Clinical trial NCT02612857
Conditions: Dermatomyositis
Keywords: dermatomyositis IMO-8400 Pioneer
Sponsor: Idera Pharmaceuticals, Inc.
Start date: 2015-11-01; Completion date: 2018-06-01
Enrollment: 30 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine how safe and effective IMO-8400 is in adults with dermatomyositis.

Detailed description:
This study will evaluate the safety and efficacy of IMO-8400 in adults with active dermatomyositis (DM).

Arms: arm 1: normal saline subcutaneous injections once a week for 24 weeks. arm 2: IMO-8400 Dose Group 1 subcutaneous injections once a week for 24 weeks. arm 3: IMO-8400 Dose Group 2 subcutaneous injections once a week for 24 weeks.
Interventions: intervention 1: IMO-8400 Dose Group 1 intervention 2: IMO-8400 Dose Group 2 intervention 3: Placebo
Intervention descriptions: intervention 1: IMO-8400 Dose 1 subcutaneous injections once a week for 24 weeks. intervention 2: IMO-8400 Dose 2 subcutaneous injections once a week for 24 weeks. intervention 3: normal saline subcutaneous injections once a week for 24 weeks.

Protocol documents:
Prot_001.pdf: 
IDERA PHARMACEUTICALS, INC. 
PROPRIETARY AND CONFIDENTIAL 
PROTOCOL VERSION 6.0 
Clinical Study Protocol 
8400-211 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial of IMO-8400 
in Patients with Dermatomyositis 
Investigational Drug: IMO-8400 
IND: 
125410 
Sponsor: 
Idera Pharmaceuticals, Inc. 
167 Sidney Street  
Cambridge, MA 02139 
Telephone: 617-679-5500 
Protocol Number: 
8400-211 
Protocol Version: 
Version 6.0 
Version Date: 
 27 January 2017 


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IDERA PHARMACEUTICALS, INC. 
PROPRIETARY AND CONFIDENTIAL 
PROTOCOL VERSION 6.0 
Protocol Approval Page 
Study Title 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial 
of IMO-8400 In Patients with Dermatomyositis 
Protocol Number: 
8400-211 
Protocol Version: 
Version 6.0 
Date: 
 27 January 2017 
Approved for the Sponsor by: 
Joanna Horobin, MB, ChB 
Senior Vice President, Chief 
Medical Officer 
Idera Pharmaceuticals, Inc. 
Signature 
Date 
(ddmmmyyyy) 
REVISION HISTORY 
Version 
Date 
Comment 
1.0 
11 June 2015 
IND submission 
2.0 
22 July 2015 
Revisions based on FDA review 
3.0 
26 August 2015 
Revisions based on IRB/IEC reviews and operational considerations 
4.0 
29 February 2016 
(No patients were enrolled under Protocol Version 4.0) 
5.0 
12 May 2016 
Revisions based on FDA feedback 
6.0 
27 January 2017 
Revisions based on investigator feedback and operational considerations 
DocuSign Envelope ID: 11470108-E173-497B-915F-C51B43F7D674


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IDERA PHARMACEUTICALS, INC. 
PROPRIETARY AND CONFIDENTIAL 
PROTOCOL VERSION 6.0 
Study Contact Information 
Any serious adverse event (SAE) must be reported within 24 hours. See Section 11.3 for 
detailed adverse event reporting procedures. 
Table 1. 
Study Contact Information 
Role in Study 
Name, Title, Address 
Telephone / fax / email 
Sponsor Medical Monitor 
Joanna Horobin, MB, ChB 
Senior Vice President, Chief 
Medical Officer 
Idera Pharmaceuticals, Inc. 
167 Sidney Street, Cambridge, 
MA 02139 
Phone: +1 (617) 679-5510 
Email: Jhorobin@iderapharma.com 
CRO Medical Monitor 
Tomasz Knurowski MD 
Senior Director of Medical 
Services 
TMC Pharma 
Lodge Farm Barn, Elvetham 
Park Estate 
Fleet Road, Hartley Wintney 
Hants, RG27 8AS,  UK 
Phone: +44 (0) 1252 842255 
Mobile: +44 (0) 07590 882843 
Email: 
tomasz.knurowski@tmcpharma.com 
24-Hour SAE Reporting 
PAREXEL International 
Clinical Studies Safety Center 
US Telephone number/SAE Hotline: 
Durham, NC +1-919-294-5268 
Fax number: +1-919-544-3572 
US Email: 
NorthAmerica_Medical@parexel.com 
UK Telephone number/SAE Hotline: 
Uxbridge +44 1895 273434 
Fax number: Uxbridge +44 1895 
231847 
UK Email: DrugSafety@parexel.com 


