Conditions: Systemic Lupus Erythematosus
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 64
Healthy volunteers: no

Brief summary:
This study evaluates the impact of 13 bi-weekly intravenous infusions of RSLV-132 on the cutaneous manifestations in subjects with systemic lupus erythematosus.

Detailed description:

Arms:
arm 1: 10 mg/kg RSLV-132 arm 2: Saline placebo

Interventions: intervention 1: RSLV-132 intervention 2: Placebo
Intervention descriptions: intervention 1: RNase-Fc fusion protein intervention 2: Saline placebo

Protocol document:
Prot_000.pdf: 
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RSLV-132 
PROTOCOL 132-03 
 
 
 
A PHASE 2A, DOUBLE-BLIND, PLACEBO-
CONTROLLED STUDY OF RSLV-132 IN SUBJECTS 
WITH SYSTEMIC LUPUS ERYTHEMATOSUS 
 
 
 
RESOLVE THERAPEUTICS, LLC 
454 N. 34TH STREET 
SEATTLE, WASHINGTON 98103 
 


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Protocol Title: 
A Phase 2a, Double-Blind, Placebo-Controlled Study of 
RSLV-132 in Subjects With Systemic Lupus Erythematosus 
Protocol Number: 
132-03 
Investigational Product: 
RSLV-132 
IND Number: 
117593 
Current Version: 
5.0 
Prior Version: 
4.0 
Date of Publication: 
27 April 2017 
Sponsor: 
Resolve Therapeutics, LLC 
454 N. 34th Street 
Seattle, WA, 98103 
(208) 727-7010 (Office Telephone No.) 
(206) 545-2897 (Office Facsimile No.) 
 
Sponsor Contact: 
James Posada, PhD 
454 N. 34th Street 
Seattle, WA, 98103 
jp@resolvebio.com 
(208) 727-7010 (Cell) 
 
Medical Monitor 
Emergency Sponsor Contact 
Dan Burge, MD 
454 N. 34th Street 
Seattle, WA, 98103 
dan@burgeconsulting.com 
(425) 802-3359 (Cell) 
 
Investigators: 
Multicenter Study: Investigator information on file at 
Resolve Therapeutics. 
Clinical Laboratories: 
Resolve Therapeutics Laboratories 
454 N. 34th Street 
Seattle, WA 98103 
 
 
ICON Development Solutions, LLC 
8282 Halsey Road 
Whitesboro, NY  13492 
 
 
Q2 Solutions 
5927 South Miami Blvd., Suite 100 
Morrisville, NC  27560 


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Myriad RBM, Inc. 
3300 Duval Rd. 
Austin, TX  78759 
 
University of Washington Medical Center 
Clinical Immunology Lab, Room NW275 
1959 NE Pacific 
Seattle, WA  98195 
 
Sponsor Approval: 
 
 
 
 
 
James Posada, PhD 
Chief Executive Officer 
 


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1 
PROTOCOL SYNOPSIS 
Name of Sponsor: 
Resolve Therapeutics, LLC 
Name of Investigational Product: 
RSLV-132 
Name of Active Ingredient: 
RNase-IgG Fc 
Number and Title of Study:  
Protocol 132-03: A Phase 2a, Double-Blind, Placebo-Controlled Study of RSLV-132 in 
subjects with Systemic Lupus Erythematosus (SLE) 
Phase of development:   
2a 
Study period:  
Patient participation duration: 28 days of screening followed by 22 weeks of treatment and 8 
weeks of follow up (approximately 34 weeks total). 
 
Planned study conduct duration: approximately 24 months total (from enrollment of first 
subject to completion of follow-up for last patient). 
Objectives:  
• assess the impact of 13 IV infusions of RSLV-132 on cutaneous lupus disease activity 
using the CLASI activity score. 
• assess improvement in disease activity using SLEDAI-2K, BILAG-2004 and PGA; 
• evaluate the immunogenicity of RSLV-132 in subjects with SLE; 
• assess improvement in tender or swollen joint count; 
• assess improvement in patient reported outcomes using the FACIT-Fatigue scale; 
• assess the ability of subjects to reduce oral steroids at Day 169; 
• evaluate the safety and tolerability of 22 weeks of RSLV-132 exposure; 
• assess the proportion of subjects achieving a 50% improvement in CLASI activity 
score 
• assess the following exploratory endpoints 
o evaluate the impact of RSLV-132 treatment on gene expression profile; 
o evaluate the impact of RSLV-132 treatment on autoantibody and complement 
profiles; 
o evaluate the impact of RSLV-132 on serum protein levels; 
o assess the impact of RSLV-132 on the CLASI damage score 
 


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Study design: 
This is a multi-center, double-blind, placebo-controlled study to evaluate the impact of 13 
intravenous infusions of RSLV-132 in approximately 50 patients with SLE. Each of the 
approximately 50 subjects will be randomized 2:1 (active:placebo) and will receive 13 
infusions of 10 mg/kg of RSLV-132 or placebo as follows on days: 
 
• 1, 8, 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, and 155 
 
Potential subjects will be screened to assess their eligibility to enter the study within 28 days 
prior to study entry (i.e., prior to Baseline visit).  Following Baseline evaluations on Day 1, 
subjects will receive their first infusion of RSLV-132 or placebo.  Subjects will return to the 
research unit for follow-up visits as described in Appendix A.   
Dose selection rationale:  The dose level was chosen based on safety and tolerability data from 
Protocol 132-02 (multiple ascending dose study in SLE patients).   
RSLV-132 shall be prepared for each subject from individual stock vials provided by Sponsor.  
Details of dilution, dose preparation, and administration instructions will be provided in the 
Study Drug Reference Manual. The dose for each individual shall be based on the subject’s 
body weight. 
Number of subjects (planned):  
It is anticipated that approximately 50 subjects will be enrolled in the study 
Number of Study Centers (planned):  
Approximately 15-20 study sites in the United States, Canada and Europe will be involved in 
the study. 
Diagnosis and main criteria for inclusion:  
Subjects with SLE, including cutaneous manifestations of SLE and a CLASI score ≥ 10, and 
positive serology (increased levels of one or more of the following: Ro-52/60, La, Sm, 
SmRNP, U1 RNP A/68) at Screening will be eligible for the study. 
Inclusion Criteria: 
Subjects who meet the following criteria may be included in the study: 
1. diagnosis of SLE meeting four of the eleven criteria in the 1997 Update of the 1982 
American College of Rheumatology Revised Criteria and a history of active SLE 
including cutaneous involvement at Screening; 
2. SLE with cutaneous manifestations and a CLASI activity score of ≥10 at Screening; 
3. elevated levels of any one of the following autoantibodies: 
• Ro-52/60, La, Sm, SmRNP, U1 RNP A/68 (local or central laboratory); 
4. no change in medications for the treatment of SLE for the previous 30 days prior to 
Baseline; 
5. able to communicate and able to provide valid, written informed consent; 
6. ages 18 to 70, inclusive; 


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7. minimum weight of 45 kg; 
8. Female participants shall be either of non-child-bearing potential (permanently 
sterilized by tubal occlusion, hysterectomy, or bilateral salpingectomy), or menopausal 
(more than one year since last menstrual cycle and confirmed by blood FSH levels ≥ 
22 mIU/mL) OR practicing highly effective contraception (e.g., oral, injectable, 
implantable or transdermal contraceptives, a non-hormonal intrauterine device [IUD] 
with spermicide; female condom with spermicide; contraceptive sponge with 
spermicide; an intravaginal system, a diaphragm with spermicide; cervical cap with 
spermicide; a male sexual partner who agrees to use a male condom with spermicide; a 
sterile sexual partner) for at least 2 months prior to dosing and until 110 days following 
the End of Study.  
9. Male participants must agree to use a male condom with spermicide from the first dose 
until 90 days after the last dose.  Male participants must also agree not to donate sperm 
from the first dose until 90 days after the last dose. 
Exclusion Criteria: 
The following will exclude potential subjects from the study: 
1. severe, active CNS involvement at Screening; 
2. severe renal involvement at Screening (urine protein/creatinine ratio of >200 
mg/mmol, or an estimated creatinine clearance of <30 mL/min); 
3. use of cyclophosphamide within 3 months of the Baseline visit; 
4. use of rituximab within 6 months of the Baseline visit; 
5. use of belimumab within 3 months of the Baseline visit; 
6. use of background medications within 1 month of Baseline in excess of: 
i. 
mycophenolate mofetil > 3 g/day; 
ii. 
azathioprine > 200 mg/day; 
iii. 
methotrexate > 25 mg/week; 
iv. 
hydroxychloroquine > 400 mg/day; 
v. 
prednisone (or equivalent) > 15 mg/day; 
7. use of an intravenous steroid “pulse” within 2 months of Baseline; 
8. use of an intramuscular steroid injection within 1 month of Baseline; 
9. change in SLE medications within 1 month of Baseline; 
10. the presence of a clinically significant infection in the judgement of the Investigator 
within seven days prior to the receipt of the first dose of study drug; 
11. positive viral load test for hepatitis B, C, or HIV at Screening; 
12. participation in another clinical trial with receipt of an investigational product within 3 
months or 5 half- lives, of last administration (whichever is longer) from Baseline; 
13. positive pregnancy test at Screening or at Baseline; 
14. female subjects currently breast feeding at Baseline; 
15. inability or unwillingness to comply with protocol-specified procedures which, in the 
opinion of the Investigator, would make the subject unsuitable for study participation. 


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CRITERIA FOR EVALUATION: 
Clinical measures: 
• CLASI (both activity and damage scores) 
• SLEDAI-2K 
• BILAG-2004 
• PGA 
• Tender and swollen joint count 
Pharmacodynamics: 
• Gene expression profiling of peripheral blood mononuclear cells (PBMCs) 
• Analysis of serum proteins 
• Autoantibody profiling 
Patient reported outcomes: 
• FACIT-Fatigue patient reported fatigue index  
Evaluations by Day: 
Screening Procedures 
• informed consent; 
• evaluation of inclusion/exclusion criteria; 
• complete medical and medication history; 
• demographic data; 
• weight and height; 
• physical examinations; 
• vital signs; 
• clinical laboratory evaluations (Chem-20, CBC, and UA); 
• viral load tests for hepatitis B, C, and HIV; 
• serum pregnancy test; 
• measurement of cutaneous disease activity (CLASI); 
• Photographs of cutaneous disease activity; 
• autoantibody profile (Ro-52/60, La, Sm, SmRNP, U1 RNP A/68) (local or central 
laboratory); 
• FSH (when required to confirm menopause in female subjects) 
Baseline Procedures 
• confirmation of inclusion/exclusion criteria; 
• interim medical and medication history; 
• physical examination; 
• vital signs; 
• adverse event baseline assessment; 


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• measurement of cutaneous disease activity (CLASI); 
• photographs of cutaneous manifestations of lupus; 
• measurement of SLE activity (SLEDAI-2K, BILAG-2004, PGA);  
• tender and swollen joint count; 
• patient reported outcome, FACIT fatigue index; 
• serum for study drug concentration; 
• clinical laboratory evaluations (Chem-20, CBC, and UA); 
• whole blood for measurement of gene expression; 
• serum for protein analysis; 
• serum for measurement of RNase activity; 
• evaluation of autoantibody profile (dsDNA, Ro-52/60, La, Sm, SmRNP, U1 RNP 
A/68) from local or central laboratory; 
• serum for complement analysis, C3 and C4; 
• assessment of antibodies to RSLV-132; 
• urine pregnancy test; 
• study drug administration. 
Additional Procedures   
The following procedures will be performed at various visits during the study.  A total of 
twelve post-baseline visits will occur; once weekly for two weeks, then every two weeks for 
20 weeks, plus an end of study visit 8 weeks after visit 13: 
• physical exam; 
• vital signs; 
• adverse event assessment; 
• medication history; 
• measurement of cutaneous disease activity (CLASI); 
• measurement of SLE activity (SLEDAI-2K, BILAG-2004, PGA); 
• tender and swollen joint count; 
• FACIT-fatigue index patient reported outcome;  
• photographs of cutaneous manifestations of lupus; 
• serum sample for study drug concentration; 
• serum sample for measurement of RNase activity; 
• serum for protein analysis; 
• whole blood for gene expression profile; 
• serum sample for autoantibody profile (dsDNA, Sm, Ro-52/60, La, SmRNP, U1 RNP 
A/68) from local or central laboratory; 
• serum for complement analysis, C3 and C4; 
• clinical laboratory evaluations (Chem-20, CBC, and UA); 


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• serum sample for assessment of antibodies to RSLV-132; 
• pregnancy test; 
• study drug administration. 
 


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2 
TABLE OF CONTENTS 
1 
PROTOCOL SYNOPSIS ............................................................................................ 4 
2 
TABLE OF CONTENTS .......................................................................................... 10 
2.1 
List of Tables ............................................................................................................... 12 
2.2 
List of Abbreviations and Definitions of Terms .......................................................... 12 
3 
INTRODUCTION...................................................................................................... 14 
3.1 
Systemic Lupus Erythematosus, Immune Complexes, Human Safety Data with 
RSLV-132 .................................................................................................................... 14 
3.2 
RSLV-132 .................................................................................................................... 15 
3.3 
Study Rationale ............................................................................................................ 16 
3.4 
RSLV-132 Human Safety Data ................................................................................... 16 
3.4.1 
Study 132-01 – Single Ascending Dose Study Summary: .......................................... 17 
3.4.2 
Study 132-02 Multiple Ascending Dose Study Summary: Safety............................... 17 
4 
TRIAL OBJECTIVES AND PURPOSE ................................................................. 18 
4.1 
Primary Objective ........................................................................................................ 18 
4.2 
Secondary Objectives................................................................................................... 18 
4.3 
Exploratory Measures .................................................................................................. 18 
5 
INVESTIGATIONAL PLAN ................................................................................... 19 
5.1 
Overall Study Design and Plan .................................................................................... 19 
5.2 
Number of Subjects and Centers .................................................................................. 19 
5.3 
Estimated Study Duration ............................................................................................ 19 
6 
SELECTION AND WITHDRAWAL OF SUBJECTS .......................................... 20 
6.1 
Subject Inclusion Criteria ............................................................................................ 20 
6.2 
CLASI Score Entry Criteria – Adjudication ................................................................ 20 
6.3 
Subject Exclusion Criteria ........................................................................................... 20 
6.4 
Subject Withdrawal Criteria ........................................................................................ 21 
6.5 
Women of Child-Bearing Potential ............................................................................. 21 
7 
TREATMENT OF SUBJECTS ................................................................................ 23 
7.1 
Description of Study Drug ........................................................................................... 23 
7.2 
Treatment Compliance ................................................................................................. 23 
7.3 
Concomitant Medications ............................................................................................ 23 
7.4 
Steroid Tapering........................................................................................................... 23 
7.5 
Treatment of Flares ...................................................................................................... 24 
7.6 
Randomization and Blinding ....................................................................................... 24 
8 
STUDY DRUG MATERIALS AND MANAGEMENT ......................................... 25 
8.1 
Study Drug ................................................................................................................... 25 
8.2 
Placebo ......................................................................................................................... 25 
8.3 
Study Drug Packaging, Labeling, Storage, Shipping, and Preparation ....................... 25 
8.4 
Study Drug Administration .......................................................................................... 25 
8.5 
Study Drug Accountability .......................................................................................... 26 
8.6 
Study Drug Handling and Disposal ............................................................................. 26 
9 
ASSESSMENT OF SAFETY .................................................................................... 27 


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9.1 
Adverse Event Definition ............................................................................................ 27 
9.2 
Serious Adverse Event Definitions .............................................................................. 28 
9.3 
Adverse Event Reporting ............................................................................................. 28 
9.4 
Serious Adverse Event Reporting Requirements ......................................................... 28 
9.5 
Non-Serious Adverse Event Reporting Requirements ................................................ 29 
9.6 
Adverse Event Follow Up ............................................................................................ 29 
9.7 
Severity Assessment .................................................................................................... 29 
9.8 
Causality Assessment................................................................................................... 29 
9.9 
Abnormal Test Findings .............................................................................................. 29 
9.10 
Hospitalization ............................................................................................................. 30 
10 
ASSESSMENT OF PHARMACOKINETICS ........................................................ 31 
10.1 
Measurement of RSLV-132 Drug Levels .................................................................... 31 
10.2 
Pharmacokinetic Analysis ............................................................................................ 31 
11 
STATISTICS .............................................................................................................. 32 
11.1 
Subject Population for Efficacy/Activity Analysis ...................................................... 32 
11.2 
Analysis of the Primary Objective ............................................................................... 32 
11.3 
Analysis of the Secondary Objectives ......................................................................... 32 
11.4 
Exploratory Analysis ................................................................................................... 32 
11.5 
Subject Population for Safety Analysis ....................................................................... 32 
11.6 
Sample Size .................................................................................................................. 33 
12 
STUDY PROCEDURES ........................................................................................... 34 
12.1 
Evaluations ................................................................................................................... 34 
12.2 
Screening Procedures ................................................................................................... 34 
12.3 
Baseline (Day 1) Procedures ........................................................................................ 35 
12.4 
Procedures on Days 8, 15, 43, 71, 99, 127, and 155 .................................................... 35 
12.5 
Procedures on Days 29, 57, 85, 113, 141, and 169/End of Treatment (EOT) ............. 35 
12.6 
End of Study Day 215 Evaluations .............................................................................. 36 
12.7 
Vital Signs .................................................................................................................... 36 
12.8 
Medical/Medication History ........................................................................................ 36 
12.9 
CLASI Clinical Assessment ........................................................................................ 37 
12.10 
SLEDAI-2K, BILAG-2004, PGA, and Tender and Swollen Joint Count Clinical 
Assessments ................................................................................................................. 37 
12.11 
Study Drug Concentration ........................................................................................... 37 
12.12 
Gene Expression Analysis ........................................................................................... 37 
12.13 
Protein Analysis ........................................................................................................... 37 
12.14 
Anti-Drug Antibodies .................................................................................................. 37 
12.15 
RNase Activity Assessments ....................................................................................... 37 
12.16 
Autoantibody Profile .................................................................................................... 38 
13 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS ..................................... 39 
13.1 
Study Monitoring ......................................................................................................... 39 
13.2 
Audits and Inspections ................................................................................................. 39 
13.3 
Institutional Review Board .......................................................................................... 39 
14 
ETHICS ...................................................................................................................... 41 
14.1 
Ethical Conduct of the Study ....................................................................................... 41 


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14.2 
Written Informed Consent ........................................................................................... 41 
14.3 
Disclosure .................................................................................................................... 41 
15 
DATA HANDLING AND RECORDKEEPING ..................................................... 42 
15.1 
Inspection of Records .................................................................................................. 42 
16 
REFERENCES ........................................................................................................... 43 
17 
APPENDICES ............................................................................................................ 46 
17.1 
Appendix A:  Study Procedures ................................................................................... 46 
17.2 
Appendix B: Clinical Laboratory Evaluations ............................................................. 48 
17.3 
Appendix C: Investigator Protocol Agreement Page ................................................... 49 
17.4 
Appendix D:  ACR SLE Classification Criteria .......................................................... 50 
17.5 
Appendix E:  Summary of Changes............................................................................. 52 
 
