related activity (either a second treatment 
within the burst window or a burst treatment outside the burst window), as determined by 
the investigator, will be considered escape therapy (see Section 4.2.2.3.4) and will be 
recorded in the Corticosteroid Medication eCRF.   
Use of burst therapy to treat worsening of lupus will be captured on the Adverse Event 
eCRF (see Section 5.3.5.9).  If any patient needs additional corticosteroids for this or 
any other reason, the Medical Monitor needs to be informed and the reason recorded on 
the Corticosteroid Medication eCRF (see Section 4.2.2.3.4).   
4.2.2.3.4 
Escape Therapy 
If an increase in immunosuppressive therapy (referred to as “escape therapy”) is 
deemed medically necessary due to increased SLE disease activity, the patient will be 
given escape therapy, which will be recorded on the Immunosuppressant Review and/or 
Corticosteroid Medication eCRFs.  Patients receiving the following escape therapies, 
after informing the Medical Monitor, will be allowed to remain on study drug but will be 
considered a protocol-defined “non-responder” in the secondary efficacy analysis:   
• 
IV steroids  
• 
OCS doses exceeding the limits described in Section 4.2.2.3.3  
• 
New or increased doses of an immunosuppressant medication up to the maximum 
allowed in the study (see Section 4.3.1)  
 
NOTE:  Any combination of azathioprine, methotrexate, mycophenolate mofetil, or 
mycophenolic sodium is prohibited during the study while the patient is receiving study 
treatment (see Section 4.3.2).  
Whenever possible, a patient being evaluated for escape therapy will undergo 
assessment at either an unscheduled or flare visit prior to the increase in 
immunosuppression in order to quantify and record the increased disease activity, 
unless this occurs at a scheduled study visit (see Appendix 1).   


 
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If the patient requires any further treatment for SLE activity beyond the escape therapy 
described above (e.g., prohibited medications as defined in Section 4.3.2 or any 
accepted immunosuppressant that exceeds the maximum dose as defined by the 
protocol or any increase in therapy not approved by the Medical Monitor), the patient 
should be discontinued from study treatment and return for the 8-week safety follow-up 
visit (see Section 4.5.1).   
Use of escape therapy to treat worsening of lupus will be captured on the Adverse Event 
eCRF (see Section 5.3.5.9).  If any patient needs additional corticosteroids for this or 
any other reason, the Medical Monitor needs to be informed and the reason recorded on 
the Corticosteroid Medication eCRF.   
4.2.2.4 
Background Standard of Care Therapy Compliance 
As in Study GA30044, all patients will be expected to continue to record their OCS 
intake using a diary and as instructed by study staff.  Patients will record changes in their 
OCS dose using a paper diary and as instructed by study staff.  OCS usage will be 
recorded in the Corticosteroid Medication eCRF. 
4.2.3 
Investigational Medicinal Product Accountability 
All IMPs required for completion of this study (GDC-0853) will be provided by the 
Sponsor where required by local health authority regulations.  The study site will 
acknowledge receipt of IMPs using the interactive voice and Web-based response 
system (IxRS) to confirm the shipment condition and content.  Any damaged shipments 
will be replaced.  
IMPs either will be disposed of at the study site according to the study site’s institutional 
standard operating procedure or will be returned to the Sponsor with the appropriate 
documentation.  The site’s method of IMP destruction must be agreed to by the Sponsor.  
The site must obtain written authorization from the Sponsor before any IMP is destroyed, 
and IMP destruction must be documented on the appropriate form. 
Accurate records of all IMPs received at, dispensed from, returned to, and disposed of by 
the study site should be recorded on the Drug Inventory Log. 
4.2.4 
Continued Access to GDC-0853 
Currently, the Sponsor (Genentech, a member of the Roche Group) does not have any 
plans to provide Sponsor study drug GDC-0853 or any other study treatments or 
interventions to patients who have completed Study GA30066.  The Sponsor may 
evaluate whether to continue providing GDC-0853 in accordance with the Roche Global 
Policy on Continued Access to Investigational Medicinal Product, available at the 
following Web site: 
http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf  


 
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4.3 
CONCOMITANT THERAPY, PROHIBITED FOOD, AND 
ADDITIONAL RESTRICTIONS 
Concomitant therapy includes any medication (e.g., prescription drugs, over-the-counter 
drugs, vaccines, herbal or homeopathic remedies, nutritional supplements) used by a 
patient from 7 days prior to initiation of study drug through 8 weeks after the last dose of 
study drug.  All concomitant medication taken during the study must be documented on 
the eCRF along with indication, daily dose, and start and stop dates of administration.  
Adverse events related to the administration of a concomitant medication or the 
performance of a procedure must also be documented on the appropriate adverse event 
page of the eCRF. 
It is recommended that patients avoid changing other prescription or non-prescription 
drugs, vitamins, and dietary supplements within 7 days or 5 half-lives, whichever is 
longer, prior to the first dose of study medication and throughout the study. 
4.3.1 
Permitted Therapy  
Concomitant immunosuppressant and antimalarial medications can be used up to the 
doses shown in Table 2. 
Table 2 
Permitted Dose Ranges for Immunosuppressant and Antimalarial 
Medications  
Azathioprine  
Up to 2.5 mg/kg/day 
Methotrexate 
Up to 25 mg/week 
Mycophenolate mofetil 
Up to 2500 mg/day 
Mycophenolic sodium 
Up to1800 mg/day 
Hydroxychloroquine 
Up to 400 mg/day 
Chloroquine 
Up to 250 mg/day 
Quinacrine 
Up to 200 mg/day 
Other 
 
Note:  Other medications may be permitted (in consultation with the Medical Monitor). 
 
Addition, discontinuation, and dose adjustment of concomitant medications for 
conditions other than SLE are discouraged but permitted when required for the safe and 
effective treatment of patients.  
Any case of medication intolerance or toxicity must be recorded as an adverse event 
and any dose modification recorded in the eCRF.    
Certain combinations of the SLE therapies below are not permitted (see Section 4.3.2) 


 
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4.3.1.1 
Antimalarials  
Antimalarial medications (e.g., hydroxychloroquine, chloroquine, quinacrine), including 
combinations of up to two antimalarials, are permitted.  Replacement of one antimalarial 
with another may be allowed in cases where there is limited supply of the original 
medication or if there are issues with toxicity or intolerance.   
4.3.1.2 
Mycophenolate Mofetil/Mycophenolic Acid 
Patients who are taking mycophenolate mofetil (or mycophenolic acid) at permitted 
doses (see Table 2) will be eligible to participate in the OLE.  When mycophenolic acid is 
used instead of mycophenolate mofetil, a 360-mg dose of mycophenolic acid is 
considered to be equivalent to a 500-mg dose of mycophenolate mofetil.  
Mycophenolate mofetil may interact with oral contraceptives, decreasing their 
effectiveness; however, patients enrolling in this study and using hormonal 
contraceptives as a method of contraception are required to also use a barrier, such as a 
male condom. 
4.3.1.3 
Azathioprine  
Prior to starting azathioprine, it is strongly recommended to test patients for thiopurine 
methyltransferase variant alleles that have been associated with decreased activity in 
vitro and lead to the accumulation of the drug and/or its metabolites.  
4.3.1.4 
Methotrexate  
To prevent methotrexate-associated adverse events, all patients on methotrexate are 
required to take folic acid or equivalent (e.g., 1 mg/day) at a stable dose of at least 
5 mg/week or equivalent. 
4.3.1.5 
Non-Steroidal Anti-inflammatory Drugs 
As needed use of NSAIDs should be avoided within 24 hours before a visit where clinical 
efficacy assessments are scheduled to be performed and recorded.    
Aspirin can be taken to reduce cardiovascular risk, but the dose is not to exceed 
325 mg/day.   
In order to prevent NSAID-related GI complications in high-risk patients, concomitant 
acid reducing agents (e.g., PPIs) should be used according to local guidelines (see 
Section 5.1.1.3). 
4.3.1.6 
ACE Inhibitors and ARBs  
For patients who are on angiotensin converting enzyme (ACE) inhibitors or angiotensin 
receptor blockers (ARBs) at study entry, doses of ACE inhibitors or ARBs should be kept 
stable throughout the first half of the trial whenever possible. 
4.3.1.7 
Dietary Supplements  
For the purposes of this protocol, dietary supplements are defined as vitamins, minerals, 
purified food substances, and herbals with pharmaceutical properties.  Vitamins, 


 
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minerals, and purified food substances are allowed in amounts not known to be 
associated with adverse events (e.g., hypervitaminosis).  Herbals with pharmaceutical 
properties are allowed only if there is acceptable evidence of no CYP3A inhibition or 
induction (refer to Appendix 7 for a list of prohibited concomitant medications, including 
herbal products, as well as Section 4.3.2.2).  Otherwise, herbals with pharmaceutical 
properties must be discontinued for at least 4 weeks prior to the first dose of study 
medication, unless there is sufficient data available regarding the duration of an herbal 
medication’s PK and PD effects to allow a shorter washout to be specified 
(e.g., 5 half-lives).  Please direct any questions to the Medical Monitor. 
4.3.1.8 
Acid Reducing Agents  
Patients who use short-acting antacids (e.g., Maalox®, Pepto-Bismol®, Rolaids® for 
symptomatic relief of heartburn) should take GDC-0853 or matching placebo 2 hours 
before or 2 hours after short-acting antacid administration because gastric acid improves 
GDC-0853 absorption.  Patients may be treated with PPIs or H2RAs at up to the 
maximum recommended dose according to local labeling.  The dose is recommended to 
remain stable throughout the study.  At visits with scheduled PK assessments (see 
Appendix 1), any use of PPIs (see Section 4.2.2.1), H2RA, and/or short-acting antacids 
should be recorded as concomitant medications, including the date and time of last 
administration prior to the clinic visit. 
4.3.2 
Prohibited Therapy 
A listing of concomitant medications and foods that are prohibited or should be used with 
caution due to potential PK drug−drug interactions is provided in Appendix 7.  Biologic 
response modifiers and disease-modifying antirheumatic drugs other than mentioned 
above are not allowed during this study, and any use will require discontinuation of study 
treatment.   
Specifically, the use of the following therapies is prohibited in conjunction with study drug 
treatment: 
• 
All biological agents (e.g., tumor necrosis factor inhibitors, IL-17, IL-12/23, abatacept, 
denosumab) including biosimilars (investigational or approved) 
• 
Anti-CD20 monoclonal antibody 
• 
Belimumab (Benlysta) 
• 
Chlorambucil 
• 
Cyclophosphamide 
• 
Heparin, low molecular weight heparin, and other injectable systemic anticoagulants 
• 
Immunosorbent column 
• 
Investigational therapy other than study drug 
• 
Oral anticoagulants, including but not limited to warfarin, dabigatran, rivaroxaban, 
and apixaban  


 
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• 
Sirolimus 
• 
Systemic calcineurin inhibitors (e.g., tacrolimus, cyclosporine) 
• 
Tocilizumab and other anti-IL6R or anti-IL6 agents  
• 
Tofacitinib and other JAK inhibitors 
• 
Any combination of azathioprine, methotrexate, mycophenolate mofetil, or 
mycophenolic sodium 
 
Please see Appendix 7 for additional prohibited therapies during this study. 
4.3.2.1 
Live or Attenuated Vaccinations 
Immunization with a live or attenuated vaccine is prohibited within and for the duration of 
study participation, including the 8-week follow-up period after the administration of the 
last dose.  See Section 5.1.1.2 for further details and precautions around vaccinations. 
4.3.2.2 
CYP3A Inhibition 
In vitro studies suggest that GDC-0853 is a CYP3A inhibitor with inhibitory constant 
values of approximately 10 µM (Study 13-0384).  
 
 
; however, it is possible that 
GDC-0853 inhibition of CYP3A may alter the metabolism of CYP3A substrates, including 
estrogen derivatives, such as ethinylestradiol, subsequently leading to an increase in 
plasma concentrations of these drugs (see the GDC-0853 Investigator’s Brochure).   
There is a moderate to high potential for a drug−drug interaction with any medication 
that is metabolized by CYP3A.  Plasma concentrations of the medications in the 
following categories (listed in detail in Appendix 7) may increase; therefore, they should 
be used with caution unless otherwise specified in Section 4.3.2: 
• 
Sensitive CYP3A substrates 
• 
CYP3A substrates with a narrow therapeutic index  
 
Ethinylestradiol is metabolized by CYP3A; therefore, plasma concentrations may 
increase in the presence of GDC-0853.  The use of hormone-replacement therapy 
containing ethinylestradiol or hormonal contraceptives containing ethinylestradiol, with 
the concomitant use of a barrier method, is permitted during this study (see Appendix 5); 
however, these agents should be used with caution and patients should be counseled 
regarding the potential risks and benefit of these medications per the local prescribing 
information.  Any increase in ethinylestradiol plasma concentrations is anticipated to be 
modest at most because CYP-mediated oxidation appears to be a relatively minor 
component of orally administered ethinylestradiol (Zhang et al. 2007).  Although 
contraceptive efficacy is not expected to be impacted, increased ethinylestradiol plasma 
concentrations may lead to an increase in common side effects, such as nausea, breast 
tenderness, and headaches, and to a theoretical increase in rare dose-related events, 
such as thromboembolism (Inman et al. 1970).   


 
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In vitro data suggest that GDC-0853 is metabolized by CYP3A and there is a moderate 
to high potential for a drug−drug interaction with any medication that strongly inhibits or 
induces this enzyme.  Therefore, medications in the following categories (listed in detail 
in Appendix 7 should be avoided until the last dose of study drug.  If use of one of these 
medications is necessary, the risks and benefits should be discussed with the Medical 
Monitor prior to concomitant administration with study drug. 
• 
Moderate or strong CYP3A inhibitors 
• 
Moderate or strong CYP3A inducers  
 
The medications listed in Appendix 7 are not necessarily comprehensive.  Thus, the 
investigator should consult the prescribing information for any concomitant medication 
as well as the Internet references provided below when determining whether a certain 
medication is metabolized by or strongly inhibits or induces CYP3A.  The investigator 
should contact the Medical Monitor if questions arise regarding medications not listed 
above.   
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/G
uidances/UCM292362.pdf 
http://medicine.iupui.edu/clinpharm/ddis/table.aspx 
 
4.3.3 
Prohibited Food  
Use of the following foods is prohibited during the study due to their effects on the 
CYP450 3A4 enzyme, which is involved in GDC-0853 metabolism:  grapefruit, Seville 
orange, pomegranate, or star fruit juice or products, which all contain furanocoumarin 
derivatives.  Please refer to Appendix 7 for additional information.  
4.3.4 
Additional Restrictions 
It is strongly recommended that patients be fasting ≥4 hours prior to fasting lipid draws 
as well as predose PK draws (see Appendix 1).  
4.4 
STUDY ASSESSMENTS  
The schedule of activities to be performed during the study is provided in Appendix 1.  
All activities must be performed and documented for each patient. 
4.4.1 
Informed Consent Forms and Screening Log 
Written informed consent for participation in the study must be obtained before 
performing any study-related procedures.  Informed Consent Forms for enrolled patients 
and for patients who are not subsequently enrolled will be maintained at the study site. 
All screening evaluations must be completed and reviewed to confirm that patients meet 
all eligibility criteria before enrollment.  The investigator will maintain a screening log to 
record details of all patients screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 


 
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Patients entering the OLE study may be consented after meeting entry criteria for 
Study GA30066, which may include use of qualifying test results from the Week 44 visit 
or later from Study GA30044.  
4.4.2 
Physical Examinations 
A complete physical examination should be performed on Day 1 and should include an 
evaluation of the head, eyes, ears, nose, and throat, and the cardiovascular, 
dermatological, musculoskeletal, respiratory, GI, genitourinary, and neurological systems.  
Any abnormality identified at baseline should be recorded on the General Medical 
History and Baseline Conditions eCRF.  Particular attention should be given to 
evaluation of potential manifestations of active SLE and of infections or other medical 
conditions, which could place the patient at increased risk.  
At subsequent visits (or as clinically indicated), limited, efficacy assessment−directed or 
symptom-directed physical examinations should be performed.  Changes from baseline 
abnormalities should be recorded in patient notes.  New or worsened clinically significant 
abnormalities should be recorded as adverse events on the Adverse Event eCRF. 
4.4.3 
Vital Signs  
Vital signs will include measurements of respiratory rate, pulse rate, temperature, and 
systolic and diastolic blood pressure while the patient is in a seated position for at least 5 
minutes. 
4.4.4 
Tuberculin Purified Protein Derivative Skin Test 
Testing for TB should only be performed during Study GA30066 if it did not take place at 
the Week 44 visit or later in Study GA30044. The QFT should be used as the screening 
test for TB (if this was the initial method for testing in Study GA30044) and, if 
indeterminate, this QFT test should be followed by a repeat QFT or a T-SPOT test.  If 
QFT is not available, a Mantoux PPD skin test will be performed and read locally.  The 
PPD skin test will be performed per the CDC guidelines using 5 tuberculin units per 0.1 
mL [5TU].  An intradermal injection into flexor or dorsal surface of forearm will be 
performed. 
4.4.5 
SLE Disease Activity Assessments 
The following applicable SLE disease activity assessments will be used in this study:  
BILAG-2004, SLEDAI-2K, SFI, GTCI, Systemic Lupus International Collaborating Clinics 
(SLICC), CLASI, PGA, and Patient’s Global Assessment.  Throughout the study, each 
assessment ideally should be conducted by the same assessor, if possible.  Detailed 
instructions and training on the use of clinical instruments performed by the investigators 
in this study will be provided by the Sponsor or Sponsor designee. Investigators must 
demonstrate the ability to perform disease activity assessments and/or they must 
provide valid training certificates obtained within 2 years of the start of the parent Study 
GA30044 for versions used in this study. 


 
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Investigators who have completed the disease assessment trainings during the main 
Study GA30044 or up to 2 years prior to the beginning of the Study GA30044 do not 
need to retake the training.  
4.4.5.1 
BILAG-2004 Index  
The BILAG-2004 Index will be used as a method to assess disease activity in this study. 
The BILAG-2004 assesses 97 clinical signs, symptoms, and laboratory parameters 
across 9 organ or system domains:  constitutional, mucocutaneous, neuropsychiatric, 
musculoskeletal, cardiorespiratory, GI, ophthalmic, renal, and hematological.  The 
97 symptoms are rated with respect to severity over the previous month (4 weeks) and 
with respect to any change from the previous examination (new, improving, stable, 
worsening, absent).  For each of the 9 domains, a single, alphabetic score (i.e., 
A through E) is then derived from the examination results in each organ category.   
Detailed instructions and training on the use of the BILAG-2004 will be provided as 
described in Appendix 9 and Section 4.4.5. 
4.4.5.2 
SLEDAI-2K and SELENA-SLEDAI Flare Index  
SLEDAI-2K measures disease activity at the visit or within the preceding 28 days.   
The SFI categorizes SLE flare as “mild or moderate” or “severe” based on six variables 
(Petri et al. 1999; Buyon et al. 2005; Petri et al. 2005): 
• 
Change in SELENA-SLEDAI or SLEDAI-2K score from the most recent assessment 
to current 
• 
Change in signs or symptoms of disease activity 
• 
Change in prednisone dosage 
• 
Use of new medications for disease activity or hospitalization 
• 
Change in PGA score  
• 
Hospitalization for activity (severe flare only) 
 
Detailed instructions and training on the use of the SLEDAI-2K will be provided during 
training sessions at each investigator meeting (for the parent Study GA30044) and 
through online resources.  It is critical that investigators have a thorough understanding 
of both the SLEDAI-2K and the SFI and the differences between them.  The 
investigators who trained during the Investigators Meeting for the main Study GA30044 
and/or who are using the online resources available for the main Study GA30044 do not 
need to take the training again. 
The SFI will be modified such that severe flares triggered only by an increase in 
SLEDAI-2K score to > 12 alone will be excluded.  One or more other items defining 
severe flare in the SFI needed to be present for a severe flare to be recorded.  This 
modification was made because patients entering the trial with high disease activity 


 
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(e.g., ≥ 11) could too easily trigger a severe flare by minor increases in the SLEDAI-2K 
score. 
4.4.5.3 
Glucocorticoid Toxicity Change Index  
The GTI is an exploratory standardized measure of damage related to use of 
glucocorticoids (see Appendix 3).  The GTCI will be incorporated into this study to better 
quantify the accrual of damage linked to corticosteroid use in patients with lupus and 
may allow for an improved understanding of SOC and patient phenotype. 
4.4.5.4 
SLICC/ACR Damage Index for Systemic Lupus Erythematosus 
The SLICC/American College of Rheumatology (ACR) Damage Index for SLE will be 
utilized to assess organ damage as opposed to the collection of disease activity (see 
Appendix 8).   Damage is defined as non-reversible change not related to active 
inflammation. 
4.4.5.5 
Cutaneous Lupus Erythematosus Disease Area and Severity 
Index (CLASI) 
The CLASI is an instrument designed to capture SLE-specific mucocutaneous disease 
manifestations (see Appendix 12).  It comprises a score for the activity of the disease 
and a score for the damage caused by the disease.  The CLASI should be completed at 
intervals as indicated in the schedule of activities for any patient who has 
mucocutaneous manifestations of SLE at a given study visit and at all subsequent visits.  
The CLASI will be used to capture mucocutaneous disease in any patient with 
mucocutaneous disease manifestations as outlined in the schedule of activities (see 
Appendix 1).  
It is important that only SLE-specific lesions are included in this assessment.  Training in 
the use of the CLASI will be available online and will be required for any new investigator 
entering in the OLE study who has not completed the training during Study GA30044 or 
within 2 years from the beginning of Study GA30044.  
4.4.5.6 
Physician’s Global Assessment (PGA) 
The PGA (see Appendix 13) is a visual analog scale (VAS).  Physicians are to rate the 
patient’s disease activity over the past 28 days and place a vertical tick mark on a 100-
mm analog scale that is gradated from 0 to 3.  The left-hand extreme of the line is 
described as “None” and the right-hand extreme as “Severe.”  Patient history, results of 
the physical examination, as well as pertinent laboratory values should be taken into 
account when rating the patient’s disease activity.  Physicians should also refer to the 
value recorded at the previous visit and move the tick mark as appropriate. 
4.4.5.7 
Patient’s Global Assessment 
The Patient’s Global Assessment is a VAS (see Appendix 14).  The patient’s overall 
assessment of their current disease activity is measured using a vertical tick mark on a 
100-mm VAS.  The left-hand extreme of the line is described as “None” (symptom-free) 
and the right–hand extreme as “Maximum.” 


 
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4.4.6 
Systemic Lupus Erythematosus Responder Index (SRI) 
The SRI is a categorical assessment that evaluates disease activity in SLE based on the 
different organ systems.  This index utilizes a combined evaluation of the BILAG-2004, 
SLEDAI-2K, and PGA (Sections, 4.4.5.1; 4.4.5.2; 4.4.5.6 to measure response to 
treatment.  The SRI-4 primary endpoint defines response as meeting each of the 
following criteria at Week 48 compared with baseline:  
• 
≥ 4 point reduction in SLEDAI-2K score, and 
• 
No new BILAG A organ domain score or two new BILAG B organ domain scores, 
and 
• 
No worsening (worsening defined as a > 0.3 point increase) in the PGA. 
 
4.4.6.1 
Optional Photography 
For patients with cutaneous manifestations of SLE, optional photographs of the affected 
areas may be taken to document change over time while the patient is receiving study 
treatment.  Photography is an optional assessment for patients who sign the optional 
photography consent and is contingent on Institutional Review Board or Ethics 
Committee (IRB/EC) approval. 
4.4.7 
Laboratory, Biomarker, and Other Biological Samples  
Laboratory assessments will be performed as indicated in the schedule of activities (see 
Appendix 1).  All laboratory tests will be sent to one or more central laboratories for 
analysis, with the exception of serum and urine pregnancy tests and erythrocyte 
sedimentation rate (ESR), which will be conducted locally. 
At clinic visits at which study drug will be administered, laboratory samples should 
generally be drawn before the administration of study drug and after the administration 
of PRO assessments (e.g., pain questionnaires).  On Week 24, PRO assessments will 
follow PK sample collection and treatment administration (see Appendix 1). 
Samples for the following laboratory tests will be sent to the study site's local laboratory 
for analysis: 
• 
ESR   
ESR can be performed at local laboratory or as point-of-care test in clinic.  The 
kits to perform the test will be provided by the central laboratory. 
• 
Pregnancy test 
Urine pregnancy tests will be performed at specified visits for women of 
childbearing potential (including those who have had a tubal ligation).  If a urine 
pregnancy test is positive, it must be confirmed by a serum pregnancy test.  
Should a positive result be recorded at any time, the procedures detailed in 
Section 5.4.3 should be followed.  


 
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• 
Direct Coombs test 
The direct Coombs test will be performed at a local laboratory per the SOA and 
should be used if the patient develops anemia that may be autoimmune in 
etiology.  
• 
T-SPOT test for TB 
The T-SPOT test may be performed at a local laboratory (optional, if not 
performed at the Week 44 visit or later in Study GA30044). 
 
Samples for the following laboratory tests will be sent to one or several central 
laboratories for analysis: 
• 
Anti-double stranded DNA 
• 
Autoantibody panel:  anti-Smith, anti-RNP, anti-Ro, anti-La, anti-cardiolipin, and 
anti-B2 glycoprotein 
• 
C3, C4, and CH50 
• 
Chemistry panel (serum or plasma):  electrolytes (Na, K, Cl, bicarbonate, 
phosphorus), blood urea nitrogen, creatinine, glucose, ALT, AST, amylase, lipase, 
total and direct bilirubin, ALP, GGT, albumin, globulin, total protein, calcium, uric 
acid  
• 
CK, aldolase, and LDH 
• 
Coagulation panel: INR, aPTT, PT 
• 
High sensitivity C-reactive protein 
• 
Fasting Lipids:  triglycerides, HDL, LDL, glycosylated hemoglobin (HbA1C), and 
total cholesterol 
• 
Hematology:  hemoglobin, hematocrit, RBC count, calculated indices (mean 
corpuscular volume, mean corpuscular hemoglobin [MCH], MCH concentration, red 
cell distribution width), platelets, WBC with differential  
• 
Immunology:  total Igs, IgG, IgM, IgE, and IgA 
• 
T, B, and natural killer cells  
• 
Urinalysis:  dipstick (blood, protein, glucose, nitrites, and leukocyte esterase), 
microscopic analysis (RBC, WBC, red cell casts, white cell casts, epithelial cells) 
• 
Viral serology:  
− 
Hepatitis B:  HBsAg, total HBcAb, hepatitis B surface antibody, and HCV 
antibody (if not performed at the Week 44 visit or later in Study GA30044) 
• 
QFT; if QFT not available, a PPD skin test will be administered if clinically indicated 
(if not performed at the Week 44 visit or later in Study GA30044) 
 
The following samples will be sent to the Sponsor or a designee for analysis: 
• 
Plasma samples for PK analysis and metabolite identification, as needed. 
 