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PROPRIETARY AND CONFIDENTIAL 
PROTOCOL VERSION 6.0 
TABLE OF CONTENTS 
REVISION HISTORY.....................................................................................................................2 
TABLE OF CONTENTS .................................................................................................................4 
LIST OF IN-TEXT TABLES ........................................................................................................10 
LIST OF IN-TEXT FIGURES.......................................................................................................10 
LIST OF APPENDICES ................................................................................................................10 
1 
ABBREVIATIONS AND TERMS ............................................................................11 
2 
SYNOPSIS .................................................................................................................15 
3 
SCHEDULE OF EVENTS .........................................................................................23 
4 
BACKGROUND ........................................................................................................25 
 
Purpose of Study .........................................................................................................25 
 
Dermatomyositis Overview ........................................................................................25 
 
IMO-8400 as a Potential Therapy for the Treatment of DM ......................................26 
5 
STUDY OBJECTIVES ..............................................................................................27 
 
Primary .......................................................................................................................27 
 
Exploratory .................................................................................................................27 
6 
STUDY ENDPOINTS AND DESIGN ......................................................................28 
 
Study Endpoints ..........................................................................................................28 
6.1.1 
Primary Endpoints ......................................................................................................28 
6.1.1.1 
Primary Safety and Tolerability Endpoints ................................................................28 
6.1.1.2 
Primary Efficacy Endpoint .........................................................................................28 
6.1.2 
Exploratory Endpoints ................................................................................................28 
6.1.2.1 
Exploratory Efficacy Endpoints .................................................................................28 
6.1.2.2 
Pharmacokinetic Endpoints ........................................................................................29 
6.1.2.3 
Pharmacodynamic Endpoints .....................................................................................29 
6.1.2.4 
Disease-specific Autoantibody Endpoint ...................................................................29 
6.1.2.5 
Immunogenicity Endpoint ..........................................................................................29 
 
Study Design ...............................................................................................................29 
6.2.1 
Benefits and Risk Assessment ....................................................................................32 
 
Patient Study Participation and Study Completion ....................................................35 
6.3.1 
Patient Participation ....................................................................................................35 
6.3.2 
Premature Patient Discontinuation or Treatment Discontinuation .............................35 


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PROTOCOL VERSION 6.0 
6.3.3 
Overall Study Completion ..........................................................................................35 
7 
PATIENT POPULATION AND SELECTION .........................................................36 
 
Inclusion Criteria ........................................................................................................36 
 
Exclusion Criteria .......................................................................................................39 
 
Patient Rescreening ....................................................................................................41 
8 
STUDY DRUG ADMINISTRATION .......................................................................42 
 
Treatments Administered ............................................................................................42 
 
Investigational Product(s) ...........................................................................................42 
8.2.1 
Packaging and Labeling ..............................................................................................42 
8.2.2 
Storage ........................................................................................................................43 
8.2.3 
Preparation and Administration of the Product ..........................................................43 
8.2.4 
Administration of the Product Outside the Clinic ......................................................43 
8.2.5 
Instructions for Delays in Dosing ...............................................................................43 
 
Safety Monitoring and Drug Dose Interruption..........................................................44 
8.3.1 
Laboratory Abnormalities and Adverse Events Requiring Evaluation and 
Potential Drug Interruption or Discontinuation ..........................................................44 
8.3.2 
Laboratory Abnormalities Requiring Evaluation and Potential Drug 
Interruption or Discontinuation ..................................................................................44 
8.3.3 
Instructions for Resuming Study Drug Administration after an Interruption 
for Safety Concerns Due to General Laboratory Abnormalities or Adverse 
Events .........................................................................................................................45 
8.3.4 
Instructions for Resuming Study Drug Administration after an Interruption 
for Safety Concerns Due to Safety Laboratory Abnormalities ...................................46 
8.3.5 
Serious Adverse Events Requiring Discontinuation of Study Drug ...........................46 
8.3.6 
Instructions for Discontinuation of Study Drug Administration for Safety 
Concerns .....................................................................................................................46 
 