2.1 
List of Tables 
Table 1: 
Abbreviations and specialist terms 
12 
Table 2: 
Study Drug 
25 
2.2 
List of Abbreviations and Definitions of Terms 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: Abbreviations and specialist terms 
Abbreviation or 
specialist term 
Explanation 
ACR 
American College of Rheumatology 
ADA 
anti-drug antibodies 
AE 
adverse event/experience 
ALT 
alanine aminotransferase (alanine transaminase) 
ANA 
anti-nuclear antibody 
AST 
aspartate aminotransferase (aspartate transaminase) 
BILAG 
British isles lupus activity group 
cSFI 
classic (SELENA)-SLEDAI flare index 
CBC 
complete blood count (hematology clinical laboratory evaluations) 
CFR 
code of federal regulations 
Chem-20 
chemistry panel of 20 analytes 
CLASI 
cutaneous lupus erythematosus disease area and severity index 
CNS 
central nervous system 
CRA 
clinical research associate 
CRF 
case report form 
CRO 
clinical research organization 
DNase 
deoxyribonuclease 
ELISA 
enzyme-linked immunosorbent assay 
ESR 
erythrocyte sedimentation rate 


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Abbreviation or 
specialist term 
Explanation 
FDA 
food and drug administration 
FSH 
Follicle-stimulating Hormone 
GCP 
good clinical practice 
HBs Ag 
hepatitis B surface antigen 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
IC 
Immune complex 
ICF 
informed consent form 
ICH 
international committee on harmonization 
IFN 
interferon 
IgG 
immunoglobulin G 
IgM 
immunoglobulin M 
IL-1 RA 
Interleukin-1 receptor antagonist 
IRB 
institutional review board 
ISM 
interferon signature metric (score) 
IUD 
intrauterine device 
IV 
intravenous 
MTD 
maximum tolerated dose 
OCS 
Oral Corticosteroids 
PCR 
polymerase chain reaction 
pDC 
plasmacytoid dendritic cells 
PGA 
physician’s global assessment 
PK 
pharmacokinetic 
PMN 
polymorphonuclear (cells) 
RNA 
ribonucleic Acid 
SAE 
serious adverse event/experience 
SELENA 
safety of estrogens in lupus erythematosus national assessment 
SLE 
systemic lupus erythematosus 
SLEDAI 
Systemic Lupus Erythematosus Disease Activity Index SELENA 
Modification 
TLR 
toll-like receptor 
UA 
urinalysis 
ULN 
upper limit of normal 
 


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3 
INTRODUCTION 
3.1 
Systemic Lupus Erythematosus, Immune Complexes, Human Safety Data with 
RSLV-132 
Systemic Lupus Erythematosus (SLE) is a heterogeneous autoimmune disorder affecting many 
tissues and organs including skin, kidney and brain [22].   Despite wide inter-patient diversity 
with respect to clinical manifestations, a common characteristic of SLE patients is the presence 
of circulating autoantibodies directed against nuclear antigens [24, 19].  The presence of these 
autoantibodies signifies that host immune tolerance has been compromised.  The physiological 
cause underlying the loss of tolerance is unclear, but current theories include that SLE patients’ 
cells are predisposed to undergo capricious apoptosis or that host mechanisms involved in 
clearance of apoptotic cells/debris are impaired [27, 16].  In either scenario, the extracellular 
accumulation of nuclear-associated antigens, including nucleic acid-containing complexes, elicits 
B-cells to produce antibodies that recognize these normally sequestered components as foreign 
antigens.  As a result, immune tolerance is broken 
When complexed with their respective antigens, SLE patient autoantibodies form immune 
complexes (ICs) which can promote activation of immune cells in vitro.  For example, ICs 
formed following incubation of SLE patient sera with necrotic and/or apoptotic cell extracts (a 
source of nuclear antigens), are effective agonists for activating plasmacytoid dendritic cells 
(pDCs) to produce type 1 interferon (IFN) [5].  Circulating ICs recovered from SLE patients are 
also capable of eliciting IFN-α output from pDCs in culture, though lower abundance of the 
endogenous complexes relative to the quantities formed following addition of exogenous 
antigens promotes smaller quantities of cytokine production [1, 8].  ICs also are capable of 
stimulating B-cells resulting in NF-κB activation and proliferation [15, 6].  Moreover, SLE 
patient ICs have been reported to activate human polymorphonuclear (PMN) cell activities 
including chemotaxis, the oxidative burst response, and netosis [17, 7].   In addition to effects on 
immune cells, ICs can deposit within tissues (e.g. kidney, blood vessels) where their physical 
accumulation and associated inflammation appear to disrupt normal homeostatic function [21, 3].  
Overall, ICs are positioned at the apex of an effector cascade which instigates and drives SLE 
disease pathology.   
Many common SLE patient autoantibodies are directed against nucleic acids or to proteins that 
bind to non-coding RNAs.  Importantly, recent studies have established that nucleic acids 
associated with SLE patient ICs are capable of activating Toll-like receptors (TLRs) [12, 18, 14, 
4, 13].  Although TLRs are thought to operate as key elements of the innate immune system by 
recognizing pathogen-associated molecular components, it is now clear that host nucleic acids 
also can activate specific family members including TLR7, TLR8, and TLR9 [26].   Cells 
expressing these receptors do so without distributing them to the cell surface; rather, TLRs 7/8/9 
are sequestered within endosomes [26].  This positioning is postulated to minimize interaction 
with host nucleic acids.  However, when present within an IC, nucleic acid antigens are actively 
internalized into cells via receptor-mediated endocytosis.  Effector Fc, complement, and B-cell 
receptors all may facilitate entry of nucleic acid containing ICs into endosomes [18, 14].  Once 
internalized, the nucleic acid cargo is positioned to bind to and activate resident endosomal 
TLRs.  Activated TLRs, in turn, promote type 1 IFN from pDCs, activate PMNs, and promote B-


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cell proliferation and autoantibody production.  Thus, the nucleic acid-containing antigens are 
envisioned to contribute to multiple aspects of SLE disease pathophysiology. 
Evidence of the importance of TLR-induced signaling to autoimmunity is further suggested by a 
mouse transgenic line engineered to overexpresses TLR7 [9].  Overexpression of this receptor is 
associated with development of spontaneous autoimmunity.  A substantial increase in TLR7 
expression is associated with enhanced mortality, an increase in circulating anti-DNA antibodies, 
and dendritic cell dysregulation [9].  Given that the transgenic mice do not require an exogenous 
agonist to promote the autoimmune phenotype, these findings suggest that elevation of the 
receptor’s steady state expression is sufficient to tilt the homeostatic balance from a state where 
immune tolerance is maintained to one where tolerance is broken.  Since TLR7 is known to 
recognize RNA-containing ligands [11], the spontaneous development of autoimmunity in the 
TLR7 transgenic animals suggests that endogenous RNAs are contributing to the 
pathophysiological response.   Importantly, when the TLR7 receptor transgenic mice are crossed 
with a mouse line over expressing bovine RNase under control of a serum albumin promoter, the 
double transgenic descendants demonstrate increased survival, reduced activation of T and B 
lymphocytes, and reduced hepatic inflammation [25].  Thus, the addition of a secreted 
ribonuclease to the system appears to attenuate the heightened state of autoimmunity, 
presumably by degradation of the endogenous TLR7 ligands. 
Evidence also exists in humans suggesting that TLRs and nucleases impact SLE.  A mutation 
within the promoter of the TLR7 gene is reported to enhance TLR7 expression and to be a risk 
factor for development of SLE [23].  In addition, polymorphisms within TLRs 7/8/9 have been 
linked to SLE patients [10].  Likewise, mutations resulting in loss of DNase1 or DNase1L3 each 
have been reported as predisposing to the development of SLE [28, 2]. Moreover, genetic 
association studies have established a link between the 3’-5’ exonuclease Trex1 and SLE [20].   
Therefore, in both mice and humans the balance between the levels of endogenous nucleic acid-
containing ligands and expression of the nucleic acid-sensing TLRs appears key in regulating 
cellular immune responses and autoimmunity. 
3.2 
RSLV-132 
RSLV-132 is a novel therapeutic being developed for the treatment of SLE.  This fully human 
biologic (Figure 1) consists of RNase1 (also known as pancreatic RNase) fused to the N-
terminus of the Fc segment of IgG1.  The attachment of the Fc segment is intended to extend the 
circulatory half-life of the RNase and by so doing reduce the frequency of administration.  
RSLV-132 is intended to utilize the RNase to break down RNA containing immune complexes, 
thereby reducing the activation of TLRs, decreasing the production of type 1 IFN and decreasing 
the proliferation of B-cells and autoantibody production.   


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Figure 1: Schematic of RSLV-132 
 
3.3 
Study Rationale 
Chronic systemic inflammation is the hallmark of SLE.  There is a preponderance of scientific 
and clinical evidence that supports the concept that RNA associated with autoantibodies 
specifically delivered to immune system cells triggers multiple inflammatory pathways.  
Many investigative drugs either currently or previously tested in lupus are designed to inhibit key 
inflammatory cytokines such as Interferon-α, Interferon-γ, or B-cell targets such as CD-20, or 
CD22.  All of these targets lie downstream of the initial triggering event and may be only one of 
the pathways involved in SLE inflammation.   
RNA-containing immune complexes circulating in SLE patient blood are specifically delivered 
to Fc receptor-bearing cells and internalized resulting in the activation of TLRs and the 
activation of myriad downstream inflammatory pathways.  RSLV-132 is an enzymatically active 
RNase with a long circulating half-life that is designed to digest the RNA contained in these 
immune complexes and thereby render the immune complexes biologically inert.  The 
therapeutic hypothesis is that over time depleting the blood of RNA immune complexes will 
decrease the activation of multiple pro-inflammatory cascades and thereby decrease the overall 
SLE inflammation. 
3.4 
RSLV-132 Human Safety Data 
Two safety studies in humans have been conducted to date with RSLV-132; a single ascending 
dose study in 32 healthy volunteers, and a multiple ascending dose study in 32 subjects with 
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3.4.1 
Study 132-01 – Single Ascending Dose Study Summary: 
This first-in-man study was a double-blind, placebo-controlled study conducted in healthy 
volunteers in a phase one unit to assess the safety and tolerability of a single, escalating IV dose 
of RSLV-132 (0.3 mg/kg – 10.0 mg/kg).  There we no SAEs, or drug discontinuations due to an 
AE.  The drug was well tolerated at all doses tested and an MTD was not reached.  The serum 
half-life of the drug was measured to be approximately 16 days.  None of the subjects in the 
study were positive for anti RSLV-132 antibodies.  
3.4.2 
Study 132-02 Multiple Ascending Dose Study Summary: Safety 
This was a multi-center, double-blind, placebo-controlled study with successive escalating 
cohorts to assess the safety and tolerability of repeated IV doses (0.3 mg/kg – 10.0 mg.kg) of 
RSLV-132 in SLE subjects with inactive or mild disease.  The MTD was not reached at the 
highest dose of RSLV-132 tested.  Repeated administration of RSLV-132 doses was generally 
well tolerated by the subjects in this study. Across all dose cohorts, AEs were observed at the 
same overall incidence in RSLV 132 subjects as placebo subjects (6/8 subjects [75%] versus 
18/24 subjects [75%]). The incidence of AEs and the average number of events per subject did 
not increase with increasing dose level. The most frequently reported AEs in the RSLV 132 arm 
were headache, nausea, and upper respiratory tract infection, each of which occurred in 5 
subjects (20.8%). The majority of AEs in this study were Grade 1 in severity; 13 subjects (10 
RSLV-132 and 3 placebo subjects) experienced Grade 2 AEs, and one subject in Cohort 1 of the 
RSLV-132 arm experienced a Grade 3 AE of acute cholecystitis (this event was also reported as 
the only SAE in the study). No Grade 4 or Grade 5 events occurred. Adverse events judged to be 
related to blinded study drug were reported for 38% of placebo subjects and 29% of RSLV 132 
subjects. No dose related trends were observed for any adverse event. No deaths due to AEs 
occurred. All subjects had at least one out-of-range chemistry, hematology, or urinalysis value, 
but no values were considered clinically significant in RSLV-132 subjects. No dose-dependent 
trends were observed in the incidence of out-of-range values and no concerning patterns of 
laboratory abnormalities were detected. No notable differences between treatment groups and no 
trends over the course of the study were observed in vital signs or physical findings. No 
clinically significant ECG abnormalities were reported during the study. No confirmed positive 
anti-RSLV-132 antibodies were detected in any of the subjects in this 113-day study. 


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4 
TRIAL OBJECTIVES AND PURPOSE 
The present study is designed as a proof-of-concept study to demonstrate clinical activity of 
RSLV-132 in a cohort of SLE subjects with active cutaneous manifestations of SLE.  Evidence 
of clinical activity is sought in a smaller, more homogeneous subset of lupus subjects prior to 
embarking on a larger phase 2 dose ranging study. 
4.1 
Primary Objective 
• assess the impact of 13 IV infusions of RSLV-132 on cutaneous lupus disease activity 
using the CLASI activity score comparing Baseline with Day 85 and Day 169 among the 
drug-treated and placebo groups. 
4.2 
Secondary Objectives 
At Days 85 and 169: 
• assess disease activity using SLEDAI-2K, BILAG-2004 and PGA; 
• evaluate the immunogenicity of RSLV-132 in subjects with SLE; 
• assess improvement in tender or swollen joint count; 
• assess improvement in patient reported outcomes using the FACIT-Fatigue scale; 
• assess the proportion of subjects achieving a 50% improvement in CLASI activity score 
At Day 169: 
• assess the ability of subjects to reduce oral steroids at Day 169 relative to Day 85; 
• evaluate the safety and tolerability of 22 weeks of RSLV-132 exposure; 
4.3 
Exploratory Measures 
• evaluate the impact of RSLV-132 treatment on gene expression profile; 
• evaluate the impact of RSLV-132 treatment on autoantibody and complement profiles; 
• evaluate the impact of RSLV-132 on serum protein levels; 
• assess the impact of RSLV-132 on the CLASI damage score 


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5 
INVESTIGATIONAL PLAN 
5.1 
Overall Study Design and Plan 
This is a multi-center, double-blind, placebo-controlled study of approximately fifty subjects 
with SLE.  Potential subjects will be screened to assess their eligibility to enter the study within 
twenty-eight days prior to study entry (i.e., prior to Baseline visit). 
Subjects will be evaluated during screening for evidence of active, evaluable cutaneous 
manifestations of SLE which will be measured by the investigator using the CLASI score and 
documented using photography.  The photographs will be adjudicated by a dermatologist with 
expertise in the use of the CLASI tool in SLE clinical trials in order to confirm the subject meets 
the CLASI entry criteria. 
Following Baseline evaluations on Day 1, subjects will receive their first intravenous infusion of 
RSLV-132.   Subjects will return to the research unit for additional visits as described in 
Appendix A.   
The subjects will be randomized 2:1 (active:placebo) to receive IV administrations of 10 mg/kg 
of study drug or placebo as follows on days: 
• 1, 8, 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, and 155 
5.2 
Number of Subjects and Centers 
Approximately 50 subjects will be enrolled at approximately 15-20 clinical centers in the United 
States, Canada and Europe. 
5.3 
Estimated Study Duration 
Each subject will be screened within twenty-eight days of admission to the study center 
(Baseline visit).  The duration of the study from Baseline visit to End of Study visit, excluding 
the screening period is approximately 30 weeks for each subject. 


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6 
SELECTION AND WITHDRAWAL OF SUBJECTS 
Subjects who meet all of the inclusion criteria and none of the exclusion criteria will be eligible 
to be enrolled into the study. 
6.1 
Subject Inclusion Criteria 
Subjects who meet the following criteria may be included in the study: 
1. diagnosis of SLE by meeting four of the eleven ACR criteria described in the 1997 
update of the 1982 SLE criteria (see Appendix D) including cutaneous involvement at 
Screening; 
2. cutaneous manifestations of SLE and a CLASI activity score of ≥10 at Screening; 
3. elevated levels of any one of the following autoantibodies (local or central laboratory): 
• Ro-52/60, La, Sm, SmRNP, U1 RNP A/68; 
4. no changes to SLE medications in the 30 days prior to Baseline; 
5. able to communicate and able to provide valid, written informed consent; 
6. ages 18 to 70 inclusive; 
7. minimum weight of 45 kg;  
8. Female participants shall be either of non-child-bearing potential (permanently sterilized 
by tubal occlusion, hysterectomy, or bilateral salpingectomy, or menopausal more than 
one year since last menstrual cycle and confirmed by ensuring blood FSH levels ≥ 22 
mIU/mL);  OR practicing highly effective contraception (e.g., oral, implantable, 
transdermal or injectable contraceptives, a non-hormonal intrauterine device [IUD] with 
spermicide; female condom with spermicide; contraceptive sponge with spermicide; 
intravaginal system, diaphragm with spermicide; cervical cap with spermicide; a male 
sexual partner who agrees to use a male condom with spermicide; a sterile sexual partner) 
for at least 2 months prior to dosing and until 110 days following the End of Study.  
9. Male participants must agree to use a male condom with spermicide from the first dose 
until 90 days after the last dose. Male participants must agree not to donate sperm from 
the first dose until 90 days after the last dose. 
6.2 
CLASI Score Entry Criteria – Adjudication 
Prior to being enrolled in the study, each patient’s cutaneous SLE disease activity measure and 
photographs of the cutaneous areas of disease involvement will be submitted to and reviewed by 
an adjudicator.  The adjudicator is a dermatologist with extensive experience in reviewing 
cutaneous clinical data from SLE subjects in a clinical trial setting.  The adjudicator will review 
the photographs of the cutaneous disease to confirm the subject meets the entry criteria and is 
eligible for the study.  
6.3 
Subject Exclusion Criteria 
The following will exclude potential subjects from the study: 
1. severe, active CNS involvement at Screening; 


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2. severe renal involvement (urine protein/creatinine ratio of >200 mg/mmol, or an 
estimated creatinine clearance of <30 mL/min) at Screening; 
3. use of cyclophosphamide within 3 months of Baseline; 
4. use of background medications within 1 month of Baseline in excess of: 
a. mycophenolate mofetil > 3 g/day; 
b. azathioprine > 200 mg/day; 
c. methotrexate > 25 mg/week; 
d. hydroxychloroquine > 400 mg/day; 
e. prednisone (or equivalent) > 15 mg/day; 
5. use of an intravenous corticosteroid “pulse” within 2 months of Baseline; 
6. use of an intramuscular steroid injection within 1 month of Baseline; 
7. use of rituximab within 6 months of Baseline; 
8. use of belimumab within 3 months of Baseline; 
9. acute infection or history of acute infection within seven days prior to Baseline; 
10. positive viral load test for hepatitis B, C or HIV at Screening; 
11. receipt of an investigational product within 3 months of Baseline or five half-lives 
(whichever is longer); 
12. positive pregnancy test at Screening or at Baseline; 
13. female subjects currently breast feeding at Baseline; 
14. inability or unwillingness to comply with study restrictions, return for follow up 
appointments, or other considerations, in the opinion of the Investigator, which would 
make the candidate unsuitable for study participation. 
6.4 
Subject Withdrawal Criteria 
Subjects will be informed that they are free to withdraw from the study at any time and for any 
reason. The Investigator may remove a subject from investigational treatment if, in the 
Investigator's opinion, it is not in the best interest of the subject to continue. Notification of 
discontinuation of investigational treatment will be made immediately to the Sponsor. In case of 
premature discontinuation of investigational treatment, efforts will be made to perform all End of 
Treatment (EOT) assessments and an End of Study (EOS) visit outlined in (Appendix A). 
 