 
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For sampling procedures, storage conditions, and shipment instructions, see the 
laboratory manual. 
Unless the patient gives specific consent for his or her leftover samples to be stored for 
optional exploratory research (see Section 4.4.10), biological samples will be destroyed 
when the final Clinical Study Report has been completed, with the following exception: 
• 
Plasma samples collected for PK analysis will be destroyed no later than 5 years 
after the final Clinical Study Report has been completed. 
 
When a patient withdraws from the study, samples collected prior to the date of 
withdrawal may still be analyzed, unless the patient specifically requests that the 
samples be destroyed or local laws require destruction of the samples. However, if 
samples have been tested prior to withdrawal, results from those tests will remain as 
part of the overall research data. 
Data arising from sample analysis, including data on germline mutations, will be subject 
to the confidentiality standards described in Section 8.4. 
4.4.8 
Electrocardiograms 
All ECG recordings must be performed using a standard, high-quality, high-fidelity, 
digital ECG machine equipped with computer-based interval measurements and 
provided by the Sponsor.  Lead placement should be as consistent as possible.   
Single ECG recordings will be obtained at specified timepoints, as outlined in the 
schedule of activities (see Appendix 1).  ECG recordings may be obtained at 
unscheduled and other timepoints as indicated.  
ECG recordings must be performed after the patient has been resting in a supine 
position for at least 10 minutes.  All ECGs are to be obtained prior to other procedures 
scheduled at that same time (e.g., vital sign measurements, blood draws) whenever 
possible.  Circumstances that may induce changes in heart rate, including environmental 
distractions (e.g., television, radio, conversation) should be avoided during the pre-ECG 
resting period and during ECG recording. 
For safety monitoring purposes, the investigator must review, sign, and date all ECG 
tracings.  Paper copies of ECG tracings will be kept as part of the patient's permanent 
study file at the site.  Digital recordings will be stored at a central laboratory.  The 
following should be recorded in the appropriate eCRF:  heart rate, RR interval, QRS 
interval, PR duration, uncorrected QT interval, and QTcF based on the machine 
readings of the individual ECG tracings.  Any morphologic waveform changes or other 
ECG abnormalities must be documented on the eCRF.  If considered appropriate by the 
Sponsor, ECGs may be analyzed retrospectively at a central laboratory. 


 
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If at a particular postdose timepoint, the mean QTcF is > 500 msec and/or 60 msec 
longer than the baseline value, triplicate ECGs must be recorded, ideally within the next 
5 minutes, and triplicate ECG monitoring should continue at least hourly until the QTcF 
has stabilized on two successive ECGs.  Triplicate ECG recordings will be obtained 
within approximately 2−5 minutes of each other. The Medical Monitor should be notified.  
SOC treatment for QT prolongation may be instituted per the discretion of the 
investigator.  If a PK sample is not scheduled for that timepoint, an unscheduled PK 
sample should be obtained.  A decision on study drug discontinuation should be made, 
as described in Section 5.1.  The investigator should also evaluate the patient for 
potential concurrent risk factors (e.g., electrolyte abnormalities, co-medications known to 
prolong the QT interval, severe bradycardia). 
4.4.9 
Patient-Reported Outcomes 
PRO data will be collected via questionnaires to more fully characterize the clinical 
profile of GDC-0853.  The questionnaires, translated into the local language as required, 
will be completed in their entirety at specified timepoints during the study.  To ensure 
instrument validity and that data standards meet health authority requirements, 
questionnaires will be self-administered before the patient or clinician receives any 
information on disease status, prior to the performance of non-PRO assessments, and 
prior to the administration of study treatment, unless otherwise specified.   
Patients will use paper-based questionnaires to capture PRO data.  The instructions for 
completing the questionnaires will be provided by the investigator staff.   
4.4.10 
Samples for Research Biosample Repository  
4.4.10.1 
Overview of the Research Biosample Repository 
The Research Biosample Repository (RBR) is a centrally administered group of facilities 
used for the long-term storage of human biologic specimens, including body fluids, solid 
tissues, and derivatives thereof (e.g., DNA, RNA, proteins, peptides).  The collection, 
storage, and analysis of RBR specimens will facilitate the rational design of new 
pharmaceutical agents and the development of diagnostic tests, which may allow for 
individualized drug therapy for patients in the future. 
RBR specimens will be used to achieve the following objectives: 
• 
To study the association of biomarkers with efficacy, adverse events, or disease 
progression 
• 
To increase knowledge and understanding of disease biology 
• 
To study drug response, including drug effects and the processes of drug absorption 
and disposition 
• 
To develop biomarker or diagnostic assays and establish the performance 
characteristics of these assays 
 


 
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4.4.10.2 
Approval by the Institutional Review Board or Ethics 
Committee 
Collection and submission of biological samples to the RBR is contingent upon the 
review and approval of the exploratory research and the RBR portion of the Informed 
Consent Form by each site's IRB/EC and, if applicable, an appropriate regulatory body.  
If a site has not been granted approval for RBR sampling, this section of the protocol 
(Section 4.4.10) will not be applicable at that site. 
4.4.10.3 
Sample Collection 
The following samples will be stored in the RBR and used for research purposes, 
including, but not limited to, research on biomarkers related to GDC-0853 or diseases: 
• 
Leftover blood, serum, plasma, and urine samples 
 
The above samples may be sent to one or more laboratories for DNA extraction to 
enable analysis of germline mutations, somatic mutations via whole genome sequencing 
(WGS), next-generation sequencing, or other genomic analysis methods.   
Genomics is increasingly informing researcher's understanding of disease pathobiology.  
WGS provides a comprehensive characterization of the genome and, along with clinical 
data collected in this study, may increase the opportunity for developing new therapeutic 
approaches.  Data will be analyzed in the context of this study but will also be explored 
in aggregate with data from other studies.  The availability of a larger dataset will assist 
in identification of important pathways, guiding the development of new targeted agents. 
For sampling procedures, storage conditions, and shipment instructions, see the 
laboratory manual.   
RBR specimens are to be stored until they are no longer needed or until they are 
exhausted.  However, the RBR storage period will be in accordance with the 
IRB/EC-approved Informed Consent Form and applicable laws (e.g., health authority 
requirements). 
4.4.10.4 
Confidentiality 
Specimens and associated data will be labeled with a unique patient identification 
number. 
Patient medical information associated with RBR specimens is confidential and may be 
disclosed to third parties only as permitted by the Informed Consent Form (or separate 
authorization for use and disclosure of personal health information) signed by the patient, 
unless permitted or required by law. 
Given the complexity and exploratory nature of the analyses, data derived from RBR 
specimens will generally not be provided to study investigators or patients unless 
required by law.  The aggregate results of any conducted research will be available in 
accordance with the effective Sponsor policy on study data publication. 


 
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Data generated from RBR specimens must be available for inspection upon request by 
representatives of national and local health authorities, and Sponsor monitors, 
representatives, and collaborators, as appropriate. 
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of the RBR data will become and remain the exclusive and unburdened property 
of the Sponsor, except where agreed otherwise. 
4.4.10.5 
Consent to Participate in the Research Biosample Repository 
The Informed Consent Form will contain a separate section that addresses participation 
in the RBR.  The investigator or authorized designee will explain to each patient the 
objectives, methods, and potential hazards of participation in the RBR.  Patients will be 
told that they are free to refuse to participate and may withdraw their specimens at any 
time and for any reason during the storage period.  A separate, specific signature will be 
required to document a patient's agreement to provide optional RBR specimens.  
Patients who decline to participate will not provide a separate signature. 
The investigator should document whether or not the patient has given consent to 
participate and (if applicable) the date(s) of consent, by completing the RBR Research 
Sample Informed Consent eCRF. 
In the event of an RBR participant's death or loss of competence, the participant's 
specimens and data will continue to be used as part of the RBR research. 
4.4.10.6 
Withdrawal from the Research Biosample Repository 
Patients who give consent to provide RBR specimens have the right to withdraw their 
consent at any time for any reason.  However, if RBR specimens have been tested prior 
to withdawal of consent, results from those tests will remain as part of the overall 
research data.  If a patient wishes to withdraw consent to the testing of his or her 
specimens, the investigator must inform the Medical Monitor in writing of the patient's 
wishes through use of the appropriate RBR Subject Withdrawal Form and, if the trial is 
ongoing, must enter the date of withdrawal on the RBR Research Sample Withdrawal of 
Informed Consent eCRF.  The patient will be provided with instructions on how to 
withdraw consent after the trial is closed.  A patient's withdrawal from Study GA30066 
does not, by itself, constitute withdrawal of specimens from the RBR.  Likewise, a 
patient's withdrawal from the RBR does not constitute withdrawal from Study GA30066. 
4.4.10.7 
Monitoring and Oversight 
RBR specimens will be tracked in a manner consistent with Good Clinical Practice by a 
quality-controlled, auditable, and appropriately validated laboratory information 
management system, to ensure compliance with data confidentiality as well as 
adherence to authorized use of specimens as specified in this protocol and in the 
Informed Consent Form.  Sponsor monitors and auditors will have direct access to 
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of verifying the data provided to the Sponsor.  The site will permit monitoring, audits, 
IRB/EC review, and health authority inspections by providing direct access to source 
data and documents related to the RBR samples. 
4.5 
TREATMENT, PATIENT, STUDY, AND SITE DISCONTINUATION 
4.5.1 
Study Treatment Discontinuation 
Patients must discontinue study treatment and return for a safety follow-up visit if they 
experience any of the following (see Table 3): 
• 
Requirement of any prohibited medication as defined in Section 4.3.2  
• 
Treated with accepted immunosuppressant that exceeds the maximum dose as 
defined by the protocol (see Section 4.3.1) 
• 
Combination immunosuppressant medications not allowed in the inclusion and 
exclusion criteria (see Section 4.1)  
• 
Grade > 2 AST or ALT elevation: (AST or ALT > 3 × ULN) in combination with total 
bilirubin > 2 × ULN or clinical jaundice as defined by Hy’s Law 
• 
Grade ≥ 3 AST or ALT elevation:  (AST or ALT > 5 × ULN) 
• 
Grade 4 Neutropenia:  ANC  500/mm³ 
• 
Grade 4 Lymphopenia:  ALC  200/mm³ 
• 
Grade 4 Thrombocytopenia:  platelet count  25,000/mm³ 
• 
Pregnancy 
• 
Malignancy (with the exception of non-serious local and resectable basal or 
squamous cell carcinoma of the skin) 
• 
An episode of torsades de pointes 
 
Patients must discontinue study treatment if they are receiving any treatments that are 
not specifically permitted in this protocol (see Section 4.3.1) and approved by the 
Medical Monitor.  
Investigators may discontinue study treatment for: 
• 
Any medical condition that the investigator or Sponsor determines may jeopardize 
the patient’s safety if he or she continues to receive study treatment 
• 
Investigator or Sponsor determines it is in the best interest of the patient 
• 
Patient non-compliance 
The primary reason for study treatment discontinuation should be documented on the 
appropriate eCRF.  Patients who discontinue study treatment prematurely will not be 
replaced. 
In some cases, study treatment may be resumed if approved by both the investigator 
and the Medical Monitor.   


 
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4.5.2 
Patient Discontinuation from Study 
Patients have the right to voluntarily withdraw from the study at any time for any reason.  
In addition, the investigator has the right to withdraw a patient from the study at any time.  
Reasons for withdrawal from the study may include, but are not limited to, the following: 
• 
Patient withdrawal of consent at any time 
• 
Any medical condition that the investigator or Sponsor determines may jeopardize 
the patient’s safety if he or she continues in the study 
• 
Investigator or Sponsor determines it is in the best interest of the patient 
• 
Patient non-compliance, as per Principal Investigator’s discretion 
• 
Study termination or site closure 
 
Every effort should be made to obtain information on patients who withdraw from the 
study.  The primary reason for withdrawal from the study should be documented on the 
appropriate eCRF.  However, patients will not be followed for any reason after consent 
has been withdrawn.  Patients who withdraw from the study will not be replaced. 
If a patient discontinues the study prior to the Week 48 treatment completion visit, an 
early termination visit should be conducted.  If possible, the investigator will clarify the 
following:  
• 
If the patient withdrew consent for the remaining study procedures OR  
• 
If the patient withdrew consent for the remaining study procedures as well as the 
use of all banked samples OR 
• 
If the patient withdrew consent for the remaining study procedures as well as all use 
of study acquired clinical and laboratory data 
 
These patients should return for the 8-week safety follow-up visit in this study (see 
Appendix 1).  If the patient is unable to return for a follow-up visit, the trial site may 
contact the patient by telephone to determine their clinical status.   
Patients who discontinue the study during the safety follow-up period but prior to 
completion of the 8-week safety follow-up will be asked to return to the clinic within 
30 days (± 7 days) after the last dose of study drug or last scheduled visit for an early 
termination visit. 
4.5.3 
Study Discontinuation 
The Sponsor has the right to terminate this study at any time.  Reasons for terminating 
the study may include, but are not limited to, the following: 
• 
The incidence or severity of adverse events in this or other studies indicates a 
potential health hazard to patients. 
• 
Patient enrollment is unsatisfactory. 
 
The Sponsor will notify the investigator if the Sponsor decides to discontinue the study. 


 
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4.5.4 
Site Discontinuation 
The Sponsor has the right to close a site at any time.  Reasons for closing a site may 
include, but are not limited to, the following: 
• 
Poor protocol adherence 
• 
Inaccurate or incomplete data recording 
• 
Non-compliance with the International Council for Harmonisation (ICH) guideline for 
Good Clinical Practice 
• 
No study activity (i.e., all patients have completed the study and all obligations have 
been fulfilled) 
 
5. 
ASSESSMENT OF SAFETY  
5.1 
SAFETY PLAN 
To protect patient safety, an IMC in collaboration with a Scientific Oversight Committee 
will monitor safety throughout the study (see Section 3.1.1). 
The safety risk management plan for patients in this study is based on nonclinical and 
clinical experience with GDC-0853 in completed and ongoing studies, as well as in 
published literature on other BTK inhibitors, and takes into account the population under 
study.  The important potential safety risks for GDC-0853 are outlined below.  Please 
refer to the GDC-0853 Investigator’s Brochure for a complete summary of safety 
information.   
Several measures will be taken to ensure the safety of patients participating in this study.  
Eligibility criteria have been designed to exclude patients at higher risk for potential 
toxicities.  Patients will undergo safety monitoring during the study, including monitoring 
of vital signs, physical examination, ECGs, and routine laboratory safety assessments 
(hematology, chemistry, and urinalysis) and assessment of the nature, frequency, and 
severity of adverse events.  In addition, guidelines for managing potential adverse 
events, including criteria for treatment interruption or discontinuation, and enhanced 
safety reporting are provided below and in Table 4.   
5.1.1 
Safety Plan for Potential Risks Associated with GDC-0853  
5.1.1.1 
Infections 
On the basis of the well-described phenotype of patients with XLA, a primary 
immunodeficiency of B cells and Ig production, it is anticipated that inhibitors of BTK may 
raise the risk for certain bacterial infections (Lederman and Winkelstein 1985; Broides et 
al. 2006), enteroviral infections (Misbah et al. 1992; Ziegner et al. 2002), intestinal 
infections with Giardia and Campylobacter species (Winkelstein et al. 2006; van den 
Bruele et al. 2010), or other opportunistic infections that are primarily cleared by B-cell 
adaptive immune responses.  This risk is likely independent of the patient’s sex for 
exogenously administered GDC-0853.   


 
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Unlike XLA, GDC-0853 is a reversible inhibitor of BTK that will be initiated after the 
immune system has developed, and so the degree to which GDC-0853 antagonism of 
BTK signaling may suppress immune activity or resemble XLA is unknown.  However, 
data to date suggest that since BTK inhibitors target only the kinase domain, other BTK 
activities may remain intact and IgG levels in patients with an established immune 
system may not be significantly depleted (Byrd et al. 2013).   
Effects on lymphocytes and Igs in rats and dogs were reversible and considered to be 
related to pharmacological activity involving BTK inhibition.  See Section 1.3.1 for related 
primary nonclinical toxicity findings and Section 4 of the GDC-0853 Investigator’s 
Brochure for further details.   
To date, no immune-challenge experiments (e.g., T-dependent antigen response test) 
have been conducted in animals.  It is not known if these effects on B cells and IgG 
concentrations in animals will translate to humans or if such changes would have 
functional/deleterious impact on immune function. 
Infections, including pneumonia and fatal influenza, have occurred in patients with B-cell 
malignancies treated with GDC-0853.  In studies with healthy subjects with single doses 
and with dosing for 14 days, self-limited Grade 1 events of nasopharyngitis were 
reported but did not lead to any change in study drug dosing.  One 
 subject had 
asymptomatic bacteriuria, which resolved while study drug dosing continued. 
Total Ig concentrations will be measured regularly throughout the study.  All patients in 
the study should be monitored for fever and potential infectious complications, including 
opportunistic infections and TB, and should be evaluated promptly.  Physicians or a 
health care provider should give patients advice to prevent potential transmission of and 
exposure to endemic infections according to local or CDC guidelines.  Patients should 
be advised to seek immediate medical attention if they develop signs and symptoms 
suggestive of an infection.  All infections occurring during the study that require 
treatment, including, but not limited to, respiratory infections, cutaneous infections, 
urinary tract and systemic viral infections, and episodes of suspicious or febrile diarrhea, 
should be evaluated using serology or polymerase chain reaction, if available, and 
cultured if feasible. Any identified organisms should be noted in the Adverse Event 
eCRF.  Any serious infection, any infection requiring IV antimicrobials (i.e., any Grade 3 
infection), or any opportunistic infection is considered an AESI and should be reported to 
the Sponsor in an expedited manner as outlined in Section 5.2.3. 
Guidelines for management of study treatment in the event that a patient experiences an 
infection are provided in Table 3. 
5.1.1.2 
Vaccinations 
The effect of GDC-0853 upon the efficacy of vaccinations is unknown.  It is 
recommended that appropriate vaccinations per EULAR recommendations (van Assen 


 
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et al. 2011) or local guidelines be up to date before participation in Study GA30044.  
Immunization with a live or attenuated vaccine is prohibited for the duration of study 
participation, including the safety follow-up period after the administration of the last 
dose; however, inactivated vaccine formulations are permitted (e.g., seasonal injectable 
influenza).   
In addition, current routine household contact with children or others who have been 
vaccinated with live vaccine components may pose an unknown risk to the patient during 
study treatment with GDC-0853.  Some of these vaccines include varicella (“chickenpox”) 
vaccine, oral polio vaccine, and the inhaled flu vaccine.  Following vaccination with live 
component vaccines, the virus may be shed in bodily fluids, including stool, and there is 
a potential risk that the virus may be transmitted to the patient.  
General guidelines for immunosuppressed patients suggest that exposure to vaccinated 
individuals should be avoided following vaccination with these vaccines for the stated 
time periods: 
• 
Varicella or attenuated typhoid fever vaccination for 4 weeks following vaccination 
• 
Oral polio vaccination for 6 weeks following vaccination 
• 
Attenuated rotavirus vaccine for 10 days following vaccination 
• 
FluMist (inhaled flu vaccine) for 1 week following vaccination 
 
5.1.1.3 
Bleeding 
No decrease in platelets, changes in coagulation parameters (e.g., PT/PTT), or bleeding 
events were observed in nonclinical studies with GDC-0853.  Bleeding events, including 
non-serious CTCAE Grade 1 bruising and serious Grade ≥ 3 GI bleeding, have been 
reported in patients with hematological malignancies treated with GDC-0853 in 
Study GO29089.  The GI bleeding events have not been dose related, and the events 
occurred in patients who were taking concomitant NSAIDs/acetylsalicylic acid and who 
had a history of gastroesophageal or peptic ulcer disease.  The impact of BTK inhibition 
as a potential risk factor for bleeding is unknown.  BTK is expressed in platelets and is 
involved in platelet function via GPVI/collagen−receptor signaling and GP1b−receptor 
signaling.  Platelets from patients with XLA, a genetic deficiency of BTK, demonstrate 
decreased activation in response to submaximal collagen stimulation but normal 
response to thrombin; clinically, there is no reported bleeding propensity of patients with 
XLA (Howard et al. 2006). 
Bruising or bleeding events related to GDC-0853 have not been reported in healthy 
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It is unknown if GDC-0853 will increase the risk of bleeding in patients, especially in 
those patients receiving antiplatelet or anticoagulant therapies.  As a precautionary 
safety measure, patients will be excluded from participation in the blinded 
Study GA30044 if they have a need for any of the following:  
• 
Systemic anticoagulation with warfarin or other oral or injectable anti-coagulants or 
anti-platelet agents (other than NSAIDs, aspirin, and other salicylates) 
• 
Any history of hospitalizations or transfusion for a GI bleed 
• 
Any history of a hemorrhagic cerebrovascular accident 
• 
Any history of spontaneous intracranial hemorrhage 
• 
Traumatic intracranial hemorrhage within 10 years prior to the study 
• 
Known bleeding diathesis 
 
Patients should be advised to seek immediate medical attention if they develop signs 
and symptoms suggestive of clinically significant bleeding.  
Several risk factors including patient age, comorbidities, concurrent medications, prior 
medical history, and Helicobacter pylori infection have been demonstrated in a variety of 
studies to increase the risk of NSAID-related GI injury (Lanza et al. 2009).  It is unknown 
if GDC-0853 will increase the risk of bleeding in patients receiving NSAIDs.  Therefore, 
in order to prevent NSAID-related GI complications in high-risk patients, concomitant use 
of PPI should be considered (Bhatt et al. 2008) and used according to local or 
recognized guidelines (e.g., ACCF/ACG/AHA 2008 Expert Consensus Document). 
Patients at high risk for NSAID-related GI toxicity include the following: 
• 
Patients using both aspirin and an NSAID 
• 
Patients with a history of ulcer disease 
• 
Patients with one or more of the following: 
– 
Age ≥ 60 years 
– 
High-dose NSAID use 
– 
Concurrent corticosteroid use 
– 
Dyspepsia or gastroesophageal reflux disease symptoms 
 
Any bleeding event Grade ≥ 2 is considered an AESI and should be reported to the 
Sponsor in an expedited manner as outlined in Section 5.2.3.   
Guidelines for management of study treatment in the event that bleeding is observed in 
patients are provided in Table 3. 
5.1.1.4 
Cytopenias 
Cytopenias have been observed in patients with hematological malignancies who 
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been monitorable and clinically manageable (see the GDC-0853 Investigator’s Brochure 
for further details).   
Patients should be monitored regularly with hematology laboratory evaluations as 
outlined in the schedule of activities (see Appendix 1) and should receive appropriate 
supportive care as clinically indicated.  Patients should be advised to seek immediate 
medical attention if they develop signs and symptoms suggestive of cytopenias (e.g., 
persistent fever, bruising, bleeding, pallor).  
Guidelines for the management of study treatment, including dose holding, in the event 
of cytopenias in patients are provided in Table 3.   
5.1.1.5 
Gastrointestinal Effects 
Body weight gain and food consumption changes have been observed in animals, 
including nonsignificant increases in male Wistar-Han rats administered ≥ 2 mg/kg/day 
(4.3 µM • hr) for 6 months and significant reductions in rats administered 100 mg/kg/day 
(1438 µM • hr) and dogs administered 25 mg/kg (180 µM • hr) for 4 weeks.  These effects 
on body weight gain and food consumption were reversible following discontinuation of 
GDC-0853 dosing. 
Grade 1 diarrhea, nausea, and abdominal pain have been reported in patients with 
hematological malignancies treated with GDC-0853; however, the events resolved and 
have not led to study drug discontinuation.  Healthy subjects in the MAD study 
(GA29347) reported events of mild self-limited nausea.   
Throughout the study, patients will be monitored for GI side effects, including weight 
changes.  Guidelines for management of study treatment in the event of GI side effects 
in patients are provided in Table 3.  
5.1.1.6 
Hepatotoxicity 
Evidence of hepatobiliary injury was observed in animals administered relatively high 
doses of GDC-0853 in repeat-dose toxicity studies (see Section 1.3.1 for related primary 
nonclinical toxicity findings).   
In clinical studies to date, including single dosing and multiple dosing for 14 days in 
healthy subjects and daily dosing for up to 2 years in patients with hematological 
malignancies, there have been no adverse events of liver enzyme elevations or trends 
towards elevations in laboratory evaluations.   
As a safety risk−mitigation measure, to be eligible for the blinded study GA30044, AST 
and/or ALT levels should be no more than 1.5 times the ULN and total bilirubin levels 
should be ≤ 1.2 × ULN at the Week 44 visit or later (prior to entry into Study GA30066).  
Safety monitoring for potential hepatotoxicity includes baseline and routine evaluations 
of AST/ALT and total bilirubin levels throughout the study as outlined in the schedule of 
activities (see Appendix 1).   