Method of Assigning Patients to Treatment ...............................................................47 
8.4.1 
Blinding and Randomization ......................................................................................47 
8.4.1.1 
Screening Procedures ..................................................................................................47 
8.4.1.2 
Randomization ............................................................................................................47 
8.4.1.3 
Blinding ......................................................................................................................47 
8.4.2 
Emergency Unblinding ...............................................................................................47 
 
Treatment Compliance ................................................................................................48 
9 
PRIOR AND CONCOMITANT MEDICATIONS ....................................................49 


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Permitted Concomitant Medications ..........................................................................49 
 
Stabilization and Washout Period for Permitted Concomitant Medications ..............49 
 
Prohibited Concomitant Medications .........................................................................51 
9.3.1 
Washout Period for Prohibited Medications ...............................................................51 
10 
EXPLANATION OF STUDY PROCEDURES .........................................................53 
 
Pretreatment, Treatment and Follow-up Periods ........................................................53 
10.1.1 
Screening Visit (Visit 1) and Screening Period ..........................................................53 
10.1.2 
Baseline Visit (Visit 2, Day 1) ....................................................................................54 
10.1.3 
Treatment Period (Visit 2/Week 1 through Visit 25/Week 24) ..................................54 
10.1.4 
End-of-Treatment Visit (Visit 26) and Early Termination Visit ................................54 
10.1.5 
End-of-Study Visit (Visit 27/Week 29) ......................................................................55 
10.1.6 
Unscheduled Visits .....................................................................................................55 
 
Description of Assessments ........................................................................................55 
10.2.1 
Informed Consent .......................................................................................................55 
10.2.2 
Inclusion/Exclusion Criteria .......................................................................................55 
10.2.3 
Demographic Information and Medical History .........................................................55 
10.2.4 
Physical Examination Including Weight and Height ..................................................55 
10.2.5 
Skin Photography........................................................................................................56 
10.2.6 
Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) ..................56 
10.2.7 
Skin Biopsy .................................................................................................................56 
10.2.8 
International Myositis Assessment Clinical Study (IMACS) Core Set 
Measures .....................................................................................................................57 
10.2.8.1 
Manual Muscle Testing (MMT8) ...............................................................................57 
10.2.8.2 
Muscle Enzymes .........................................................................................................57 
10.2.9 
Short Form-36 Health Survey .....................................................................................57 
10.2.10 
Timed Function Tests .................................................................................................58 
10.2.10.1 
Timed 10-meter Walk-run Test (10MWR) .................................................................58 
10.2.10.2 
Timed Up and Go (TUG) ...........................................................................................58 
10.2.10.3 
4 Stair Climb Test .......................................................................................................58 
10.2.11 
5-D Itch Scale (5D Pruritis Scale) ..............................................................................58 
10.2.12 
Clinical Laboratory Tests ...........................................................................................58 
10.2.12.1 
Routine Safety Laboratory Assessments ....................................................................60 


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10.2.12.2 
Safety Laboratory Assessments ..................................................................................61 
10.2.13 
12-Lead Electrocardiogram (ECG) .............................................................................61 
10.2.14 
Pregnancy test .............................................................................................................61 
10.2.15 
IMO-8400 Plasma Concentration ...............................................................................61 
10.2.16 
Autoantibodies ............................................................................................................62 
10.2.17 
Interferon (IFN) Gene Expression ..............................................................................62 
10.2.18 
Histology.....................................................................................................................62 
10.2.19 
Serum Cytokines .........................................................................................................62 
10.2.20 
Immunogenicity ..........................................................................................................62 
10.2.21 
Vital Signs ..................................................................................................................62 
10.2.22 
Concomitant Medications/Therapies/Procedures During Treatment .........................62 
10.2.23 
Blood Volume Collection Summary ..........................................................................63 
11 
ADVERSE EVENT REPORTING ............................................................................64 
 