If a subject wishes to withdraw from the study, the site staff should confirm whether the subject 
is agreeable to continue the assessments without the investigational treatment or if they wish no 
further involvement in the study. In the latter case no further study-related evaluations will be 
performed and no additional data will be collected.   
The date and the reason for discontinuation of investigational treatment or withdrawal from the 
study will be recorded on the subject’s Case Report Form (CRF). Subjects that withdraw after 
receiving study drug will not be replaced. 
6.5 
Women of Child-Bearing Potential 
As women of ages 18 to 70 years old are eligible to enroll in this study, all women will be 
considered to be of child-bearing potential unless: 


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• the subject has undergone a surgical sterilization procedure (e.g. bilateral oophorectomy, 
hysterectomy, or tubal ligation); 
• the subject is greater than 12 months past her last menstrual cycle and menopause is 
confirmed by ensuring blood FSH levels ≥ 22 mIU/mL 
Pregnancy tests will be performed at Screening, Baseline, and End of Study visits for women of 
childbearing potential. 


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7 
TREATMENT OF SUBJECTS 
7.1 
Description of Study Drug 
RSLV-132 is a novel therapeutic candidate.  This fully human biologic consists of RNase1 (also 
known as pancreatic RNase) fused to the N-terminus of the Fc portion of IgG1.   The attachment 
of the Fc domain is intended to extend the serum half-life of the RNase and reduce the frequency 
of administration.  RSLV-132 is provided in single-use vials for dilution for intravenous 
infusion.  Two lots of drug have been used in the study; lot 1-FIN-1778 which was provided at 
9.5 mg/mL, and lot 1-FIN-2899 which was provided at 10.0 mg/mL. 
7.2 
Treatment Compliance 
Study drug will be administered at the clinical site by trained study staff according to the Study 
Drug Reference Manual provided by the Sponsor. 
7.3 
Concomitant Medications 
Subjects entering the study who had no changes to their SLE medications in the previous 30 days 
prior to the Baseline visit shall remain on the background medications at the same doses 
throughout the study.  With the exception of decreases in OCS, no changes in lupus medications 
shall be permitted during the study, including the addition of topical steroids or topical 
tacrolimus, except for the rescue of a lupus flare. 
7.4 
Steroid Tapering 
One of the objectives of the study is to evaluate the potential steroid sparing effects of RSLV-
132.  Steroid doses should remain stable through Day 85.  Thereafter, Investigators shall 
decrease the use of oral corticosteroids beginning on Day 85 using the guidance below.  No 
further steroid decreases should occur from Day 141 through Day 169. 
• Subjects receiving >7.5 mg of prednisone or equivalent daily AND demonstrating a 
clinical improvement in the cutaneous manifestations of lupus as measured by a decrease 
in the CLASI activity by 50% compared with Baseline shall decrease oral corticosteroids 
as follows: 
o Decrease prednisone (or equivalent) by 2.5 mg/day  
o If the prednisone dose (or equivalent) remains greater than 7.5 mg/day AND 
cutaneous disease activity remains improved (CLASI activity score decreased by 
50% compared with baseline) AND prednisone has been stable for 2 weeks, 
reduce prednisone by an additional 2.5 mg; repeat after 2 more weeks.   
o If prednisone reduced to 7.5 mg, see below,  
o If after a decrease in prednisone, the CLASI is no longer decreased (compared to 
baseline) by 50%, the investigator may increase the prednisone to the previous 
daily dose (not to exceed the baseline dose) 
• Subjects receiving ≤7.5 mg/of prednisone or equivalent daily AND demonstrating 
clinical improvement in the cutaneous manifestations of lupus as measured by a decrease 


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in the CLASI activity score by 50% compared with baseline, the investigator may, at 
his/her discretion, decrease prednisone by no greater than 2.5 mg/day every other week. 
7.5 
Treatment of Flares 
Investigators should treat lupus flares as they deem appropriate with the minimum amount of 
corticosteroid necessary and should return the subject to baseline steroid dose as quickly as 
medically reasonable.  Should a subject require more than steroids for a lupus flare, investigators 
should treat as necessary and notify the medical monitor. 
7.6 
Randomization and Blinding 
This will be a double-blind, placebo-controlled study. As such, except for the specifically 
designated unblinded study site pharmacist, the investigator, sponsor, and remaining study site 
clinical staff will be blinded as to treatment.  Ongoing drug accountability will be monitored by 
an unblinded monitor. 
Except in a medical emergency, the investigator or designee and blinded study site clinical staff 
will remain blinded during the conduct of the study and until such time that all discrepancies in 
the clinical database are resolved (i.e., at the time of the database lock). The date/initials and 
reason for the investigator and/or clinical staff removing the study blind will be documented. 


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8 
STUDY DRUG MATERIALS AND MANAGEMENT 
8.1 
Study Drug 
RSLV-132 is presented as a single-use, preservative-free vial of sterile solution concentrate for 
dilution for intravenous infusion at a strength of either 9.5 mg/mL or 10.0 mg/mL.  The 
formulation buffer contains 10 mM sodium citrate pH 6.0, 220 mM trehalose and 50 mM L-
arginine. All excipients meet multiple compendia requirements and are not of animal origin. 
The Sponsor, or designee, will provide the investigator with adequate quantities of the study 
drugs (see Table 2). 
Table 2: Study Drug 
Study Drug 
RSLV-132 
Forma 
Sterile injectable solution for intravenous administration packaged in a 
single-use vial.  RSLV-132 will be diluted in saline for infusion. 
Strength 
 Lot 1-FIN-1778, 9.5 mg/mL 
 
Lot 1-FIN-2899, 10.0 mg/mL 
a  
Specific ingredients/purity will be identified on the Certificate of Analysis (or equivalent) that is supplied with the study 
drug. The lot numbers for each concentration of the study drugs will be provided to the clinical site by the 
supplier/manufacturer and will be on vial labels. 
8.2 
Placebo 
Placebo will be sterile saline for infusion and will be provided by each site and prepared by the 
unblinded pharmacist.  
8.3 
Study Drug Packaging, Labeling, Storage, Shipping, and Preparation 
The study drug will be provided to the sites in single use vials, clearly labeled with drug name 
and lot number.  Study drug will be stored at <-20°C under secure conditions and protected from 
light. Prior to administration to the subject, individual dosing solutions will be prepared from a 
vial as detailed in the Study Drug Reference Manual.   Details of study drug packaging, labeling, 
storage, shipping, and preparation, including preparation of matching placebo doses, will 
likewise be provided in the Study Drug Reference Manual.  
8.4 
Study Drug Administration 
RSLV-132 or placebo will be administered intravenously at 10 mg/kg at baseline, then weekly 
for two weeks and then once every 2 weeks for the next 20 weeks (13 administrations) to 
subjects with SLE. The preparation of the study drug and rate of infusion will be provided in the 
Study Drug Reference Manual. For each dose, the date, actual infusion rate, start and stop time 
of infusion will be recorded in the source documents and transcribed into the CRFs. 


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8.5 
Study Drug Accountability 
The unblinded pharmacist will maintain an accurate record of the receipt of the Investigational 
Product as shipped by the Sponsor (or designee), including the date received. In addition, an 
accurate drug disposition record will be kept, specifying the amount dispensed to each subject 
and the date of dispensation.  
8.6 
Study Drug Handling and Disposal 
At the completion of the study, all unused drug supplies will be destroyed by the sites after final 
accountability and reconciliation with the dispensing log. 


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9 
ASSESSMENT OF SAFETY 
Safety of the treatment will be compared between the two groups by assessing adverse events 
and laboratory results as well as any physical findings that have changed from baseline. 
All patients who have received any infusion with either RSLV-132 or placebo will be included in 
the overall analysis of safety. All data relating to safety will be listed and summarized by 
treatment group using descriptive statistics. The change from baseline for each of the vital signs 
parameters will also be computed and included in individual patient listings and descriptive 
summaries.  
Deaths that occur during the study and the proportion of subjects discontinuing the study due to 
adverse events will as well be summarized by treatment group. 
All adverse events will be coded and tabulated by MedDRA System Organ Class (SOC) and 
preferred term (PT) and presented in descending frequency. Adverse events will also be 
tabulated by severity and relationship to the study medication. Serious adverse events will be 
summarized separately. 
9.1 
Adverse Event Definition 
An adverse event (AE) is any untoward medical occurrence in a subject administered a 
pharmaceutical product that does not necessarily have a causal relationship with this treatment. 
Adverse events may be reported by the subject, discovered by Investigator questioning, or 
detected through PE, a laboratory test requiring further attention, or other means. 
Adverse events can therefore be any unfavorable or unintended sign, symptom or disease 
temporally associated with the use of an investigational medicinal product, whether or not 
considered related to the investigational medicinal product. Adverse events include: 
• Any sign, medical diagnosis or symptom 
• Any new undesirable medical experience or unfavorable and unintended worsening of an 
existing condition that occurs during or after treatment, whether or not considered related 
to study drug 
• Abnormal laboratory results that have associated symptoms or findings, require specific 
treatment, or require a change in subject management.   
Whenever possible, the Investigator should group signs or symptoms that constitute a single 
diagnosis under a single event term. For example, cough, rhinitis and sneezing might be grouped 
together as “upper respiratory tract infection”. If possible, abnormal laboratory results that meet 
the definition of an AE (that warrant management, investigation or treatment) should be reported 
as a clinical diagnosis rather than the abnormal value itself (e.g., “anemia” rather than “decreased 
blood count”).  Adverse events will be graded according to the Rheumatology CTC (Woodworth 
et al., J. Rheumatology 2007; 34(6): 1401-1414). 


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9.2 
Serious Adverse Event Definitions 
An AE is classified as serious if it meets any of the following criteria: 
• Results in death 
• Is life-threatening 
o This definition implies that the subject, in the view of the Investigator, was at 
immediate risk of death at the time of the event. It does not include an event that, 
had it occurred in a more severe form, might have caused death. 
• Requires in-patient hospitalization or prolongs an existing hospitalization 
o Hospitalizations for surgeries planned before study entry, for social reasons, or for 
normal disease management procedures (including treatment adjustment) are not 
to be considered SAEs according to this criterion. 
• Results in persistent or significant disability and/or incapacity 
• Results in an adverse outcome in a child or fetus of a patient exposed to the study 
treatment regimen before conception of during pregnancy. 
• Otherwise considered medically important in the judgment of a health care professional. 
Medical and scientific judgment should determine whether an AE is classified as an SAE 
in many situations. Medically important conditions that may not result in death, not be 
life-threatening, nor require hospitalization, may be considered SAEs when they may 
jeopardize the subject or may require intervention to prevent one of the outcomes listed 
above. Examples of such events are allergic bronchospasm requiring intensive treatment 
in an emergency room, blood dyscrasias or convulsions that do not result in in-patient 
hospitalization. 
9.3 
Adverse Event Reporting 
All AEs, both serious and non-serious, will be recorded on the AE CRF at each visit from the 
time the subject receives the first dose of study medication until the End of Study visit.   
9.4 
Serious Adverse Event Reporting Requirements 
SAEs will be reported to Resolve on the SAE report form within 24 hours of awareness of the 
event by the investigator.   
In the event that the investigator does not become aware of the occurrence of a SAE 
immediately, the investigator is to report the event within 24 hours of his/her first awareness of 
the SAE. 
Any SAE occurring any time after the reporting period must be promptly reported if a causal 
relationship to investigational product is suspected.   
The initial report should include as much relevant information as possible but at a minimum 
should include subject Number, date of event onset, event term/description of event, 
investigator’s assessment of relationship to study drug. 


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For all SAEs, the investigator is obligated to pursue and provide information to Resolve or its 
designee in accordance with the timeframes for reporting specified above.  In addition, an 
investigator may be requested by Resolve to obtain specific additional follow-up information in 
an expedited fashion.  This information may be more detailed than that captured on the AE case 
report form.  In general, this will include a description of the AE in sufficient detail to allow for a 
complete medical assessment of the case and independent determination of possible causality.  
Information on other possible causes of the event, such as concomitant medications and illnesses 
must be provided.  All new information including final outcome should be submitted as soon as 
possible. 
9.5 
Non-Serious Adverse Event Reporting Requirements 
Non-serious AEs are to be reported on the AE CRFs, which are to be submitted as outlined in the 
study guidelines. 
9.6 
Adverse Event Follow Up 
For adverse events with a causal relationship to the investigational product, follow-up by the 
investigator is required until the event or its sequelae resolve, stabilize or are explained.  
9.7 
Severity Assessment 
As required on the AE case report forms, the investigator will assess the severity of an event 
according to the Rheumatology CTC (Woodworth et al., J. Rheumatology 2007; 34(6): 1401-
1414). 
9.8 
Causality Assessment 
The investigator’s assessment of causality must be provided for all AEs (serious and non-
serious).  Causality is determined as not related, possibly related, or definitely related according 
to the following definitions: 
• Not related: The event can be readily attributed to other factors such as the subject’s 
clinical state, environmental factors, or other concomitant medications or therapies 
administered. 
• Possibly Related: Follows a reasonable temporal sequence from administration and is 
unlikely to be attributed to the subject's clinical state or environmental factors or other 
therapies administered. 
• Definitely related:  Clear-cut temporal association with study drug administration with 
improvement on cessation of study drug AND cannot be readily attributed to other 
factors such as the subject’s clinical state, environmental factors, or other concomitant 
medications or therapies administered. 
9.9 
Abnormal Test Findings 
When laboratory results are outside the normal range, a decision regarding whether the result is 
of clinical significance or not shall be made by the Investigator and shall be based, in part, upon 


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the nature and degree of the observed abnormality. Abnormal evaluations may be repeated, to 
rule out lab error. 
The criteria for determining whether an abnormal objective test finding should be reported as an 
AE are as follows:  
• Test result is associated with accompanying symptoms, and/or; 
• Test result requires additional diagnostic testing or medical/surgical intervention, and/or; 
• Test result is considered to be an AE by the investigator or Sponsor. 
An abnormal test result, in the absence of any of the above conditions, does not constitute an AE. 
Any abnormal test result that is determined to be an error does not require reporting as an AE. 
9.10 
Hospitalization 
AEs reported from the clinical study associated with subject hospitalization or prolongation of 
subject hospitalization, are considered serious. 
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical AE is 
not an SAE.  Examples include: 
• Admission for treatment of a preexisting condition not associated with the development 
of a new AE or with a worsening of the preexisting condition (e.g., for work-up of 
persistent pre-treatment lab abnormality); 
• Social admission (e.g., subject has no place to sleep); 
• Administrative admission (e.g., for yearly physical exam); 
• Protocol-specified admission during a clinical study (e.g., for a procedure required by the 
study protocol); 
• Pre-planned or optional admission not associated with a precipitating clinical AE. 


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10 
ASSESSMENT OF PHARMACOKINETICS 
10.1 
Measurement of RSLV-132 Drug Levels 
RSLV-132 drug levels in subject serum samples will be quantitated by two different assays; a 
validated ELISA assay that directly measures RSLV-132 (ICON Laboratories), and a catalytic 
activity assay that measures the RNase enzyme activity of RSLV-132 (Resolve Therapeutics, 
LLC). 
10.2 
Pharmacokinetic Analysis 
Pharmacokinetic (PK) parameters will be calculated for each subject, whenever possible, based 
on the serum concentrations of RSLV-132. 


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11 
STATISTICS 
A statistical analysis plan will be prepared after completion of the final protocol and will be 
finalized before database lock. The statistical analysis plan will include more details on the 
statistical analysis and presentation of the data.  The fundamentals of the analysis are listed 
below.  Data will be analyzed and reported by subject’s sex and gender.  
11.1 
Subject Population for Efficacy/Activity Analysis 
The efficacy/activity analysis set will include all subjects randomized and that receive at least 
one dose of study drug. 
11.2 
Analysis of the Primary Objective 
The primary objective is a comparison of the mean improvement (from Baseline to Day 85; or 
Baseline to Day 169 in CLASI Activity scores of those in the efficacy analysis set receiving 
RSLV-132 and those receiving placebo. 
11.3 
Analysis of the Secondary Objectives 
The following secondary objectives will be compared between the two treatment arms: 
• The immunogenicity of RSLV-132 as measured by the presence of RSLV-132 antibodies 
• Improvements (from Baseline to Day 85 and Day 169) in the SLEDAI-2K, PGA, and 
BILAG-2004 scores  
• Improvement (from Baseline to Day 85 and Day 169) in the FACIT-Fatigue scale  
• Improvements (from Baseline to Day 85 and Day 169) in tender or swollen joint count 
• Reduction in oral steroids at Day 169 relative to Day 85 
• The proportion of subjects achieving a 50% improvement in CLASI activity score 
11.4 
Exploratory Analysis 
Differences between the gene expression profiles, autoantibody and complement profiles, and 
serum protein levels will be compared between the two treatment arms.  A comparison will be 
made of the mean improvement (from Baseline to Day 85; or Baseline to Day 169 in CLASI 
damage scores of those randomized to be treated with RSLV-132 and those randomized to 
receive placebo. 
11.5 
Subject Population for Safety Analysis 
The safety of RSLV-132 will be compared between the two arms using the following safety 
parameters:  adverse events, previous and concomitant medications, previous and concomitant 
diseases and laboratory data. The safety population will include all patients who received any 
treatment with either RSLV-132 or placebo. Randomized patients that receive the incorrect 
therapy from that intended will be summarized in the group according to the therapy actually 
received. Patients who are not randomized but who receive treatment or placebo will also be 
included in the safety population and summarized according to the therapy actually received. In 


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the unlikely event of a patient commencing one study therapy and crossing over to the other, the 
data for that patient will be included in summaries and analyses with the original group. 
11.6 
Sample Size 
The sample size chosen for this study was based upon precedent set by other studies of similar 
nature and was not based on power calculations. 


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12 
STUDY PROCEDURES 
12.1 
Evaluations 
Evaluations are summarized in Appendix A. During the course of the study approximately 295 
mL of blood will be drawn.  A central laboratory will perform all evaluations with the following 
exceptions: 
• anti-drug antibody evaluations will be performed by ICON. 
• autoantibody assessments will be performed by the University of Washington Clinical 
Laboratory. 
• measurement of drug concentration by will be performed by ICON. 
• measurement of RNase enzyme activity will be conducted by Resolve Therapeutics. 
• serum protein analysis will be conducted by Myriad RBM. 
• blood-cell gene expression analysis will be performed by Q2 Solutions. 
• Each site will perform a urine pregnancy test on females at the baseline visit only 
Every attempt will be made to perform evaluations on the scheduled day and time, as 
appropriate. If evaluations cannot be performed on the day of the scheduled visit a window of ± 
3 days may be applied for visit Days 8 through 155 and ±5 days for Day 169 and Day 215. In the 
event visit windows are utilized the minimum interval between administrations of RSLV-132 
should be 10 calendar days. 
All scheduled study visits should occur on the specified number of days after Baseline, even if a 
preceding visit occurred off-schedule.  
12.2 
Screening Procedures 
The following Screening procedures will be performed for all potential subjects at a visit 
conducted within 28 days of study entry (prior to Baseline): 
• informed consent; 
• assess inclusion/exclusion criteria; 
• demographic data; 
• weight, and height; 
• viral load for hepatitis-B and C and HIV (Appendix B); 
• physical examination; 
• pregnancy test (serum); 
• medical and medication history; 
• vital signs (temperature, respiratory rate, blood pressure and pulse); 
• clinical laboratory evaluations (including Chem-20, CBC, and UA), laboratory 
evaluations may be repeated if abnormal; 
• measurement of cutaneous SLE activity (CLASI); 
• photographs of cutaneous SLE lesions for adjudication (if CLASI ≥10); 
• evaluation of autoantibody profile (Ro-52/60, La, Sm, SmRNP, U1 RNP A/68) local or 
central laboratory. 