 
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Laboratory results of Grade ≥ 3 (> 5 × ULN) AST or ALT elevation, or ALT or AST 
elevations > 3 × ULN in combination with clinical jaundice (total bilirubin > 2 × ULN) are 
considered AESIs and should be reported to the Sponsor in an expedited manner as 
outlined in Section 5.2.3.  
Guidelines for the management of study treatment in the event of hepatotoxicity in 
patients are provided in Table 3.   
5.1.1.7 
Cardiovascular Effects 
GDC-0853 is considered to have a low potential to cause QT interval prolongation or to 
directly affect other cardiovascular parameters at therapeutic exposures.  A minimal 
increase in QTc (7 msec or 3%) interval was noted at 45 mg/kg in the single-dose 
cardiovascular safety pharmacology study in telemetry-instrumented dogs.  Based on 
extrapolated/interpolated toxicokinetic data, the unbound Cmax at 45 mg/kg (considered a 
NOAEL) 
 
  There were no GDC-0853−related changes in ECG parameters in the 
repeat-dose 4-week or 9-month dog toxicity studies.   
Analysis of ECG data from the SAD and MAD studies in healthy subjects did not 
demonstrate any significant increase in either QRS interval or QTcF intervals.  However, 
cardiac safety will continue to be evaluated in all patients at baseline and throughout the 
study, with routine monitoring of vital signs (including pulse rate and blood pressure), 
collection of routine safety ECGs, triplicate ECGs, and collection of adverse events (see 
Appendix 1). 
Management of patients with sustained QTcF prolongation (QTcF that is > 500 msec 
and/or > 60 msec longer than the baseline value [from Study GA30044] on at least two 
ECG measurements > 30 minutes apart) should include close monitoring, with ECGs 
repeated at least hourly until two successive ECGs show stabilization of the findings, 
correction of any electrolyte abnormalities, and possible discontinuation of other 
concomitant medications that are known to prolong the QT interval.  Consultation with a 
cardiologist or electrophysiologist is recommended to help in the management of such 
patients.  The Medical Monitor should be notified as soon as possible (see Section 4.4.7 
and Section 4.4.8). 
Guidelines for management of study treatment in the event of cardiovascular effects in 
patients are provided in Table 3. 
5.1.1.8 
Vascular Inflammation 
 
  The translatability of the nonclinical findings to 
humans is unknown; however, Beagle dogs are susceptible to spontaneous 
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to any drug-induced effects.  Further, there are several examples of approved therapies 
for which there is no correlation between the finding of vasculitis in dogs or rats at 
clinically relevant exposures and adverse outcomes in patients (FDA 2003; FDA 2011).   
As a safety risk−mitigation measure, CBC, creatinine, and urinalysis will be monitored in 
all patients during the study.   
Guidelines for management of study treatment in the event of a new treatment emergent 
vasculitis in patients are provided in Table 3. 
5.1.1.9 
Malignancy 
The impact of BTK inhibition on the development of malignancies is not known; however, 
malignancies have been identified as a potential concern for immunomodulatory agents.  
Malignancies have been reported in patients with XLA, including lymphoreticular 
malignancies, gastric and colorectal adenocarcinoma, and squamous cell carcinoma of 
the lung. 
All malignancies are considered AESIs for this study and should be reported to the 
Sponsor in an expedited manner as outlined in Section 5.2.3.   
Guidelines for management of study treatment in the event of malignancies in patients 
are provided in Table 3.  Please refer to the GDC-0853 Investigator’s Brochure for 
further details. 
5.1.2 
Management of Study Treatment in Patients Who Experience 
Specific Adverse Events 
Guidelines for management of GDC-0853 in patients who experience specific adverse 
events are provided in Table 3.  These guidelines do not cover all possible clinical 
scenarios; please consult the Medical Monitor when there are any questions about 
specific adverse events.  For a potential dose reduction for other adverse events not 
listed in the table, please consult the Medical Monitor.     
 


 
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Table 3 
Guidelines for Management of GDC-0853 in Patients Who 
Experience Specific Adverse Events  
Event 
Action to Be Taken a 
Infection b 
 
Serious infection or any infection 
requiring treatment with a 
prolonged oral or IV antimicrobial 
agent 
Withhold GDC-0853. Once the infection has resolved 
consult with Medical Monitor to discuss potential 
resumption of GDC-0853. 
Self-limited infections that require 
treatment 
Withhold GDC-0853 during antimicrobial therapy. 
Bleeding 
Any Grade ≥ 2 bleeding event is considered an AESI 
and should be reported to the Sponsor in an 
expedited manner. 
 
For Grade 3 or higher bleeding events or any serious 
bleeding event, withhold GDC-0853 and consult with 
the Medical Monitor.  Once the bleeding event has 
resolved, consult with Medical Monitor to discuss the 
potential resumption of GDC-0853. 
Neutropenia c 
 
Grade 2:  ANC >1000−1500/mm3 
Maintain GDC-0853 dosing. 
Grade 3:  ANC 500−1000/mm3 
For the first occurrence of a Grade 3 neutrophil 
count decreased, withhold GDC-0853 and recheck the 
CBC in 7 days.  If the neutrophil count has recovered 
to Grade 1 (> 1500/mm3) or baseline, resume dosing 
at 200 mg BID unless there is a concurrent serious or 
Grade 3 infection.  If still at Grade 2 (1000−1500/mm3) 
and above baseline, consult with the Medical Monitor 
regarding further dosing instructions.  If the Grade 3 
neutropenia persists, discontinue GDC-0853. 
For the second occurrence of Grade 3 neutrophil 
count decreased, withhold GDC-0853 and recheck the 
CBC in 7 days.  If the neutrophil count has recovered 
to Grade 1 (> 1500/mm3) or baseline, restart 
GDC-0853 at the lower dose of 200 mg QD for 1 week 
and recheck CBC after 1 week at the lower dose.  If at 
Grade 2 (1000−1500/mm3) and below baseline, 
consult with the Medical Monitor regarding further 
dosing instructions.  If the Grade 3 neutrophil count 
persists, discontinue GDC-0853. 
For the third occurrence of Grade 3 neutrophil count 
decreased, withhold GDC-0853 and confirm.  If 
Grade 3 neutrophil count decreased is confirmed, 
discontinue GDC-0853. 
Grade 4:  ANC  500/mm3 
Withhold GDC-0853 and confirm.  If Grade 4 
neutrophil count decreased is confirmed, discontinue 
GDC-0853. 
 


 
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Table 3 
Guidelines for Management of GDC-0853 in Patients Who 
Experience Specific Adverse Events (cont.) 
 
Event 
Action to Be Taken a 
Treatment emergent Grade 2 
lymphopenia: lymphocyte count 
500−800/mm³ 
Maintain study treatment dosing unless concurrent active 
infection or other clinical concern. 
Treatment emergent Grade 3 
lymphopenia: lymphocyte count 
200−500/mm³ 
For the first occurrence of treatment emergent Grade 3 
lymphopenia, withhold GDC-0853 and recheck CBC in 
7 days.  If lymphocyte count has recovered to >500/mm3 
(Grade 2 or less severe), resume study treatment unless 
there is a concurrent serious or Grade 3 infection.  If 
Grade 3 lymphopenia persists, discuss with the Medical 
Monitor. 
For the second occurrence of Grade 3 lymphopenia, 
withhold GDC-0853 and recheck CBC in 7 days.  If 
lymphocyte count has recovered to > 500/mm3 (Grade 2 or 
less severe), restart GDC 0853 at the lower dose of 
200 mg QD for one week and recheck CBC.  If still at 
 800/mm3 (Grade 2 or more severe), consult with medical 
monitor regarding further dosing instructions. 
For the third occurrence of Grade 3 lymphopenia, 
withhold GDC-0853 and confirm.  If Grade 3 lymphopenia 
is confirmed, discontinue GDC-0853. 
Grade 4 Lymphopenia: 
lymphocyte count  200/mm³ 
Withhold GDC-0853 and confirm.  If Grade 4 lymphopenia 
is confirmed, discontinue GDC-0853. 
Thrombocytopenia d 
 
Treatment Emergent Grade 1:  
PLT > 75,000/mm3 
In the absence of bleeding event(s), maintain GDC-0853 
dosing. 
Treatment emergent Grade 2:  
PLT 50,000−75,000/mm3 
For the first occurrence, in the absence of SLE flare, 
hold GDC-0853 and recheck CBC in 7 days.  If platelet 
count has recovered to > 75,000/mm3 or to baseline, 
resume GDC-0853.  If platelet count remains 
  75,000/mm3, discuss with the Medical Monitor and 
consider reducing GDC-0853 dose to 200 mg QD. 
For recurrence in the absence of bleeding events, 
discuss with the Medical Monitor and consider reducing 
GDC-0853 dose to 200 mg QD. 
Grade > 3:  PLT  50,000/mm3 
For the first occurrence, in the absence of SLE flare, 
hold GDC-0853 and recheck platelets in 7 days.  If platelet 
count has recovered to baseline or above 75,000/mm3 
(Grade 1), resume study treatment.  If platelet count has 
recovered to 50,000−75,000/mm3 (and this is not baseline) 
in the absence of bleeding events, consider reducing 
GDC-0853 dose to 200 mg QD for 1 week and recheck 
platelets.  If still at  75,000/mm3, consult with Medical 
Monitor regarding further dosing instructions.  For further 
occurrences or persistent Grade 3 treatment-emergent 
thrombocytopenia in the absence of SLE flare, after 
withholding or dose-reducing GDC-0853, and in the 
absence of bleeding events, discuss with the Medical 
Monitor or discontinue study treatment.  
Grade 4:  PLT < 25,000/mm³ 
Discontinue GDC-0853. 
 


 
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Table 3 
Guidelines for Management of GDC-0853 in Patients Who 
Experience Specific Adverse Events (cont.) 
 
Event 
Action to Be Taken a 
Gastrointestinal effects 
 
Nausea, vomiting, and/or diarrhea 
Manage according to site institutional guidelines.  
Consider administration of GDC-0853 with food as 
possible mitigation strategy. 
Consider reducing GDC-0853 dose to 200 mg QD and 
discuss with Medical Monitor.   
Malignancy 
 
Any malignancy (with the 
exception of non-serious local 
and resectable basal or 
squamous cell carcinoma of the 
skin) 
Discontinue GDC-0853.  Report event as an AESI to 
the Sponsor in an expedited manner. 
Hepatotoxicity 
 
Any AST or ALT > 3.0−5.0 × ULN  
Withhold GDC-0853 and consult with the Medical 
Monitor. 
AST or ALT elevation  > 3 × ULN in 
combination with total bilirubin 
> 2 × ULN, of which at least 35% is 
direct bilirubin, or clinical jaundice  
Discontinue GDC-0853 and consult with the Medical 
Monitor.  Recheck liver laboratory tests, including 
AST/ALT, ALP, and total bilirubin, and CBC with 
differential (to determine eosinophil count), within 
1 week (preferably within 72 hours).  Assess patient for 
signs/symptoms of hepatic failure and for other causes 
of liver dysfunction (e.g. viral hepatitis, concomitant 
medications, etc.).  Continue to monitor liver function 
tests until abnormalities resolve.  Report Hy’s Law 
cases as AESI to the Sponsor in an expedited manner. 
Any AST or ALT > 5 × ULN 
Discontinue GDC-0853 and consult with the Medical 
Monitor.  Recheck liver laboratory tests, including 
AST/ALT, ALP, and total bilirubin, and CBC with 
differential (to determine eosinophil count), within 
1 week (preferably within 72 hours).  Assess patient for 
signs/symptoms of hepatic failure and for other causes 
of liver dysfunction (e.g., viral hepatitis, concomitant 
medications).  Continue to monitor liver function tests 
until abnormalities resolve. Elevations of AST or ALT of 
> 5 × ULN should be reported as AESIs to the Sponsor 
in an expedited manner. 
Cardiovascular effects  
 
Sustained (at least two ECG 
measurements > 30 minutes apart) 
QTcF that is > 500 msec and/or 
> 60 msec longer than the baseline 
value 
Unless there is a clear alternative cause other than 
study drug, discontinue GDC-0853. e 
 


 
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Table 3 
Guidelines for Management of GDC-0853 in Patients Who 
Experience Specific Adverse Events (cont.) 
 
Event 
Action to Be Taken a 
Sustained absolute QTcF that is 
> 515 msec 
Unless there is a clear alternative cause other than 
study drug, discontinue GDC-0853. e 
An episode of torsades de pointes 
or a new ECG finding of clinical 
concern 
Discontinue GDC-0853. e 
Vascular Inflammation 
 
Vasculitis 
Consult with the Medical Monitor.  
AESI = adverse event of special interest; BID = twice a day; PLT = platelet count; QD = once a 
day; QTcF = QT interval corrected using Fridericia’s formula; SLE = systemic lupus 
erythematosus; ULN = upper limit of normal. 
a Any patient who discontinues GDC-0853 should enter safety follow-up if possible. 
b Appropriate laboratory investigations, including, but not limited to, cultures, should be 
performed to establish the etiology of any serious infection.   
c Patients withdrawn from the study because of a reduced neutrophil count must be 
followed closely for signs of infection, with treatment as deemed appropriate by the 
investigator, and must have a repeat WBC count with differential performed weekly until 
the ANC is above 1000 cells/mm³ (1.0 × 109/L).  If the ANC does not return to above 
1000 cells/mm³ (1.0 × 109/L) within 2 months (or sooner if deemed necessary by the 
investigator), a hematology referral is recommended. 
d Patients withdrawn from the study because of a reduced platelet count must have a 
repeat platelet count weekly until the count is above 50,000 cells/mm³ (50 × 109/L); 
additional management and treatment should be as deemed appropriate by the 
investigator.   
e In rare circumstances, it may be acceptable to resume GDC-0853, provided that any ECG 
abnormalities have resolved and that the patient is appropriately monitored.  Clinical 
judgment should be applied and discussion with the Medical Monitor should occur. 
 
5.2 
SAFETY PARAMETERS AND DEFINITIONS 
Safety assessments will consist of monitoring and recording adverse events, including 
serious adverse events and adverse events of special interest, performing 
protocol-specified safety laboratory assessments, measuring protocol-specified vital 
signs, and conducting other protocol-specified tests that are deemed critical to the safety 
evaluation of the study. 
Certain types of events require immediate reporting to the Sponsor, as outlined in 
Section 5.4.  


 
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5.2.1 
Adverse Events 
According to the ICH guideline for Good Clinical Practice, an adverse event is any 
untoward medical occurrence in a clinical investigation subject administered a 
pharmaceutical product, regardless of causal attribution.  An adverse event can 
therefore be any of the following: 
• 
Any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product 
• 
Any new disease or exacerbation of an existing disease (a worsening in the 
character, frequency, or severity of a known condition), except as described in 
Section 5.3.5.9.   
• 
Recurrence of an intermittent medical condition (e.g., headache) not present at 
baseline 
• 
Any deterioration in a laboratory value or other clinical test (e.g., ECG, X-ray) that is 
associated with symptoms or leads to a change in study treatment or concomitant 
treatment or discontinuation from study drug 
• 
Adverse events that are related to a protocol-mandated intervention, including those 
that occur prior to assignment of study treatment (e.g., screening invasive 
procedures such as biopsies) 
 
5.2.2 
Serious Adverse Events (Immediately Reportable to the 
Sponsor) 
A serious adverse event is any adverse event that meets any of the following criteria: 
• 
Is fatal (i.e., the adverse event actually causes or leads to death) 
• 
Is life threatening (i.e., the adverse event, in the view of the investigator, places the 
patient at immediate risk of death) 
This does not include any adverse event that had it occurred in a more severe 
form or was allowed to continue might have caused death. 
• 
Requires or prolongs inpatient hospitalization (see Section 5.3.5.10) 
• 
Results in persistent or significant disability/incapacity (i.e., the adverse event 
results in substantial disruption of the patient’s ability to conduct normal life 
functions) 
• 
Is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to 
study drug 
• 
Is a significant medical event in the investigator's judgment (e.g., may jeopardize the 
patient or may require medical/surgical intervention to prevent one of the outcomes 
listed above) 
 
The terms "severe" and "serious" are not synonymous.  Severity refers to the intensity of 
an adverse event (e.g., rated as mild, moderate, or severe, or according to NCI CTCAE; 


 
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see Section 5.3.3); the event itself may be of relatively minor medical significance (such 
as severe headache without any further findings). 
Severity and seriousness need to be independently assessed for each adverse event 
recorded on the eCRF. 
Serious adverse events are required to be reported by the investigator to the Sponsor 
immediately (i.e., no more than 24 hours after learning of the event; see Section 5.4.2 for 
reporting instructions). 
5.2.3 
Adverse Events of Special Interest (Immediately Reportable to 
the Sponsor) 
AESIs are required to be reported by the investigator to the Sponsor immediately 
(i.e., no more than 24 hours after learning of the event; see Section 5.4.2 for reporting 
instructions).  AESIs for this study include the following: 
AESIs for GDC-0853 
• 
Any serious infection, any infections requiring IV antimicrobials and any 
opportunistic infections 
• 
Any bleeding event Grade 2 or above 
• 
All malignancies 
• 
A laboratory result of Grade ≥ 3 (i.e., > 5 × ULN) AST or ALT elevation 
 
AESIs for General Drug Development 
• 
Cases of potential drug-induced liver injury that include an elevated ALT or AST in 
combination with either an elevated bilirubin or clinical jaundice, as defined by Hy’s 
Law (see Section 5.3.5.6) 
• 
Suspected transmission of an infectious agent by the study drug, as defined below: 
Any organism, virus, or infectious particle (e.g., prion protein transmitting 
transmissible spongiform encephalopathy), pathogenic or non-pathogenic, is 
considered an infectious agent.  A transmission of an infectious agent may be 
suspected from clinical symptoms or laboratory findings that indicate an 
infection in a patient exposed to a medicinal product.  This term applies only 
when a contamination of the study drug is suspected. 
 
5.3 
METHODS AND TIMING FOR CAPTURING AND ASSESSING 
SAFETY PARAMETERS 
The investigator is responsible for ensuring that all adverse events (see Section 5.2.1 for 
definition) are recorded on the Adverse Event eCRF and reported to the Sponsor in 
accordance with instructions provided in this section and in Sections 5.4−Section 5.6.   


 
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For each adverse event recorded on the Adverse Event eCRF, the investigator will make 
an assessment of seriousness (see Section 5.2.2 for seriousness criteria), severity (see 
Section 5.3.3), and causality (see Section 5.3.4).   
5.3.1 
Adverse Event Reporting Period 
Investigators will seek information on adverse events at each patient contact.  All 
adverse events, whether reported by the patient or noted by study personnel, will be 
recorded in the patient’s medical record and on the Adverse Event eCRF. 
After informed consent has been obtained but prior to initiation of study drug, only 
serious adverse events caused by a protocol-mandated intervention (e.g., invasive 
procedures such as biopsies, discontinuation of medications) should be reported 
(see Section 5.4.2 for instructions for reporting serious adverse events). 
After initiation of study drug, all adverse events will be reported until 8 weeks after the 
last dose of study drug the patient receives. 
Instructions for reporting adverse events that occur after the adverse event reporting 
period are provided in Section 5.6. 
5.3.2 
Eliciting Adverse Event Information 
A consistent methodology of non-directive questioning should be adopted for eliciting 
adverse event information at all patient evaluation timepoints.  Examples of non-directive 
questions include the following: 
"How have you felt since your last clinic visit?" 
"Have you had any new or changed health problems since you were last here?"  
 
5.3.3 
Assessment of Severity of Adverse Events 
The adverse event severity grading scale for the NCI CTCAE (v4.0) will be used for 
assessing adverse event severity.  Table 4 will be used for assessing severity for 
adverse events that are not specifically listed in the NCI CTCAE. 


 
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Table 4 
Adverse Event Severity Grading Scale for Events Not Specifically 
Listed in NCI CTCAE 
Grade 
Severity 
1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
or intervention not indicated 
2 
Moderate; minimal, local, or non-invasive intervention indicated; or limiting 
age-appropriate instrumental activities of daily living a 
3 
Severe or medically significant, but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; or 
limiting self-care activities of daily living b, c 
4 
Life-threatening consequences or urgent intervention indicated d 
5 
Death related to adverse event d 
NCI CTCAE = National Cancer Institute Common Terminology Criteria for Adverse Events. 
Note:  Based on the most recent version of NCI CTCAE (v4.0), which can be found at:   
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm 
a Instrumental activities of daily living refer to preparing meals, shopping for groceries or 
clothes, using the telephone, managing money, etc. 
b Examples of self-care activities of daily living include bathing, dressing and undressing, 
feeding oneself, using the toilet, and taking medications, as performed by patients who are 
not bedridden. 
c If an event is assessed as a "significant medical event," it must be reported as a serious 
adverse event (see Section 5.4.2 for reporting instructions), per the definition of serious 
adverse event in Section 5.2.2. 
d Grade 4 and 5 events must be reported as serious adverse events (see Section 5.4.2 for 
reporting instructions), per the definition of serious adverse event in Section 5.2.2. 
  
5.3.4 
Assessment of Causality of Adverse Events 
Investigators should use their knowledge of the patient, the circumstances surrounding 
the event, and an evaluation of any potential alternative causes to determine whether an 
adverse event is considered to be related to the study drug, indicating "yes" or "no" 
accordingly.  The following guidance should be taken into consideration (see also 
Table 5): 
• 
Temporal relationship of event onset to the initiation of study drug 
• 
Course of the event, with special consideration of the effects of dose reduction, 
discontinuation of study drug, or reintroduction of study drug (as applicable) 
• 
Known association of the event with the study drug or with similar treatments 
• 
Known association of the event with the disease under study 
• 
Presence of risk factors in the patient or use of concomitant medications known to 
increase the occurrence of the event 
• 
Presence of non-treatment-related factors that are known to be associated with the 
occurrence of the event 
 


 
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Table 5 
Causal Attribution Guidance 
Is the adverse event suspected to be caused by the study drug on the basis of facts, evidence, 
science-based rationales, and clinical judgment? 
YES 
There is a plausible temporal relationship between the onset of the adverse event and 
administration of the study drug, and the adverse event cannot be readily explained by 
the patient's clinical state, intercurrent illness, or concomitant therapies; and/or the 
adverse event follows a known pattern of response to the study drug; and/or the 
adverse event abates or resolves upon discontinuation of the study drug or dose 
reduction and, if applicable, reappears upon re-challenge. 
NO 
An adverse event will be considered related, unless it fulfills the criteria specified below.   
Evidence exists that the adverse event has an etiology other than the study drug 
(e.g., preexisting medical condition, underlying disease, intercurrent illness, 
or concomitant medication); and/or the adverse event has no plausible temporal 
relationship to administration of the study drug (e.g., cancer diagnosed 2 days after 
first dose of study drug). 
 
For patients receiving combination therapy, causality will be assessed individually for 
each protocol-mandated therapy. 
5.3.5 
Procedures for Recording Adverse Events 
Investigators should use correct medical terminology/concepts when recording adverse 
events on the Adverse Event eCRF.  Avoid colloquialisms and abbreviations. 
Only one adverse event term should be recorded in the event field on the Adverse Event 
eCRF. 
5.3.5.1 
Diagnosis versus Signs and Symptoms 
A diagnosis (if known) should be recorded on the Adverse Event eCRF rather than 
individual signs and symptoms (e.g., record only liver failure or hepatitis rather than 
jaundice, asterixis, and elevated transaminases).  However, if a constellation of signs 
and/or symptoms cannot be medically characterized as a single diagnosis or syndrome 
at the time of reporting, each individual event should be recorded on the Adverse Event 
eCRF.  If a diagnosis is subsequently established, all previously reported adverse events 
based on signs and symptoms should be nullified and replaced by one adverse event 
report based on the single diagnosis, with a starting date that corresponds to the starting 
date of the first symptom of the eventual diagnosis. 
5.3.5.2 
Adverse Events That Are Secondary to Other Events 
In general, adverse events that are secondary to other events (e.g., cascade events or 
clinical sequelae) should be identified by their primary cause, with the exception of 
severe or serious secondary events.  A medically significant secondary adverse event 
that is separated in time from the initiating event should be recorded as an independent 
event on the Adverse Event eCRF.  For example: 
• 
If vomiting results in mild dehydration with no additional treatment in a healthy adult, 
only vomiting should be reported on the eCRF. 


 
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• 
If vomiting results in severe dehydration, both events should be reported separately 
on the eCRF. 
• 
If a severe GI hemorrhage leads to renal failure, both events should be reported 
separately on the eCRF. 
• 
If dizziness leads to a fall and consequent fracture, all three events should be 
reported separately on the eCRF. 
• 
If neutropenia is accompanied by an infection, both events should be reported 
separately on the eCRF. 
 
All adverse events should be recorded separately on the Adverse Event eCRF if it is 
unclear as to whether the events are associated. 
5.3.5.3 
Persistent or Recurrent Adverse Events 
A persistent adverse event is one that extends continuously, without resolution, between 
patient evaluation timepoints.  Such events should only be recorded once on the 
Adverse Event eCRF.  The initial severity (intensity or grade) of the event will be 
recorded at the time the event is first reported.  If a persistent adverse event becomes 
more severe, the most extreme severity should also be recorded on the Adverse Event 
eCRF.  If the event becomes serious, it should be reported to the Sponsor immediately 
(i.e., no more than 24 hours after learning that the event became serious; see 
Section 5.4.2 for reporting instructions).  The Adverse Event eCRF should be updated 
by changing the event from "non-serious" to "serious," providing the date that the event 
became serious, and completing all data fields related to serious adverse events. 
A recurrent adverse event is one that resolves between patient evaluation timepoints 
and subsequently recurs.  Each recurrence of an adverse event should be recorded as a 
separate event on the Adverse Event eCRF. 
5.3.5.4 
Abnormal Laboratory Values 
Not every laboratory abnormality qualifies as an adverse event.  A laboratory test result 
must be reported as an adverse event if it meets any of the following criteria: 
• 
Is accompanied by clinical symptoms 
• 
Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation) 
• 
Results in a medical intervention (e.g., potassium supplementation for hypokalemia) 
or a change in concomitant therapy 
• 
Is clinically significant in the investigator’s judgment  
 
It is the investigator’s responsibility to review all laboratory findings.  Medical and 
scientific judgment should be exercised in deciding whether an isolated laboratory 
abnormality should be classified as an adverse event. 


 
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If a clinically significant laboratory abnormality is a sign of a disease or syndrome 
(e.g., ALP and bilirubin 5 × ULN associated with cholestasis), only the diagnosis 
(i.e., cholestasis) should be recorded on the Adverse Event eCRF. 
If a clinically significant laboratory abnormality is not a sign of a disease or syndrome, 
the abnormality itself should be recorded on the Adverse Event eCRF, along with a 
descriptor indicating whether the test result is above or below the normal range 
(e.g., "elevated potassium," as opposed to "abnormal potassium").  If the laboratory 
abnormality can be characterized by a precise clinical term per standard definitions, the 
clinical term should be recorded as the adverse event.  For example, an elevated serum 
potassium level of 7.0 mEq/L should be recorded as "hyperkalemia." 
Observations of the same clinically significant laboratory abnormality from visit to visit 
should only be recorded once on the Adverse Event eCRF (see Section 5.3.5.3 for 
details on recording persistent adverse events). 
5.3.5.5 
Abnormal Vital Sign Values 
Not every vital sign abnormality qualifies as an adverse event.  A vital sign result must 
be reported as an adverse event if it meets any of the following criteria: 
• 
Is accompanied by clinical symptoms 
• 
Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation) 
• 
Results in a medical intervention or a change in concomitant therapy 
• 
Is clinically significant in the investigator’s judgment  
 
It is the investigator’s responsibility to review all vital sign findings.  Medical and scientific 
judgment should be exercised in deciding whether an isolated vital sign abnormality 
should be classified as an adverse event. 
If a clinically significant vital sign abnormality is a sign of a disease or syndrome 
(e.g., high blood pressure), only the diagnosis (i.e., hypertension) should be recorded on 
the Adverse Event eCRF. 
Observations of the same clinically significant vital sign abnormality from visit to visit 
should only be recorded once on the Adverse Event eCRF (see Section  5.3.5.3 for 
details on recording persistent adverse events). 