Definition of Adverse Events .....................................................................................64 
11.1.1 
Adverse Event (AE) ....................................................................................................64 
11.1.2 
Serious Adverse Events (SAE) ...................................................................................64 
11.1.3 
Suspected and Unexpected Serious Adverse Reaction (SUSAR) ..............................65 
 
Evaluation of Adverse Events ....................................................................................65 
11.2.1 
Description of Event ...................................................................................................66 
11.2.2 
Date and Time of Onset ..............................................................................................66 
11.2.3 
Relationship to Study Drug ........................................................................................66 
11.2.4 
Severity .......................................................................................................................66 
11.2.5 
Action Taken with Study Medication upon Occurrence of an Adverse Event ...........67 
11.2.6 
Actions Taken for Management of AE .......................................................................67 
11.2.7 
Outcome of AEs .........................................................................................................67 
11.2.8 
Injection Site Reactions ..............................................................................................68 
 
Reporting Serious Adverse Events .............................................................................68 
 
Follow Up of Adverse Events/Serious Adverse Events .............................................69 
 
Other Reportable Events .............................................................................................70 
12 
WITHDRAWAL OF PATIENTS ..............................................................................71 
13 
DATA COLLECTION, QUALITY ASSURANCE, AND MANAGEMENT ..........72 
 
Data Collection and Recording ...................................................................................72 


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Data Quality Assurance ..............................................................................................72 
 
Data Management .......................................................................................................72 
 
Protocol Violations .....................................................................................................72 
14 
STATISTICAL METHODS AND PLANNED ANALYSES ...................................74 
 
General Considerations ...............................................................................................74 
 
Determination of Sample Size ....................................................................................74 
 
Analysis Sets ...............................................................................................................74 
 
Statistical Analyses .....................................................................................................74 
14.4.1 
Demographic and Baseline Characteristics ................................................................74 
14.4.2 
Study Conduct and Patient Disposition ......................................................................74 
14.4.3 
Treatment Compliance ................................................................................................75 
14.4.4 
Efficacy Analyses .......................................................................................................75 
14.4.5 
Safety Analyses ..........................................................................................................75 
14.4.5.1 
Physical Examination and Vital Signs ........................................................................75 
14.4.5.2 
Clinical Laboratory Tests ...........................................................................................75 
14.4.5.3 
Adverse Events ...........................................................................................................75 
14.4.5.4 
Electrocardiograms .....................................................................................................76 
14.4.5.5 
Concomitant Medications and Therapies ...................................................................76 
14.4.5.6 
Injection Site Reactions ..............................................................................................76 
14.4.6 
Pharmacokinetic Analyses ..........................................................................................76 
14.4.7 
Pharmacodynamic, Disease-specific Autoantibodies, and Immunogenicity 
Analyses ......................................................................................................................76 
 
Significance Levels .....................................................................................................76 
 
Missing or Invalid Data ..............................................................................................76 
15 
STUDY COMMITTEES ............................................................................................77 
 
Data Monitoring Committee (DMC) ..........................................................................77 
 
Patient Safety Committee (PSC) ................................................................................77 
16 
SPECIAL REQUIREMENTS AND PROCEDURES................................................78 
 
Compliance with Ethical and Regulatory Guidelines .................................................78 
 
Institutional and Ethics Review ..................................................................................78 
 
Confidentiality ............................................................................................................78 
 
Changes to the Conduct of the Study or Protocol .......................................................78 


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Investigator Responsibilities .......................................................................................79 
16.5.1 
Patient Informed Consent ...........................................................................................79 
16.5.2 
Case Report Forms .....................................................................................................79 
16.5.3 
Record Retention ........................................................................................................80 
16.5.4 
Monitoring and Auditing ............................................................................................80 
16.5.5 
Study or Site Termination ...........................................................................................80 
16.5.6 
Investigational Product Control ..................................................................................81 
16.5.6.1 
Accountability of Study Drug .....................................................................................81 
16.5.6.2 
Disposition of Unused Study Drug .............................................................................81 
16.5.6.3 
Product Handling and Complaints Reporting .............................................................81 
16.5.7 
Public Notification of Study Conduct.........................................................................81 
16.5.8 
Dissemination of Results ............................................................................................81 
16.5.9 
Clinical Study Report .................................................................................................82 
16.5.10 
Communication with Regulatory Authorities .............................................................82 
17 
STUDY RATIONALE ...............................................................................................83 
 