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12.3 
Baseline (Day 1) Procedures 
Prior to study drug administration (pre-dose procedures): 
• the inclusion/exclusion criteria will be re-evaluated (CLASI score and concomitant 
medications only); 
• directed physical examination; 
• pregnancy test (urine); 
• AE Assessment; 
• interim medical/medication history; 
• vital signs (temperature, respiratory rate, blood pressure and pulse); 
• clinical laboratory evaluations (Chem-20, CBC, and UA); 
• measurement of SLE disease activity (CLASI, SLEDAI-2K, BILAG-2004, PGA); 
• tender and swollen joint count 
• photographs of cutaneous SLE lesions; 
• FACIT Index (subject completes form); 
• serum sample for study drug concentration;  
• serum for protein analysis; 
• serum sample for measurement of RNase activity; 
• whole blood for gene expression profile; 
• serum sample for autoantibody profile (Ro-52/60, La, Sm, SmRNP, U1 RNP A/68, 
dsDNA) C3 and C4 (local or central laboratory); 
• serum for assessment of antibodies to RSLV-132; 
• after completion of above assessments: 
o study drug administration 
12.4 
Procedures on Days 8, 15, 43, 71, 99, 127, and 155 
Prior to study drug administration (pre-dose procedures): 
• adverse event assessment; 
• interim medication history; 
• vital signs (temperature, respiratory rate, blood pressure and pulse); 
• serum for assessment of anti-RSLV-132 antibodies (Day 15 only) 
• measurement of cutaneous disease activity (CLASI) – (Days 99, 127 and 155 only); 
• after completion of above assessments: 
o study drug administration 
12.5 
Procedures on Days 29, 57, 85, 113, 141, and 169/End of Treatment (EOT) 
Prior to study drug administration (pre-dose procedures): 
• directed physical examination; 
• adverse event assessment; 
• interim medication history; 
• vital signs (temperature, respiratory rate, blood pressure and pulse); 


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• Chem-20, CBC, UA; 
• measurement of SLE activity (SLEDAI-2K, BILAG-2004, PGA); 
• measurement of cutaneous disease activity (CLASI); 
• tender and swollen joint count; 
• photographs of cutaneous disease activity (Days 85 and 169 only); 
• FACIT fatigue index (subject completes form) (Days 85 and 169 only); 
• serum for study drug concentration (Days 29, 85, and 169 only); 
• serum for protein analysis (Day 85 and 169 only); 
• serum for RNase activity (Days 29, 85, and 169 only); 
• whole blood for gene expression profile (Days 29, 85, and 169 only); 
• serum for autoantibody profile (Ro-52/60, La, Sm, SmRNP, U1 RNP A/68, dsDNA) C3 
and C4 (local or central laboratory); 
• serum for assessment of anti-RSLV-132 antibodies (Days 29 and 85 only); 
• after completion of above assessments: 
o study drug administration (except Day 169) 
12.6 
End of Study Day 215 Evaluations 
The following procedures will be performed on Day 215: 
• directed physical examination; 
• pregnancy test (serum). 
• adverse event assessment; 
• interim medication history; 
• vital signs (including temperature, respiratory rate, and seated blood pressure and pulse); 
• clinical laboratory evaluations (Chem-20, CBC, and UA); 
• serum for study drug concentration; 
• serum for measurement of RNase activity; 
• whole blood for gene expression profile; 
• serum for assessment of antibodies to RSLV-132; 
12.7 
Vital Signs 
Vital signs (including temperature, respiratory rate, and seated blood pressure and pulse) will be 
obtained. Blood pressure and pulse will be measured after the subject has been seated for at least 
five minutes. 
12.8 
Medical/Medication History 
Subjects arriving at the clinical unit for the Screening visit will have a complete medical history 
performed including the current and past medications the subject has been using.  At subsequent 
visits to the clinic only an interim medical/medication history shall be performed to determine 
what changes to the subject’s symptoms and medications have taken place since the last visit.  


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12.9 
CLASI Clinical Assessment 
A CLASI assessment shall be performed for each subject at scheduled visits to determine the 
SLE disease activity for each subject at the visit.  The assessment will include determination of 
both the CLASI Activity Score and the CLASI Damage Score.  The assessment shall be 
performed by a qualified, licensed rheumatologist that has completed training provided by the 
Lupus Foundation of America (LFA) on the use of the instrument. 
12.10 
SLEDAI-2K, BILAG-2004, PGA, and Tender and Swollen Joint Count Clinical 
Assessments 
SLEDAI-2K, PGA, BILAG-2004, and tender and swollen joint count assessments shall be 
performed for each subject at scheduled visits to determine the SLE disease activity for each 
subject at the visit.  The above mentioned clinical assessments shall be performed by a qualified, 
licensed rheumatologist that has experience in performing such assessments and has participated 
in clinical trials in which such measurements were performed. 
12.11 
Study Drug Concentration 
Serum samples will be analyzed using a validated, competitive ELISA assay to determine the 
serum concentration of study drug at selected visits during the study. 
12.12 
Gene Expression Analysis 
RNA will be extracted from whole blood to measure the expression level of genes that are 
related to inflammatory pathways though to be involved in SLE.  Samples will be obtained at 
selected visits during the study from Baseline to the End of Study visit. 
12.13 
Protein Analysis 
Serum samples will be obtained at various visits during the study to analyze the level of 
circulating serum proteins.  The protein analysis will measure protein levels related to the 
inflammatory process.  The analysis will be carried out using a multiplexed immunoassay.   
12.14 
Anti-Drug Antibodies 
Serum will be analyzed by ICON for the presence of anti-RSLV 132 antibodies using a validated 
immunoassay. Each positive serum sample will be evaluated for ADA specificity by repeating 
the immunoassay in the presence of an excess of RSLV-132. Confirmed positive, specific serum 
samples will be titered by serial dilution and a numerical titer will be assigned. 
12.15 
RNase Activity Assessments 
RNase activity will be determined by Resolve Therapeutics using a qualified analytical 
procedure.  Serum samples for RNase activity will be collected, processed, stored and shipped 
according to instructions provided in a separate study manual.  Samples will be obtained 
periodically during the study from Baseline to the End of Study visit. 


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12.16 
Autoantibody Profile 
Serum samples will be analyzed using validated methods.  The analysis shall provide values for 
the following autoantibodies and indicate if the result is positive, equivocal, or negative using the 
validated assay range for the testing laboratory: Ro-52/60, La, Sm, SmRNP, U1 RNP A/68, and 
dsDNA. 


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13 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
The Investigator(s) will permit trial-related monitoring, audits, IRB review, and regulatory 
inspection(s) by providing direct access to source data/documents. 
13.1 
Study Monitoring 
Blinded Study Monitors will be responsible for monitoring this clinical trial. The Study Monitors 
will monitor the study conduct, proper CRF and source documentation completion.  To this end, 
the Study Monitors will visit the study site at suitable intervals and be in frequent contact 
through verbal and written communication. It is essential that the Study Monitors have access to 
all documents (related to the study and the individual participants) at each monitoring visit. In 
turn, the Study Monitors will adhere to all requirements for subject confidentiality as outlined in 
the Informed Consent Form (ICF). The investigator and investigator’s staff will be expected to 
cooperate with the Study Monitors, to be available during a portion of the monitoring visit to 
answer questions, and to provide any missing information.   
An unblinded monitor will periodically visit each site to evaluate drug compliance and 
accountability but will not be involved in the monitoring of any clinical data. 
13.2 
Audits and Inspections 
A Quality Assurance representative from Resolve or a clinical research organization may 
conduct audits at the study site(s). Audits will include, but are not limited to, drug supply, 
presence of required documents, the informed consent process, laboratory specimen processing, 
and comparison of CRFs with source documents. The Investigator agrees to cooperate with 
audits conducted at a reasonable time and in a reasonable manner. 
Regulatory authorities may also audit the Investigator during or after the study. The Investigator 
should contact Resolve Therapeutics immediately if this occurs, and must fully cooperate with 
the audits conducted at a reasonable time in a reasonable manner. 
The Investigator is required to make all study documentation promptly available for inspection, 
review or audit at the study site upon request by sponsor, its representatives, or any appropriate 
regulatory agencies. 
13.3 
Institutional Review Board 
In accordance with 21 CFR 56, the protocol, advertisement, and ICF will be reviewed and 
approved by the IRB. The Sponsor will supply relevant material for the investigator to submit to 
the IRB for the protocol’s review and approval. Verification of the IRB unconditional approval 
of the protocol and the written ICF statement will be transmitted to the investigator. 
The IRB will be informed by the investigator of subsequent protocol amendments and of serious 
and unexpected AEs. Approval for protocol amendments will be transmitted in writing to the 
investigator. If requested, the investigator will permit audits by the IRB and regulatory 
inspections by providing direct access to source data/documents. 


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The investigator will provide the IRB with progress reports at appropriate intervals (not to 
exceed one year) and a Study Progress Report following the completion, termination, or 
discontinuation of the investigator’s participation in the study. 


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14 
ETHICS 
14.1 
Ethical Conduct of the Study 
The study procedures outlined in this protocol will be conducted in accordance with the U.S. 
Code of Federal Regulations governing Protection of Human Subjects (21 CFR 50), Financial 
Disclosure by Clinical Investigators (21 CFR 54), Institutional Review Boards (21 CFR 56), 
Investigational New Drug Application (21 CFR 312), and Applications for FDA Approval to 
Market a New Drug (21 CFR 314), as appropriate. As such, these sections of U.S. Title 21 CFR, 
along with the applicable International Conference on Harmonization (ICH) Guidelines, are 
commonly known as Good Clinical Practices, which are consistent with the Declaration of 
Helsinki. 
14.2 
Written Informed Consent 
Written informed consent for the study will be obtained from all subjects before protocol specific 
procedures are carried out. The ICF generated by the IRB will be approved (along with the 
protocol) by the IRB and will be acceptable to the Sponsor. 
The investigator (or designee) will explain the nature of the study and the action of the test 
product. The subjects will be informed that participation is voluntary and that they can withdraw 
from the study at any time. In accordance with 21 CFR 50, the informed consent process shall be 
documented by the use of a written ICF approved by the IRB and will be signed by the subject 
prior to protocol-specific procedures being performed.  The subject will be given a copy of the 
signed consent, and the original will be maintained with the subject’s records. 
14.3 
Disclosure 
All information provided regarding the study, as well as all information collected/documented 
during the course of the study, will be regarded as confidential. The investigator agrees not to 
disclose such information in any way without prior written permission from the Sponsor. 
Any publication of the results, either in part or in total (articles in journals or newspapers, oral 
presentations, abstracts, etc.) by the Investigator(s) or their representative(s), shall require prior 
notification and review, within a reasonable time frame, by the Sponsor, and cannot be made in 
violation of the Sponsor’s confidentiality restrictions or to the detriment of the Sponsor’s 
intellectual property rights. 


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15 
DATA HANDLING AND RECORDKEEPING 
There will be no alterations in the protocol without agreement between the Sponsor and the 
investigator.  There will be no alterations in the protocol affecting subject safety without the 
express written approval of the Sponsor, investigator, and the IRB.   
Investigators are required to prepare and maintain adequate and accurate case histories that 
record all observations and other data pertinent to the investigation on each individual 
administered the investigational drug or employed as a control in the investigation. Case histories 
include the case report forms and supporting data including, for example, signed and dated 
consent forms and medical records including, for example, progress notes of the physician, the 
individual's hospital chart(s), and the nurses' notes. The case history for each individual shall 
document that informed consent was obtained prior to participation in the study 
The results from screening and data collected during the study will be recorded in the subject’s 
CRF (either paper or electronic CRF). To maintain confidentiality, the subjects/patients will be 
identified only by numbers and/or initials.  The completed CRFs will be transferred to the 
Sponsor or designee. Copies of each CRF will be retained by the Investigator. All source 
documents, records, and reports will be retained by the study site in accordance with 21 CFR 
312.62(c).  Data handling and record keeping are further described in the Data Management 
Plan. 
15.1 
Inspection of Records 
All primary data, or copies thereof (e.g., laboratory records, CRFs, data sheets, correspondence, 
photographs, drug accountability records, and computer records), which are a result of the 
original observations and activities of the study and are necessary for the reconstruction and 
evaluation of any study report, will be retained in the study site archives for a period of 2 years 
following the date a marketing application is approved for the drug for the indication for which it 
is being investigated; or, if no application is to be filed or if the application is not approved for 
such indication, until 2 years after the investigation is discontinued and FDA is notified. 


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16 
REFERENCES 
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antibodies in circulating immune complexes in SLE.  Lupus 21:586-595. 
2. Al-Mayouf, S.M., Sunker, A., Abdwani, R., Al  Abrawi, S., Almurshedi, F., Alhashmi, N., 
Al Sonbul, A., Sewairi, W., Qari, A., Abdallah, E., Al-Owain, M., Al Motywee, S., Al-
Rayes, H., Hashem, M., Khalak, H, Al-Jebali, L., and Alkuraya, F.  2011.  Loss-of-function 
variant in DNASE1L3 causes a familial form of systemic lupus erythematosus.  Nat. Gen. 
43:1186-1188.  
3. Arbuckle, M.R., McClain, M.T., Rubertone, M.V., Scofield, R.H., Dennis, G.J., James, J.A., 
and Harley, J.B.  2003.  Development of autoantibodies before the clinical onset of systemic 
lupus erythematosus.  N. Engl. J. Med. 349:1526-1533. 
4. Barrat, F.J., Meeker, T., Gregorio, J., Chan, J.H., Uematsu, S., Akira, S., Chang, B., 
Duramad, O., Coffman, R.L.  2005.  Nucleic acids of mammalian origin can act as 
endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus.  
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lupus IgG is a potent IFN-inducer.  J. Immunol. 165:3519-3526. 
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Corley, R.B., Rothstein, T.L., Lund, F.E., Behrens, T.W., and Marshak-Rothstein, A.  2007.  
Functional outcome of B cell activation by chromatin immune complex engagement of the B 
cell receptor and TLR9.  J. Immunol. 179:7397-7405. 
7. Chen, K., Nishi, H., Travers, R., Tsuboi, N., Martinod, K, Wagner, D.D., Stan, R., Croce, K., 
and Mayadas, T.N.  2012.  Endocytosis of soluble immune complexes leads to their clearance 
by FcRIIIB but induces neutrophil extracellular traps via FcRIIA in vivo.  Blood 120:4421-
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8. Chiang, E.Y., Yu, X., and Grogan, J.L.  2011.  Immune complex-mediated cell activation 
from systemic lupus erythematosus and rheumatoid arthritis patients elaborate different 
requirements for IRAK1/4 kinase across human cell types.  J. Immunol. 186:1279-1288. 
9. Deane, J.A., Pisitkun, P., Barrett, R.S., Feigenbaum, L., Town, T., Ward, J.M., Flavell, R.A. 
and Bolland, S.  2007.  Control of Toll-like receptor 7 expression is essential to restrict 
autoimmunity and dendritic cell proliferation.  Immunity 27:801-810. 
10. dos Santos, B.P., Valverde, J.V., Rohr, P., Monticielo, O.A., Brenol, J.C.T., Xavier, R.M., 
and Chies, J.A.B.  2012.  TLR7/8/9 polymorphisms and their associations in systemic lupus 
erythematosus patients from Southern Brazil.  Lupus 21:302-309. 
11. Gantier, M.P., Tong, S., Behlke, M.A., Xu, D., Phipps, S., Foster, P.S., and Williams, B.R. 
2008.  TLR7 is involved in sequence-specific sensing of single-stranded RNAs in human 
macrophages.  J. Immunol. 180:2117-21124. 
12. Hoffman RW, Gazitt T, Foecking MF, et al. U1 RNA induces innate immunity signaling. 
Arth & Rheum. 2004;50:2891-2896. 
13. Kelly-Scumpia, K.M., Nacionales, D.C., Scumpia, P.O., Weinstein, J.S., Narain, S., 
Moldawer, L.L., Satoh, M., and Reeves, W.H.  2007.  In vivo adjuvant activity of the RNA 
component of the smRNP lupus autoantigen.  Arth. & Rheum. 56:3379-3386. 
14. Lau, C.M., Broughton, C., Tabor, A.S., Akira, S., Flavell, R.A., Mamula, M.J., Christensen, 
S.R., Shlomchik, M.J., Viglianti, G.A., Rifkin, I.R., and Marshak-Rothstein, A.  2005.  RNA-


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associated autoantigens activate B cells by combined B cell antigen/Toll-like receptor 7 
engagement.  J. Exp. Med. 202:1171-1177. 
15. Leadbetter, E.A., Rifkin, I.R., Hohlbaum, A.M., Beaudette, B.C., Shlomchik, M.J., and 
Marshak-Rothstein, A.  2002.  Chromatin-IgG complexes activate B-cells by dual 
engagement of IgM and Toll-like receptors.  Nature 416:603-607. 
16. Liu, Z. and Davidson, A.  2012.  Taming lupus – a new understanding of pathogenesis is 
leading to clinical advances.  Nat. Med. 18:871-882. 
17. Lood, C., Allhorn, M., Lood, R., Gullstrand, B., Olin, A.I., Ronnblom, L., Truedsson, L., 
Colling, M., and Bengtsson, A.A.  2012.  IgG glycan hydrolysis by endoglycosidase S 
diminishes the proinflammatory properties of immune complexes from patients with 
systemic lupus erythematosus.  Arth. & Rheum. 64:2698-2706. 
18. Means, T.K., Latz, E., Hayashi, F., Murali, M.R., Golenbock, D.T., and Luster, A.D. 2005.  
Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and 
TLR9.  J. Clin. Invest. 115:407-417. 
19. Moder, K.G., Wener, M.H., Weisman, M.H., Ishimori, M.L., Wallace, D.J., Buckeridge, D., 
and Homburger, H.A.   2007.  Measurement of antinuclear antibodies by multiplex 
immunoassay: a prospective multicenter clinical evaluation.  J. Rheumat. 34:978-986. 
20. Namjou, B., Kothari, P.H., Kelly, K.A., Glenn, S.B., Ojwang, J.O., Adler, A., Alarcon-
Riquelme, M.E., Gallant, C.J., Boackle, S.A., Criswell, L.A., Kimberly, R.P., Brown, E., 
Edberg, J., Stevens, A.M., Jacob, C.O., Tsao, B.P., Gilkeson, G.S., Kamen, D.L., Merrill, 
J.T., Petri, M., Goldman, R.R., Vila, L.M., Anaya, J.-M., Niewold, T.B., Martin, J., Pons-
Estel, B.A., Sabio, J.M., Callejas, J.L., Vyse, T.J., Bae, S.-C., Perrino, F.W., Breedman, B.I., 
Scofield, R.H., Moser, K.L., Gaffney, P.M., James, J.A., Langefeld, C.D., Kaufman, K.M., 
Harley, J.B., and Atkinson, J.P.  2011. Evaluation of the TREX1 gene in a large multi-
ancestral lupus cohort.  Genes Immun. 12:270-279. 
21. Nowling, T.K. and Gilkeson, G.S.  2011.  Mechanisms of tissue injury in lupus nephritis.  
Arth. Res. & Ther. 13:250. 
22. O’Neill, S. and Cervera, R. 2010.  Systemic lupus erythematosus.  Best Pract. Res. Clin. 
Rheumatol. 24:841-855. 
23. Shen, N., Fu, Q., Deng, Y., Qian, X., Zhao, J., Kaufman, K.M., Wu, Y.L., Yu, C.Y., Tang, 
Y., Chen, J.-Y., Wanling, Y., Wong, M., Kawaska, A., Tsuchlya, N., Sumida, T., 
Kawaguchi, Y., Howe, H.S., Mok, M.Y., Band, S.-Y., Liu, F.-L., Chang, D.-M., Takasaki, 
Y., Hashimoto, H., Harley, J.B., Guthridge, J.M., Grossman, J.M., Cantor, R.M., Song, 
Y.W., Bae, S.-C., Chen, S., Hahn, B.H., Lau, Y.L., and Tsao, B.P.  2010.  Sex-specific 
association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus.  
Proc. Natl. Acad. Sci. 107:15838-15843. 
24. Solomon, D.H., Kavanaugh, A.J., and Schur, P.H.  2002. American College of 
Rheumatology Ad Hoc Committee on Immunologic Testing Guidelines.  Evidenced-based 
guidelines for the use of immunologic tests: antinuclear antibody testing.  Arthritis Rheum. 
2002. 47:434-444. 
25. Sun, X., Wiedeman, A., Agrawal, N., Teal, T.H., Tanaka, L., Hudkins, K.L., Alpers, C.E., 
Bolland, S., Buechler, M., Hamerman, J., Ledbetter, J.A., Liggitt, D., and Elkon, K.B.  2013.  
Increased RNase expression reduces inflammation and prolongs survival in TLR7 transgenic 
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26. Theofilopoulos, A.N., Gonzalez-Quintial, R., Lawson, B.R., Koh, Y.T., Stern, M.E., Kono, 
D.H., Beutler, B., and Baccala, R.  2010.  Sensors of the innate immune system: their link to 
rheumatic diseases.  Nat.  Rev. Rheum. 6:146-156. 
27. Tsokos, G.C. 2011.  Systemic Lupus Erythematosus.  N. Eng. J. Med. 365:2110-2121. 
28. Yasutomo, K., Horiuchi, T., Kagami, S., Tsukamoto, H., Hashimura, C., Urushihara, M., and 
Kuroda, Y.  2001.  Mutation of DNASE1 in people with systemic lupus erythematosus.  Nat. 
Gen. 28:313-314 
 