 
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5.3.5.6 
Abnormal Liver Function Tests 
The finding of an elevated ALT or AST (> 3 × ULN) in combination with either an elevated 
total bilirubin (> 2 × ULN) or clinical jaundice in the absence of cholestasis or other 
causes of hyperbilirubinemia is considered to be an indicator of severe liver injury (as 
defined by Hy's Law).  Therefore, investigators must report as an adverse event the 
occurrence of either of the following: 
• 
Treatment-emergent ALT or AST > 3 × ULN in combination with total bilirubin 
> 2 × ULN 
• 
Treatment-emergent ALT or AST > 3 × ULN in combination with clinical jaundice 
 
The finding of an elevation in ALT or AST (> 5 × ULN), even in the absence of elevation 
of total bilirubin (> 2 × ULN) or clinical jaundice, is considered an AESI and subject to 
expedited reporting requirements. 
The most appropriate diagnosis or (if a diagnosis cannot be established) the abnormal 
laboratory values should be recorded on the Adverse Event eCRF (see Section 5.3.5.4) 
and reported to the Sponsor immediately (i.e., no more than 24 hours after learning of 
the event), either as a serious adverse event or an AESI (see Section 5.4.2). 
5.3.5.7 
Deaths 
All deaths that occur during the protocol-specified adverse event reporting period (see 
Section 5.3.1), regardless of relationship to study drug, must be recorded on the 
Adverse Event eCRF and immediately reported to the Sponsor (see Section 5.4.2).  This 
includes death attributed to progression of lupus. 
Death should be considered an outcome and not a distinct event.  The event or condition 
that caused or contributed to the fatal outcome should be recorded as the single medical 
concept on the Adverse Event eCRF.  Generally, only one such event should be 
reported.  If the cause of death is unknown and cannot be ascertained at the time of 
reporting, "unexplained death" should be recorded on the Adverse Event eCRF.  If the 
cause of death later becomes available (e.g., after autopsy), "unexplained death" should 
be replaced by the established cause of death.  The term "sudden death" should not be 
used unless combined with the presumed cause of death (e.g., "sudden cardiac death"). 
If the death is attributed to progression of lupus, refer to the eCRF reporting guidelines 
for recording onto the Adverse Event eCRF.   
Deaths that occur after the adverse event reporting period should be reported as 
described in Section 5.6. 
5.3.5.8 
Preexisting Medical Conditions 
A preexisting medical condition is one that is present at the screening visit for the parent 
Study GA30044.  Such conditions should be recorded on the General Medical History 
and Baseline Conditions eCRF. 


 
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A preexisting medical condition should be recorded as an adverse event only if the 
frequency, severity, or character of the condition worsens during the study.  When 
recording such events on the Adverse Event eCRF, it is important to convey the concept 
that the preexisting condition has changed by including applicable descriptors 
(e.g., "more frequent headaches"). 
5.3.5.9 
Lack of Efficacy or Worsening of Lupus 
Medical occurrences or symptoms of deterioration that are anticipated as part of lupus 
should be recorded as an adverse event if judged by the investigator to have 
unexpectedly worsened in severity or frequency or changed in nature at any time during 
the study.  When recording an unanticipated worsening of lupus on the Adverse Event 
eCRF, it is important to convey the concept that the condition has changed by including 
applicable descriptors. 
5.3.5.10 
Hospitalization or Prolonged Hospitalization 
Any adverse event that results in hospitalization (i.e., inpatient admission to a hospital) 
or prolonged hospitalization should be documented and reported as a serious adverse 
event (per the definition of serious adverse event in Section 5.2.2), except as outlined 
below.   
An event that leads to hospitalization under the following circumstances should not be 
reported as an adverse event or a serious adverse event: 
• 
Hospitalization for respite care 
• 
Hospitalization for a preexisting condition, provided that all of the following criteria 
are met: 
The hospitalization was planned prior to the study or was scheduled during the 
study when elective surgery became necessary because of the expected 
normal progression of the disease 
The patient has not experienced an adverse event 
 
An event that leads to hospitalization under the following circumstances is not 
considered to be a serious adverse event, but should be reported as an adverse event 
instead: 
• 
Hospitalization that was necessary because of patient requirement for outpatient 
care outside of normal outpatient clinic operating hours 
 
5.3.5.11 
Adverse Events Associated with an Overdose or Error in Drug 
Administration 
An overdose is the accidental or intentional use of a drug in an amount higher than the 
dose being studied.  An overdose or incorrect administration of study treatment is not itself 
an adverse event, but it may result in an adverse event.  All adverse events associated with 
an overdose or incorrect administration of study drug should be recorded on the Adverse 
Event eCRF.  If the associated adverse event fulfills seriousness criteria, the event should 


 
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be reported to the Sponsor immediately (i.e., no more than 24 hours after learning of the 
event; see Section 5.4.2).  No safety data related to overdosing of GDC-0853 are available. 
5.3.5.12 
Patient-Reported Outcome Data 
Adverse event reports will not be derived from PRO data by the Sponsor, and safety 
analyses will not be performed using PRO data.  However, if any PRO responses 
suggestive of a possible adverse event are identified during site review of the PRO data, 
the investigator will determine whether the criteria for an adverse event have been met 
and, if so, will report the event on the Adverse Event eCRF. 
5.4 
IMMEDIATE REPORTING REQUIREMENTS FROM 
INVESTIGATOR TO SPONSOR 
Certain events require immediate reporting to allow the Sponsor to take appropriate 
measures to address potential new risks in a clinical trial.  The investigator must report 
such events to the Sponsor immediately; under no circumstances should reporting take 
place more than 24 hours after the investigator learns of the event.  The following is a list 
of events that the investigator must report to the Sponsor within 24 hours after learning 
of the event, regardless of relationship to study drug: 
• 
Serious adverse events (see Section 5.4.2 for further details) 
• 
AESIs (see Section 5.4.2 for further details) 
• 
Pregnancies (see Section 5.4.3 for further details) 
 
The investigator must report new significant follow-up information for these events to the 
Sponsor immediately (i.e., no more than 24 hours after becoming aware of the 
information).  New significant information includes the following: 
• 
New signs or symptoms or a change in the diagnosis 
• 
Significant new diagnostic test results 
• 
Change in causality based on new information 
• 
Change in the event’s outcome, including recovery 
• 
Additional narrative information on the clinical course of the event 
 
Investigators must also comply with local requirements for reporting serious adverse 
events to the local health authority and IRB/EC. 
5.4.1 
Emergency Medical Contacts 
Medical Monitor Contact Information  
Genentech Medical Monitor contact information for all sites: 
Medical Monitor: 
, M.D. 
Telephone No: 
, U.S.) 
 


 
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 Medical Monitor contact information: 
Medical Monitor: 
, M.D. 
Telephone No.: 
(
, Argentina) 
 
Emergency Telephone Nos.  
 
 
  
5.4.2 
Reporting Requirements for Serious Adverse Events and 
Adverse Events of Special Interest 
5.4.2.1 
Events That Occur prior to Study Drug Initiation 
After informed consent has been obtained but prior to initiation of study drug, only 
serious adverse events caused by a protocol-mandated intervention should be reported.  
The Serious Adverse Event/Adverse Event of Special Interest Reporting Form provided 
to investigators should be completed and submitted to the Sponsor or its designee 
immediately (i.e., no more than 24 hours after learning of the event), either by faxing or 
by scanning and emailing the form using the fax number or email address provided to 
investigators. 
5.4.2.2 
Events That Occur after Study Drug Initiation 
After initiation of study drug, serious adverse events and AESIs will be reported until 
8 weeks after the last dose of study drug the patients receives either in Study GA30044 
or in this study.  Investigators should record all case details that can be gathered 
immediately (i.e., within 24 hours after learning of the event) on the Adverse Event eCRF 
and submit the report via the electronic data capture (EDC) system.  A report will be 
generated and sent to Safety Risk Management by the EDC system. 
In the event that the EDC system is unavailable, the paper Clinical Trial Serious Adverse 
Event/Adverse Event of Special Interest Reporting Form provided to investigators should 
be completed and submitted to the Sponsor or its designee immediately (i.e., no more 
than 24 hours after learning of the event), either by faxing or by scanning and emailing 
the form using the fax number or email address provided to investigators.  Once the 
EDC system is available, all information will need to be entered and submitted via the 
EDC system.   
Instructions for reporting serious adverse events that occur after the last dose of study 
treatment are provided in Section 5.6. 
5.4.3 
Reporting Requirements for Pregnancies 
5.4.3.1 
Pregnancies in Female Patients 
Female patients of childbearing potential will be instructed to immediately inform the 
investigator if they become pregnant during the study or within 8 weeks after the last 
dose of study drug.  A paper Clinical Trial Pregnancy Reporting Form should be 
completed and submitted to the Sponsor or its designee immediately (i.e., no more than 


 
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24 hours after learning of the pregnancy), either by faxing or by scanning and emailing 
the form using the fax number or email address provided to investigators.  Pregnancy 
should not be recorded on the Adverse Event eCRF.  The investigator should 
discontinue study drug and counsel the patient, discussing the risks of the pregnancy 
and the possible effects on the fetus.  Monitoring of the patient should continue until 
conclusion of the pregnancy.  Any serious adverse events associated with the 
pregnancy (e.g., an event in the fetus, an event in the mother during or after the 
pregnancy, or a congenital anomaly/birth defect in the child) should be reported on the 
Adverse Event eCRF.  In addition, the investigator will submit a Clinical Trial Pregnancy 
Reporting Form when updated information on the course and outcome of the pregnancy 
becomes available.   
5.4.3.2 
Pregnancies in Female Partners of Male Patients 
Male patients will be instructed through the Informed Consent Form to immediately 
inform the investigator if their partner becomes pregnant during the study or within 
120 days (4 months) after the last dose of study drug.  A paper Clinical Trial Pregnancy 
Reporting Form should be completed and submitted to the Sponsor or its designee 
immediately (i.e., no more than 24 hours after learning of the pregnancy), either by 
faxing or by scanning and emailing the form using the fax number or email address 
provided to investigators.  Attempts should be made to collect and report details of the 
course and outcome of any pregnancy in the partner of a male patient exposed to study 
drug.  The pregnant partner will need to sign an Authorization for Use and Disclosure of 
Pregnancy Health Information to allow for follow-up on her pregnancy.  After the 
authorization has been signed, the investigator will submit a Clinical Trial Pregnancy 
Reporting Form when updated information on the course and outcome of the pregnancy 
becomes available.  An investigator who is contacted by the male patient or his pregnant 
partner may provide information on the risks of the pregnancy and the possible effects 
on the fetus, to support an informed decision in cooperation with the treating physician 
and/or obstetrician. 
5.4.3.3 
Congenital Anomalies/Birth Defects and Abortions 
Any congenital anomaly/birth defect in a child born to a female patient exposed to study 
drug or the female partner of a male patient exposed to study drug should be classified 
as a serious adverse event, recorded on the Adverse Event eCRF, and reported to the 
Sponsor immediately (i.e., no more than 24 hours after learning of the event; see 
Section 5.4.2).  Any abortion should be reported in the same fashion (as the Sponsor 
considers abortions to be medically significant). 
5.5 
FOLLOW-UP OF PATIENTS AFTER ADVERSE EVENTS 
5.5.1 
Investigator Follow-Up 
The investigator should follow each adverse event until the event has resolved to baseline 
grade or better, the event is assessed as stable by the investigator, the patient is lost to 
follow-up, or the patient withdraws consent.  Every effort should be made to follow all 


 
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serious adverse events considered to be related to study drug or trial-related procedures 
until a final outcome can be reported. 
During the study period, resolution of adverse events (with dates) should be documented 
on the Adverse Event eCRF and in the patient’s medical record to facilitate source data 
verification. 
All pregnancies reported during the study should be followed until pregnancy outcome. 
5.5.2 
Sponsor Follow-Up 
For serious adverse events, adverse events of special interest, and pregnancies, the 
Sponsor or a designee may follow up by telephone, fax, email, and/or a monitoring visit 
to obtain additional case details and outcome information (e.g., from hospital discharge 
summaries, consultant reports, autopsy reports) in order to perform an independent 
medical assessment of the reported case. 
5.6 
ADVERSE EVENTS THAT OCCUR AFTER THE ADVERSE 
EVENT REPORTING PERIOD 
The Sponsor should be notified if the investigator becomes aware of any serious 
adverse event that occurs after the end of the adverse event reporting period (defined as 
8 weeks after the last dose of study drug the patient receives), if the event is believed to 
be related to prior study drug treatment.  These events should be reported through use 
of the Adverse Event eCRF.  However, if the EDC system is not available, the 
investigator should report these events directly to the Sponsor or its designee, either by 
faxing or by scanning and emailing the paper Clinical Trial Serious Adverse 
Event/Adverse Event of Special Interest Reporting Form using the fax number or email 
address provided to investigators. 
5.7 
EXPEDITED REPORTING TO HEALTH AUTHORITIES, 
INVESTIGATORS, INSTITUTIONAL REVIEW BOARDS, AND 
ETHICS COMMITTEES 
The Sponsor will promptly evaluate all serious adverse events and adverse events of 
special interest against cumulative product experience to identify and expeditiously 
communicate possible new safety findings to investigators, IRBs, ECs, and applicable 
health authorities based on applicable legislation. 
To determine reporting requirements for single adverse event cases, the Sponsor will 
assess the expectedness of these events using the GDC-0853 Investigator’s Brochure. 
 
The Sponsor will compare the severity of each event and the cumulative event 
frequency reported for the study with the severity and frequency reported in the 
applicable reference document. 


 
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Reporting requirements will also be based on the investigator's assessment of causality 
and seriousness, with allowance for upgrading by the Sponsor as needed. 
An unblinded IMC and Scientific Oversight Committee will monitor the incidence of 
adverse events during the study.  An aggregate report of any clinically relevant 
imbalances that do not favor the test product will be submitted to health authorities. 
6. 
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN 
6.1 
DETERMINATION OF SAMPLE SIZE 
No formal sample size calculations were performed for this OLE study. The maximum 
number of patients eligible for enrollment is approximately 240 (i.e., all patients enrolled 
in Study GA30044). 
6.2 
SUMMARIES OF CONDUCT OF STUDY 
The number of patients who enroll, discontinue, or complete the study will be 
summarized.  Reasons for premature study withdrawal will be listed and summarized. 
Enrollment and major protocol deviations will be listed and evaluated for their potential 
effects on the interpretation of the study results.  
6.3 
SUMMARIES OF DEMOGRAPHIC AND BASELINE 
CHARACTERISTICS 
Demographic and baseline characteristics such as age, sex, weight, and disease activity 
will be summarized using means or medians for continuous variables and proportions for 
categorical variables.  Medical history including diagnoses and treatment will be 
tabulated. 
6.4 
SAFETY ANALYSES 
The analyses will include all patients who received at least one dose of the study drug 
during this OLE study.  Safety will be analyzed based on reported/documented adverse 
events including AESIs, and changes in laboratory results, ECGs, physical findings,and 
vital signs.  
6.5 
EFFICACY ANALYSES 
Patient efficacy data will be summarized separated by treatment cohort during the 
blinded study (GA30044), in addition to overall summaries.  Efficacy summary will be 
based on the intent-to-treat population, defined as all eligible patients enrolled into this 
OLE study.  Analyses of additional study populations (e.g., completers and per protocol 
[excluding major protocol violators]) will be performed as supportive evaluations.  
Additional subgroup analyses may be conducted on an exploratory basis.  Details will be 
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6.6 
PHARMACOKINETIC ANALYSES 
The PK analyses will include patients with sufficient data to enable estimation of key 
parameters (e.g., area under the concentration−time curve, predose concentrations, and 
half-life).   
Systemic GDC-0853 exposure will be evaluated using a population PK approach, and 
estimates of PK parameters will be generated.  The extent of inter-patient variability will 
be evaluated, and potential sources of variability will be assessed.  Relationships 
between exposure, efficacy, and safety endpoints will be explored and additional 
PK analyses will be conducted during and/or at the end of the study as appropriate. 
6.7 
INTERIM ANALYSIS 
No formal interim analysis is planned.  Data cuts may be performed at appropriate time 
points for inclusion in the submission with the main studies to support the safety profile. 
7. 
DATA COLLECTION AND MANAGEMENT 
7.1 
DATA QUALITY ASSURANCE 
The Sponsor will be responsible for data management of this study, including quality 
checking of the data.  Data entered manually will be collected via EDC through use of 
eCRFs.  Sites will be responsible for data entry into the EDC system.  In the event of 
discrepant data, the Sponsor and its designee will request data clarification from the 
sites, which the sites will resolve electronically in the EDC system. 
The Sponsor or functional service provider will produce an EDC Study Specification 
document that describes the quality checking to be performed on the data.  Central 
laboratory data and any other electronic data will be sent directly to the Sponsor, using 
the Sponsor’s standard procedures to handle and process the electronic transfer of 
these data. 
eCRFs and correction documentation will be maintained in the EDC system’s audit trail.  
System backups for data stored by the Sponsor and records retention for the study data 
will be consistent with the Sponsor’s standard procedures. 
PRO data will be collected on paper questionnaires.  The data from the questionnaires 
will be entered into the EDC system by site staff. 


 
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7.2 
ELECTRONIC CASE REPORT FORMS  
eCRFs are to be completed through use of a Sponsor-designated EDC system.  Sites 
will receive training and have access to a manual for appropriate eCRF completion.  
eCRFs will be submitted electronically to the Sponsor and should be handled in 
accordance with instructions from the Sponsor. 
All eCRFs should be completed by designated, trained site staff.  eCRFs should be 
reviewed and electronically signed and dated by the investigator or a designee. 
At the end of the study, the investigator will receive patient data for his or her site in a 
readable format on a compact disc that must be kept with the study records.  
Acknowledgement of receipt of the compact disc is required. 
7.3 
SOURCE DATA DOCUMENTATION 
Study monitors will perform ongoing source data verification and review to confirm that 
critical protocol data (i.e., source data) entered into the eCRFs by authorized site 
personnel are accurate, complete, and verifiable from source documents.  
Source documents (paper or electronic) are those in which patient data are recorded 
and documented for the first time.  They include, but are not limited to, hospital records, 
clinical and office charts, laboratory notes, memoranda, PROs, evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies of 
transcriptions that are certified after verification as being accurate and complete, 
microfiche, photographic negatives, microfilm or magnetic media, X-rays, patient files, 
and records kept at pharmacies, laboratories, and medico-technical departments 
involved in a clinical trial. 
Before study initiation, the types of source documents that are to be generated will be 
clearly defined in the Trial Monitoring Plan.  This includes any protocol data to be 
entered directly into the eCRFs (i.e., no prior written or electronic record of the data) and 
considered source data. 
Source documents that are required to verify the validity and completeness of data 
entered into the eCRFs must not be obliterated or destroyed and must be retained per 
the policy for retention of records described in Section 7.5. 
To facilitate source data verification, the investigators and institutions must provide the 
Sponsor direct access to applicable source documents and reports for trial-related 
monitoring, Sponsor audits, and IRB/EC review.  The study site must also allow 
inspection by applicable health authorities. 
7.4 
USE OF COMPUTERIZED SYSTEMS 
When clinical observations are entered directly into a study site’s computerized medical 
record system (i.e., in lieu of original hardcopy records), the electronic record can serve 


 
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as the source document if the system has been validated in accordance with health 
authority requirements pertaining to computerized systems used in clinical research.  An 
acceptable computerized data collection system allows preservation of the original entry 
of data.  If original data are modified, the system should maintain a viewable audit trail 
that shows the original data as well as the reason for the change, name of the person 
making the change, and date of the change. 
7.5 
RETENTION OF RECORDS 
Records and documents pertaining to the conduct of this study and the distribution of 
IMP, including eCRFs, electronic or paper PRO data (if applicable), Informed Consent 
Forms, laboratory test results, and medication inventory records, must be retained by the 
Principal Investigator for at least 15 years after completion or discontinuation of the 
study or for the length of time required by relevant national or local health authorities, 
whichever is longer.  After that period of time, the documents may be destroyed, subject 
to local regulations.   
No records may be disposed of without the written approval of the Sponsor.  Written 
notification should be provided to the Sponsor prior to transferring any records to 
another party or moving them to another location. 
8. 
ETHICAL CONSIDERATIONS 
8.1 
COMPLIANCE WITH LAWS AND REGULATIONS 
This study will be conducted in full conformance with the ICH E6 guideline for Good 
Clinical Practice and the principles of the Declaration of Helsinki, or the laws and 
regulations of the country in which the research is conducted, whichever affords the 
greater protection to the individual.  The study will comply with the requirements of the 
ICH E2A guideline (Clinical Safety Data Management:  Definitions and Standards for 
Expedited Reporting).  Studies conducted in the United States or under a U.S. 
Investigational New Drug (IND) application will comply with U.S. Food and Drug 
Administration regulations and applicable local, state, and federal laws.  Studies 
conducted in the European Union or European Economic Area will comply with the E.U. 
Clinical Trial Directive (2001/20/EC). 
8.2 
INFORMED CONSENT 
The Sponsor’s sample Informed Consent Form (and ancillary sample Informed Consent 
Forms such as a Child’s Informed Assent Form or Mobile Nursing Informed Consent 
Form, if applicable) will be provided to each site.  If applicable, it will be provided in a 
certified translation of the local language.  The Sponsor or its designee must review and 
approve any proposed deviations from the Sponsor's sample Informed Consent Forms 
or any alternate consent forms proposed by the site (collectively, the "Consent Forms") 
before IRB/EC submission.  The final IRB/EC−approved Consent Forms must be 
provided to the Sponsor for health authority submission purposes according to local 
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If applicable, the Informed Consent Form will contain separate sections for any optional 
procedures.  The investigator or authorized designee will explain to each patient the 
objectives, methods, and potential risks associated with each optional procedure.  
Patients will be told that they are free to refuse to participate and may withdraw their 
consent at any time for any reason.  A separate, specific signature will be required to 
document a patient's agreement to participate in optional procedures.  Patients who 
decline to participate will not provide a separate signature. 
The Consent Forms must be signed and dated by the patient or the patient’s legally 
authorized representative before his or her participation in the study.  The case history or 
clinical records for each patient shall document the informed consent process and that 
written informed consent was obtained prior to participation in the study. 
The Consent Forms should be revised whenever there are changes to study procedures 
or when new information becomes available that may affect the willingness of the patient 
to participate.  The final revised IRB/EC-approved Consent Forms must be provided to 
the Sponsor for health authority submission purposes. 
Patients must be re-consented to the most current version of the Consent Forms (or to a 
significant new information/findings addendum in accordance with applicable laws and 
IRB/EC policy) during their participation in the study.  For any updated or revised 
Consent Forms, the case history or clinical records for each patient shall document the 
informed consent process and that written informed consent was obtained using the 
updated/revised Consent Forms for continued participation in the study. 
A copy of each signed Consent Form must be provided to the patient or the patient’s 
legally authorized representative.  All signed and dated Consent Forms must remain in 
each patient’s study file or in the site file and must be available for verification by study 
monitors at any time. 
For sites in the United States, each Consent Form may also include patient authorization 
to allow use and disclosure of personal health information in compliance with the U.S. 
Health Insurance Portability and Accountability Act (HIPAA) of 1996.  If the site utilizes a 
separate Authorization Form for patient authorization for use and disclosure of personal 
health information under the HIPAA regulations, the review, approval, and other 
processes outlined above apply except that IRB review and approval may not be 
required per study site policies. 
8.3 
INSTITUTIONAL REVIEW BOARD OR ETHICS COMMITTEE 
This protocol, the Informed Consent Forms, any information to be given to the patient, 
and relevant supporting information must be submitted to the IRB/EC by the Principal 
Investigator and reviewed and approved by the IRB/EC before the study is initiated.  
In addition, any patient recruitment materials must be approved by the IRB/EC.  


 
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The Principal Investigator is responsible for providing written summaries of the status of 
the study to the IRB/EC annually or more frequently in accordance with the requirements, 
policies, and procedures established by the IRB/EC.  Investigators are also responsible 
for promptly informing the IRB/EC of any protocol amendments (see Section 9.6). 
In addition to the requirements for reporting all adverse events to the Sponsor, 
investigators must comply with requirements for reporting serious adverse events to the 
local health authority and IRB/EC.  Investigators may receive written IND safety reports 
or other safety-related communications from the Sponsor.  Investigators are responsible 
for ensuring that such reports are reviewed and processed in accordance with health 
authority requirements and the policies and procedures established by their IRB/EC, and 
archived in the site’s study file.  
8.4 
CONFIDENTIALITY 
The Sponsor maintains confidentiality standards by coding each patient enrolled in the 
study through assignment of a unique patient identification number.  This means that 
patient names are not included in data sets that are transmitted to any Sponsor location. 
Patient medical information obtained by this study is confidential and may be disclosed 
to third parties only as permitted by the Informed Consent Form (or separate 
authorization for use and disclosure of personal health information) signed by the patient, 
unless permitted or required by law. 
Medical information may be given to a patient’s personal physician or other appropriate 
medical personnel responsible for the patient’s welfare, for treatment purposes. 
Given the complexity and exploratory nature of the analyses, data derived from 
exploratory biomarker specimens will generally not be provided to study investigators or 
patients unless required by law.  The aggregate results of any conducted research will 
be available in accordance with the effective Sponsor policy on study data publication 
(see Section 9.5). 
Data generated by this study must be available for inspection upon request by 
representatives of national and local health authorities, Sponsor monitors, 
representatives, and collaborators, and the IRB/EC for each study site, as appropriate. 
8.5 
FINANCIAL DISCLOSURE 
Investigators will provide the Sponsor with sufficient, accurate financial information in 
accordance with local regulations to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate health authorities.  
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study (see definition of end of 
study in Section 3.2). 