Study Design ...............................................................................................................83 
 
Selection of Study Population ....................................................................................83 
17.2.1 
Baseline Disease Activity Assessment .......................................................................84 
17.2.2 
Dose Selection ............................................................................................................84 
17.2.2.1 
Estimation of Human Equivalent Dosages from Animal Models of 
Autoimmune Disease ..................................................................................................84 
17.2.2.2 
Safety Profile of Selected Doses .................................................................................84 
 
Appropriateness of Efficacy Assessments ..................................................................85 
17.3.1 
CDASI ........................................................................................................................85 
17.3.2 
IMACS ........................................................................................................................86 
17.3.2.1 
Manual Muscle Testing (MMT8) ...............................................................................86 
17.3.2.2 
Muscle Enzyme Levels ...............................................................................................86 
17.3.3 
Timed Function Tests .................................................................................................87 
17.3.4 
5-D Itch Scale (5-D Pruritis Scale) .............................................................................87 
17.3.5 
SF-36...........................................................................................................................87 
 
Safety Monitoring .......................................................................................................87 
 
Overview of Human Safety Experience .....................................................................88 


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PROTOCOL VERSION 6.0 
18 
REFERENCES ...........................................................................................................89 
 
LIST OF IN-TEXT TABLES 
Table 1. 
Study Contact Information ...........................................................................................3 
Table 2. 
Physical and Chemical Properties of Active Ingredient (Drug Substance) ................42 
Table 3. 
Safety Monitoring Parameters and Actions ................................................................45 
Table 4. 
Stable Regimens of Permitted Concomitant Medications ..........................................50 
Table 5. 
Washout Period for Prohibited Concomitant Medications .........................................51 
Table 6. 
Washout Period for Prohibited Concomitant Medications .........................................52 
Table 7. 
Routine Safety Laboratory Assessments ....................................................................60 
Table 8. 
Safety Laboratory Assessments ..................................................................................61 
 
LIST OF IN-TEXT FIGURES 
Figure 1: Study Schematic .............................................................................................................30 
LIST OF APPENDICES 
APPENDIX 1. 
AGE AND GENDER-APPROPRIATE CANCER WORK-UP 
GUIDELINES FOR WOMEN ...................................................................................93 
APPENDIX 2. 
AGE AND GENDER-APPROPRIATE CANCER WORK-UP 
GUIDELINES FOR MEN ..........................................................................................95 
APPENDIX 3. 
BOHAN AND PETER DIAGNOSTIC CRITERIA FOR 
DERMATOMYOSITIS ..............................................................................................96 
APPENDIX 4. 
CUTANEOUS DERMATOMYOSITIS DISEASE AREA AND 
SEVERITY INDEX (CDASI) VERSION 2...............................................................97 
APPENDIX 5. 
IMACS FORM 04: MANUAL MUSCLE TESTING 8 SCORING 
SHEET ........................................................................................................................99 
APPENDIX 6. 
IMACS FORM 06: SERUM LEVELS OF MUSCLE ENZYMES.................101 
APPENDIX 7. 
SF-36 HEALTH SURVEY ..............................................................................102 
APPENDIX 8. 
5-D ITCH SCALE (ALSO KNOWN AS THE 5-D PRURITIS 
SCALE) ....................................................................................................................108 
APPENDIX 9. 
INVESTIGATOR’S AGREEMENT ...............................................................110 
 


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1 
ABBREVIATIONS AND TERMS 
10MWR 
10-meter walk-run test 
A:G ratio 
albumin: globulin ratio 
ACTH 
adrenocorticotropin 
AE 
adverse event(s) 
ALD 
aldolase 
ALT 
alanine transaminase 
ANC 
absolute neutrophil count 
Anti-HBc 
hepatitis B core antibody test 
Anti-HCV 
hepatitis C virus antibody test 
aPTT 
activated partial thromboplastin time 
AST 
aspartate transaminase 
AUC 
area under the curve 
BCG 
Bacille Calmette-Guerin 
C3 
complement component 3 
C4 
complement component 4 
CDASI 
Cutaneous Dermatomyositis Disease Area and Severity Index 
CFR 
Code of Federal Regulations 
CH50 
hemolytic complement activity 
CK 
creatine kinase 
Cmax 
maximum plasma concentration 
CRO 
clinical research organization 
CRP 
C-reactive protein 
CS 
clinically significant 
CSMs 
Core Set Measures 
CSR 
Clinical Study Report 
CT 
computed tomography 
CXR 
chest x-ray 
DLBCL 
diffuse arge B-cell lymphoma 
DM 
dermatomyositis 
DMC 
Data Monitoring Committee 
DOI 
definition of improvement 
dsDNA 
double-stranded deoxyribonucleic acid 