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17 
APPENDICES 
17.1 
Appendix A:  Study Procedures 
Study Procedures 
Screen 
(-28 to 
-1) 
Baseline 
Day 1 
Day 
8 
Day 
15 
Day 
29 
Day 
43 
Day 
57 
Day 
71 
Day 
85 
Day 
99 
Day 
113 
Day 
127 
Day 
141 
Day 
155 
Day 
169 
(EOT) 
Day 
215 
(EOS) 
Acceptable Visit 
Window (days) 
 
 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 5 
+ 5 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion  
X 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight, height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis, HIV tests 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam 
X 
Xb 
 
 
Xb 
 
Xb 
 
Xb 
 
Xb 
 
Xb 
 
Xb 
Xb 
Pregnancy tests 
Xc 
Xd 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xc 
AE assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medical/medication 
history 
X 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chem-20, CBC, 
UA 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
SLEDAI, BILAG, 
PGA, joint count 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
CLASI 
X 
X 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
Photographs of 
cutaneous disease 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 


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Study Procedures 
Screen 
(-28 to 
-1) 
Baseline 
Day 1 
Day 
8 
Day 
15 
Day 
29 
Day 
43 
Day 
57 
Day 
71 
Day 
85 
Day 
99 
Day 
113 
Day 
127 
Day 
141 
Day 
155 
Day 
169 
(EOT) 
Day 
215 
(EOS) 
Acceptable Visit 
Window (days) 
 
 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 5 
+ 5 
FACIT index 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
Serum for study 
drug concentration 
 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
Serum for protein 
analysis 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
Serum for RNase 
activity 
 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
Whole blood for 
gene expression 
 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
Serum for 
autoantibody, C3, 
C4 profile 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Serum for ADA 
 
X 
 
X 
X 
 
 
 
X 
 
 
 
 
 
 
X 
Study Drug 
administration 
 
Xf 
X 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
 
 
a 
CLASI activity and damage score and confirm no changes in SLE medications only 
b 
directed physical exam 
c 
serum pregnancy test for women of childbearing potential (7.4) 
d 
urine pregnancy test for women of childbearing potential (7.4) 
e 
interim medical/medication history only 
f 
RSLV-132 or placebo shall be administered according to the infusion rate and time set forth in the Study Drug Reference Manual 
 
 


Resolve Therapeutics  
 Protocol 132-03 
 
Confidential 
Version 5 27 April 2017  
Page 48 of 52 
17.2 
Appendix B: Clinical Laboratory Evaluations 
Chemistry (Chem-20): 
Hematology (CBC): 
Other Tests: 
Albumin 
Alkaline Phosphatase 
ALT 
AST 
Bicarbonate 
BUN 
Calcium 
Chloride 
Cholesterol 
Creatinine 
GGT 
Glucose 
Lactate dehydrogenase 
Phosphate 
Potassium 
Sodium 
Total Bilirubin 
Total Protein 
Triglycerides 
Uric acid 
Hematocrit 
Hemoglobin 
Mean corpuscular 
hemoglobin 
Mean corpuscular 
hemoglobin concentration 
Mean corpuscular volume 
Platelet count 
Red blood cell count 
White blood cell count 
White blood cell differential 
(Percent and Absolute): 
Basophils 
Eosinophils 
Lymphocytes 
Monocytes 
Neutrophils 
Bands 
Hepatitis B, and C HIV 
Pregnancy Test (serum and 
urine qualitative) 
RNase activity 
Study drug concentration 
Serum protein analysis 
Anti-RSLV-132 antibodies 
Autoantibody profile 
C3 and C4 
Gene expression  
FSH 
Complete Urinalysis (UA): 
 
 
pH and Specific Gravity 
Bilirubin 
Glucose 
Ketones 
Leukocytes 
Nitrite 
Occult blood 
Protein (Albumin/Creatinine) 
Urobilinogen 
Microscopic (RBC, WBC) 
 
 
 


Resolve Therapeutics  
 Protocol 132-03 
 
Confidential 
Version 5 27 April 2017  
Page 49 of 52 
17.3 
Appendix C: Investigator Protocol Agreement Page 
By signing, I confirm that my staff and I have read and understand this protocol, and agree to 
comply with the conduct and terms of this study. My staff and I have agreed to abide by the 
following responsibilities: 
• To conduct the study in compliance with Sponsor agreements, this protocol, any future 
amendments, any conditions of the governing reviewing EC/IRB or regulatory agency, 
and with any other study conduct procedures implemented by Resolve Therapeutics. 
• To supervise all testing involving human subjects. 
• To abide by FDA regulations, Good Clinical Practices (GCP), and all applicable regional 
regulations.  
• Ensure that the requirements for obtaining informed consent from each study participant 
or their legal representative are met. 
• To report any Serious Adverse Events to Resolve Therapeutics in a timely manner as 
required by the protocol. 
• To report any Serious Adverse Events to the IRB in a timely manner. 
• To report Non-Serious Adverse Events as required by the protocol. 
• To assure access by Resolve Therapeutics representatives to original source documents. 
• To maintain confidentiality and assure security of Resolve Therapeutics confidential 
documents that include but are not limited to: the protocol, case report forms, 
Investigator’s Brochure, final study documents, manuscript drafts, unpublished data, 
sponsor correspondence, etc. 
• To cooperate fully with any study related GCP audit as performed by the sponsor’s 
quality assurance group. 
• To cooperate fully with any regulatory agency audit. 
 
Principal Investigator (printed name): 
 
 
 
 
 
 
 
 
 
 
 
Principal Investigator (signature): 
 
 
 
 
 
 
 
 
Date Signed (mm/dd/yyyy) 
 
 
 


Resolve Therapeutics  
 Protocol 132-03 
 
Confidential 
Version 5 27 April 2017  
Page 50 of 52 
17.4 
Appendix D:  ACR SLE Classification Criteria 
1997 Update of the 1982 American College of Rheumatology revised criteria for classification of 
systemic lupus erythematosus 
1. Malar Rash 
Fixed erythema, flat or raised, over the malar eminences, tending to spare 
the nasolabial folds 
2. Discoid rash 
Erythematous raised patches with adherent keratotic scaling and follicular 
plugging; atrophic scarring may occur in older lesions 
3. Photosensitivity 
Skin rash as a result of unusual reaction to sunlight, by patient history or 
physician observation 
4. Oral ulcers 
Oral or nasopharyngeal ulceration, usually painless, observed by physician 
5. Nonerosive arthritis 
Involving 2 or more peripheral joints, characterized by tenderness, swelling, 
or effusion 
6. Pleuritis or pericarditis 
1. Pleuritis--convincing history of pleuritic pain or rubbing heard by a 
physician or evidence of pleural effusion 
 
OR 
2. Pericarditis--documented by electrocardigram or rub or evidence of 
pericardial effusion 
7. Renal disorder 
1. Persistent proteinuria > 0.5 grams per day or > than 3+ if quantitation 
not performed 
 
OR 
2. Cellular casts--may be red cell, hemoglobin, granular, tubular, or 
mixed 
8. Neurologic disorder 
3. Seizures--in the absence of offending drugs or known metabolic 
derangements; e.g., uremia, ketoacidosis, or electrolyte imbalance 
 
OR 
4. Psychosis--in the absence of offending drugs or known metabolic 
derangements, e.g., uremia, ketoacidosis, or electrolyte imbalance 
9. Hematologic disorder 
1. Hemolytic anemia--with reticulocytosis 
OR 
2. Leukopenia--< 4,000/mm3 on ≥ 2 occasions 
OR 
3. Lyphopenia--< 1,500/ mm3 on ≥ 2 occasions 
OR 
4. Thrombocytopenia--<100,000/ mm3 in the absence of offending drugs 


Resolve Therapeutics  
 Protocol 132-03 
 
Confidential 
Version 5 27 April 2017  
Page 51 of 52 
10. Immunologic disorder 
1. Anti-DNA: antibody to native DNA in abnormal titer 
OR 
2. Anti-Sm: presence of antibody to Sm nuclear antigen 
OR 
3. Positive finding of antiphospholipid antibodies on: 
1. an abnormal serum level of IgG or IgM anticardiolipin antibodies, 
2. a positive test result for lupus anticoagulant using a standard 
method, or 
3. a false-positive test result for at least 6 months confirmed by 
Treponema pallidum immobilization or fluorescent treponemal 
antibody absorption test 
11. Positive antinuclear antibody 
An abnormal titer of antinuclear antibody by immunofluorescence or an 
equivalent assay at any point in time and in the absence of drugs 
 


Resolve Therapeutics  
 Protocol 132-03 
 
Confidential 
Version 5 27 April 2017  
Page 52 of 52 
17.5 
Appendix E:  Summary of Changes 
 
From Version 4.0 to Version 5.0 
Overall 
1. Clarified that there are two lot numbers and concentrations of study 
drug. 
2. Clarified which assessments should be performed for subjects that 
discontinue early from the study. 
3. Clarified that all AEs, both serious and non-serious, will be recorded on 
the AE CRF at each visit from the time the subject receives the first 
dose of study medication until the End of Study visit.   
Section 
Details of Changes 
Title Page 
• Updated Version, Prior Version, Date of Publication  
• Updated version number and date to footer 
6.4 
Updated section to clarify that efforts will be made to perform all End of 
Treatment (EOT) assessments and an End of Study (EOS) visit outlined in 
(Appendix A). 
7.1 
Clarified RSLV-132 is provided in single-use vials for dilution for 
intravenous infusion.  Two lots of drug have been used in the study; lot 1-
FIN-1778 which was provided at 9.5 mg/mL, and lot 1-FIN-2899 which 
was provided at 10.0 mg/mL. 
8.1 
Clarified RSLV-132 is presented as a single-use, preservative-free vial of 
sterile solution concentrate for dilution for intravenous infusion at a 
strength of either 9.5 mg/mL or 10.0 mg/mL. 
 
Table 2: 
Added Lot 1-FIN-1778, 9.5 mg/mL and Lot 1-FIN-2899, 10.0 mg/mL 
 
Footnote:  
Clarified the lot numbers for each concentration of the study drugs will be 
provided to the clinical site by the supplier/manufacturer and will be on vial 
labels. 
9.3 
Clarified all AEs, both serious and non-serious, will be recorded on the AE 
CRF at each visit from the time the subject receives the first dose of study 
medication until the End of Study visit. 
17.5 
Appendix E 
Updated table with summary of changes. 
 

SAP_001.pdf: 
Statistical Analysis Plan 
Resolve Therapeutics, Inc. 
 
Final 3.0 
Page 1 of 37 
March 10, 2020 
Statistical Analysis Plan 
 
Sponsor:   Resolve Therapeutics, Inc.    
Protocol Number: 132-03 
Protocol Version / Date:  Final 5.0 / April 27, 2017 
Protocol Title:  A Phase 2a, Double Blind, Placebo Controlled Study of 
RSLV-132 in Subjects with Systemic Lupus Erythematosus (SLE) 
Author: Emily Woolley, MS; Axio, A Cytel Company 
Version / Date: Final 3.0 / March 10, 2020 
 
 


Statistical Analysis Plan 
Resolve Therapeutics, Inc. 
 
Final 3.0 
Page 2 of 37 
March 10, 2020 
TABLE OF CONTENTS 
1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ...... 5 
2. 
INTRODUCTION .......................................................................... 7 
2.1. 
STUDY OBJECTIVES ........................................................................................................................ 7 
2.1.1. 
Primary Objective ................................................................................................................... 7 
2.1.2. 
Secondary Objectives .............................................................................................................. 7 
2.1.3. 
Exploratory Measures ............................................................................................................. 8 
2.2. 
ENDPOINTS ..................................................................................................................................... 8 
2.2.1. 
Efficacy Endpoints .................................................................................................................. 8 
2.2.1.1. 
Primary Efficacy Endpoints ............................................................................................. 8 
2.2.1.2. 
Secondary Efficacy Endpoints ......................................................................................... 8 
2.2.1.3. 
Exploratory Efficacy Measures ........................................................................................ 9 
2.2.2. 
Safety Measures ...................................................................................................................... 9 
2.3. 
STUDY DESIGN................................................................................................................................ 9 
2.3.1. 
Study Population ..................................................................................................................... 9 
2.3.2. 
Treatment Groups and Dosing .............................................................................................. 10 
2.3.3. 
Study Visits and Assessments ................................................................................................ 10 
2.3.4. 
Concomitant Medications ..................................................................................................... 14 
2.3.4.1. 
Steroid Tapering ............................................................................................................ 14 
2.3.4.2. 
Treatment of Flares ........................................................................................................ 14 
2.3.5. 
Subject Withdrawal ............................................................................................................... 15 
2.3.6. 
Randomization and Blinding ................................................................................................. 15 
2.3.7. 
Sample Size and Power ......................................................................................................... 16 
3. 
GENERAL CONSIDERATION FOR DATA ANALYSES .............. 16 
3.1. 
ANALYSIS SETS ............................................................................................................................ 16 
3.1.1. 
Intent-to-Treat Analysis Set ................................................................................................... 16 
3.1.2. 
Full Analysis Set .................................................................................................................... 16 
3.1.3. 
Safety Analysis Set ................................................................................................................. 16 
3.2. 
STATISTICAL ANALYSIS ISSUES ................................................................................................... 17 
3.2.1. 
Strata and Covariates ........................................................................................................... 17 
3.2.2. 
Examination of Subject Subsets............................................................................................. 17 
3.2.3. 
Multiple Comparisons ........................................................................................................... 17 
3.2.4. 
Multi-center Studies .............................................................................................................. 17 
3.2.5. 
Missing Data and Outliers .................................................................................................... 17 
3.2.6. 
Data Conventions and Transformations ............................................................................... 17 
3.2.7. 
Study Baseline and Study Day ............................................................................................... 17 
3.2.8. 
Visit Windows ........................................................................................................................ 18 
4. 
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE 18 
5. 
GENERAL ANALYSIS METHODS ............................................. 18 
6. 
SUBJECT DISPOSITION........................................................... 19 


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Resolve Therapeutics, Inc. 
 
Final 3.0 
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6.1. 
ENROLLMENT AND DISPOSITION OF SUBJECTS ............................................................................ 19 
6.2. 
EXTENT OF EXPOSURE .................................................................................................................. 19 
6.3. 
PROTOCOL DEVIATIONS ............................................................................................................... 20 
7. 
BASELINE DATA ....................................................................... 20 
7.1. 
DEMOGRAPHIC AND BASELINE CHARACTERISTICS ...................................................................... 20 
7.2. 
MEDICAL HISTORY ....................................................................................................................... 21 
8. 
PRIOR AND CONCOMITANT MEDICATIONS .......................... 21 
8.1. 
MEDICATIONS ............................................................................................................................... 21 
9. 
EFFICACY ANALYSES .............................................................. 21 
9.1. 
ANALYSIS OF PRIMARY EFFICACY ENDPOINTS ............................................................................ 22 
9.2. 
ANALYSIS OF SECONDARY EFFICACY ENDPOINTS ....................................................................... 23 
9.2.1. 
SLEDAI-2K ........................................................................................................................... 23 
9.2.2. 
BILAG-2004 .......................................................................................................................... 23 
9.2.3. 
PGA ....................................................................................................................................... 24 
9.2.4. 
FACIT-Fatigue Scale ............................................................................................................ 24 
9.2.5. 
Tender and Swollen Joint Count ........................................................................................... 26 
9.2.6. 
Oral Steroids Tapering ......................................................................................................... 26 
9.2.7. 
CLASI Activity Score Improvement ....................................................................................... 27 
9.3. 
EXPLORATORY EFFICACY ANALYSIS ........................................................................................... 28 
9.3.1. 
Autoantibody and Complement Profiles................................................................................ 28 
9.3.2. 
Gene Expression Profiles ...................................................................................................... 29 
9.3.3. 
Serum Protein Levels ............................................................................................................ 29 
9.3.4. 
CLASI Damage Score ........................................................................................................... 29 
10. SAFETY ANALYSES .................................................................. 29 
10.1. 
ADVERSE EVENTS ..................................................................................................................... 29 
10.1.1. 
Overall Adverse Events ..................................................................................................... 30 
10.1.2. 
Incidence of Adverse Events .............................................................................................. 30 
10.1.3. 
Relationship of Adverse Event to Study Drug .................................................................... 31 
10.1.4. 
Severity of Adverse Event .................................................................................................. 31 
10.1.5. 
Serious Adverse Events ...................................................................................................... 31 
10.1.6. 
Adverse Events Leading to Hospitalization / Study Drug Discontinuation / Study 
Termination ......................................................................................................................................... 31 
10.2. 
LABORATORY AND OTHER SAFETY ASSESSMENTS .................................................................. 31 
10.2.1. 
Laboratory Blood and Urine Samples ............................................................................... 32 
10.2.2. 
Hepatitis and HIV Tests ..................................................................................................... 32 
10.2.3. 
Vital Signs .......................................................................................................................... 32 
10.2.4. 
Physical Exam ................................................................................................................... 32 
10.3. 
IMMUNOGENICITY ANALYSES .................................................................................................. 33 
11. PHARMACOKINETIC ANALYSES ............................................ 33 
12. SAP REVISION .......................................................................... 34 


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Resolve Therapeutics, Inc. 
 
Final 3.0 
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March 10, 2020 
13. APPENDIX I:  FACIT-FATIQUE SCALE SAS SCORING ............ 36 
 


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Resolve Therapeutics, Inc. 
 