 
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9. 
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION 
9.1 
STUDY DOCUMENTATION 
The investigator must maintain adequate and accurate records to enable the conduct of 
the study to be fully documented, including, but not limited to, the protocol, protocol 
amendments, Informed Consent Forms, and documentation of IRB/EC and 
governmental approval.  In addition, at the end of the study, the investigator will receive 
the patient data, including an audit trail containing a complete record of all changes to 
data. 
9.2 
PROTOCOL DEVIATIONS 
The investigator should document and explain any protocol deviations.  The investigator 
should promptly report any deviations that might have an impact on patient safety and 
data integrity to the Sponsor and to the IRB/EC in accordance with established IRB/EC 
policies and procedures.  The Sponsor will review all protocol deviations and assess 
whether any represent a serious breach of Good Clinical Practice guidelines and require 
reporting to health authorities.  As per the Sponsor's standard operating procedures, 
prospective requests to deviate from the protocol, including requests to waive protocol 
eligibility criteria, are not allowed. 
9.3 
SITE INSPECTIONS 
Site visits will be conducted by the Sponsor or an authorized representative for 
inspection of study data, subjects’ medical records, and eCRFs.  The investigator will 
permit national and local health authorities; Sponsor monitors, representatives, and 
collaborators; and the IRBs/ECs to inspect facilities and records relevant to this study. 
9.4 
ADMINISTRATIVE STRUCTURE 
The study will be conducted globally and include approximately 240 patients.  The 
contract research organization 
 will be responsible for submission to IRB/ECs 
for approval of the study protocol, patient recruitment, study conduct, data collection, 
and reporting. 
9.5 
PUBLICATION OF DATA AND PROTECTION OF TRADE 
SECRETS 
Regardless of the outcome of a trial, the Sponsor is dedicated to openly providing 
information on the trial to healthcare professionals and to the public, both at scientific 
congresses and in peer-reviewed journals.  The Sponsor will comply with all 
requirements for publication of study results.  For more information, refer to the Roche 
Global Policy on Sharing of Clinical Trials Data at the following Web site: 
www.roche.com/roche_global_policy_on_sharing_of_clinical_study_information.pdf 


 
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The results of this study may be published or presented at scientific congresses.  For all 
clinical trials in patients involving an IMP for which a marketing authorization application 
has been filed or approved in any country, the Sponsor aims to submit a journal 
manuscript reporting primary clinical trial results within 6 months after the availability of 
the respective Clinical Study Report.  In addition, for all clinical trials in patients involving 
an IMP for which a marketing authorization application has been filed or approved in any 
country, the Sponsor aims to publish results from analyses of additional endpoints and 
exploratory data that are clinically meaningful and statistically sound. 
The investigator must agree to submit all manuscripts or abstracts to the Sponsor prior 
to submission for publication or presentation.  This allows the Sponsor to protect 
proprietary information and to provide comments based on information from other 
studies that may not yet be available to the investigator. 
In accordance with standard editorial and ethical practice, the Sponsor will generally 
support publication of multicenter trials only in their entirety and not as individual center 
data.  In this case, a coordinating investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements.  Any formal publication 
of the study in which contribution of Sponsor personnel exceeded that of conventional 
monitoring will be considered as a joint publication by the investigator and the 
appropriate Sponsor personnel. 
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of data from this study will become and remain the exclusive and unburdened 
property of the Sponsor, except where agreed otherwise. 
9.6 
PROTOCOL AMENDMENTS 
Any protocol amendments will be prepared by the Sponsor.  Protocol amendments will 
be submitted to the IRB/EC and to regulatory authorities in accordance with local 
regulatory requirements. 
Approval must be obtained from the IRB/EC and regulatory authorities (as locally 
required) before implementation of any changes, except for changes necessary to 
eliminate an immediate hazard to patients or changes that involve logistical or 
administrative aspects only (e.g., change in Medical Monitor or contact information). 


 
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10. 
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GDC-0853—Genentech, Inc. 
96/ Protocol GA30066, Version 1  
Appendix 1  
Schedule of Activities 
Study Week 
Treatment 
SFU 
UV d FV e ET 
0 a, b 
1 c 
4 
8 
12 a 
16 
20 
24 a 
28 
32 
36 a 
40 
44 
48 a 
56 
Day 
(Visit Window) 
1 
8 
(± 1) 
29 
(± 4 
57 
(± 4) 
85 
(± 4) 
113 
(± 4) 
141 
(± 4) 
169 
(± 4) 
197 
(± 7) 
225 
(± 7) 
253 
(± 7) 
281 
(± 7) 
309 
(± 7) 
337 
(± 7) 
393 
(± 7) 
Informed consent f 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications g 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Adverse events  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Vital signs h 
x 
 
x 
x 
x 
 
 
x 
 
 
x 
 
 
x 
x 
x 
x 
x 
Weight 
x 
 
x 
 
x 
 
 
x 
 
 
x 
 
 
x 
x 
x 
x 
x 
Height 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete PE i 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Limited PE j 
 
 
x 
x 
x 
 
 
x 
 
 
x 
 
 
x 
x 
x 
x 
x 
MTB screening k 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Viral Serology l 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-Lead ECG m 
x  
 
x  
  
  
 
 
x  
 
 
 
 
 
x  
x 
x 
 
x 
CK, aldolase, and LDH n 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
x 
 
Direct Coombs test o 
x 
 
x 
x 
x 
 
 
x 
 
 
x 
 
 
x 
x 
x 
x 
x 
Hematology p 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Chemistry panel q 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Coagulation panel r 
x 
 
 
 
 
 
 
x 
 
 
 
 
 
x 
 
x 
 
x 


Appendix 1  
Schedule of Activities (cont.) 
GDC-0853—Genentech, Inc. 
97/ Protocol GA30066, Version 1  
Study Week 
Treatment 
SFU 
UV d FV e ET 
0 a, b 
1 c 
4 
8 
12 a 
16 
20 
24 a 
28 
32 
36 a 
40 
44 
48 a 
56 
Day 
(Visit Window) 
1 
8 
(± 1) 
29 
(± 4 
57 
(± 4) 
85 
(± 4) 
113 
(± 4) 
141 
(± 4) 
169 
(± 4) 
197 
(± 7) 
225 
(± 7) 
253 
(± 7) 
281 
(± 7) 
309 
(± 7) 
337 
(± 7) 
393 
(± 7) 
Total Ig, IgG, IgM, IgE, IgA s 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
x 
x 
x 
x 
CRP 
x 
 
x 
 
x 
 
 
x 
 
 
x 
 
 
x 
x 
x 
x 
x 
Pregnancy test t 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
TBNK  
x 
 
x 
 
x 
 
 
x 
 
 
x 
 
 
x 
x 
x 
x 
x 
ESR (on site or at local laboratory)  
x 
 
x 
 
 
 
 
x 
 
 
x 
 
 
x 
 
x 
x 
x 
Urinalysis u 
x 
 
x 
x 
x 
 
 
x 
 
 
x 
 
 
x 
x 
x 
x 
x 
C3, C4, CH50 v 
x 
 
x 
x 
x 
 
 
x 
 
 
x 
 
 
x 
x 
x 
x 
x 
Autoantibody panel w 
x 
 
 
 
 
 
 
x 
 
 
 
 
 
x 
 
 
 
 
Anti-dsDNA 
x 
 
x 
x 
x 
 
 
x 
 
 
x 
 
 
x 
x 
x 
x 
x 
Protein creatinine ratio x 
x 
 
x 
x 
x 
 
 
x 
 
 
x 
 
 
x  
x  
 
x 
x 
Plasma PK sample y 
x 
 
 
 
 
 
 
x  
 
 
 
 
 
x 
 
x 
x 
x 
BILAG-2004 
x 
 
x 
x 
x 
 
 
x 
 
 
x 
 
 
x 
x 
x 
x 
x 
SLEDAI-2K and SFI 
x 
 
x 
x 
x 
 
 
x 
 
 
x 
 
 
x 
x 
x 
x 
x 
GTCI and fasting lipids z  
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
 
SLICC damage index 
x 
 
 
 
 
 
 
x 
 
 
 
 
 
x 
 
 
 
 
CLASI 
x 
 
x 
 
x 
 
 
x 
 
 
x 
 
 
x 
x 
x 
x 
x 
Optional photographic documentation 
aa  
x 
 
x 
 
x 
 
 
x 
 
 
x 
 
 
x 
x 
x 
x 
x 


Appendix 1  
Schedule of Activities (cont.) 
GDC-0853—Genentech, Inc. 
98/ Protocol GA30066, Version 1  
Study Week 
Treatment 
SFU 
UV d FV e ET 
0 a, b 
1 c 
4 
8 
12 a 
16 
20 
24 a 
28 
32 
36 a 
40 
44 
48 a 
56 
Day 
(Visit Window) 
1 
8 
(± 1) 
29 
(± 4 
57 
(± 4) 
85 
(± 4) 
113 
(± 4) 
141 
(± 4) 
169 
(± 4) 
197 
(± 7) 
225 
(± 7) 
253 
(± 7) 
281 
(± 7) 
309 
(± 7) 
337 
(± 7) 
393 
(± 7) 
PGA bb 
x 
 
x 
x 
x 
 
 
x 
 
 
x 
 
 
x 
x 
x 
x 
x 
Patient’s Global Assessment  cc 
x 
 
x 
x 
x 
 
 
x 
 
 
x 
 
 
x 
x 
x 
x 
x 
Drug dispensing 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
GDC-0853 administration in clinic dd 
x ee 
 
 
 
 
 
 
x 
 
 
 
 
 
 
 
 
 
 
BID = twice a day; BILAG = British Isles Lupus Assessment Group; CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity Index; 
CRP = C-reactive protein; dsDNA = double stranded DNA; EC = Ethics Committee; eCRF = electronic Case Report Form; ESR = erythrocyte sedimentation 
rate; ET = early termination; FMV = first morning void; FV = flare visit; GGT = gamma-glutamyl transpeptidase; GTCI = Glucocorticoid Toxicity Index; 
H2RA = H2 receptor antagonist; HbA1C = glycosylated hemoglobin; HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; 
HBsAg = hepatitis B surface antigen; HCV Ab = hepatitis C virus antibody; IRB = Institutional Review Board; MCH = mean corpuscular hemoglobin; 
MCHC = mean corpuscular hemoglobin concentration; MCV = mean corpuscular volume; MTB = mycobacterium tuberculosis; OCS = oral corticosteroid; 
OLE = open-label extension; PE = physical examination; PGA = Physician's Global Assessment; PK = pharmacokinetic; PPD = purified protein derivative; 
PPI = proton pump inhibitor; PRO = patient-reported outcome; QFT = QuantiFERON−TB Gold; RDW = red cell distribution width; SFI = SELENA-SLEDAI 
Flare Index; SFU = safety follow-up; SLE = systemic lupus erythematosus; SLEDAI-2K = SLE Disease Activity Index 2000; SLICC = Systemic Lupus 
International Collaborating Clinics; TB = tuberculosis; TBNK = T, B, and natural killer cells; UV = unscheduled visit. 
a A morning clinic visit (fasting ≥ 4 hours prior to PK blood draw) is strongly recommended for PK visits on Day 1 and Week 24.  For other study visits, 
morning visits are recommended.  In addition, the patient should be fasting ≥ 4 hours for fasting lipid assessments at Day 1, Weeks 12, 24, 36, and 48. 
b Day 1 OLE assessments that overlap with Week 48 assessments in the blinded Study GA30044 do not need to be repeated.  Therefore, Week 48 
assessments in Study GA30044 should be used as the Day 1 assessments of Study GA30066.  
 


Appendix 1  
Schedule of Activities (cont.) 
GDC-0853—Genentech, Inc. 
99/ Protocol GA30066, Version 1  
c Patients will receive a telephone call from study staff to follow up for assessment of adverse events and concomitant medications.  
d At an unscheduled visit, adverse events and concomitant medications must be assessed.  All other assessments are to be performed only if medically 
indicated based on the reason for the unscheduled visit.  If the patient returns for an unscheduled visit or regular study visit and has any evidence of 
increased SLE-activity requiring treatment, perform all assessments required for a flare visit. 
e A flare visit is any unscheduled visit where the patient may require escalation of treatment for increased SLE activity.  Assessments are to be 
performed only if medically indicated based on the reason for the flare visit. 
f Patients entering the OLE study may be consented after meeting entry criteria for Study GA30066, which may include use of qualifying test results 
from the Week 44 visit or later from Study GA30044 (see Section 4.4.1). 
g Starting at Day 1, all patients must record their OCS use as instructed by study staff (see Section 4.2.2.4).  
h Includes respiratory rate, pulse rate, temperature, and systolic and diastolic blood pressure while the patient is in a seated position for at least 
5 minutes. 
i Includes an evaluation of the head, eyes, ears, nose, and throat, and the cardiovascular, dermatological, musculoskeletal, respiratory, gastrointestinal, 
genitourinary, and neurological systems.  Any abnormality identified at baseline should be recorded on the General Medical History and Baseline 
Conditions eCRF.  Particular attention should be given to evaluation of potential manifestations of active SLE (see Appendix 9 BILAG-2004 Index; 
Appendix 10 SLEDAI-2K; and Appendix 12 CLASI) and of infections or other medical conditions, which could place the patient at increased risk. 
j Limited, efficacy assessment−directed or symptom-directed physical examinations should be performed that also allow for completion of SLEDAI-2K 
and BILAG-2004 assessments.  Changes from baseline abnormalities should be recorded in patient notes.  New or worsened clinically significant 
abnormalities should be recorded as adverse events on the Adverse Event eCRF. 
k  MTB testing should be performed only for patients who did not complete testing at Week 44 or later of Study GA30044.  Follow the same method of 
testing and assessment that was completed during screening period.  In most cases, QFT is to be used as the initial TB screening test, and if 
indeterminate, this should be followed by either a repeat QFT or a T-SPOT test.  A PPD skin test should be performed only if QFT is not available.  
l Hepatitis B and C testing should be performed only for patients who did not complete testing at Week 44 or later of Study GA30044. Includes HBsAg, 
HBsAb, HBcAb, HCV Ab. 
m ECG recordings must be performed after the patient has been resting in a supine position for at least 10 minutes.  All ECGs are to be obtained prior to 
the other procedures scheduled at that same time (e.g., vital sign measurements, blood draws) if possible.  Body position should be consistently 
maintained for each ECG evaluation to prevent changes in heart rate.  Environmental distractions (e.g., television, radio, conversation) should be 
avoided during the pre-ECG resting period and during ECG recording.  ECGs for each patient should be obtained from the same machine whenever 
possible. 
n May be collected throughout treatment period as needed to complete disease activity measures (e.g., SLEDAI-2K and BILAG-2004). 
o If the Coombs test is needed, it should be performed at a local laboratory. 


Appendix 1  
Schedule of Activities (cont.) 
GDC-0853—Genentech, Inc. 
100/ Protocol GA30066, Version 1  
 p Includes hemoglobin, hematocrit, RBC count, calculated indices (MCV, MCH, MCHC, RDW), platelet count, and WBC count with differential. 
q Includes electrolytes (Na, K, Cl, bicarbonate, phosphorus), blood urea nitrogen, creatinine, glucose, ALT, AST, amylase, lipase, total and direct 
bilirubin, ALP, GGT, albumin, globulin, total protein, calcium, and uric acid. 
r Includes INR, aPTT, and PT. 
s Includes total Igs, IgG, IgM, IgE, and IgA. 
t Urine pregnancy tests will be performed locally at specified visits for women of childbearing potential (including those who have had a tubal ligation).  If 
a urine pregnancy test is positive, it must be confirmed by a serum pregnancy test (performed locally). 
u Includes dipstick (blood, protein, glucose, nitrites, and leukocyte esterase), microscopic analysis (RBC, WBC, red cell casts, white cell casts).  
v C3, C4, and CH50 conducted on the same day as the SLEDAI-2K. 
w Includes anti-Smith, anti-RNP, anti-Ro, anti-La, anti-cardiolipin, and anti-B2 glycoprotein. 
x FMV urine samples should be collected at all visits unless the patient forgets to collect the FMV or forgets to bring the urine to the visit (refer to 
laboratory manual for details on urine collection instructions), in which case a random urine sample is acceptable.  
y Collect prior to drug administration.   
z Fasting lipid panel includes triglycerides, HDL, LDL, HbA1C, and total cholesterol.  The patient should be fasting (≥ 4 hours). 
aa Photography is contingent upon the review and approval by each site's IRB/EC and, if applicable, an appropriate regulatory body. 
bb The same clinician should complete the PGA throughout the study. 
cc To ensure instrument validity and that data standards meet health authority requirements, the questionnaire will be self-administered before the patient 
or clinician receives any information on disease status, prior to the performance of non-PRO assessments, and prior to the administration of study 
treatment, unless otherwise specified.   
dd Patients will receive GDC-0853 BID starting on Day 1 and ending on the evening prior to the Week 48 visit of Study GA30066.  GDC-0853 should be 
taken with water by mouth.  The dates and times of the most recent prior meal and most recent prior dose of short-acting antacid, PPI, or H2RA, last 
dose of oral study drug (prior to clinic visit), and timing of study drug administration in clinic should be recorded at clinic visits with PK and/or fasting 
lipid assessments. 
ee The last dose of blinded study drug in Study GA30044 is the p.m. dose on the evening before the Week 48 visit for all patients.  For patients 
continuing into the OLE Study GA30066, the first open-label dose of GDC-0853 should be the a.m. dose on Week 48 (which is Day 1 of 
Study GA30066). 
 
 


 
GDC-0853—Genentech, Inc. 
101/ Protocol GA30066, Version 1  
Appendix 2  
Types and Doses of Standard Oral Treatments for Systemic 
Lupus Erythematosus Permitted in Study  
Oral corticosteroids a 
Equivalent dose (mg) 
Hydrocortisone 
20 
Cortisone acetate  
25 
Prednisone 
5 
Prednisolone 
5 
Methylprednisolone 
4 
Dexamethasone  
0.75 
Betamethasone  
0.75 
Triamcinolone 
4 
Beclometasone  
0.75 
Deflazacort 
6 
Other c 
 
Oral Immunosuppression and antimalarials b  
Azathioprine  
1 to 2.5 mg/kg/day 
Methotrexate 
7.5 to 25 mg/week 
Mycophenolate mofetil 
500 to 2500 mg/day 
Mycophenolic sodium 
360 to1800 mg/day 
Hydroxychloroquine 
200 to 400 mg/day 
Chloroquine 
100 to 250 mg/day 
Quinacrine 
100 to 200 mg/day 
Other c 
 
a Cortisol (hydrocortisone) is the standard of comparison for glucocorticoid potency.  
Hydrocortisone is the name used for pharmaceutical preparations of cortisol. 
b Any combination of azathioprine, methotrexate, mycophenolate mofetil, or mycophenolic 
sodium is prohibited. 
c Other medications may apply based on region and should be consulted with the Medical 
Monitor. 
 
 


 
GDC-0853—Genentech, Inc. 
102/ Protocol GA30066, Version 1  
Appendix 3  
Glucocorticoid Toxicity Change Index 
COMPOSITE GLUCOCORTICOID TOXICITY CHANGE INDEX 
1. 
Body mass index (BMI) (compared to baseline) 
a) Improvement (in either direction) by more than 2 BMI units toward normal BMI 
(normal range = 18.5−24.9 kg/m2) 
b) No significant change (BMI remains within ± 2 BMI units compared with baseline) 
or BMI remains within the normal range 
c) 
Moderate increase in BMI (increase by more than 2 but less than 5 BMI units to 
above the upper limit of normal BMI [24.9 kg/m2]) 
d) Major increase in BMI (increase by more than 5 BMI units to above normal BMI 
[24.9 kg/m2]) 
 
2. Glucose tolerance (compared to baseline) 
a) Improvement in glucose tolerance:  
• 
HbA1c (glycosylated hemoglobin) declined > 10% from baseline without 
medication increase 
OR 
• 
Decrease in diabetic medication without an increase in HbA1c of > 10% or 
HbA1c  5.7% 
b) No significant change in glucose tolerance: 
• 
HbA1c within 10% of baseline or HbA1c  5.7% and no change in 
medication  
OR  
• 
HbA1c increased to > 10% of baseline due to a decrease in medication  
OR  
• 
Improvement in glucose tolerance > 10% due to an increase in medication 
c) 
Worsening of glucose tolerance or medication status:  
• 
HbA1c increased to > 10% and HbA1c > 5.7% without a change in 
medication  
OR  
• 
Increase in diabetic medication with  10% increase in HbA1c 
d) Worsening of glucose tolerance despite treatment: 
• 
HbA1c > 5.7% and increased to > 10% of baseline and an increase in 
diabetic medication 
 


 
 
Appendix 3  
Glucocorticoid Toxicity Change Index (cont.)  
GDC-0853—Genentech, Inc. 
103/ Protocol GA30066, Version 1  
3. 
Blood pressure (BP) (compared to baseline) 
a) Improvement in BP:  
• 
Decrease in BP of > 10% of baseline without medication increase 
OR 
• 
Decrease in medication without an increase in BP of > 10% or systolic BP 
≤ 120 and diastolic BP ≤ 85 
b) No significant change in BP: 
• 
BP within 10% of baseline or systolic BP ≤ 120 and diastolic BP ≤ 85 and no 
change in medication  
OR  
• 
Deterioration in either systolic or diastolic BP > 10% due to a decrease in 
medication 
OR  
• 
An improvement in either systolic or diastolic BP of > 10% due to an 
increase in medication 
c) 
Worsening of hypertension:  
• 
Increase in BP of > 10% such that the systolic BP exceeds 120 mmHg or 
the diastolic BP exceeds 85 mmHg without a change in medication  
OR  
• 
Increase in anti-hypertensive medication without an improvement in 
BP > 10% 
d) Worsening of hypertension despite treatment: 
• 
Increase in BP of > 10% such that the systolic BP exceeds 120 mmHg or 
the diastolic BP exceeds 85 mmHg and an increase in medication 
 
4. 
Hyperlipidemia (compared to baseline) 
a) Improvement in lipids:  
• 
Decrease in LDL concentration > 10% of baseline without medication 
increase toward the target range  
OR 
• 
Decrease in medication without an increase in LDL of > 10% or LDL 
remains within target range 


 
 
Appendix 3  
Glucocorticoid Toxicity Change Index (cont.)  
GDC-0853—Genentech, Inc. 
104/ Protocol GA30066, Version 1  
b) No significant change in LDL: 
• 
LDL within 10% of baseline or within the target range for patient and no 
change in medication  
OR  
• 
Increase in LDL > 10% due to a decrease in medication 
OR  
• 
Improvement in LDL of > 10% due to an increase in medication 
c) 
Worsening of LDL or medication status:  
• 
Increase in LDL of > 10% to above target range without increase in 
medication 
OR  
• 
Increase in medication without > 10% change in LDL 
d) Worsening of LDL despite treatment: 
• 
Increase in LDL of > 10% and an increase in medication 
5. 
Steroid myopathy 
a) No steroid myopathy 
b) Mild steroid myopathy (weakness without functional limitation) 
c) 
Moderate steroid myopathy (weakness with functional limitation) 
See steroid myopathy definitions below. 
6. 
Skin  
a) No skin toxicity 
b) Mild  
c) 
Moderate  
See skin definitions below. 
7. 
Neuropsychiatric  
a) No neuropsychiatric symptoms 
b) Mild 
c) 
Moderate  
See neuropsychiatry definitions below. 


 
 
Appendix 3  
Glucocorticoid Toxicity Change Index (cont.)  
GDC-0853—Genentech, Inc. 
105/ Protocol GA30066, Version 1  
8. 
Infection (since last assessment)  
a) No significant infection 
b) Specific infections  Grade 3 (oral or vaginal candidiasis, uncomplicated zoster) 
c) 
Grade 3  
See infection notes below. 
9. 
Bone mineral density (BMD) (compared to baseline) 
a) Improvement − increase in BMD by > 3% 
b) No significant change (BMD between − 3% and + 3%) 
c) 
Deterioration  − decrease by ≥ 3%  
% refers to total BMD in gms/cm2. 
If BMD not evaluated, then option “b” should be selected. 
 
GLUCOCORTICOID-INDUCED MYOPATHY DEFINITIONS 
• 
Glucocorticoid-induced myopathy is defined as mild symmetrical weakness of the 
proximal muscles and/or neck flexors associated with steroid therapy and not due to 
any other apparent cause.  Muscle enzymes are typically within normal limits. 
• 
Mild and moderate myopathy are defined by muscle strength of 4 on the standard 
Medical Research Council strength testing scale.  A 4 means weaker than normal 
but greater than anti-gravity strength.  
• 
“Mild” is Grade 4 weakness that does not functionally limit the patient.  
• 
”Moderate” is Grade 4 weakness that does impose functional limitations on the 
patient, interfering with normal daily activities. 
• 
Note that inability to rise from a chair without assistance constitutes severe 
glucocorticoid-induced myopathy (Specific Domain). 
 