Final 3.0 
Page 5 of 37 
March 10, 2020 
1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ADA 
Anti-drug antibodies 
AE 
Adverse event 
ATC 
Anatomical Therapeutic Chemical Classification 
BILAG 
British Isles Lupus Activity Group 
bpm 
Beats per minute 
°C 
Celsius  
CLASI 
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
CRF 
Case report form 
CRO 
Contract Research Organization 
CSR 
Clinical study report 
DBP 
Diastolic blood pressure 
eCRF 
Electronic case report form 
°F 
Fahrenheit 
FACIT 
Functional Assessment of Chronic Illness Therapy 
FAS 
Full analysis set 
HIV 
Human immunodeficiency virus 
IR 
Incidence rate of the adverse event 
ITT 
Intent-to-Treat analysis set 
IV 
Intravenous 
IWRS 
Interactive Web Response System 
LOCF 
Last observation carried forward 
MedDRA 
Medical Dictionary for Regulatory Activities  
mg 
 
Milligram 
mg/kg 
Milligram per kilogram 
mm 
Millimeter 
mm Hg 
Millimeter of mercury 
OCS 
Oral Corticosteroids 


Statistical Analysis Plan 
Resolve Therapeutics, Inc. 
 
Final 3.0 
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March 10, 2020 
PGA 
Physician’s global assessment 
PK 
Pharmacokinetic 
PT 
Preferred term 
RNA 
Ribonucleic acid 
RR 
Respiratory rate 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SAS 
Safety analysis set 
SBP 
Systolic blood pressure 
SD 
Standard deviation 
SELENA 
Safety of estrogens in lupus erythematosus national assessment 
SLE 
Systemic lupus erythematosus 
SLEDAI 
Systemic Lupus Erythematosus Disease Activity Index SELENA 
Modification 
SOC 
System organ class 
TEAE 
Treatment Emergent Adverse Event 
WHO 
World Health Organization 
 


Statistical Analysis Plan 
Resolve Therapeutics, Inc. 
 
Final 3.0 
Page 7 of 37 
March 10, 2020 
2. 
INTRODUCTION 
This document presents the statistical analysis plan (SAP) for Resolve Therapeutics, Inc. 
based on protocol 132-03: A Phase 2a, Double Blind, Placebo Controlled Study of 
RSLV-132 in Subjects with Systemic Lupus Erythematosus.  The analyses described in 
this document will be performed for the final clinical study report (CSR).  Any deviations 
from the statistical analysis plan will be described and a justification given in the final 
CSR.   
All analyses will be conducted using SAS version 9.3 or higher.  
2.1. 
Study Objectives 
2.1.1. 
Primary Objective 
The primary objective of the study is: 
• to assess the impact of 13 intravenous (IV) infusions of RSLV-132 on 
cutaneous lupus disease activity using the Cutaneous Lupus Erythematosus 
Disease Area and Severity Index (CLASI) activity score comparing Baseline 
with Day 85 and Day 169 among the drug-treated and placebo groups. 
2.1.2. 
 Secondary Objectives 
The secondary objectives of the study are: 
At Days 85 and 169: 
• to assess disease activity using Systemic Lupus Erythematosus Disease 
Activity Index SELENA (safety of estrogens in lupus erythematosus national 
assessment) Modification (SLEDAI-2K), British Isles Lupus Activity Group 
(BILAG-2004) and physician’s global assessment (PGA); 
• to evaluate the immunogenicity of RSLV-132 in subjects with systemic lupus 
erythematosus; 
• to assess improvement in tender or swollen joint count; 
• to assess improvement in patient reported outcomes using the Functional 
Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale; 
• to assess the proportion of subjects achieving a 50% improvement in CLASI 
activity score. 
 


Statistical Analysis Plan 
Resolve Therapeutics, Inc. 
 
Final 3.0 
Page 8 of 37 
March 10, 2020 
At Day 169: 
• to assess the ability of subjects to reduce oral steroids at Day 169 relative to 
Day 85; 
• to evaluate the safety and tolerability of 22 weeks of RSLV-132 exposure. 
2.1.3. 
Exploratory Measures 
The exploratory measures of the study are: 
• to evaluate the impact of RSLV-132 treatment on gene expression profile; 
• to evaluate the impact of RSLV-132 treatment on autoantibody and 
complement profiles; 
• to evaluate the impact of RSLV-132 on serum protein levels; 
• to assess the impact of RSLV-132 on the CLASI damage score. 
2.2. 
Endpoints 
2.2.1. 
Efficacy Endpoints 
2.2.1.1. 
Primary Efficacy Endpoints 
• Compare the treatment group difference in the mean improvement from 
Baseline to Day 85 in CLASI Activity scores of those in the efficacy analysis 
set receiving RSLV-132 and those receiving placebo. 
• Compare the treatment group difference in the mean improvement from 
Baseline to Day 169 in CLASI Activity scores of those in the efficacy analysis 
set receiving RSLV-132 and those receiving placebo. 
2.2.1.2. 
Secondary Efficacy Endpoints 
Compare the treatment group difference on the following endpoints: 
• Improvements (from baseline to Day 85 and Day 169) in the SLEDAI-2K, 
BILAG-2004, and PGA scores 
• Improvement (from Baseline to Day 85 and Day 169) in the FACIT-Fatigue 
scale 
• Improvements (from Baseline to Day 85 and Day 169) in tender or swollen 
joint count 
• Reduction in oral steroids at day 169 relative to Day 85 


Statistical Analysis Plan 
Resolve Therapeutics, Inc. 
 
Final 3.0 
Page 9 of 37 
March 10, 2020 
• The proportion of subjects achieving a 50% improvement in CLASI Activity 
score 
2.2.1.3. 
Exploratory Efficacy Measures 
• Evaluate the differences on the gene expression profiles between the two 
treatment groups 
• Evaluate the difference on the autoantibody and complement profiles between 
the two treatment groups 
• Evaluate the difference on the serum protein levels between the two treatment 
groups 
• Compare the mean improvement (from Baseline to Day 85; or Baseline to 
Day 169) in CLASI damage scores of those randomized to be treated with 
RSLV-132 and those randomized to receive placebo.  
2.2.2. 
Safety Measures 
• Reported adverse events  
• Changes in laboratory values and vital signs from baseline  
• Evaluate the immunogenicity of RSLV-132 as measured by the presence of 
RSLV-132 antibodies 
2.3. 
Study Design 
2.3.1. 
Study Population 
This is a Phase 2a, multi-center, double-blind, placebo-controlled study to evaluate the 
impact of 13 intravenous infusions of RSLV-132 in subjects with Systemic Lupus 
Erythematosus.  The study population will be 18 to 70 years male or female with SLE, 
including cutaneous manifestations of SLE and a CLASI score of ≥10 at Screening, and 
elevated levels of any one of the Ro-52/60, La, Sm, SmRNP, U1 RNP A/68 
autoantibodies at Screening (local or central laboratory). 
Approximately 50 subjects will be enrolled at approximately 15-20 clinical centers in the 
United States.  Study subjects who are eligible for enrollment and have provided written 
informed consent will be randomized 2:1 (Active:Placebo) to receive 13 infusions of 10 
milligram per kilogram (mg/kg) of RSLV-132 or Placebo.  


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Final 3.0 
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March 10, 2020 
2.3.2. 
Treatment Groups and Dosing 
Following Baseline evaluations on Day 1, randomized subjects will receive their first infusion 
of RSLV-132 or Placebo.  RSLV-132 or Placebo will be administered intravenously at 10 
mg/kg at baseline, then weekly for two weeks and then once every 2 weeks for the next 20 
weeks (13 administrations) to subjects with SLE. 
RSLV-132 shall be prepared for each subject from individual stock vials provided by Sponsor. 
Details of dilution, dose preparation, and administration instructions will be provided in the 
Study Drug Reference Manual.  The dose for each individual shall be based on the subject’s 
baseline body weight. 
2.3.3. 
 Study Visits and Assessments 
Potential subjects will be screened to assess their eligibility to enter the study within 28 days 
prior to study entry (i.e., prior to Baseline visit).  Following Baseline evaluations on Day 1, 
randomized subjects will receive their first intravenous infusion of RSLV-132 or Placebo.  
Subjects will return to the research unit for additional visits as described in Table 1 Study 
Procedures. 
Subject participation duration: 28 days of screening followed by 22 weeks of treatment and 8 
weeks of follow up (approximately 34 weeks total).  The duration of the study from Baseline 
visit to End of Study visit, excluding the screening period is approximately 30 weeks for each 
subject.  Study assessments are outlined in Table 1. 


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Resolve Therapeutics, Inc. 
 
Final 3.0 
    
 
 
Page 11 of 37 
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Table 1: Study Procedures 
Study Procedures 
Screen 
(-28 to 
-1) 
Baseline 
Day 1 
Day 
8 
Day 
15 
Day 
29 
Day 
43 
Day 
57 
Day 
71 
Day 
85 
Day 
99 
Day 
113 
Day 
127 
Day 
141 
Day 
155 
Day 
169 
(EOT) 
Day 
215 
(EOS) 
Acceptable Visit 
Window (days) 
 
 
 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 5 
+ 5 
Informed Consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion  
 
X 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight, height 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis, HIV tests 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam 
 
X 
Xb 
 
 
Xb 
 
Xb 
 
Xb 
 
Xb 
 
Xb 
 
Xb 
Xb 
Pregnancy tests 
 
Xc 
Xd 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xc 
AE assessment 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medical/medication 
history 
 
X 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Vital signs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chem-20, CBC, 
UA 
 
 
 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 


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Resolve Therapeutics, Inc. 
 
Final 3.0 
    
 
 
Page 12 of 37 
March 10, 2020 
Study Procedures 
Screen 
(-28 to 
-1) 
Baseline 
Day 1 
Day 
8 
Day 
15 
Day 
29 
Day 
43 
Day 
57 
Day 
71 
Day 
85 
Day 
99 
Day 
113 
Day 
127 
Day 
141 
Day 
155 
Day 
169 
(EOT) 
Day 
215 
(EOS) 
Acceptable Visit 
Window (days) 
 
 
 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 5 
+ 5 
 
SLEDAI, BILAG, 
PGA, joint count 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
CLASI 
 
X 
X 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
Photographs of 
cutaneous disease 
 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
FACIT index 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
Serum for study 
drug concentration 
 
 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
Serum for protein 
analysis 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
Serum for RNase 
activity 
 
 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
Whole blood for 
gene expression 
 
 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
Serum for 
autoantibody, C3, 
C4 profile 
 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 


Statistical Analysis Plan 
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Final 3.0 
    
 
 
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Study Procedures 
Screen 
(-28 to 
-1) 
Baseline 
Day 1 
Day 
8 
Day 
15 
Day 
29 
Day 
43 
Day 
57 
Day 
71 
Day 
85 
Day 
99 
Day 
113 
Day 
127 
Day 
141 
Day 
155 
Day 
169 
(EOT) 
Day 
215 
(EOS) 
Acceptable Visit 
Window (days) 
 
 
 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 5 
+ 5 
Serum for ADA 
 
 
X 
 
X 
X 
 
 
 
X 
 
 
 
 
 
 
X 
Study Drug 
administration 
 
 
Xf 
X 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
Xf 
 
 
 
a CLASI activity and damage score and confirm no changes in SLE medications only 
b directed physical exam 
c serum pregnancy test for women of childbearing potential (6.5) 
d urine pregnancy test for women of childbearing potential (6.5) 
e interim medical/medication history only 
f RSLV-132 or placebo shall be administered according to the infusion rate and time set forth in the Study Drug Reference Manual 
 
 


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2.3.4. 
Concomitant Medications  
Subjects entering the study who had no changes to their SLE medications in the previous 30 days 
prior to the Baseline visit shall remain on the background medications at the same doses 
throughout the study.  With the exception of decreases in Oral Corticosteroids (OCS), no 
changes in lupus medications shall be permitted during the study, including the addition of 
topical steroids or topical tacrolimus, except for the rescue of a lupus flare. 
2.3.4.1. 
Steroid Tapering 
One of the objectives of the study is to evaluate the potential steroid sparing effects of RSLV-
132.  Steroid doses should remain stable through Day 85.  Therefore, Investigators shall decrease 
the use of oral corticosteroids beginning on Day 85 using the guidance below.  No further steroid 
decreases should occur from Day 141 through Day 169. 
• Subjects receiving >7.5 milligram (mg) of prednisone or equivalent daily AND 
demonstrating a clinical improvement in the cutaneous manifestations of lupus as 
measured by a decrease in the CLASI activity by 50% compared with Baseline shall 
decrease oral corticosteroids as follows: 
o Decrease prednisone (or equivalent) by 2.5 mg/day 
o If the prednisone dose (or equivalent) remains greater than 7.5 mg/day AND 
cutaneous disease activity remains improved (CLASI activity score decreased 
by 50% compared with baseline) AND prednisone has been stable for 2 
weeks, reduce prednisone by an additional 2.5 mg; repeat after 2 more weeks. 
o If prednisone reduced to 7.5 mg, see below, 
o If after a decrease in prednisone, the CLASI is no longer decreased (compared 
to baseline) by 50%, the investigator may increase the prednisone to the 
previous daily dose (not to exceed the baseline dose) 
• Subjects receiving ≤7.5 mg/of prednisone or equivalent daily AND demonstrating 
clinical improvement in the cutaneous manifestations of lupus as measured by a 
decrease in the CLASI activity score by 50% compared with baseline, the investigator 
may, at his/her discretion, decrease prednisone by no greater than 2.5 mg/day every 
other week. 
2.3.4.2. 
Treatment of Flares 
Investigators should treat lupus flares as they deem appropriate with the minimum amount of 
corticosteroid necessary and should return the subject to baseline steroid dose as quickly as 
medically reasonable.  Should a subject require more than steroids for a lupus flare, investigators 
should treat as necessary and notify the medical monitor. 
 


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2.3.5. 
Subject Withdrawal 
Subjects will be informed that they are free to withdraw from the study at any time and for any 
reason.  The Investigator may remove a subject from investigational treatment if, in the 
Investigator's opinion, it is not in the best interest of the subject to continue.  Notification of 
discontinuation of investigational treatment will be made immediately to the Sponsor.  In case of 
premature discontinuation of investigational treatment, efforts will be made to perform all End of 
Treatment (EOT) assessments and an End of Study (EOS) visit outlined in SAP Section 2.3.3 
Table 1. 
If a subject wishes to withdraw from the study, the site staff should confirm whether the subject 
is agreeable to continue the assessments without the investigational treatment or if they wish no 
further involvement in the study.  In the latter case no further study-related evaluations will be 
performed and no additional data will be collected. 
The date and the reason for discontinuation of investigational treatment or withdrawal from the 
study will be recorded on the subject’s Case Report Form (CRF).  Subjects that withdraw after 
receiving study drug will not be replaced. 
2.3.6. 
Randomization and Blinding 
This will be a double-blind, placebo-controlled study.  As such, except for the specifically 
designated unblinded study site pharmacist, the investigator, sponsor, and remaining study site 
clinical staff will be blinded as to treatment.  Ongoing drug accountability will be monitored by 
an unblinded monitor. 
A randomization code will be computer-generated by a contract research organization (CRO) 
Axio Research LLC.  Subjects meeting the study entry criteria will be randomized via an 
interactive web response system (IWRS).  Subjects will be randomized in a 2:1 ratio to either 
RSLV-132 or Placebo.  The randomization schedule will be generated by the randomization 
statistician at Axio Research (who is not on the project team) or designee and maintained in a 
secure and limited-access location separate from the study investigator and members of the 
project team.  The study subject, investigative staff, the Sponsor, the Sponsor study team 
(includes contractors and vendors), excluding the unblinded study site pharmacist and unblinded 
monitor mentioned above, will be blinded to treatment assignments during the study. 
Except in a medical emergency, the investigator or designee and blinded study site clinical staff 
will remain blinded during the conduct of the study and until database lock.  
If any other unblinding event occurs in addition to the ones mentioned above, it will be 
documented in a separate document other than this SAP. 


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2.3.7. 
Sample Size and Power  
The sample size of approximately 50 subjects chosen for this study was based upon precedent set 
by other studies of similar nature and was not based on power calculations.  Therefore no formal 
hypothesis testing will be performed. 
P-values obtained from the analyses, if they are generated, will be used for obtaining information 
only and will be evaluated at the two-sided alpha level of 0.05. 
3. 
GENERAL CONSIDERATION FOR DATA ANALYSES 
3.1. 
Analysis Sets 
3.1.1. 
Intent-to-Treat Analysis Set   
The Intent-to-Treat (ITT) Analysis Set is defined as all subjects who were randomized, 
regardless of whether the subject actually received any study drug (RSLV-132 or Placebo).  The 
subject will be included in the treatment group to which they were randomized. 
3.1.2. 
Full Analysis Set   
The Full Analysis Set (FAS) is a modified ITT and is defined as all subjects randomized who 
received at least one dose of study drug (RSLV-132 or Placebo).  The subject will be included in 
the treatment group to which they were randomized.  The Full Analysis Set is equivalent to the 
Efficacy Analysis Set defined in the study protocol and can be used interchangeably.  For the 
purpose of generating the summary tables and by subject listings under the description of this 
SAP, the term of Full Analysis Set will be used.  
3.1.3. 
Safety Analysis Set   
The Safety Analysis Set (SAS) is defined as all subjects who received any treatment with either 
RSLV-132 or placebo.  
Randomized subjects that receive the incorrect therapy from that intended will be summarized in 
the group according to the therapy actually received.  Subjects who are not randomized but who 
receive treatment or placebo will also be included and summarized according to the therapy 
actually received.  In the unlikely event of a subject commencing one study therapy and crossing 
over to the other, the data for that subject will be included in summaries and analyses with the 
original group. 


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3.2. 
Statistical Analysis Issues 
3.2.1. 
Strata and Covariates 
There is no stratification and covariate analysis planned for this study.  However, if there is any 
stratification and covariate analysis performed in an ad hoc exploratory nature, it will be noted in 
the final CSR. 
3.2.2. 
Examination of Subject Subsets 
There is no subgroup analysis planned for this study.  However, if there is any subgroup analysis 
performed in an ad hoc exploratory nature, it will be noted in the final CSR. 
3.2.3. 
Multiple Comparisons 
No formal hypothesis testing and no multiple comparisons will be conducted for this study. 
3.2.4. 
Multi-center Studies 
The study will be conducted from approximately 15-20 centers in the United States.  
Randomization to the treatment groups will not be stratified by study site due to small sample 
size.  Subjects from all centers will be pooled for summaries. 
3.2.5. 
Missing Data and Outliers 
Every attempt will be made to capture all study data.  For subjects whose visit value is missing, 
the last observation will be carried forward (LOCF) for the efficacy analyses.  Any missing, 
unused, or spurious data will be noted in the final CSR.   
3.2.6. 
Data Conventions and Transformations  
Laboratory numeric data may be recorded with a ‘<’ or ‘>’ sign (i.e. < 0.1 or > 0.1).  In order to 
summarize the data, the original value will be converted to 0.09 in the case of < 0.1 and to 0.11 
in the case of > 0.1.  The same principle will be used if the data has additional extended 
significant digits.  The actual values will be presented in the data listings.  
3.2.7. 
Study Baseline and Study Day 
Baseline is defined as the last assessment prior to the first dose of study drug (RSLV-132 or 
Placebo) at Day 1.  Measurements that are obtained after the first dose of study drug will be 
considered post-baseline values.    Change from baseline is defined as post-baseline assessment 
minus baseline assessment.  


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Study day for events on or after the date of the first dose will be defined as the number of days 
from the date of the first dose of study drug, plus 1 day, so that the date of the first dose will be 
defined as Day 1.  For events before the date of the first dose, study day will be calculated as the 
difference in days between the date of the first dose and the date of interest.  Thus, the day before 
the date of the first dose will be defined as Day -1. 
3.2.8. 
Visit Windows  
The case report form nominal visits and visit windows will be used in the summaries.  In general, 
unscheduled visits will not be summarized unless otherwise noted.  
4. 
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE 
There is no interim analysis and data monitoring committee planned for this study. 
5. 
GENERAL ANALYSIS METHODS 
Continuous variables will be summarized using descriptive statistics including number of 
subjects (n), mean, standard deviation (SD), median, minimum, and maximum.  Categorical 
variables will be summarized using frequencies and percentages.  Percentages will be calculated 
using the total number of subjects in each treatment group for each applicable population and/or 
subpopulation, unless otherwise noted. 
Number of subjects, minimums, and maximums will be calculated to the same number of 
decimal places as the source data.  Means, standard deviations and quartiles will be calculated to 
one more decimal place than the source data.  Percentages will be calculated to one decimal 
place.  Zero count cells will be displayed as “0” with percentage of (0%).  Unless otherwise 
noted, summaries will be performed by the treatment group (Placebo and RSLV-132 10 mg/kg).  
If statistical tests are performed, the tests will be done at the two-sided, 5% significance level to 
compare Placebo vs. RSLV-132 10 mg/kg, unless otherwise specified.  The point estimate and 
95% confidence interval (CI) for the treatment differences may be displayed along with the p-
value for the treatment comparison.  P-values will be presented to three decimal places.  P-values 
< 0.0005 will be presented as < 0.001.  P-values greater than 0.999 will be presented as > 0.999. 
In the absence of any predefined hypotheses in this study, the general strategy of the analysis 
will be to examine the data summaries for any trends amongst the treatment groups.  No formal 
hypothesis testing will be carried out.  P-values obtained from statistical testing of the analyses 
will be used for descriptive purposes only. 


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All data collected in the clinical database will be included in the data listings, as appropriate. 
Subjects who were randomized and never treated will be accounted for in the data listings. 
6. 
SUBJECT DISPOSITION  
6.1. 
Enrollment and Disposition of Subjects 
Subjects’ enrollment and disposition will be summarized by treatment group on two different 
analysis sets.  The reasons for discontinuation will be listed in the order as they appear on the 
electronic case report form (eCRF). 
Summary based on the ITT analysis set will include all randomized subjects and will be 
summarize for the following.  The percentages will be calculated based on the number of 
subjects randomized in each of the treatment group.  
• Number and percentage of subjects randomized 
• Number and percentage of subjects randomized and discontinued prior to treatment 
• The reason for discontinuation prior to treatment 
Summary based on the FAS will include all randomized and treated subjects and will be 
summarize for the following.  The percentages will be calculated based on the number of 
subjects randomized and treated in each of the treatment group. 
• Number and percentage of subjects randomized and treated (Placebo or RSLV-132 10 
mg/kg) 
• Number and percentage of subjects randomized and treated who completed the study 
• Number and percentage of subjects randomized and treated who discontinued from the 
study 
• The reasons for study discontinuation 
• Number and percentage of randomized and treated subjects included in each analysis set 
6.2. 
Extent of Exposure 
RSLV-132 or Placebo will be administered intravenously at 10 mg/kg at baseline, then weekly 
for two weeks and then once every 2 weeks for the next 20 weeks (13 administrations) to 
subjects with SLE. 
Total duration of study drug dosing (Days), total number of infusions, total duration of infusion 
(Hours), total volume infused (mL) and total duration of study drug exposure will be 
summarized by treatment group on SAS.  The number and percentage subjects with overall 


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infusion status (completed, interrupted or terminated) during the treatment period and the reason 
for interrupted or terminated will be summarized by treatment group on SAS.  The percentages 
will be calculated based on the number of subjects in each treatment group of the SAS. 
Total duration of study drug dosing will be calculated as the total number of days from the first 
dose date to the last dose date plus 1 regardless of temporarily dose interruptions.  Total number 
of infusions will be calculated as the sum from each infusion segment (if the infusion was 
interrupted and then started again).  Total duration of infusion in hours will be calculated as the 
total minutes from each infusion segment (if the infusion was interrupted and then started again) 
start time to end time. 
Overall infusion completed is defined as a subject without any infusion interruptions or 
terminations during the study.  
Total duration of study drug exposure (Days) is defined as the sum of (study Day 1 to the last 
visit date plus 1).  
6.3. 
Protocol Deviations 
Deviations from the protocol will be documented on an ongoing basis on the protocol deviations 
eCRF throughout the study.  Major protocol deviations will be determined prior to the database 
lock.  The number and percentage of subjects within each major deviation category will be 
summarized by treatment group on the FAS.  The percentages will be calculated based on the 
number of subjects in each treatment group of the FAS.  The deviations collected on the eCRF 
will be listed.   
Inclusion and exclusion criteria data will be listed for all subjects. 
7. 
 BASELINE DATA 
7.1. 
Demographic and Baseline Characteristics 
Demographic (age [years], gender, race, ethnicity, height [cm], weight [kg], BMI [kg/m2]) and 
baseline characteristics (CLASI activity score, Number and percentage subjects with oral 
corticosteroids dose [Overall mean, 0 mg/day, >0 and ≤7.5 mg/day, >7.5 mg/day]) will be 
summarized descriptively by treatment group on the FAS.  For categorical parameters, the 
percentages will be calculated based on the number of subjects in each treatment group of the 
FAS. 
  


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7.2. 
Medical History  
Number and percentage of subjects with medical history body systems will be summarized by 
treatment group for the FAS. 
A subject with multiple occurrence of the same body system will be counted only once.  Medical 
history body systems will be sorted alphabetically.  The percentages will be calculated based on 
the number of subjects in each treatment group of the FAS. 
8. 
PRIOR AND CONCOMITANT MEDICATIONS 
8.1. 
Medications  
Prior and concomitant medications will be coded using the World Health Organization (WHO) 
drug dictionary for anatomical therapeutic chemical classification (ATC) and preferred drug 
name.  The most current version of dictionary available will be used for the coding.  Number and 
percentage of subjects with each of the coded medications will be summarized by treatment 
group on the FAS.  A subject who used multiple medications will be counted only once for each 
ATC and preferred drug name.  ATC and preferred drug name within each ATC will be sorted 
alphabetically.  The percentages will be calculated based on the number of subjects in each 
treatment group of the FAS.  Prior and concomitant medications will be summarized separately.  
No inferential statistics will be performed. 
Prior medications are defined as any medications that started and stopped prior to the date of first 
dose of study drug (RSLV-132 or Placebo).  Concomitant medications are defined as any 
medications that started or were ongoing at or after the date of first dose of study drug (RSLV-
132 or Placebo).  Where a medication recorded with a partially or fully missing start/stop date or 
time, and it is unclear as to whether the medication is concomitant, it will be assumed that it is 
concomitant. 
9. 
EFFICACY ANALYSES 
Efficacy analyses include assessing improvement in disease activity using CLASI, SLEDAI-2K, 
BILAG-2004, PGA, and FACIT-Fatigue scores; tender or swollen joint count; oral steroids use; 
as well as evaluating the autoantibody and complement profiles. 
Each assessment will be summarized descriptively by treatment group on the FAS for all study 
visits at which the data were collected.  No statistical testing will be performed, unless otherwise 
specified. 


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All data will be listed. 
9.1. 
Analysis of Primary Efficacy Endpoints 
The primary efficacy endpoints are the improvements from Baseline (Day 1) to Day 85 and 
Baseline to Day 169 CLASI Activity scores. 
CLASI Activity assessment will be performed for each subject at scheduled visits to determine 
the SLE disease activity for each subject at the visit.  The assessment includes each anatomical 
location.  The total score of the Activity subsection (defined as the sum of the scores from each 
anatomical location) will be used in the summary.  The improvements from Baseline (Day 1) to 
Day 85 and from Baseline (Day 1) to Day 169 in the total activity score will be evaluated as part 
of the primary efficacy endpoints.  Lower score represents less disease activity. 
Summary of observed values: Observed values of total Activity score and the change and percent 
change from baseline at each scheduled visit will be summarized.   In addition to the LOCF 
imputation described below, the primary endpoints (change from Baseline on observed values) 
will be analyzed using Mixed effect Model Repeat Measurement (MMRM) method.  The 
MMRM model will include the fixed categorical effects of treatment, random effect visit, and 
treatment-by-visit interaction, as well as continuous fixed covariates of baseline score and 
baseline score-by-visit interaction.  An unstructured covariance structure of random effect will 
be used for modeling the within-subject errors. 
Summary of imputed values: LOCF imputed values and the change and percent change from 
Baseline (Day 1) in the CLASI Activity total score at Days 85 and 169 and at each scheduled 
visit will also be analyzed.  The two-sample t-test will be used for the treatment group 
comparison on the change from Baseline. 
Summary of non-censored values: Non-censored values and LOCF imputed non-censored values 
as well as the change and percent change from Baseline (Day 1) in the CLASI Activity total 
score at Days 85 and 169 and at each scheduled visit will also be analyzed. The two-sample t-test 
will be used for the treatment group comparison on the change from Baseline. The following 
values will be censored based on blinded review before database lock:  
a. Values obtained within 60 days of a steroid (systemic/oral/topical but not 
ophthalmic or inhaled) dose that is increased above baseline for more than one 
day 
b. Addition of other systemic agents for lupus (such as antimalarials, 
methotrexate, rituximab, dapsone) 


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9.2. 
Analysis of Secondary Efficacy Endpoints 
The secondary efficacy endpoints are including the following: 
• Improvements (from baseline to Day 85 and Day 169) in the SLEDAI-2K, BILAG-2004, 
PGA, and FACIT-Fatigue scores 
• Improvements in tender or swollen joint count (from baseline to Day 85 and Day 169) 
• Reduction in oral steroids at Day 169 relative to Day 85 
• The proportion of subjects achieving a 50% improvement in CLASI Activity score (from 
baseline to Day 85 and Day 169) 
9.2.1. 
SLEDAI-2K 
Systemic Lupus Erythematosus Disease Activity Index SELENA Modification will be performed 
for each subject at scheduled visits to determine the SLE disease activity for each subject at the 
visit.  The total score (defined as the sum of weights next to descriptors marked present) will be 
summarized.  The improvements from Baseline (Day 1) to Day 85 and from Baseline (Day 1) to 
Day 169 in SLEDAI-2K total scores will be evaluated as part of the secondary efficacy 
endpoints.  Lower score represents less disease activity. 
Summary of observed values: Observed values of total score and the change from baseline at 
each scheduled visit will be summarized.   In addition to the LOCF imputation described below, 
the change from Baseline on observed values will be analyzed using Mixed effect Model Repeat 
Measurement (MMRM) method as described in the SAP Section 9.1. 
Summary of imputed values: Imputed values and the change from Baseline (Day 1) in the 
SLEDAI-2K total score at each scheduled visit will also be analyzed.  The two-sample t-test will 
be used for the treatment group comparison on the change from Baseline.  LOCF will be used to 
impute missing values on the FAS. 
9.2.2. 
BILAG-2004 
BILAG-2004 Index Assessment will be performed for each subject at scheduled visits to 
determine the SLE disease activity for each subject at the visit.  The assessment includes 
subsections of Constitutional, Mucocutaneous, Neuropsychiatry, Musculoskeletal, 
Cardiorespiratory, Gastrointestinal, Ophthalmic, Renal and Hematological.  Each subsection will 
be scored with Category of Zero or Non-Zero for analysis.  Any category checked other than 
“Not Present” or “Not Done” will be treated as the Non-Zero category except for the Renal and 
Hematology panels.  The category of Zero or Non-Zero will be presented in the summary.  The 
improvements from Baseline (Day 1) to Day 85 and from Baseline (Day 1) to Day 169 in 
BILAG-2004 Index Assessment category of Zero or Non-Zero will be evaluated as part of the 


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secondary efficacy endpoints.  Zero category represents no disease activity present for the body 
system.  The detailed specifications of Zero or Non-Zero category rules for the Renal and 
Hematology panels will be stated in the analysis dataset specification document rather than in 
this SAP”. 
Summary of observed values: Observed values of the Zero and Non-Zero categories and the 
change from baseline at each scheduled visit (indicated by a shift from the baseline category) 
will be summarized for each subsection.  The percentages will be calculated based on the actual 
number of subjects at each visit in each treatment group of the FAS.  No statistical testing will be 
performed. 
Summary of imputed values: Imputed values of the Zero and Non-Zero categories and the 
change from Baseline (Day 1) for the BILAG-2004 Index Assessment at each scheduled visit 
(indicated by a shift from the baseline category) will be summarized for each subsection.  LOCF 
will be used to impute missing values on the FAS.  No statistical testing will be performed. 
9.2.3. 
PGA 
Physicians Global Assessment will be performed for each subject at scheduled visits to 
determine the SLE disease activity for each subject at the visit.  The assessment is measured on a 
0 to 100 Millimeter (mm) scale with score 0 to be No Disease Activity and score 100 to be the 
most Severe Disease Activity.  The improvements from Baseline (Day 1) to Day 85 and from 
Baseline (Day 1) to Day 169 in PGA scores will be evaluated as part of the secondary efficacy 
endpoints. 
Summary of observed values: Observed values and the change from baseline at each scheduled 
visit will be summarized.   In addition to the LOCF imputation described below, the change from 
Baseline will be analyzed using Mixed effect Model Repeat Measurement (MMRM) method as 
described in the SAP Section 9.1. 
Summary of imputed values: Imputed values and the change from Baseline (Day 1) in the PGA 
score at each scheduled visit will also be analyzed.  The two-sample t-test will be used for the 
treatment group comparison on the change from Baseline.  LOCF will be used to impute missing 
values on the FAS. 
9.2.4. 
FACIT-Fatigue Scale 
FACIT-Fatigue Scale assessment is a subject reported outcome.  It will be performed by each 
subject at scheduled visits to determine the SLE disease activity for each subject at the visit.  The 
improvements from Baseline (Day 1) to Day 85 and from Baseline (Day 1) to Day 169 in 


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FACIT-Fatigue assessment total scores will be evaluated as part of the secondary efficacy 
endpoints. 
FACIT-Fatigue assessment has 13 questions and is measured with scores of 0 (Not at all), 1 (A 
little bit), 2 (Somewhat), 3 (Quite a bit) or 4 (Very much).  All FACIT-Fatigue scales are scored 
so that a higher score is better.  As each of the 13 items of the FACIT-Fatigue scale ranges from 
0-4, the range of possible scores is 0-52, with 0 being the worst possible score and 52 the best.  
To obtain the 0-52 score, each negatively-worded item response is recoded so that 0 is a bad 
response and 4 is good response.  All responses are added with equal weight to obtain the total 
score.  In cases where some answers may be missing, a total score is prorated from the scores of 
answered items, as long as more than 50% of the items (i.e., at least 7 of 13) were answered.  
If there are missing items, subscale scores can be prorated.  This is done by multiplying the sum 
of the subscale by the number of items in the subscale, then dividing by the number of items 
actually answered.  This can be done by using the formula below: 
Prorated subscale score = [Sum of item scores] x [N of items in subscale] / [N of items 
answered]  
A computer program written in SAS for the FACIT-Fatigue Scale scoring is available in 
Appendix I of the SAP. 
Summary of observed values: Observed values of total score and the change from baseline at 
each scheduled visit will be summarized.   In addition to the LOCF imputation described below, 
the change from Baseline on observed values will be analyzed using Mixed effect Model Repeat 
Measurement (MMRM) method as described in the SAP Section 9.1. 
Summary of imputed values: Imputed values and the change from Baseline (Day 1) in the 
FACIT-Fatigue Scale total score at each scheduled visit will also be analyzed.  The two-sample 
t-test will be used for the treatment group comparison on the change from Baseline.  LOCF will 
be used to impute missing values on the FAS. 
Summary of non-censored values: Non-censored values and LOCF imputed non-censored values 
as well as the change and percent change from Baseline (Day 1) in the FACIT-Fatigue Scale 
total score at Days 85 and 169 and at each scheduled visit will also be analyzed. The two-sample 
t-test will be used for the treatment group comparison on the change from Baseline. The 
following values will be censored based on blinded review before database lock:  
a. Values obtained within 60 days of a steroid (systemic/oral/topical but not 
ophthalmic or inhaled) dose that is increased above baseline for more than one 
day 


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b. Addition of other systemic agents for lupus (such as antimalarials, 
methotrexate, rituximab, dapsone) 
 
9.2.5. 
Tender and Swollen Joint Count 
Tender and swollen joint count assessment will be performed for each subject at scheduled visits 
to determine the SLE disease activity for each subject at the visit.  Tender and swollen joint 
count assessment includes total of 28 joints (left and right metacarpalphalangeal joints and 
proximal interphylangeal joints, wrist, elbow, shoulder and knee).  The total Tender and Swollen 
Joint Count will be summarized.  The improvements from Baseline (Day 1) to Day 85 and from 
Baseline (Day 1) to Day 169 in tender and swollen total joint count will be evaluated as part of 
the secondary efficacy endpoints.  Lower joint count represents less disease activity. 
Summary of observed values: Observed values of total tender and swollen joint count and the 
change from baseline at each scheduled visit will be summarized.   In addition to the LOCF 
imputation described below, the change from Baseline on observed values will be analyzed using 
Mixed effect Model Repeat Measurement (MMRM) method as described in the SAP Section 9.1. 
Summary of imputed values: Imputed values and the change from Baseline (Day 1) in the tender 
and swollen total joint count at each scheduled visit will also be analyzed.  The two-sample t-test 
will be used for the treatment group comparison on the change from Baseline.  LOCF will be 
used to impute missing values on the FAS. 
9.2.6. 
Oral Steroids Tapering 
One of the objectives of the study is to evaluate the steroid sparing effects of RSLV-132.  The 
Investigators shall decrease the use of oral corticosteroids beginning on Day 85 using the 
guidance stated under SAP Section 2.3.4.1.  No further steroid decreases should occur from Day 
141 through Day 169.  The reduction in oral steroids at Day 169 relative to Day 85 will be 
evaluated as part of the secondary efficacy endpoints. 
Summary of observed values: (1) For those who were on any oral corticosteroids at Day 85, 
observed of corticosteroids dose values and the change from Day 85 at Day 169 will be 
summarized.  (2) For those who were on any oral corticosteroids with >7.5 mg/day at Day 85, 
observed of corticosteroids dose values and the change from Day 85 at Day 169 will be 
summarized. 
The summary of (1) or (2) will only be performed if there are 25% or more of the subjects in the 
RSLV-132 group were on any oral corticosteroids at Day 85 or were on any oral corticosteroids 
with >7.5 mg/day at Day 85 respectively.  No statistical testing will be performed.  


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Dose equivalence to Prednisone: 
Medication 
Dose Equivalence to 10 mg 
Dose Equivalence to 7.5 mg 
Oral Prednisone 
10 mg 
7.5 mg 
Cortisone 
50 mg 
37.5 mg 
Hydrocortisone 
40 mg 
30 mg 
Methylprednisolone 
8 mg 
6 mg 
Prednisolone 
10 mg 
7.5 mg 
Betamethasone 
1.2 mg 
0.9 mg 
Dexamethasone 
1.5 mg 
1.125 mg 
Budesonide 
2.25 mg 
1.6875 mg 
Deflazacort 
12 mg 
9 mg 
 
 
9.2.7. 
CLASI Activity Score Improvement 
CLASI Activity assessment will be performed for each subject at scheduled visits to determine 
the SLE disease activity for each subject at the visit.  The assessment includes each anatomical 
location.  Proportion of subjects achieving a 50% improvement (decrease) in CLASI total 
Activity score (defined as the sum of the scores from each anatomical location) will be evaluated 
as part of the secondary efficacy endpoints. 
Summary of observed values: The number and percentage of subjects achieving a 50% 
improvement in CLASI Activity subsection score from baseline at each scheduled visit will be 
summarized.  The percentages will be calculated based on the actual number of subjects at each 
visit in each treatment group of the FAS.  No statistical testing will be performed. 
Summary of imputed values: The number and percentage of subjects achieving a 50% 
improvement in CLASI Activity subsection score from baseline at each scheduled visit will also 
be analyzed on the imputed values.  Fisher’s exact test will be used for the treatment group 
comparison.  LOCF will be used to impute missing values on the FAS. 