SEVERITY OF GLUCOCORTICOID TOXICITY IN THE SKIN 
Manifestations to be considered: 
• 
Acneiform rash 
• 
Easy bruising 
• 
Hirsutism 
• 
Atrophy/striae 
• 
Erosions/tears/ulcerations 


 
 
Appendix 3  
Glucocorticoid Toxicity Change Index (cont.)  
GDC-0853—Genentech, Inc. 
106/ Protocol GA30066, Version 1  
Skin 6b. Mild 
Skin 6c. Moderate 
Severe (Specific Domain) 
Acneiform rash (Grades 1−2) 
Acneiform rash (Grade 3) 
Acneiform rash (Grade 4) 
Easy bruising (Grade 1) 
Easy bruising (Grade 2) 
 
Hirsutism (Grade 1) 
Hirsutism (Grade 2) 
 
Atrophy/striae (Grade 1) 
Atrophy/striae (Grade 2) 
Atrophy/striae (Grade 3) 
Erosions/tears/ulcerations 
(Grade 1) 
Erosions/tears/ulcerations 
(Grade 2) 
Erosions/tears/ulcerations 
(Grade 3) 
  
Acneiform rash 
• 
Grade 1:  Papules and/or pustules covering  10% body surface area (BSA), which 
may or may not be associated with symptoms of pruritus or tenderness 
• 
Grade 2:  Papules and/or pustules covering 10%−30% BSA, which may or may not 
be associated with symptoms of pruritus or tenderness; associated with 
psychosocial impact; limiting instrumental activities of daily living (ADL) 
• 
Grade 3:  Papules and/or pustules covering > 30% BSA, which may or may not be 
associated with symptoms of pruritus or tenderness; limiting self-care ADL; 
associated with local superinfection with oral antibiotics indicated 
• 
Grade 4:  Papules and/or pustules covering any % BSA, which may or may not be 
associated with symptoms of pruritus or tenderness and are associated with 
extensive superinfection with IV antibiotics indicated; life-threatening consequences 
 
Easy bruising 
• 
Grade 1:  Localized or in a dependent area 
• 
Grade 2:  Generalized 
 
Hirsutism:  In women, increase in length, thickness, or density of hair in a male 
distribution 
• 
Grade 1:  Hirsutism that the patient is able to camouflage by periodic shaving, 
bleaching, or removal of hair 
• 
Grade 2:  Hirsutism that requires daily shaving or consistent destructive means of 
hair removal to camouflage; associated with psychosocial impact 
Atrophy/striae 
• 
Grade 1:  Covering  10% BSA; associated with telangiectasias or changes in skin 
color 
• 
Grade 2:  Covering 10%−30% BSA; associated with striae or adnexal structure loss 
• 
Grade 3:  Covering > 30% BSA; associated with ulceration 
 


 
 
Appendix 3  
Glucocorticoid Toxicity Change Index (cont.)  
GDC-0853—Genentech, Inc. 
107/ Protocol GA30066, Version 1  
Erosions/tears/ulcerations 
• 
Grade 1:  Combined area of ulcers  1 cm; non-blanchable erythema of intact skin 
associated with warmth or erythema 
• 
Grade 2:  Combined area of ulcers 1−2 cm; partial thickness skin loss involving skin 
or subcutaneous fat 
• 
Grade 3:  Combined area of ulcers > 2 cm; full-thickness skin loss involving damage 
to or necrosis of subcutaneous tissue that may extend down to fascia 
 
SEVERITY OF NEUROPSYCHIATRIC GLUCOCORTICOID TOXICITY 
Manifestations to be considered:  
• 
Insomnia 
• 
Mania 
• 
Cognitive impairment 
• 
Depression 
 
7b. MildNo Functional 
Impairment 
7c. ModerateFunctional 
Impairment 
Severe (Specific Domain) 
Insomnia 
Insomnia 
 
Mania (Grade 1) 
Mania (Grade 2) 
Mania (Grade 3) 
Cognitive impairment 
(Grade 1) 
Cognitive impairment (Grade 
2) 
Cognitive impairment 
(Grade 3) 
Depression (Grade 1) 
Depression (Grade 2) 
Depression (Grade 3) 
  
DEFINITIONS OF SEVERITY WITHIN THE NEUROPSYCHIATRIC DOMAIN 
Insomnia:  Dissatisfaction with sleep quality and difficulty initiating or maintaining 
sleep or early morning awakening 
• 
Grade 1:  Not associated with functional impairment 
• 
Grade 2:  Associated with functional impairment; recorded as moderate toxicity 
 
Mania 
• 
Grade 1:  Slightly or occasionally elevated or irritable mood and 0−1 mild or 
occasional additional symptoms of inflated self-esteem, decreased need 
for sleep, increased talkativeness, feeling that thoughts are faster than 
usual, distractibility, increased activity or agitation, and impulsive actions 


 
 
Appendix 3  
Glucocorticoid Toxicity Change Index (cont.)  
GDC-0853—Genentech, Inc. 
108/ Protocol GA30066, Version 1  
• 
Grade 2:  Frequent or moderately elevated or irritable mood and 2−3 mild additional 
symptoms of inflated self-esteem, decreased need for sleep, increased 
talkativeness, feeling that thoughts are faster than usual, distractibility, 
increased activity or agitation, and impulsive actions 
• 
Grade 3:  Severe or constantly elevated or irritable mood and 4 or more additional 
symptoms of inflated self-esteem, decreased need for sleep, increased 
talkativeness, feeling that thoughts are faster than usual, distractibility, 
increased activity or agitation, and impulsive actions 
 
Cognitive impairment 
• 
Grade 1:  Minor cognitive complaints, no objective findings on mental status 
examination (i.e., not apparent to the examiner) that were not present 
before initiating steroids 
• 
Grade 2:  New moderate cognitive deficits that were not present before initiating 
steroids 
• 
Grade 3:  Frank delirium  
 
Depression 
• 
Grade 1:  Feeling slightly down or depressed and 0−2 mild or occasional additional 
symptoms of loss of interest, low energy, guilt, poor concentration, 
insomnia, restlessness, or change in appetite 
• 
Grade 2:  Frequent or moderate feelings of being down or depressed and/or 3−4 
symptoms of loss of interest, low energy, guilt, poor concentration, 
insomnia, restlessness, or change in appetite 
• 
Grade 3: Severe constant feeling of being down or depressed and/or 5 or more 
symptoms of loss of interest, low energy, guilt, poor concentration, 
insomnia, restlessness, or change in appetite and/or suicidal thoughts 
 
INFECTION NOTES 
• 
No significant infection:  No specific infections or serious infections Grade 3 or 
greater 
• 
Specific infections:  Oral or vaginal candidiasis or zoster infections without 
postherpetic neuralgia or eye involvement 
• 
Grade 3:  IV antibiotic, anti-fungal, or anti-viral intervention or hospitalization 
indicated or radiologic or operative intervention indicated or herpes zoster 
complicated by postherpetic neuralgia or eye involvement 
• 
Grade 4 or 5:  Life-threatening consequences; urgent intervention indicated or death 
from infection (Specific Domain) 
 


 
GDC-0853—Genentech, Inc. 
109/ Protocol GA30066, Version 1  
Appendix 4  
Suggested Prednisone Taper Schedule Achieving  10 mg/day 
by 12 Weeks 
 
Starting Prednisone Dose (mg/day) 
10 
20 
30 
40 
Weeks 0−2  
10 
20 
30 
40 
Weeks 3−4  
 10 
15 
25 
30 
Weeks 5−6  
 10 
10 
20 
25 
Weeks 7−8  
 10 
 10 
15 
15 
Weeks 9−10  
 10 
 10 
10 
10 
Weeks 11−12  
 10 
 10 
 10 
 10 
 
 
 


 
GDC-0853—Genentech, Inc. 
110/ Protocol GA30066, Version 1  
Appendix 5  
Childbearing Potential, Pregnancy Testing, and Contraception  
For Women 
All women of childbearing potential (including those who have had a tubal ligation) will 
have a urine pregnancy test at baseline and at subsequent clinic visits.  If a urine 
pregnancy test result is positive, study drug will not be administered until pregnancy is 
ruled out.  The result must be confirmed by a serum pregnancy test (conducted by the 
local laboratory). 
Refer to Section 5.4.3 of the protocol for management of a patient with a confirmed 
pregnancy. 
All female patients are considered to be of childbearing potential unless they meet one 
of the following criteria: 
• 
The patient has been postmenopausal (non−therapy-induced amenorrhea) for at 
least 12 continuous months with no other identified cause. 
• 
The patient had a surgical bilateral oophorectomy (with or without hysterectomy) 
more than 6 weeks prior to enrollment. 
• 
The patient had a hysterectomy. 
 
Female patients of reproductive or childbearing potential who are unwilling to use a 
method of contraception that results in a failure rate of  1 % per year or remain 
abstinent (refrain from heterosexual intercourse) during the treatment period and for at 
least 60 days after the last dose of study drug, or longer as required by local 
requirements for other standard of care medications, will be excluded from study 
participation. 
Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the 
patient.  Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation 
methods) and withdrawal are not acceptable methods of contraception. 
Examples of contraceptive methods with a failure rate of  1% per year include the 
following: 
• 
Sterilization, bilateral surgical tubal ligation 
• 
Intrauterine device 
• 
Combined oral contraceptive pill* 
• 
Contraceptive transdermal patch (estrogen and progestin containing)* 
• 
Hormonal vaginal device 
• 
Progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
Implants for contraception 
• 
Injections for contraception (with prolonged release) 


 
 
Appendix 5  
Childbearing Potential, Pregnancy Testing, and Contraception 
(cont.) 
GDC-0853—Genentech, Inc. 
111/ Protocol GA30066, Version 1  
• 
Sole sexual partner consisting of surgically sterilized male partner with appropriate 
postsurgical verification of the absence of spermatozoa in the ejaculate.  Patients 
may provide verbal confirmation that the partner completed appropriate follow-up 
after vasectomy.  Sites are not required to obtain partner medical records. 
• 
Same sex partner 
 
* Women using estrogen containing hormonal contraceptives as a method of 
contraception must also use a barrier such as a male condom in conjunction 
with the hormonal contraceptives. 
 
 
For Men 
All men must agree to remain abstinent (refrain from heterosexual intercourse) or use 
contraceptive measures and agreement to refrain from donating sperm, as defined 
below: 
• 
With female partners of childbearing potential (including those who have had a tubal 
ligation), men must remain abstinent or use a condom plus an additional 
contraceptive method that together result in a failure rate of  1% per year during the 
treatment period and for at least 120 days (4 months) after the last dose of study 
treatment.  Men must refrain from donating sperm during this same period. 
• 
With pregnant female partners, men must remain abstinent or use a condom during 
the treatment period and for at least 28 days after the last dose of study treatment to 
avoid exposing the embryo. 
 
For Men and Women 
The reliability of sexual abstinence should be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the patient.  Periodic abstinence 
(e.g., calendar, ovulation, symptothermal, and post-ovulation methods) and withdrawal 
are not acceptable methods of contraception. 


 
GDC-0853—Genentech, Inc. 
112/ Protocol GA30066, Version 1  
Appendix 6  
Bottle and Label Configuration for GDC-0853 Administration  
Label to be affixed on the study drug bottle shows a.m. (sun) versus p.m. (moon) dose.  
Site will be responsible for prepopulating the dates on the label and affixing the label to 
the bottle. 
Patients should record the time (in military time) of each dose on the label.   
 


 
GDC-0853—Genentech, Inc. 
113/ Protocol GA30066, Version 1  
Appendix 7  
Concomitant Medications  
(Including Foods and Herbal Products) 
Class 
Expected Interaction 
Recommendation 
Examples of Drugs in this Class a 
Antacids 
Decreased 
GDC-0853 
absorption due to 
increased gastric pH 
Take GDC-0853 
2 hours before or 
2 hours after antacid 
• Maalox, Pepto-Bismol, Rolaids 
Moderate 
or strong 
CYP3A 
inhibitors  
Increased GDC-0853 
plasma 
concentrations due 
to inhibition of 
metabolism 
Avoid for 7 days or 
5 half-lives 
(whichever is 
longer) prior to first 
dose of study drug 
and during the 
treatment period, 
unless otherwise 
advised by the 
Medical Monitor or 
delegate b 
• Antimicrobials (clarithromycin, 
erythromycin, itraconazole, 
ketoconazole, telithromycin, 
troleandamycin, voriconazole, 
posaconazole) 
• Antidepressants (nefazodone) 
• Antihypertensive/cardiac 
(verapamil, diltiazem) 
• Other (grapefruit juice, Seville 
orange juice, pomegranate, star 
fruit) 
CYP3A 
inducers  
Decreased 
GDC-0853 plasma 
concentrations due 
to increased 
metabolism 
Avoid for 7 days or 
5 half-lives 
(whichever is 
longer) prior to first 
dose of study drug 
and during the 
treatment period, 
unless otherwise 
advised by the 
Medical Monitor or 
delegate b 
• Antimicrobials (rifampin, 
rifapentine, rifabutin) 
• Antidepressants (St. John’s wort, 
hyperforin) 
• Antiepileptics (carbamazepine, 
phenytoin, phenobarbital, 
hyperforin) 
• Diabetes (pioglitazone, 
troglitazone) 
• Other (modafinil, bosentan) 
Sensitive 
and 
narrow 
therapeutic 
window 
CYP3A 
substrates 
Potential for 
increased plasma 
concentrations of 
CYP3A substrates 
due to inhibition of 
metabolism by 
GDC-0853 
Use with caution 
and monitor for 
adverse events 
related to CYP3A 
substrates as 
directed by product 
labeling; consult 
with the Medical 
Monitor as needed b 
• Antiemetic/prokinetic (aprepitant, 
cisapride) 
• Anti-histamine (astemizole, 
terfenadine) 
• Anti-hypertensive/cardiac 
(dronedarone, eplerenone, 
felodipine, nisoldipine, quinidine, 
ticagrelor, vardenafil) 
• Benzodiazepines (alprazolam, 
diazepam, midazolam) 
• Lipid-lowering (simvastatin, 
lovastatin) 
• Migraine (eletriptan, ergotamine) 
• Steroids (budesonide, fluticasone) 
• Other (alfentanil, buspirone, 
conivaptan, darifenacin, dasatinib, 
dihydroergotamine, fentanyl, 
lurasidone, pimozide, quetiapine, 
sildenafil, tolvaptan, triazolam) 


 
 
Appendix 7  
Concomitant Medications  
(Including Foods and Herbal Products) (cont.) 
 
GDC-0853—Genentech, Inc. 
114/ Protocol GA30066, Version 1  
a The following list is not comprehensive.  Please refer to the Web sites below for additional 
information and consult the Medical Monitor if necessary: 
U.S. FDA Table of Substrates, Inhibitors, and Inducers (Tables 3-1, 3-2, and 3-3) 
(http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteract
ionsLabeling/ucm093664.htm) 
Indiana University Department of Medicine P450 Drug Interactions Table 
(http://medicine.iupui.edu/clinpharm/ddis/clinical-table) 
b  Potential CYP3A-mediated interactions between GDC-0853 and concomitant medications will 
be reviewed by the Medical Monitor or delegate during the pre-enrollment adjudication 
process. 
 
 


 
GDC-0853—Genentech, Inc. 
115/ Protocol GA30066, Version 1  
Appendix 8  
Systemic Lupus International Collaborating Clinics/American 
College of Rheumatology Damage Index for Systemic Lupus 
Erythematosus  
Damage (non-reversible change, not related to active inflammation) occurring since onset of lupus, ascertained by 
clinical assessment and present for at least 6 months unless otherwise stated.  Repeat episodes must occur at least 6 
months apart to score 2.  The same lesion cannot be scored twice. 
 
OCULAR (either eye, by clinical assessment) 
Any cataract ever (documented by ophthalmoscopy)  
 
 
 
 
 
 
 
 
 
1 
Retinal change OR Optic atrophy (documented by ophthalmoscopy) 
 
 
 
 
 
 
 
1 
 
NEUROPSYCHIATRIC 
Cognitive impairment (eg memory deficit, difficulty with calculation, poor concentration, difficulty in spoken or 
written language, impaired performance level) OR Major psychosis 
 
 
 
 
 
 
 
1 
Seizures requiring therapy for 6 months  
 
 
 
 
 
 
 
 
 
 
 
1 
Cerebrovascular accident or surgical resection (for non-malignant causes)  
 
 
(score 2 if >1) 
 
1 (2) 
Cranial or peripheral neuropathy (excluding optic) 
 
 
 
 
 
 
 
 
 
 
1 
Transverse myelitis  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
RENAL 
Estimated/Measured GFR < 50%  
 
 
 
 
 
 
 
 
 
 
 
 
1 
Proteinuria ≥ 3.5g/24 hours 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
OR 
End-stage renal failure (regardless of dialysis or transplantation) 
 
 
 
 
 
 
 
 
3 
 
PULMONARY 
Pulmonary hypertension (right ventricular prominence or loud P2)  
 
 
 
 
 
 
 
1 
Pulmonary fibrosis (physical & radiograph) 
 
 
 
 
 
 
 
 
 
 
 
1 
Shrinking lung (radiograph) 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
Pleural fibrosis (radiograph) 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
Pulmonary infarction (radiograph) 
 
 
 
 
 
 
1 
 
CARDIOVASCULAR 
Angina OR Coronary artery bypass 
 
 
 
 
 
 
 
 
 
 
 
 
1 
Myocardial infarction ever 
 
 
 
 
 
 
 
 
 
 (score 2 if > 1) 
 
1 (2) 
Cardiomyopathy (ventricular dysfunction) 
 
 
 
 
 
 
 
 
 
 
 
1 
Valvular disease (diastolic, murmur, or systolic murmur > 3/6) 
 
 
 
 
 
 
 
 
1 
Pericarditis for 6 months OR Pericardiectomy  
 
 
 
 
 
 
 
 
 
 
1 
 
PERIPHERAL VASCULAR 
Claudication for 6 months  
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
Minor tissue loss (pulp space) 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
Significant tissue loss ever (eg loss of digit or limb)   
 
 
 
 
 
(score 2 if > 1 site)  
1 (2) 
Venous thrombosis with swelling, ulceration, OR Venous stasis 
 
 
 
 
 
 
 
 
1 
 
GASTROINTESTINAL 
Infarction or resection of bowel below duodenum, spleen, liver or gallbladder for any cause 
 (score 2 if > 1 site) 
 
1 (2) 
Mesenteric insufficiency  
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
Chronic peritonitis  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
Stricture OR Upper gastrointestinal surgery ever 
 
 
 
 
 
 
 
 
 
 
1 
 
MUSCULOSKELETAL 
Muscle atrophy or weakness 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
Deforming or erosive arthritis (including reversible deformities, excluding avascular necrosis)  
 
 
 
1 
Osteoporosis with fracture or vertebral collapse (excluding avascular necrosis)  
 
 
 
 
 
1 
Avascular necrosis (imaging)  
 
 
 
 
 
 
 
 
 
(score 2 if > 1) 
 
1 (2) 
Osteomyelitis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
SKIN 
Scarring chronic alopecia  
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
Extensive scarring or panniculum other than scalp and pulp space  
 
 
 
 
 
 
 
1 
Skin ulceration for > 6 months (excluding thrombosis) 
 
 
 
 
 
 
 
 
 
1 
 
PREMATURE GONADAL FAILURE (secondary amenorrhoea before age 40)  
 
 
 
 
 
1 
 
DIABETES MELLITUS (regardless of treatment)   
 
 
 
 
 
 
 
 
 
1 


 
 
Appendix 8  
Systemic Lupus International Collaborating Clinics /American 
College of Rheumatology Damage Index for Systemic Lupus 
Erythematosus (cont.)  
GDC-0853—Genentech, Inc. 
116/ Protocol GA30066, Version 1  
 
MALIGNANCY (exclude dysplasia) 
 
 
 
 
  
 
 
 
(score 2 if > 1 site)   
1 (2) 
Source: Gladman 1997 
 
GLOSSARY OF TERMS:  SYSTEMIC LUPUS INTERNATIONAL COLLABORATING 
CLINICS/AMERICAN COLLEGE OF RHEUMATOLOGY DAMAGE INDEX FOR 
SYSTEMIC LUPUS ERYTHEMATOSUS:  
Source:  Gladman 1996 
 
Damage: 
Non-reversible change, not related to active inflammation, occurring since diagnosis of 
lupus, ascertained by clinical assessment and present for at least 6 months unless 
otherwise stated.  Repeat episodes must occur at least 6 months apart to score 2.  The 
same lesion cannot be scored twice. 
Cataract: 
A lens opacity (cataract) in either eye, ever, whether primary or secondary to steroid 
therapy, documented by ophthalmoscopy. 
Retinal change: 
Documented by ophthalmoscopic examination, may result in field defect, legal blindness. 
Optic Atrophy: 
Documented by ophthalmoscopic examination. 
Cognitive Impairment: 
Memory deficit, difficulty with calculation, poor concentration, difficulty in spoken or 
written language, impaired performance level, documented on clinical examination or by 
formal neurocognitive testing. 
Major Psychosis: 
Altered ability to function in normal activity due to psychiatric reasons.  Severe 
disturbance in the perception of reality characterized by the following features: delusions, 
hallucinations (auditory, visual), incoherence, marked loose associations, impoverished 
thought content, marked illogical thinking, bizarre, disorganized or catatonic behavior. 
Seizures: 
Paroxysmal electrical discharge occurring in the brain and producing characteristic 
physical changes including tonic and clonic movements and certain behavioral disorders. 
Only seizures requiring therapy for 6 months are counted as damage. 
CVA: 
Cerebrovascular accident resulting in focal findings such as paresis, weakness, etc., or 
surgical resection for causes other than malignancy. 


 
 
Appendix 8  
Systemic Lupus International Collaborating Clinics /American 
College of Rheumatology Damage Index for Systemic Lupus 
Erythematosus (cont.)  
GDC-0853—Genentech, Inc. 
117/ Protocol GA30066, Version 1  
Neuropathy: 
Damage to either a cranial or peripheral nerve, excluding optic nerve, resulting in either 
motor or sensory dysfunction. 
Transverse Myelitis: 
Lower-extremity weakness or sensory loss with loss of rectal and urinary bladder 
sphincter control. 
Renal: 
Estimated or measured glomerular filtration rate  50%, proteinuria  3.5gm/24 hours, or 
end-stage renal disease (regardless of dialysis or transplantation). 
Pulmonary: 
Pulmonary hypertension (right ventricular prominence, or loud P2), pulmonary fibrosis 
(physical and radiograph), shrinking lung (radiograph), pleural fibrosis (radiograph), 
pulmonary infarction (radiograph), resection for cause other than malignancy. 
Cardiovascular: 
Angina or coronary artery bypass, myocardial infarction (documented by 
electrocardiograph and enzyme studies) ever, cardiomyopathy (ventricular dysfunction 
documented clinically), valvular disease (diastolic murmur, or systolic murmur > 3/6), 
pericarditis for 6 months, or pericardiectomy. 
Peripheral Vascular: 
Claudication, persistent for 6 months, by history, minor tissue loss, such as pulp space, 
ever, significant tissue loss, such as loss of digit or limb, or resection, ever, venous 
thrombosis with swelling, ulceration or clinical evidence of venous stasis. 
Gastrointestinal: 
Infarction or resection of bowel below duodenum, by history, resection of spleen, liver, or 
gall bladder ever, for whatever cause, mesenteric insufficiency, with diffuse abdominal 
pain on clinical examination, chronic peritonitis, with persistent abdominal pain and 
peritoneal irritations, on clinical examination, esophageal stricture, shown on endoscopy, 
upper gastrointestinal tract surgery, such as correction of stricture, ulcer surgery, etc., 
ever, by history. 
Musculoskeletal: 
Muscle atrophy or weakness, demonstrated on clinical examination, deforming or 
erosive arthritis, including reducible deformities, (excluding avascular necrosis) on 
clinical examination, osteoporosis with fracture or vertebral collapse (excluding 
avascular necrosis) demonstrated radiographically, avascular necrosis, demonstrated by 
any imaging technique, osteomyelitis, documented clinically, and supported by culture 
evidence. 


 
 
Appendix 8  
Systemic Lupus International Collaborating Clinics /American 
College of Rheumatology Damage Index for Systemic Lupus 
Erythematosus (cont.)  
GDC-0853—Genentech, Inc. 
118/ Protocol GA30066, Version 1  
Skin: 
Scarring, chronic alopecia, documented clinically, extensive scarring or panniculum 
other than scalp and pulp space, documented clinically, skin ulceration (excluding 
thrombosis) for more than 6 months. 
Premature gonadal failure: 
Secondary amenorrhea, prior to age 40. 
Diabetes: 
Diabetes requiring therapy, but regardless of treatment. 
Malignancy: 
Documented by pathologic examination, excluding dysplasias.  


 
GDC-0853—Genentech, Inc. 
119/ Protocol GA30066, Version 1  
Appendix 9  
BILAG-2004 Index Glossary 
INSTRUCTIONS 
 
• 
Only record features that are attributable to SLE disease activity and not due to 
damage, infection, thrombosis (in absence of inflammatory process) or other 
conditions 
• 
Assessment refers to manifestations occurring in the last 4 weeks compared with 
the previous 4 weeks 
• 
Activity refers to disease process which is reversible while damage refers to 
permanent process/scarring (irreversible) 
• 
Damage due to SLE should be considered as a cause of features that are 
fixed/persistent (SLICC/ACR damage index uses persistence ≥ 6 months to define 
damage) 
• 
In some manifestations, it may be difficult to differentiate SLE from other conditions 
as there may not be any specific test and the decision would then lies with the 
physician’s judgement on the balance of probabilities 
• 
Ophthalmic manifestations usually need to be assessed by an ophthalmologist and 
these items would need to be recorded after receiving the response from the 
ophthalmologist 
• 
Guidance for recording: 
 
(4) NEW  
• 
Manifestations are recorded as new when it is a new episode occurring in the last 4 
weeks (compared to the previous 4 weeks) that has not improved and this includes 
new episodes (recurrence) of old manifestations  
• 
New episode occurring in the last 4 weeks but also satisfying the criteria for 
improvement (below) would be classified as improving instead of new 
 
(3) Worse 
• 
This refers to manifestations that have deteriorated/worsened significantly in the last 
4 weeks compared to the previous 4 weeks, sufficient for consideration of increase in 
therapy 
 
(2) Same 
• 
This refers to manifestations that have been present for the last 4 weeks and the  
previous 4 weeks without significant improvement or deterioration (from the previous 
4 weeks) 
• 
This also applies to manifestations that have improved over the last 4 weeks 
compared to the previous 4 weeks but do not meet the criteria for improvement 
 


 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
120/ Protocol GA30066, Version 1  
(1) Improving 
• 
Definition of improvement:  
a) The amount of improvement is sufficient for consideration of reduction in 
therapy and would not justify escalation in therapy 
AND   
b) Improvement must be present currently and for at least 2 weeks out of the 
last 4 weeks 
OR 
Manifestation that has completely resolved and remained absent over the 
whole of last 1 week 
 
(0) Not present 
(ND) Not done 
• 
It is important to indicate if a test has not been performed (particularly laboratory  
investigations) so that this will be recorded as such in the database & not as normal 
or absent (which is the default) 
 
Y/N - Indicate if ITEM is due to SlE activity 
• 
For descriptors that are based on measurements (in renal and haematology 
systems), it is important to indicate if these are not due to lupus disease activity (for 
consideration of scoring) as they are usually recorded routinely into a database 
 
TRICKLE DOWN RULE 
• 
When item of highest level of severity is recorded, similar item of lower level of 
severity must be recorded as well (item of lower level of severity must not be 
recorded as not present) 
 
CHANGE IN SEVERITY CATEGORY 
• 
There are several items in the index which have been divided into categories of mild 
and severe (depending on definition). It is essential to record mild and severe items 
appropriately if the manifestations fulfil both criteria during the last 4 weeks 
• 
If a mild item deteriorated to the extent that it fulfilled the definition of severe   
category (ie changed into severe category) within the last 4 weeks: 
Severe item scored as new (4)  
AND mild item scored as worsening (3) 


 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
121/ Protocol GA30066, Version 1  
• 
If a severe item improved (fulfilling the improvement criteria) to the extent that it no 
longer fulfilled the definition of severe category (ie changed into mild category) 
within the last 4 weeks: 
Severe item scored as not present (0) if criteria for severe category has not 
been met over last 4 weeks 
Or as improving (1) if criteria for severe category has been met at some point 
over last 4 weeks 
AND  
mild item scored as improving (1) if it is improving over last 4 weeks  or as the 
same (2) if it has remained stable over last 4 weeks 
  




 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
123/ Protocol GA30066, Version 1  
3. Lymphadenopathy  
 
 
lymph node more than 1 cm diameter 
 
 
 
 
 
 
 
 
 
exclude infection 
 
 
 
4. Anorexia 
 
MUCOCUTANEOUS 
 
5. Severe eruption 
 
 
  
 
> 18% body surface area 
                         
any lupus rash except panniculitis, bullous lesion & 
angio-oedema 
 
body surface area (BSA) is estimated using the rules 
of nines (used to assess extent of burns) as follows: 
 
palm(excluding fingers) = 1% BSA 
each lower limb = 18% BSA 
each upper limb = 9% BSA 
torso (front) = 18% BSA 
torso (back) = 18% BSA 
head = 9% BSA 
genital (male) = 1% BSA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
124/ Protocol GA30066, Version 1  
6. Mild eruption  
≤ 18% body surface area 
any lupus rash except panniculitis, bullous 
lesion & angio-oedema 
 
malar rash must have been observed by a 
physician and has to be present 
continuously (persistent) for at least 1 week 
to be considered significant (to be recorded) 
 