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Summary of non-censored values: Non-censored values and LOCF imputed non-censored values 
will be used to summarize the number and percentage of subjects achieving a 50% improvement 
in CLASI Activity subsection score from baseline at each scheduled visit. Fisher’s exact test will 
be used for the treatment group comparisons. The following values will be censored based on 
blinded review before database lock:  
a. Values obtained within 60 days of a steroid (systemic/oral/topical but 
not ophthalmic or inhaled) dose that is increased above baseline for 
more than one day 
b. Addition of other systemic agents for lupus (such as antimalarials, 
methotrexate, rituximab, dapsone) 
 
9.3. 
Exploratory Efficacy Analysis 
The exploratory efficacy analysis are to evaluate the changes from Baseline (Day 1) as compared 
to Placebo on the following measurements: 
• Evaluate the difference on the autoantibody and complement profiles between the two 
treatment groups 
• Evaluate the differences on the gene expression profiles and the serum protein levels 
between the two treatment groups. 
• Compare the mean improvement (from Baseline to Day 85; or Baseline to Day 169 in 
CLASI damage scores of those randomized to be treated with RSLV-132 and those 
randomized to receive placebo. 
9.3.1. 
Autoantibody and Complement Profiles 
Serum samples will be analyzed by either a local or central laboratory using validated methods.  
The analysis will provide values for the following autoantibodies and indicate if the result is 
positive, negative, or equivocal using the validated assay range for the testing laboratory: Ro-
52/60, La, Sm, SmRNP, U1 RNP A/68, dsDNA.  The summary of actual values of these tests 
will also be provided.  Complement C3 and C4 values will also be summarized. 
Summary of observed values: Observed values, change from baseline and a shift from baseline 
categories at each scheduled visit of autoantibody profile will be summarized.  The percentages 
will be calculated based on the actual number of subjects at each visit in each treatment group of 
the FAS.  No statistical testing will be performed. 


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9.3.2. 
Gene Expression Profiles 
Ribonucleic acid (RNA) will be extracted from whole blood to measure the expression level of 
genes that are related to inflammatory pathways though to be involved in SLE.  Samples will be 
obtained at selected visits during the study from Baseline to the End of Study visit.  The analysis 
of gene expression profiles will be performed elsewhere and will not be a part of this SAP. 
9.3.3. 
Serum Protein Levels 
Serum samples will be obtained at various visits during the study to analyze the level of 
circulating serum proteins.  The protein analysis will measure protein levels related to the 
inflammatory process.  The analysis will be carried out using a multiplexed immunoassay.  The 
analysis of serum protein levels will be performed elsewhere and will not be a part of this SAP. 
9.3.4. 
CLASI Damage Score 
CLASI Damage assessment will be performed for each subject at scheduled visits to determine 
the SLE disease activity for each subject at the visit.  The assessment includes each anatomical 
location.  The total score of the Damage subsection (defined as the sum of the scores from each 
anatomical location) will be used in the summary.  
Summary of observed values: Observed values of total Damage score and the change from 
baseline at each scheduled visits will be summarized.  No statistical testing will be performed.   
10. 
SAFETY ANALYSES 
The safety assessment of the treatment will be compared between the two groups by adverse 
events and laboratory results as well as any physical findings that have changed from baseline.  
The safety analysis will include adverse events, concomitant medications, laboratory data, vital 
signs and immunogenicity of RSLV-132.   
All data will be summarized as observed and no data imputation will be performed. 
10.1. 
Adverse Events 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA 
version 19.0 or higher) adverse event dictionary.  If a subject experiences multiple events that 
map to a single preferred term, the greatest severity (by grade) and strongest investigator 
assessment of relationship to study drug will be reported for the applicable summaries.  
Treatment-emergent adverse events (TEAE) are defined as events for which the date of onset is 
on or after the date of first dose of study drug (RSLV-132 or Placebo).  Where an adverse event 


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(AE) collected after the date of first dose with a partially or fully missing start date or time, and it 
is unclear as to whether the AE is treatment emergent, it will be assumed that it is treatment 
emergent. 
The number and percentage of subjects with adverse events will be summarized by treatment 
group.  The percentages will be calculated based on the number of subjects in each treatment 
group of the SAS.  System organ class (SOC) and preferred term (PT) within each SOC will be 
presented in descending frequency of RSLV-132 group.  Subjects will be counted only once for 
each SOC and PT. 
All adverse events (treatment-emergent and non-treatment-emergent) will be listed.  
10.1.1. 
 Overall Adverse Events 
The number and percentage of subjects with at least one treatment-emergent adverse event will 
be summarized for the following:  
• Subjects with any treatment-emergent adverse event 
• Subjects with severe (Grade 3+) treatment-emergent adverse event 
• Subjects with any study drug related treatment-emergent adverse event  
• Any treatment-emergent adverse event leading to study drug discontinuation / study 
termination    
• Subjects with any treatment-emergent serious adverse event 
• Subjects with any study drug related treatment-emergent serious adverse event 
• Subjects with outcome of death 
10.1.2. 
 Incidence of Adverse Events 
Subjects with at least one treatment-emergent adverse event will be summarized by SOC, PT, 
and by treatment group.  The incidence rate (IR) of the event per 100 patient years for each SOC 
and PT as well as the overall patient years of each treatment group will be calculated.  IR of the 
event per 100 patient years will be calculated as (Total # of Events/Patient Year)*100].  Patient 
year will be calculated as the (Total study drug exposure / 365.25).  Total study drug exposure 
will be defined as the sum of [(Last visit date – First dose date) + 1]. 
Treatment-emergent adverse event summary by PT with descending order of frequency in the 
RSLV-132 group will also be presented by treatment group.   


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10.1.3. 
Relationship of Adverse Event to Study Drug 
Treatment-emergent adverse events with closest relationship to study drug according to the 
categories specified in the protocol (Not Related, Possibly Related and Definitely Related) will 
be summarized for related events by SOC, PT, and treatment group. 
A study drug related AE is defined as any AE that is assessed by the investigator with the 
relationships of “Possibly Related” and “Definitely Related”.  Study drug non-related AE is 
defined as any AE that assessed by investigator with the relationships of “Not Related”. 
Any treatment-emergent AEs that have a missing relationship will be presented in the summary 
table as “Related” but will be presented in the data listing with a missing relationship. 
10.1.4. 
Severity of Adverse Event 
Treatment-emergent adverse events with maximum investigator-reported severity ( Grade 1-
Mild, Grade 2-Moderate, Grade 3-Severe, Grade 4-Life Threatening and Grade 5-Fatal) will be 
summarized by SOC, PT, and treatment group. 
Any treatment-emergent AEs that have a missing severity will be presented in the summary table 
with Toxicity Grade 4 but will be presented in the data listing with a missing severity. 
10.1.5. 
Serious Adverse Events 
All treatment-emergent serious adverse events (SAEs) will be summarized by SOC, PT, and by 
treatment group.   
A summary of study drug related treatment-emergent SAEs by SOC, PT, and treatment group 
will also be presented. 
10.1.6. 
Adverse Events Leading to Hospitalization / Study Drug Discontinuation / Study 
Termination 
All treatment-emergent adverse events that lead to either required or prolonged inpatient 
hospitalization or study drug discontinuation or study termination will be summarized by SOC, 
PT, and by treatment group. 
10.2. 
Laboratory and Other Safety Assessments 
Each assessment will be summarized descriptively by treatment groups on the SAS.  For 
assessments not measured at Baseline (Day 1) pre-dose, Screening Visit value will be used as the 
baseline.  No missing data imputation will be used. 


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All data will be listed.  
10.2.1. 
Laboratory Blood and Urine Samples 
Laboratory hematology, serum chemistry and urinalysis samples will be collected for each 
subject at scheduled visits for safety evaluations.  The laboratory test parameters are listed in the 
Protocol Appendix B.  The samples are analyzed by a central laboratory. 
Observed values and the change from Baseline (Day 1) at each visit will be summarized for the 
continuous values.  Number and percentage of subjects in each category will be summarized for 
the categorical values.  In addition, the number and percentage of subjects who have the lab 
results that are noted to be “Clinically Significant” by the investigator will be summarized.  The 
percentages will be calculated based on the actual number of subjects at each visit in each 
treatment group of the SAS.  Grade 3 or higher lab toxicity (based on Rheumatology CTC Grade 
System) during the study will also be summarized. 
Serum and urine pregnancy tests are for women of childbearing potential only.  Serum 
pregnancy test will be performed at Screening Visit and Day 215 (EOS).  The samples are 
analyzed by a central laboratory.  The urine pregnancy test will be done at Baseline (Day 1) only 
and will be performed at each study site.  Serum and urine pregnancy test data will be listed only. 
10.2.2. 
Hepatitis and HIV Tests 
Test for Hepatitis B, C and human immunodeficiency virus (HIV) viral load will be performed 
for each subject at Screening Visit.  The results will be listed only.  
10.2.3. 
Vital Signs 
Vital signs will be evaluated for each subject at scheduled visits for systolic and diastolic blood 
pressure (SBP and DBP, mmHg), pulse rate (beats per minute [bpm]), respiratory rate (RR, 
breaths per minute [bpm]), and oral temperature (Fahrenheit °F).   
Observed values and the change from Baseline (Day 1) at each visit will be summarized using 
descriptive statistics.  Temperatures in Celsius (°C) will be reported for the summary.  
Fahrenheit to Celsius conversion °C = (°F - 32) x 5/9 will be used. 
10.2.4. 
Physical Exam 
Physical exam will be performed for each subject at scheduled visits.  Number and percentage of 
subjects in each body site system of Normal/Abnormal (Non-Clinically Significant [NCS] or 
Clinically Significant [CS] determinate by the investigator) category will be summarized.  The 


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percentages of Normal/Abnormal results will be calculated based on the actual number of 
subjects at each visit in each treatment group of the SAS.   
Abnormality changes from Baseline (Day 1) in terms of NCS or CS at each post-baseline visit 
will be summarized in the categories of (New, Unchanged, Worsened, or Improved).  New is 
defined as an abnormal result in the post-baseline visit compare to the normal result at baseline.  
Unchanged is defined as the same abnormal result in both the post-baseline visit and the 
baseline.  Worsened is defined as an abnormal CS result in the post-baseline visit compare to the 
abnormal NCS result at baseline.  Improved is defined as an abnormal NCS result in the post-
baseline visit compare to the abnormal CS result at baseline or a normal result in the post-
baseline visit compare to the abnormal (NCS or CS) result at baseline. 
 
10.3. 
Immunogenicity Analyses 
Serum will be analyzed for the presence of anti-RSLV 132 antibodies using a validated 
immunoassay.  Each positive serum sample will be evaluated for anti-drug antibodies (ADA) 
specificity by repeating the immunoassay in the presence of an excess of RSLV-132.  Confirmed 
positive, specific serum samples will be titered by serial dilution and a numerical titer will be 
assigned.  The immunogenicity of RSLV-132 as measured by the presence of RSLV-132 
antibodies will be evaluated as part of the safety endpoints. 
The serum samples for evaluating ADA will be collected for each subject at scheduled visits.  To 
assess immunogenicity, the number and percent of positive and negative results will be 
summarized descriptively by treatment groups on the SAS.  The percentages will be calculated 
based on the number of subjects in each treatment group with samples available at each visit. 
11. 
PHARMACOKINETIC ANALYSES 
Pharmacokinetic (PK) parameters will be calculated for each subject, whenever possible, based 
on the serum concentrations of RSLV-132.  RSLV-132 drug concentration levels will be 
summarized if it is available. The analysis of PK parameters will be performed elsewhere and 
will not be part of this SAP. 
  
 
 


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12. 
SAP REVISION 
 
Revision Date 
Section 
Summary of Revision 
Reason for Revision 
July 6, 2017 
2.3.3 
Updated Table 1 Study 
Procedures. 
Protocol Amendment 4.0 
 
2.3.5 
Updated that efforts will be 
made to perform all EOT 
and EOS assessments 
outlined in Protocol 
Appendix A. 
Protocol Amendment 5.0 
 
6.2 
Clarify the summaries. 
Per sponsor request. 
 
6.3 
Clarify to summarize the 
major protocol deviations.  
Per sponsor request. 
 
7.1 
Added the overall mean for 
prednisone or equivalent 
dose. 
Per sponsor request. 
 
7.2 
Clarify to summarize the 
Medical History Body 
Systems 
Per sponsor request. 
 
9 
Remove text “RSLV-132 
plasma levels and 
RNase activity” from 
Efficacy Analyses. 
They are not part of the 
efficacy analyses. 
 
9.2.2 
No statistical testing will be 
performed for the imputed 
values of BILAG-2004 
Index Assessment. 
Per sponsor request. 
 
9.2.6 
Specify to summarize at 
Day 169 only. 
Per sponsor request. 
 
9.2.7 
Remove text “Fisher’s exact 
test will be used for the 
treatment group 
comparison” under the 
summary of observed 
values. 
No treatment group 
comparison will be made on 
observed values. 
 
9.3.1 
Adding dsDNA as part of 
the autoantibody profile. 
Protocol Amendment 4.0 
 
 
Adding a summary for the 
actual values. 
Per sponsor request. 
 
10.1.2 
Adding patient year 
calculations for the adverse 
event summary 
Per sponsor request. 


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10.2.1 
Adding grade 3 or higher 
toxicity summaries for the 
safety lab data. 
Per sponsor request. 
 
10.2.4 
Replace text “Appendix B” 
with “Appendix A”. 
Correct protocol reference. 
 
 
Physical exam results will 
be listed only. 
Per sponsor request. 
 
 
 
 
March 10, 
2020 
3.2.7 
Revise baseline definition to 
consider screening. 
Internal document consistency. 
 
6.2 
Removing “plus 1” in the 
Total duration of infusion 
(Hours) calculation. 
Clarification. 
 
9.1, 9.2.1, 
9.2.3, 9.2.4 and 
9.2.5 
Adding repeated 
measurement analysis in 
addition to the LOCF 
imputation.  
A less biased method by 
missing data compare to 
LOCF. 
 
9.1, 9.2.4, 
9.2.7 
Add non-censored 
summaries. 
Per sponsor request. 
 
9.2.6 
Include table of Predinsone 
Equivalent dosing. 
Facilitate grouping of 
corticosteroids. 
 
10.2.4 
Adding Physical Exam 
summary by categories of 
Normal/Abnormal 
(CS/NCS). 
To be compliant with FDA 
ICH E3 guideline and to be 
consistent with Resolve 
RSLV-132-04 study. 
 
11 
PK not in scope of SAP. 
 
 
 
 


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13. 
APPENDIX I:  FACIT-FATIQUE SCALE SAS SCORING 
*======================================================================== * 
* FACIT-Fatigue subscale Version 4 Scoring Program (Unweighted)           * 
* SAS codes written for all platforms (DOS, Windows, and UNIX)            * 
* (c) Copyright, 1995-1998, Chih-Hung Chang & David Cella                 * 
* All rights reserved                                                     * 
*                                                                         * 
* Version 4                                                               * 
*                                                                         * 
* Permission is granted for use and non-profit distribution of these SAS  * 
* codes providing that all copyright notices remain intact. The right to  * 
* distribute any portion of this program for profit or as part of any     * 
* commercial product is specifically reserved for the authors of that     * 
* portion.                                                                * 
*                                                                         * 
* SAS Programmer: Jennifer Beaumont 
 
                             * 
*======================================================================== * 
 
*======================================================================== * 
* Note1: Data may be input via CARDS statement or from an external file   * 
* with an INFILE statement                                                * 
*======================================================================== *; 
 
DATA fatigue; 
  INPUT id_code $ hi7 hi12 an1-an5 an7 an8 an12 an14-an16; 
  CARDS; 
A 0 0 0 2 2 2 1 1 0 0 1 2 3 
B 2 0 4 4 0 4 1 2 2 2 0 9 9 
C 0 0 4 4 1 3 4 2 1 1 0 9 9 
D 1 0 0 3 3 3 2 3 3 9 1 1 1 
E 0 0 4 4 0 4 4 4 3 3 1 2 3 
F 3 1 1 1 0 2 1 0 0 1 0 9 9 
G 0 2 2 4 4 4 4 4 2 3 0 9 9 
H 0 0 4 4 0 4 4 4 3 3 0 9 9 
I 0 0 4 4 0 4 4 3 1 1 0 9 9 
 ; 
 
DATA SCORING; 
  SET fatigue; 
 
  ARRAY ITEM {13} hi7 hi12 an1-an5 an7 an8 an12 an14-an16; 
 
  DO I=1 TO 13; 
    IF ITEM(I)=8 OR ITEM(I)=9 THEN ITEM(I)=.; 
  END; 
 
*======================================================================== * 
* SCORE REVERSALS FOR FACIT-Fatigue subscale.                             * 
*======================================================================== *; 
      
     HI7=4-HI7; 
     HI12=4-HI12; 
     AN1=4-AN1; 
     AN2=4-AN2; 
     AN3=4-AN3; 
     AN4=4-AN4; 
     AN8=4-AN8; 
     AN12=4-AN12; 
     AN14=4-AN14; 
     AN15=4-AN15; 
     AN16=4-AN16; 
 


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*======================================================================== * 
* NUMBERS OF ITEMS ANSWERED.                                              * 
*======================================================================== *; 
 
          FAT_N = N(OF HI7 HI12 AN1-AN5 AN7 AN8 AN12 AN14-AN16); 
           
*======================================================================== * 
* PRORATED SUBSCALE SCORE =                                               * 
*  [SUM OF ITEM SCORES]x[N OF ITEMS IN SUBSCALE]/[N OF ITEMS ANSWERED]    * 
*                                                                         * 
* WHEN THERE ARE MISSING DATA, PRORATING BY SUBSCALE IN THIS WAY IS       * 
* ACCEPTABLE AS LONG AS MORE THAN 50% OF THE ITEMS WERE ANSWERED.         * 
* THE TOTAL SCORE IS CALCULATED AS THE SUM OF THE PRORATED SUBSCALE       * 
* SCORES.                                                                 * 
* THE FACT SCALE IS CONSIDERED TO BE AN ACCEPTABLE INDICATOR OF PATIENT   * 
* QUALITY OF LIFE AS LONG AS OVERALL ITEM RESPONSE RATE IS GREATER THAN   * 
* 80%.                                                                    * 
*======================================================================== *; 
 
*======================================================================= * 
* FATIGUE SUBSCALE SCORE                        
 
 
      * 
*======================================================================= *; 
 
IF (FAT_N/13 > .50) THEN 
    Fatigue = SUM(OF HI7 HI12 AN1-AN5 AN7 AN8 AN12 AN14-AN16)*13/(FAT_N); 
 
RUN; 
 
PROC MEANS DATA=SCORING; 
  VAR Fatigue; 
  TITLE 'FACIT-Fatigue subscale UNIVARIATE STATISTICS'; 
  RUN;