7. Severe angio-oedema   
 
 
 
potentially life-threatening eg: stridor 
 
angio-oedema is a variant form of urticaria  
which affects the subcutaneous, 
submucosal and deep dermal tissues 
 
8. Mild angio-oedema  
 
 
 
 
not life threatening 
 
9. Severe mucosal ulceration 
disabling (significantly interfering with oral  
intake), extensive & deep ulceration 
 
 
 
 
 
 
 
must have been observed by a physician 
 
10. Mild mucosal ulceration 
 
 
 
localised &/or non-disabling ulceration 
 
11. Severe panniculitis or bullous lupus 
any one: 
> 9% body surface area 
facial panniculitis 
     panniculitis that is beginning to ulcerate 
     panniculitis that threatens integrity of  
     subcutaneous tissue (beginning to cause   
     surface depression) on > 9% body 
surface area 
 
panniculitis presents as a palpable and 
tender  
subcutaneous induration/nodule  
 
note that established surface depression 
and atrophy alone is likely to be due to 
damage 
 
12. Mild panniculitis or bullous lupus 
≤ 9% body surface area   
does not fulfil any criteria for severe 
panniculitis (for panniculitis) 
 
13. Major cutaneous vasculitis/thrombosis resulting in extensive gangrene or ulceration 
or  
skin infarction 


 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
125/ Protocol GA30066, Version 1  
 
14. Digital infarct or nodular vasculitis   
localised single or multiple infarct(s) over  
digit(s) or tender erythematous nodule(s) 
 
15. Severe alopecia 
clinically detectable (diffuse or patchy) hair 
loss  
with scalp inflammation (redness over 
scalp) 
16. Mild alopecia 
diffuse or patchy hair loss without scalp 
inflammation (clinically detectable or by 
history) 
 
17. Peri-ungual erythema or chilblains 
chilblains are localised inflammatory lesions  
                                                                        (may ulcerate) which are precipitated by  
exposure to cold 
 
18. Splinter haemorrhages 
 
 
NEUROPSYCHIATRIC 
 
19. Aseptic meningitis 
 
 
 
 
criteria (all): acute/subacute onset 
headache 
fever 
abnormal CSF (raised protein &/or  
   lymphocyte predominance) but negative       
cultures 
 
preferably photophobia, neck stiffness and  
meningeal irritation should be present as 
well but are not essential for diagnosis 
 
exclude CNS/meningeal infection, 
intracranial    
haemorrhage 
 
20. Cerebral vasculitis 
 
 
 
 
should be present with features of vasculitis  
in another system  
 
supportive imaging &/or biopsy findings 
 
21. Demyelinating syndrome  
 
 
discrete white matter lesion with associated   
  
 
 
 
 
 
 
 
 
 
neurological deficit not recorded elsewhere 
 
ideally there should have been at least one 
previously recorded event 
 


 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
126/ Protocol GA30066, Version 1  
supportive imaging required 
 
exclude multiple sclerosis 
 
22. Myelopathy 
acute onset of rapidly evolving paraparesis 
or  
quadriparesis and/or sensory level 
 
exclude intramedullary and extramedullary  
space occupying lesion 
 
23. Acute confusional state 
acute disturbance of consciousness or level 
of arousal with reduced ability to focus, 
maintain or shift attention 
includes hypo- and hyperaroused states 
and encompasses the spectrum from 
delirium to coma 
 
24. Psychosis 
 
 
 
 
 
 
delusion or hallucinations  
 
 
 
does not occur exclusively during course of 
a delirium 
 
exclude drugs, substance abuse, primary  
psychotic disorder 
 
25. Acute inflammatory demyelinating  
 
Criteria: 
polyradiculoneuropathy 
 
 
      
 
progressive polyradiculoneuropathy 
 
loss of reflexes 
 
symmetrical involvement 
 
increased CSF protein without 
pleocytosis 
supportive electrophysiology study 
 
26. Mononeuropathy (single/multiplex)  
supportive electrophysiology study required 
 
27. Cranial neuropathy 
 
 
 
 
except optic neuropathy which is classified  
under ophthalmic system 
 
28. Plexopathy 
 
 
 
 
 
 
disorder of brachial or lumbosacral plexus  
resulting in neurological deficit not  
corresponding to territory of single root or 
nerve 
 
supportive electrophysiology study required 
 


 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
127/ Protocol GA30066, Version 1  
29. Polyneuropathy 
acute symmetrical distal sensory and/or 
motor deficit 
 
 
 
 
 
 
 
 
 
 
 
supportive electrophysiology study required 
 
30. Seizure disorder 
independent description of seizure by 
reliable witness 
 
31. Status epilepticus  
 
 
 
 
a seizure or series of seizures lasting ≥ 30  
minutes without full recovery to baseline 
 
32. Cerebrovascular disease  
 
 
any one with supporting imaging: 
       (not due to vasculitis)  
 
   
 
   stroke syndrome 
 
 
 
 
 
 
    
 
 
 
   transient ischaemic attack 
 
 
 
 
 
 
   
 
 
 
   intracranial haemorrhage 
 
 
 
 
 
 
 
exclude hypoglycaemia, cerebral sinus 
thrombosis, vascular malformation, tumour, 
abscess 
 
cerebral sinus thrombosis not included as  
definite thrombosis not considered part of 
lupus activity 
 
33. Cognitive dysfunction  
 
 
 
significant deficits in any cognitive functions: 
simple attention (ability to register & 
maintain                                                                         
information) 
complex attention 
memory (ability to register, recall & 
recognise information eg learning, recall) 
visual-spatial processing (ability to 
analyse, synthesize & manipulate 
visual-spatial information) 
language (ability to comprehend, repeat &  
   produce oral/written material eg verbal  
   fluency, naming) 
reasoning/problem solving (ability to 
reason &  
   abstract) 
psychomotor speed 
executive functions (eg planning, 
organising,  
     sequencing) 
 
in absence of disturbance of 
consciousness or level of arousal 
 


 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
128/ Protocol GA30066, Version 1  
sufficiently severe to interfere with daily  
activities 
 
neuropsychological testing should be 
done or  
corroborating history from third party if 
possible  
 
exclude substance abuse 
 
34. Movement disorder 
 
 
 
 
exclude drugs 
 
35. Autonomic disorder 
 
 
 
 
any one: 
fall in blood pressure to standing > 30/15 
mm Hg (systolic/diastolic) 
 
increase in heart rate to standing ≥ 30 
bpm 
 
loss of heart rate variation with respiration   
(max – min < 15 bpm, 
expiration:inspiration ratio < 1.2, Valsalva 
ratio < 1.4) 
 
loss of sweating over body and limbs   
(anhidrosis) by sweat test 
 
 
 
 
 
 
 
 
 
 
 
exclude drugs and diabetes mellitus 
 
36. Cerebellar ataxia 
cerebellar ataxia in isolation of other CNS 
features 
 
usually subacute presentation 
 
37. Severe lupus headache (unremitting) 
disabling headache unresponsive to 
narcotic analgesia & lasting ≥ 3 days 
 
exclude intracranial space occupying lesion  
and CNS infection 
 
38. Headache from IC hypertension 
 
exclude cerebral sinus thrombosis 
 
 


 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
129/ Protocol GA30066, Version 1  
MUSCULOSKELETAL 
 
39. Severe myositis 
significantly elevated serum muscle 
enzymes  
with significant muscle weakness 
 
exclude endocrine causes and drug-induced  
myopathy 
 
electromyography and muscle biopsy are 
used for diagnostic purpose and are not 
required to determine level of activity 
 
40. Mild myositis 
significantly elevated serum muscle 
enzymes  
with myalgia but without significant muscle  
weakness 
 
asymptomatic elevated serum muscle 
enzymes not included 
 
exclude endocrine causes and drug-induced  
myopathy 
 
electromyography and muscle biopsy are 
used for diagnostic purpose and are not 
required to determine level of activity 
 
41. Severe arthritis 
observed active synovitis ≥ 2 joints with 
marked   
loss of functional range of movements and  
significant impairment of activities of daily  
living, that has been present on several 
days (cumulatively) over the last 4 weeks 
 
42. Moderate arthritis or Tendonitis 
tendonitis/tenosynovitis or active synovitis ≥ 
1  
       or Tenosynovitis  
joint (observed or through history) with 
some loss of functional range of movements, 
that has been present on several days over 
the last 4 weeks 
 
43. Mild arthritis or Arthralgia or Myalgia 
inflammatory type of pain (worse in the 
morning with stiffness, usually improves 
with activity & not brought on by activity) 
over joints/muscle  
 


 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
130/ Protocol GA30066, Version 1  
inflammatory arthritis which does not fulfil 
the above criteria for moderate or severe 
arthritis 
 
CARDIORESPIRATORY 
 
44. Mild myocarditis  
 
 
 
 
inflammation of myocardium with raised  
cardiac enzymes &/or ECG changes and 
without resulting cardiac failure, arrhythmia 
or valvular dysfunction 
 
45. Cardiac failure 
cardiac failure due to myocarditis or non-
infective inflammation of endocardium or 
cardiac valves (endocarditis) 
 
 
cardiac failure due to myocarditis is defined 
by left ventricular ejection fraction ≤ 40% & 
pulmonary oedema or peripheral oedema 
 
cardiac failure due to acute valvular 
regurgitation (from endocarditis) can be 
associated with normal left ventricular 
ejection fraction 
 
 
diastolic heart failure is not included 
 
46. Arrhythmia 
arrhythmia (except sinus tachycardia) due 
to myocarditis or non-infective inflammation 
of endocardium or cardiac valves 
(endocarditis) 
 
 
 
 
 
 
 
 
 
 
 
confirmation by electrocardiogram required  
(history of palpitations alone inadequate) 
 
47. New valvular dysfunction 
new cardiac valvular dysfunction due to 
myocarditis or non-infective inflammation of 
endocardium or cardiac valves (endocarditis) 
 
supportive imaging required 
 
48. Pleurisy/Pericarditis 
convincing history &/or physical findings that 
you would consider treating 
 
 
in absence of cardiac tamponade or pleural 
effusion with dyspnoea 
 


 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
131/ Protocol GA30066, Version 1  
                                                                        do not score if you are unsure whether or 
not it is pleurisy/pericarditis 
 
49. Cardiac tamponade 
 
 
 
 
supportive imaging required 
50. Pleural effusion with dyspnoea  
 
supportive imaging required 
51. Pulmonary haemorrhage/vasculitis  
inflammation of pulmonary vasculature with  
haemoptysis &/or dyspnoea &/or pulmonary 
hypertension 
 
supportive imaging &/or histological 
diagnosis required 
 
52. Interstitial alveolitis/pneumonitis 
radiological features of alveolar infiltration 
not due to infection or haemorrhage 
required for diagnosis 
 
corrected gas transfer Kco reduced to < 70% 
normal or fall of > 20% if previously 
abnormal 
 
 
 
 
 
 
 
 
 
 
 
on-going activity would be determined by  
clinical findings and lung function tests, and  
repeated imaging may be required in those 
with deterioration (clinically or lung function 
tests) or failure to respond to therapy 
 
53. Shrinking lung syndrome  
 
 
acute reduction (>20% if previous 
measurement  
available) in lung volumes (to < 70% 
predicted)  
in the presence of normal corrected gas 
transfer  
(Kco) & dysfunctional diaphragmatic 
movements 
 
54. Aortitis 
 
 
 
 
 
 
 
inflammation of aorta (with or without  
dissection) with supportive imaging 
abnormalities  
 
accompanied by > 10 mm Hg difference in 
BP between arms &/or claudication of 
extremities &/or vascular bruits 
 
repeated imaging would be required to 
determine on-going activity in those with 
clinical deterioration or failure to respond to 
therapy 
 


 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
132/ Protocol GA30066, Version 1  
55. Coronary vasculitis 
 
 
 
 
 
inflammation of coronary vessels with  
radiographic evidence of non-atheromatous 
narrowing, obstruction or aneurysmal 
changes 
 
GASTROINTESTINAL 
 
56. Lupus peritonitis  
 
 
 
 
serositis presenting as acute abdomen with  
rebound/guarding 
 
57. Serositis  
 
 
 
 
 
 
not presenting as acute abdomen 
 
58. Lupus enteritis or colitis 
vasculitis or inflammation of small or large 
bowel with supportive imaging &/or biopsy 
findings 
 
59. Malabsorption 
diarrhoea with abnormal D- xylose 
absorption  
test or increased faecal fat excretion after 
exclusion of coeliac’s disease (poor 
response to gluten-free diet) and gut 
vasculitis 
 
60. Protein-losing enteropathy 
diarrhoea with hypoalbuminaemia or 
increased  
faecal excretion of iv radiolabeled albumin 
after exclusion of gut vasculitis and 
malabsorption 
 
61. Intestinal pseudo-obstruction 
subacute intestinal obstruction due to 
intestinal hypomotility 
 
62. Lupus hepatitis 
 
 
 
 
 
 
raised transaminases  
 
absence of autoantibodies specific to 
autoimmune hepatitis (eg: anti-smooth 
muscle, anti-liver cytosol 1) &/or biopsy 
appearance of chronic active hepatitis 
 
hepatitis typically lobular with no piecemeal 
necrosis 
 
exclude drug-induced and viral hepatitis 
 
63. Acute lupus cholecystitis 
 
 
 
after exclusion of gallstones and infection 
 
64. Acute lupus pancreatitis 
 
 
 
usually associated multisystem involvement 


 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
133/ Protocol GA30066, Version 1  
 
OPHTHALMIC 
 
65. Orbital inflammation 
 
 
 
 
orbital inflammation with myositis &/or extra- 
ocular muscle swelling &/or proptosis 
 
 
 
 
 
 
 
 
 
 
 
supportive imaging required 
 
66. Severe keratitis   
 
 
 
 
sight threatening 
includes:  corneal melt 
    peripheral ulcerative keratitis 
 
67. Mild keratitis  
 
 
 
 
 
not sight threatening 
 
68. Anterior uveitis 
69. Severe posterior uveitis &/or retinal   
sight-threatening &/or retinal vasculitis 
       vasculitis 
 
 
 
 
 
 
 
not due to vaso-occlusive disease 
 
70. Mild posterior uveitis &/or retinal 
 
 
not sight-threatening 
       vasculitis 
 
 
 
 
 
 
not due to vaso-occlusive disease 
 
71. Episcleritis 
 
72. Severe scleritis 
 
 
 
 
 
necrotising anterior scleritis 
anterior &/or posterior scleritis requiring  
systemic steroids/immunosuppression &/or 
not responding to NSAIDs 
 
73. Mild scleritis 
anterior &/or posterior scleritis not requiring 
systemic steroids 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
excludes necrotising anterior scleritis 
 
74. Retinal/choroidal vaso-occlusive  
 
includes: retinal arterial & venous occlusion 
disease 
 
 
 
 
 
   
 
 
serous retinal &/or retinal pigment  
epithelial detachments secondary to    
choroidal vasculopathy 
 
75. Isolated cotton-wool spots  
 
 
also known as cytoid bodies 
 
 
 
76. Optic neuritis  
 
 
 
 
 
excludes anterior ischaemic optic 
neuropathy 
 
77. Anterior ischaemic optic neuropathy 
visual loss with pale swollen optic disc due 
to occlusion of posterior ciliary arteries 
 


 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
134/ Protocol GA30066, Version 1  
RENAL 
 
78. Systolic blood pressure 
79. Diastolic blood pressure 
80. Accelerated hypertension  
 
 
blood pressure rising to > 170/110 mm Hg  
within 1 month with grade 3 or 4 Keith-
Wagener-Barker retinal changes (flame-
shaped haemorrhages or cotton-wool spots 
or papilloedema) 
 
81. Urine dipstick 
82. Urine albumin-creatinine ratio  
 
on freshly voided urine sample 
 
 
 
 
 
 
 
 
 
conversion: 1 mg/mg = 113 mg/mmol 
it is important to exclude other causes 
(especially infection) when proteinuria is 
present 
 
83. Urine protein-creatinine ratio 
 
 
on freshly voided urine sample 
 
 
 
 
 
 
 
 
 
 
 
conversion: 1 mg/mg = 113 mg/mmol 
 
it is important to exclude other causes 
(especially infection) when proteinuria is 
present 
 
84. 24 hour urine protein 
it is important to exclude other causes 
(especially infection) when proteinuria is 
present 
 
85. Nephrotic syndrome 
 
 
 
 
criteria: 
heavy proteinuria ( ≥ 3.5 g/day or protein-  
creatinine ratio ≥ 350 mg/mmol or 
albumin- 
creatinine ratio ≥ 350 mg/mmol) 
 
hypoalbuminaemia  
oedema 
 
86. Plasma/Serum creatinine  
 
 
exclude other causes for increase in 
creatinine  
(especially drugs) 
 


 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
135/ Protocol GA30066, Version 1  
87. GFR  
 
 
 
 
 
 
 
MDRD formula: 
GFR = 170 x [serum creatinine (mg/dl)]-0.999 
x  [age]-0.176 x [serum urea (mg/dl]-0.17 x  
[serum albumin (g/dl)]0.318 x [0.762 if female] 
x [1.180 if African ancestry] 
 
 
 
 
 
 
 
units = ml/min per 1.73 m2 
normal: male = 130 ± 40 
 
     female = 120 ± 40 
 
conversion: 
serum creatinine  -  mg/dl = (µmol/l)/88.5 
serum urea          -   mg/dl = (mmol/l) x 2.8 
serum albumin    -    g/dl    = (g/l)/10 
 
creatinine clearance not recommended as it 
is not reliable 
 
exclude other causes for decrease in GFR 
(especially drugs) 
 
88. Active urinary sediment 
 
 
 
pyuria (> 5 WCC/hpf or > 10 WCC/mm3 (µl))  
 
   OR 
 
haematuria (> 5 RBC/hpf or > 10 RBC/mm3 
(µl)) 
 
   OR 
 
red cell casts  
 
   OR 
 
white cell casts 
 
exclude other causes (especially infection,  
vaginal bleed, calculi) 
 
89. Histology of active nephritis 
WHO Classification (1995): (any one)  
   Class III – (a) or (b) subtypes 
   Class IV – (a), (b) or (c) subtypes 
   Class V – (a), (b), (c) or (d) subtypes 
   Vasculitis 
 
 
   OR 
 


 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
136/ Protocol GA30066, Version 1  
 
ISN/RPS Classification (2003): (any one) 
 
   Class III – (A) or (A/C) subtypes 
 
   Class IV – (A) or (A/C) subtypes 
 
   Class V 
 
   Vasculitis 
  
 
within last 3 months 
 
glomerular sclerosis without inflammation 
not included 
 
HAEMATOLOGICAL 
 
90. Haemoglobin  
 
 
 
 
 
exclude dietary deficiency & GI blood loss 
91. White cell count 
 
 
 
 
 
exclude drug-induced cause 
92. Neutrophil count  
 
 
 
 
exclude drug-induced cause 
93. Lymphocyte count 
94. Platelet count  
 
 
 
 
 
exclude drug-induced cause 
95. TTP  
 
 
 
 
 
 
 
thrombotic thrombocytopaenic purpura 
 
 
 
 
 
 
 
clinical syndrome of micro-angiopathic 
haemolytic anaemia and thrombocytopenia 
in absence of any other identifiable cause 
 
96. Evidence of active haemolysis 
positive Coombs’ test & evidence of 
haemolysis (raised bilirubin or raised 
reticulocyte count or reduced haptoglobulins 
or fragmented RBC or microspherocytes) 
 
97. Isolated positive Coombs’ test 
 
ADDITIONAL ITEMS 
 
These items are required mainly for calculation of GFR 
 
      i.  
Weight 
      ii.  
African ancestry   
 
 
 
 
      iii.  Serum urea 
      iv.  Serum albumin 
 
 
 
 


 
 
Appendix 9  
BILAG-2004 Index Glossary (cont.)  
GDC-0853—Genentech, Inc. 
137/ Protocol GA30066, Version 1  
REFERENCES 
Rule of nines diagram. Burn Center, University of Utah Health Sciences Center 
(http://uuhsc.utah.edu/burncenter/emergencycare/extent.html) 
Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular 
filtration rate from serum creatinine: a new prediction equation. Modification of Diet 
in Renal Disease Study Group. Ann Intern Med 1999;130:461−70.  
Weening JJ, D'Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in 
systemic lupus erythematosus revisited. J Am Soc Nephrol 2004;15:241−50. 


 
GDC-0853—Genentech, Inc. 
138/ Protocol GA30066, Version 1  
Appendix 10  
Systemic Lupus Erythematosus Disease Activity Index 2000  
(SLEDAI-2K) 
(Circle in SLEDAI Score column if descriptor is present at the time of the visit or in 
the preceding 4 weeks.) (The same instrument can also be used going back only 
10 days.) 
 
 
Item 
no. 
SLEDAI 
SCORE 
Descriptor 
Definition 
1 
8 
Seizure 
Recent onset, exclude metabolic, infectious or drug 
causes 
2 
8 
Psychosis 
Altered ability to function in normal activity due to 
severe disturbance in the perception of reality. Include 
hallucinations, incoherence, marked loose 
associations, impoverished thought content, marked 
illogical thinking, bizarre, disorganised, or catatonic 
behaviour. Exclude uraemia and drug causes 
3 
8 
Organic brain 
syndrome 
Altered mental function with impaired orientation, 
memory, or other intellectual function, with rapid onset 
and fluctuating clinical features, inability to sustain 
attention to environment, plus at least 2 of the 
following: perceptual disturbance, incoherent speech, 
insomnia or daytime drowsiness, or increased or 
decreased psychomotor activity. Exclude metabolic, 
infectious or drug causes 
4 
8 
Visual disturbance 
Retinal changes of SLE. Include cytoid bodies, retinal 
hemorrhages, serous exudates or hemorrhages in the 
choroid, or optic neuritis. Exclude hypertension, 
infection, or drug causes 
5 
8 
Cranial nerve 
disorder 
New onset of sensory or motor neuropathy involving 
cranial nerves 
6 
8 
Lupus headache 
Severe, persistent headache; may be migrainous, but 
must be non-responsive to narcotic analgesia THIS 
WOULD RARELY BE ATTRIBUTED TO 
SLE...ALMOST NEVER SCORED 
7 
8 
CVA 
New onset Cerebrovascular accident(s). Exclude 
arteriosclerosis 
8 
8 
Vasculitis 
Ulceration, gangrene, tender finger nodules, 
periungual infarction, splinter hemorrhages or biopsy 
or angiogram proof of vasculitis 
9 
4 
Arthritis 
>/= 2 joints with pain and signs of inflammation (i.e. 
tenderness, swelling or effusion) 
10 
4 
Myositis 
Proximal muscle aching/weakness, associated with 
elevated creatinine phosphokinase (CK)/aldolase, or 
EMG changes or a biopsy showing myositis 
11 
4 
Urinary casts 
Heme-granular or RBC casts 
12 
4 
Hematuria 
> 5 RBC/high power field. Exclude stone, infection or 
other cause 
13 
4 
Proteinuria 
> 0.5 gram/24 hours 
14 
4 
Pyuria 
> 5 WBC/high power field. Exclude infection 
15 
2 
Rash 
Inflammatory type rash 


 
 
Appendix 10  
Systemic Lupus Erythematosus Disease Activity Index  
(SLEDAI-2K) (cont.) 
 
GDC-0853—Genentech, Inc. 
139/ Protocol GA30066, Version 1  
Item 
no. 
SLEDAI 
SCORE 
Descriptor 
Definition 
16 
2 
Alopecia 
Abnormal, patchy or diffuse loss of hair 
17 
2 
Mucosal ulcers 
Oral or nasal ulcerations 
18 
2 
Pleurisy 
Pleuritic chest pain or pleural rub with effusion, or 
pleural thickening (requires objective evidence) 
19 
2 
Pericarditis 
Classic pericardial pain and/or rub, effusion with ECG 
or echocardiogram confirmation (requires an objective 
component) 
20 
2 
Low complement 
Decrease in CH50, C3 or C4 below lower limit of 
normal for testing laboratory  
21 
2 
Increased DNA 
binding 
Increased DNA binding above normal range for 
testing laboratory 
22 
1 
Fever 
> 38ºC. Exclude infectious cause 
23 
1 
Thrombocytopenia 
< 100 x 109 platelets/L, exclude drug causes 
24 
1 
Leukopenia 
< 3 x 109 WBC/L, exclude drug causes 
SCORE:       


 
 
Appendix 10  
Systemic Lupus Erythematosus Disease Activity Index  
(SLEDAI-2K) (cont.) 
 
GDC-0853—Genentech, Inc. 
140/ Protocol GA30066, Version 1  
 
GUIDELINES FOR USE OF SLEDAI-2K MODIFIED FOR 
ASSESSMENT OVER 28 DAYS:  TO ASSESS DISEASE ACTIVITY  
General guidelines for filling out the SLEDAI-2K: 
• 
The main principle to keep in mind is that this instrument is intended to 
evaluate current lupus activity and not chronic damage, severity is 
accounted for in part by the "weightedness" of the scale.  
• 
Points are given exactly as defined. 
• 
A descriptor is either scored the exact points allotted or not scored, i.e. 
given a zero. Descriptors are scored only if they are present at the time of 
the physician encounter or in the preceding 28 days. Windows acceptable 
in a clinical trial are acceptable in scoring the SLEDAI. However, it is 
never acceptable to fill in gaps which cover activity over 2-3 months or 
more. The reason for this is that disease activity at the visit might have 
changed several times in such intervals and the recording of distant 
activity becomes meaningless.  
 
Please note that in the original SLEDAI the disease activity being scored 
was meant to cover only a ten day period, the modification to 28 days is a 
more useful assessment for use in clinical trials, in order to capture 
disease activity between monthly visits. 
• 
The descriptor must be documented by the notes written in the physician 
encounter form and generally applies to the clinical data and not to the 
laboratory data. The laboratory data is strictly defined as per cutoffs and 
documentation is provided by the reports from the commercial laboratory.  
• 
Descriptors do not have to be new but can be. They can be ongoing, 
recurrent, or initial events. Each would be scored the same way. An 
example would be a malar rash or mucosal ulcer. In these situations a 
malar rash observed at the initial visit but which remains unchanged for 
the next six months, irrespective of any treatment, is scored 2 points each 
time the SLEDAI is completed. Since the nature of lupus is that 
manifestations are not usually fleeting it would be rare for descriptors to 
appear transiently during the month and not at the time of the encounter. 
This is discussed in more detail for each descriptor but is especially 


 
 
Appendix 10  
Systemic Lupus Erythematosus Disease Activity Index  
(SLEDAI-2K) (cont.) 
 
GDC-0853—Genentech, Inc. 
141/ Protocol GA30066, Version 1  
relevant for the neurologic (except for seizure or CVA), pulmonary, and 
cutaneous manifestations.  
• 
In some descriptors the exclusions written may not be exhaustive. The 
intent of the SLEDAI is that the descriptor be attributed to SLE. If the 
physician does not attribute the descriptor to SLE it should not be scored, 
but full documentation must be provided. 
Written in italics is the definition for each descriptor precisely provided in the 
SLEDAI SCORE  
SEIZURE 
Definition: Recent onset (last 28 days). Exclude metabolic, infectious or drug 
cause, or seizure due to past irreversible CNS damage. 
This descriptor is scored if the patient has had a witnessed seizure or convincing 
description (such as tongue biting or incontinence) within 30 days of the current 
encounter. The patient need not have a positive EEG, CT scan, PET scan, 
QEEG, or MRI. The CSF may be totally normal. 
A seizure is also not counted: 
1. If a metabolic cause is determined. 
2. In the presence of a proven infectious meningitis, brain abscess, or fungal 
foci. 
3. If there is a history of recent head trauma. 
4. In the presence of an offending drug. 
5. In the presence of severe hyperthermia or hypothermia. 
6. If the patient has stopped taking anticonvulsant medication. 
7. If the patient has a documented sub-therapeutic anticonvulsant drug level. 
PSYCHOSIS 
Definition: Altered ability to function in normal activity due to severe disturbance 
in the perception of reality. Include hallucinations, incoherence, marked loose 
associations, impoverished thought content, marked illogical thinking, bizarre, 
disorganized, or catatonic behavior. Exclude uremia and drug causes. 
This descriptor is scored if any of the criteria above are met. 


 
 
Appendix 10  
Systemic Lupus Erythematosus Disease Activity Index  
(SLEDAI-2K) (cont.) 
 
GDC-0853—Genentech, Inc. 
142/ Protocol GA30066, Version 1  
With regard to drug causes the most problematic situation is glucocorticoids. If 
the treating physician attributes the psychosis to glucocorticoids this descriptor 
should not be counted. 
ORGANIC BRAIN SYNDROME  
Definition: Altered mental function with impaired orientation, memory or other 
intellectual function, with rapid onset and fluctuating clinical features. Include 
clouding of consciousness with reduced capacity to focus, and inability to sustain 
attention to environment, plus at least two of the following: perceptual 
disturbance, incoherent speech, insomnia or daytime drowsiness, or increased or 
decreased psychomotor activity. Exclude metabolic, infectious or drug causes. 
a. reduced capacity to focus as exemplified by new inability to perform 
everyday mathematical computations or disorientation to person, place, 
time, or purpose 
 
OR 
b. inability to carry on a conversation 
 
OR 
c. reduction in short term memory 
PLUS:Documented abnormality on neuropsychiatric testing  
Neuropsychiatric testing may take the form of a "mini-mental-status exam" or a 
formal neuropsychiatric examination. The important aspect for scoring OBS is 
that it be reversible. Consideration should be given to the improvement of OBS 
after institution of glucocorticoids. 
This descriptor is not scored in the presence of a metabolic, infectious, or drug 
cause. If the problem is chronic this descriptor is not scored in SLEDAI but is 
scored on the damage index.  
VISUAL DISTURBANCE 
Definition: Retinal and eye changes of SLE. Include cytoid bodies, retinal 
hemorrhages, serous exudate or hemorrhages in the choroid, or optic neuritis. 
Exclude hypertension, infection or drug causes. 
This is scored exactly as defined with the understanding that it must be 
supported by objective evidence. 


 
 
Appendix 10  
Systemic Lupus Erythematosus Disease Activity Index  
(SLEDAI-2K) (cont.) 
 
GDC-0853—Genentech, Inc. 
143/ Protocol GA30066, Version 1  
CRANIAL NERVE DISORDER 
Definition: New onset of sensory or motor neuropathy involving cranial nerves. 
Include vertigo due to lupus. 
This is scored exactly as defined with the understanding that it must be 
supported by objective evidence. However, it should be noted that 
hydroxychloroquine can affect the eighth cranial nerve. 
LUPUS HEADACHE 
Definition: Severe persistent headache: may be migrainous, but must be non-
responsive to narcotic analgesia. 
For this descriptor to be counted, the headache must be present for greater than 
24 hours and must not be responsive to narcotic analgesia. Objective 
documentation need not be present although it is expected that such a complaint, 
given the severity, would prompt formal testing such as MRI, CT, LP, etc. 
Furthermore, the headache should be of sufficient severity to warrant the 
initiation of glucocorticoids or additional immunosuppressive agents. Scoring of 
this descriptor means attribution of the headache to CNS lupus. 
Most headaches, including most severe and/or migrainous headaches are 
not attributable to lupus and this descriptor should only be scored very 
rarely. 
CVA 
Definition: New onset of cerebrovascular accident (s). Exclude arteriosclerosis or 
hypertensive causes. 
This descriptor is scored if the patient has had a CVA within 28 days of the 
current encounter. A patient recovering from a CVA that was documented more 
than 28 days prior to the current encounter is not given points for this descriptor. 
A patient may have had a previous CVA but to be scored the current CVA must 
be new. 
This descriptor is scored in the presence or absence of anti-phospholipid 
antibodies, i.e., the precise pathophysiologic mechanism need not be known. 
The CVA is scored even in the presence of a normal CT or MRI. A TIA is also 
scored if the patient gives a convincing history. To exclude atherosclerosis the 


 
 
Appendix 10  
Systemic Lupus Erythematosus Disease Activity Index  
(SLEDAI-2K) (cont.) 
 
GDC-0853—Genentech, Inc. 
144/ Protocol GA30066, Version 1  
patient has to have a normal carotid and/or vertebral Doppler and cannot have 
uncontrolled hypertension. 
VASCULITIS: 
Definition: Ulceration, gangrene, tender finger nodules, periungual infarction, 
splinter hemorrhages, or biopsy or angiogram proof of vasculitis. 
To score this descriptor the above definitions must be present. For example, 
erythematous lesions on the hands or feet which may be characteristically 
considered "leukocytoclastic vasculitis" but do not fulfill at least one of the above 
definitions and if not biopsied, are not counted. Similarly livedo reticularis is not 
counted. Healed ulcers with residual scar are not to be counted, but be sure to 
count these in the damage index. A lesion consistent with erythema nodosum 
should be counted regardless of whether it is biopsied or not. Purpura in the 
presence of a normal platelet count should be counted regardless of whether it 
has been biopsied or not. 
ARTHRITIS 
Definition: Two or more joints with pain and signs of inflammation, i.e., 
tenderness, swelling, or effusion. 
Arthritis is scored if it is ongoing; it need not be new or recurrent. 
Arthritis is scored only if at least two joints manifest signs of inflammation. The 
rheumatologist must be convinced that this is active arthritis due to lupus. 
Inflammation of the tendons, ligaments, bursae, and other periarticular structures 
are not scored. For example subacromial bursitis and trochanteric bursitis are not 
scored. If further evaluation reveals osteonecrosis or osteoarthritis, this 
descriptor is not counted.  
MYOSITIS 
Definition: Proximal muscle aching/weakness, associated with elevated creatine 
phosphokinase/aldolase or electromyogram changes or a biopsy showing 
myositis. 


 
 
Appendix 10  
Systemic Lupus Erythematosus Disease Activity Index  
(SLEDAI-2K) (cont.) 
 
GDC-0853—Genentech, Inc. 
145/ Protocol GA30066, Version 1  
The patient complains of muscle aching and/or weakness in the proximal 
muscles PLUS one of the following must be present: 
1. elevated serum creatine phosphokinase and/or aldolase 
2. abnormalities on electromyogram consistent with myositis 
3. biopsy-proven myositis 
RENAL: Note that the following domains (urinary casts, hematuria, 
proteinuria, and pyuria) can only be evaluated on clean catch urinalysis 
specimens.   
URINARY CASTS 
Definition: Heme-granular or red blood cell casts. 
This is scored if red blood cell casts are seen, even if it is only one. Pigmented 
casts are counted but non-pigmented granular casts, hyaline or waxy casts are 
not counted. 
HEMATURIA 
Definition: >5 red blood cells/high power field. Exclude stone, infection or other 
cause. 
With regard to this descriptor, every attempt should be made to see patients 
when they are not menstruating. If this is not possible the urinalysis should be 
deferred until the next visit. 
This descriptor is not scored if there is documented renal calculi or infection. The 
latter must be confirmed by a positive urinary culture. However it is 
acknowledged that associated conditions such as chlamydia or urethral irritation 
may result in mild hematuria and the physician's best judgment is warranted. The 
important point is attribution: there must be other evidence of nephritis and 
other causes of hematuria must be excluded.  
In the complete absence of proteinuria, attribution of hematuria to active nephritis 
would be very unlikely unless pathology is limited to the mesangium. 
PROTEINURIA 
Definition: proteinuria of more than 0.5 g/24 hours (or equivalent by spot urine 
protein to creatinine ratio). 
Must be attributed to active lupus nephritis. 


 
 
Appendix 10  
Systemic Lupus Erythematosus Disease Activity Index  
(SLEDAI-2K) (cont.) 
 
GDC-0853—Genentech, Inc. 
146/ Protocol GA30066, Version 1  
PYURIA 
Definition: >5 white blood cells/high power field. Exclude infection. 
This descriptor is not scored if there is evidence of vaginal contamination 
(presence of any squamous epithelial cells) or a documented infection. The latter 
must be confirmed by a positive urinary culture. However, it is acknowledged that 
associated conditions such as chlamydia, trichomonas or urethral irritation may 
result in mild pyuria and the physician's best judgment is warranted. The 
important point is attribution; there must be other evidence of nephritis, 
and other causes of pyuria should be excluded. In the complete absence of 
proteinuria, attribution of hematuria to active nephritis would be very unlikely 
unless pathology is limited to the interstitium. 
RASH 
Definition: Ongoing inflammatory lupus rash. 
A rash is scored if it is ongoing, new or recurrent. Even if it is identical in terms of 
distribution and character to that observed on the last visit and the intensity is 
improved, it is counted. Therefore, despite improvement in a rash, if it is still 
ongoing it represents disease activity. The rash must be attributable to SLE. A 
description of the rash must appear in the physical exam and should include 
distribution, characteristics such as macular or papular, and size.  
The following should not be scored: 
1. Chronic scarred discoid plaques in any location. 
2. Transient malar flush, i.e., it is not raised and is evanescent 
A common problem one may encounter is the differentiation between scoring a 
lesion as "rash" and/or "vasculitis". If a lesion meets the descriptive criteria of the 
latter it should not also be counted as rash, i.e., the score would be 8 points not 
10 points. If a separate rash characteristic of SLE is present only then would 
"rash" also be scored. 
ALOPECIA: 
Definition: Ongoing abnormal, patchy or diffuse loss of hair due to active lupus. 


 
 
Appendix 10  
Systemic Lupus Erythematosus Disease Activity Index  
(SLEDAI-2K) (cont.) 
 
GDC-0853—Genentech, Inc. 
147/ Protocol GA30066, Version 1  
This should be scored if any of the following conditions are present: 
1. There is temporal thinning which is newly present for less than six months 
(if temporal alopecia is present for more than six months with no change it 
should not be counted)  
2. Areas of scalp with total bald spots if present for less than six months 
(does not need to have accompanying discoid lesion or follicular plugging) 
3. The presence of "lupus frizz" i.e., short of strands of unruly hair in the 
frontal or temporal area 
If a patient complains of hair loss and there is nothing apparent on exam this 
descriptor is not scored. 
MUCOSAL ULCERS: 
Definition: Ongoing oral or nasal ulcerations due to active lupus. 
An ulcer is scored if it is ongoing, it need not be new or recurrent. Ulcers can be 
present in either the nose or oral cavity. Erythema alone without frank ulceration 
is not sufficient to be scored, even if the erythema is present on the upper palate. 
Ulcers on the buccal mucosa and tongue are counted. 
Mucosal ulcers are not counted as vasculitis. 
PLEURISY 
Definition: Classic and severe pleuritic chest pain or pleural rub with effusion or 
new pleural thickening due to lupus. 
This descriptor is scored if the patient complains of pleuritic chest pain lasting 
greater than 12 hours. The pain should be classic, i.e., exacerbated by 
inspiration, to help distinguish it from musculoskeletal conditions such as 
costochondritis, which could be confused with pleurisy. The symptom must also 
be accompanied by objective findings.  
PERICARDITIS: 
Definition: Classic and severe pericardial pain with rub or effusion, or 
electrocardiogram or echocardiogram confirmation. 
The symptom must be accompanied by objective findings.  


 
 
Appendix 10  
Systemic Lupus Erythematosus Disease Activity Index  
(SLEDAI-2K) (cont.) 
 
GDC-0853—Genentech, Inc. 
148/ Protocol GA30066, Version 1  
LOW COMPLEMENT: 
Definition: Decrease in CH50, C3 or C4 below the lower limit of normal for testing 
laboratory. 
Exclude a low C4 or CH50 in patients with known inherited deficiency of C4.  
INCREASED DNA BINDING 
Definition: >25% binding by Farr assay or above normal range for testing 
laboratory. 
FEVER: 
Definition: >38°C. Exclude infectious cause. 
This would be scored if one of the following conditions are present: 
1. A documented temperature elevation >100.4°F or >38°C at the time of the 
visit. 
2. A convincing history from the patient that she/he has been febrile within 
the preceding 10 days prior to the visit without any signs or symptoms 
suggestive of infection. Febrile is defined as above and not simply that the 
patient felt feverish. In this case the patient need not be febrile at the time 
of the visit for a score of 2 to be given. 
As stated in the SLEDAI, fever secondary to infection is not to be scored 
although it is acknowledged that concomitant lupus activity and infection can 
occur. Fever in the presence of infection should only be scored on the SLEDAI if 
other evidence of lupus activity is present.  
THROMBOCYTOPENIA: 
Definition: <100,000 platelets/mm3. 
LEUKOPENIA: 
Definition: <3,000 white blood cells/mm3. Exclude drug causes. 
This is exactly as described, WBC <3,000/mm3. The presence of an absolute 
lymphopenia does not count in the SLEDAI. A note of caution, do not confuse 


 
 
Appendix 10  
Systemic Lupus Erythematosus Disease Activity Index  
(SLEDAI-2K) (cont.) 
 
GDC-0853—Genentech, Inc. 
149/ Protocol GA30066, Version 1  
this WBC with that used to satisfy the ACR criteria for SLE which is WBC 
<3,500/mm3. 
With regard to current use of possible offending drugs, the following guidelines 
are to be considered: 
1. The nadir after cyclophosphamide, i.e., low WBC at 10 days after 
receiving cyclophosphamide in a patient known to have a WBC ≥ 3,000 at 
the time of receiving cyclophosphamide should not be counted. 
2. Do not score leukopenia appearing after initiation of a new medication 
known to be associated with leukopenia, such as azathioprine or sulfa 
drugs. If the patient develops a WBC <3000 while taking drugs which may 
cause leukopenia, score this only if the dosage of medication is 
unchanged since the last WBC determination. 


 
GDC-0853—Genentech, Inc. 
150/ Protocol GA30066, Version 1  
Appendix 11  
SELENA-SLEDAI FLARE INDEX (SFI) 
(Can be used with any version of the SLEDAI) 
Mild or Moderate Flare 
Severe Flare 
Increase in SLEDAI by ≥ 3 
New or worse: 
Rash (discoid, photosensitive, profundus, 
cutaneous vasculitis, bullous lupus) 
Nasopharyngeal ulcers 
Pleuritis 
Pericarditis 
Arthritis 
Fever (SLE) 
Increase in SLEDAI to > 12 
New or worse (requiring doubling of prednisone to 
> 0.5 mg/kg/day or hospitalization): 
CNS-SLE 
Vasculitis 
Nephritis 
Myositis  
Platelets  60,000/mm3 
Hemolytic anemia:  Hb  7g/dL or decrease of 
Hb by > 3 g/dL 
Increase in prednisone, but not 
to >0.5 mg/kg/day 
Prednisone > 0.5 mg/kg/day 
Added NSAID or hydroxychloroquine for 
disease activity 
New cyclophosphamide, azathioprine, 
methotrexate, mycophenolate mofetil, or 
hospitalization (for SLE) 
Increase in PGA by ≥ 1.0, but not to more 
than 2.5 
Increase in PGA to > 2.5 
NSAID = nonsteroidal anti-inflammatory drug; PGA = Physician’s Global Assessment; 
SELENA = Safety of Estrogens in Lupus Erythematosus National Assessment; 
SFI = SELENA-SLEDAI Flare Index; SLE = systemic lupus erythematosus; SLEDAI = Systemic 
Lupus Erythematosus Disease Activity Index. 
 
REFERENCES 
Buyon JP, Petri MA, Kim MY, et al. The effect of combined estrogen and progesterone 
hormone replacement therapy on disease activity in systemic lupus erythematosus: 
a randomized trial. Ann Intern Med 2005;142(12 Pt 1):953−62. 
Petri M, Buyon J, Kim M. Classification and definition of major flares in SLE clinical trials. 
Lupus 1999;8:685−91. 
Petri M, Kim MY, Kalunian KC, et al. Combined oral contraceptives in women with 
systemic lupus erythematosus. N Engl J Med 2005;353:2550−8. 


 
GDC-0853—Genentech, Inc. 
151/ Protocol GA30066, Version 1  
Appendix 12  
Cutaneous Lupus Erythematosus Disease Area and Severity 
Index (CLASI) 
The Cutaneous Lupus Area and Severity Index (CLASI) comprises a score for the 
activity of the disease and a score for the damage caused by the disease 
(see Scoresheet in this appendix).  The CLASI should be completed at intervals as 
indicated in the schedule of activities (Appendix 1) for any patient who has 
mucocutaneous manifestations of systemic lupus erythematosus (SLE) at a given study 
visit and then at all subsequent visits.  
With the exception of alopecia, only skin lesions that are specific to SLE are included in 
this assessment.  The cutaneous manifestations of SLE (e.g., vasculitis) are not scored 
for the CLASI. 
1. 
localized and generalized manifestations of acute cutaneous lupus erythematosus 
(malar rash, maculopapular rash, photosensitive rash, bullous lupus erythematosus); 
2. 
subacute cutaneous lupus erythematosus (annular / polycyclic or papulosquamous / 
psoriasiform);  and 
3. 
chronic cutaneous lupus erythematosus (localized and generalized discoid lupus, 
verruccous/hyperkeratotic discoid lupus, mucosal discoid lupus, tumid lupus, 
perniotic/chilblain lupus, and lupus profundus/lupus panniculitis).  
 
Training in the use of the CLASI will be provided to Investigators.  Wherever possible, 
digital images of the lesions should be obtained. 
Activity  
Lesion activity is scored for 13 specified anatomical areas in terms of erythema 
(absent = 0; pink or faint erythema = 1; red = 2; dark red, purple, violaceous, crusted, or 
hemorrhagic = 3) and scale/hypertrophy (absent = 0; scale = 1; verruccous or 
hypertrophic = 2).  The severity score for each area is based on the worst lesion within 
that area.   
The patient is asked about mucous membrane involvement, and if this is reported, the 
affected areas are examined (absent = 0, present = 1).  
The patient is asked about hair loss in the past 30 days (patient-reported absence = 0, 
presence = 1).  Non-scarring alopecia on examination is scored by examining the scalp in 
quadrants (absent = 0; diffuse, non-inflammatory = 1; focal or patchy in one quadrant = 2; 
focal or patchy in more than one quadrant = 3).  The scores for the various anatomical 
areas are summed. 
The maximum possible score for the Activity component of the CLASI is 70.  


 
 
Appendix 12  
Cutaneous Lupus Erythematosus Disease Area and Severity 
Index (CLASI) (cont.)  
GDC-0853—Genentech, Inc. 
152/ Protocol GA30066, Version 1  
Damage  
Skin damage is scored for 12 specified anatomical areas (as for the Activity score but 
excluding the scalp, which is scored separately; see below).  Damage in each area is 
scored for dyspigmentation (absent = 0; present = 1) and for scarring, atrophy, and 
panniculitis (absent = 0; scarring = 1; severe atrophic scarring or panniculitis = 2).  As for 
the Activity component of the index, the damage severity score for each area is based 
on the worst lesion within that area.  The scores for the various anatomical areas are 
then summed. 
The patient is asked whether the dyspigmented cutaneous lesions usually remain visible 
for more than 12 months.  If so, this is taken to indicate that the lesions are permanent, 
and the dyspigmentation score is doubled.  
The scalp is examined for scarring, again by dividing into quadrants (absent = 0; scarring 
in one quadrant = 3; two quadrants = 4; three quadrants = 5; whole skull scarred = 6).  
The maximum possible score for the Damage component of the CLASI is 56.  
REFERENCE 
Albrecht J, Werth VP. Development of the CLASI as an outcome instrument for 
cutaneous lupus erythematosus. Dermatol Ther 2007;20:93−101. 
 


 
 
Appendix 12  
Cutaneous Lupus Erythematosus Disease Area and Severity 
Index (CLASI) (cont.)  
GDC-0853—Genentech, Inc. 
153/ Protocol GA30066, Version 1  
 


 
GDC-0853—Genentech, Inc. 
154/ Protocol GA30066, Version 1  
Appendix 13  
Physician’s Global Assessment 
The investigator’s global assessment of the patient’s current disease activity (using 
Physician's Global Assessment [PGA]) will be marked on a 100-mm horizontal visual 
analogue scale marked from "none" to "severe" and graded from 0 to 3 (see example 
that follows).  The investigator should refer to assessments at prior visits and move the 
tick mark according to his or her assessment of the patient’s disease activity over the 
preceding 28 days.  The PGA should be done after the investigator has done the clinical 
history and examination of the patient and has completed the British Isles Lupus 
Assessment Group, the Safety of Estrogens in Lupus Erythematosus National 
Assessment, the Systemic Lupus Erythematosus Disease Activity Index, and (where 
appropriate) the Cutaneous Lupus Erythematosus Disease Area and Severity Index and 
28-joint counts.  
Pertinent laboratory values should be taken into account before completing the PGA 
rating.  If relevant laboratory results are pending, the investigator may make a 
provisional marking on a local paper copy of the PGA case record form and finalize the 
assessment when all pertinent data is available. 
 




 
GDC-0853—Genentech, Inc. 
156/ Protocol GA30066, Version 1  
Appendix 14  
Patient’s Global Assessment 
The patient is asked to rate her or his lupus over the previous 24 hours considering all 
aspects of the disease.  This overall assessment of current disease activity will be 
marked on a 100-mm horizontal visual analogue scale (VAS) marked from “None” to 
“Maximum.”  Validated translations will be provided.  
The patient should complete this assessment without reference to assessments 
completed at previous visits and should complete the assessment prior to receiving the 
investigational medicinal product.  
The investigator or study coordinator will measure the distance in millimeters from the 
left-hand end of the VAS line and record this measurement in the box provided.  
 
 
Please answer the following question by placing a vertical mark through the 
line. 
 
On the line below, considering all the ways your lupus affects you, 
where would you rate your lupus over the last 24 hours? 
 
 
     None 
Maximum 
 
 
 
 
 
 
       mm 


 
GDC-0853—Genentech, Inc. 
157/ Protocol GA30066, Version 1  
Appendix 15  
Concomitant Medications (Including Foods and Herbal Products) 
Class 
Expected Interaction 
Recommendation 
Examples of Drugs in this Class a 
Antacids 
Decreased 
GDC-0853 
absorption due to 
increased gastric pH 
Take GDC-0853 
2 hours before or 
2 hours after antacid 
• Maalox, Pepto-Bismol, Rolaids 
Moderate 
or strong 
CYP3A 
inhibitors  
Increased GDC-0853 
plasma 
concentrations due 
to inhibition of 
metabolism 
Avoid for 7 days or 
5 half-lives 
(whichever is 
longer) prior to first 
dose of study drug 
and during the 
treatment period, 
unless otherwise 
advised by the 
Medical Monitor or 
delegate b 
• Antimicrobials (clarithromycin, 
erythromycin, itraconazole, 
ketoconazole, telithromycin, 
troleandamycin, voriconazole, 
posaconazole) 
• Antidepressants (nefazodone) 
• Antihypertensive/cardiac 
(verapamil, diltiazem) 
• Other (grapefruit juice, Seville 
orange juice, pomegranate, star 
fruit) 
CYP3A 
inducers  
Decreased 
GDC-0853 plasma 
concentrations due 
to increased 
metabolism 
Avoid for 7 days or 
5 half-lives 
(whichever is 
longer) prior to first 
dose of study drug 
and during the 
treatment period, 
unless otherwise 
advised by the 
Medical Monitor or 
delegate b 
• Antimicrobials (rifampin, 
rifapentine, rifabutin) 
• Antidepressants (St. John’s wort, 
hyperforin) 
• Antiepileptics (carbamazepine, 
phenytoin, phenobarbital, 
hyperforin) 
• Diabetes (pioglitazone, 
troglitazone) 
• Other (modafinil, bosentan) 
Sensitive 
and 
narrow 
therapeutic 
window 
CYP3A 
substrates 
Potential for 
increased plasma 
concentrations of 
CYP3A substrates 
due to inhibition of 
metabolism by 
GDC-0853 
Use with caution 
and monitor for 
adverse events 
related to CYP3A 
substrates as 
directed by product 
labeling; consult 
with the Medical 
Monitor as needed b 
• Antiemetic/prokinetic (aprepitant, 
cisapride) 
• Anti-histamine (astemizole, 
terfenadine) 
• Anti-hypertensive/cardiac 
(dronedarone, eplerenone, 
felodipine, nisoldipine, quinidine, 
ticagrelor, vardenafil) 
• Benzodiazepines (alprazolam, 
diazepam, midazolam) 
• Lipid-lowering (simvastatin, 
lovastatin) 
• Migraine (eletriptan, ergotamine) 
• Steroids (budesonide, fluticasone) 
• Other (alfentanil, buspirone, 
conivaptan, darifenacin, dasatinib, 
dihydroergotamine, fentanyl, 
lurasidone, pimozide, quetiapine, 
sildenafil, tolvaptan, triazolam) 


 
 
Appendix 15  
Concomitant Medications (Including Foods and Herbal Products) 
(cont.) 
GDC-0853—Genentech, Inc. 
158/ Protocol GA30066, Version 1  
a The following list is not comprehensive.  Please refer to the following websites for additional 
information and consult the Medical Monitor if necessary: 
U.S. FDA Table of Substrates, Inhibitors, and Inducers (Tables 3-1, 3-2, and 3-3) 
(http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteract
ionsLabeling/ucm093664.htm) 
Indiana University Department of Medicine P450 Interaction Table 
(http://medicine.iupui.edu/clinpharm/ddis/clinical-table) 
b  Potential CYP3A-mediated interactions between GDC-0853 and concomitant medications will 
be reviewed by the Medical Monitor or delegate during the pre-enrolment adjudication process