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ECG 
electrocardiogram 
eCRF 
electronic case report form 
EMG 
electromyography 
EOS 
End-of-Study 
EOT 
End-of-Treatment 
ET 
Early Termination 
EP 
European Pharmacopeia 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
eGFR 
estimated glomerular filtration rate 
GGT 
gamma-glutamyl transferase 
GMP 
Good Manufacturing Practice 
HBV 
hepatitis B virus 
HBsAG 
hepatitis B surface antigen test 
HCV 
hepatitis C virus 
HIV-1 
human immunodeficiency virus 1 
HIV-2 
human immunodeficiency virus 2 
IBM 
Inclusion Body Myositis 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IFN 
interferon 
IL 
interleukin 
IMACS 
International Myositis Assessment Clinical Study 
IND 
investigational new drug 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
ISR 
injection site reaction 
ITT 
Intent-to-Treat 
IVIG 
intravenous immunoglobulin 
IXRS 
Interactive voice/web-Response System 
LDH 
lactate dehydrogenase 
LLN 
lower limit of normal 


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mCDASIv2 
Modified CDASI version 2 
MedDRA 
Medical Dictionary for Regulatory Activities  
MMT/MMT8 
Manual Muscle Testing  
MRI 
magnetic resonance imaging 
NCS 
not clinically significant 
NF-κB 
nuclear factor kappa-light-chain-enhancer of activated B-cells 
PD 
pharmacodynamics 
PET/CT 
positron emission tomography and computed tomography 
PK 
pharmacokinetics 
PP 
per protocol 
PPD 
purified protein derivative 
PSC 
Patient Safety Committee 
PT 
prothrombin time 
RMMM 
repeated measures mixed model 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SF-36 
Short Form-36 Health Survey 
SOE 
Schedule of Events 
SRM 
Study Reference Manual 
STIR 
short τ inversion recovery  
T4 
thyroxine 
TB 
tuberculosis 
TLR 
Toll-like receptors 
Tmax 
time to maximum plasma concentration 
TNFα 
tumor necrosis factor alpha 
TSH 
thyroid stimulating hormone 
ULN 
upper limit of normal 
UK 
United Kingdom 
US 
United States 
USP 
United States Pharmacopeia 
WBC 
white blood cell 
WM 
Waldenström’s macroglobulinemia 


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WNL 
within normal limits 
 
 
 


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2 
SYNOPSIS 
Name of Sponsor/Company: 
Idera Pharmaceuticals, Inc. 
Name of Investigational Product: 
IMO-8400 for Injection 
Name of Active Ingredient: 
IMO-8400 
Title of Study: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial of IMO-8400 in Patients with Dermatomyositis 
Study Sites: This study will be conducted at approximately 20 centers 
Phase of Development: 2 
Objectives: 
Primary 
• 
To assess the safety and tolerability of IMO-8400 in adult patients with active dermatomyositis (DM) 
• 
To assess the effect of IMO-8400 on the cutaneous manifestations of DM  
Exploratory 
• 
To investigate associations between the treatment effect of IMO-8400 on indices of disease activity, 
patient-reported outcomes, and pharmacodynamic (PD) measures 
• 
To assess plasma concentrations of IMO-8400 over time 
• 
To characterize the enrolled population based on disease-specific autoantibody profiles for potential 
subgroup analyses 
• 
To assess the immunogenicity of IMO-8400 
Methodology: 
This is a 24-week, Phase 2, randomized, double-blind, placebo-controlled trial of IMO-8400 in adult patients with 
active DM. The trial is designed to assess the safety, tolerability, and treatment effect of IMO-8400 in these patients. 
Eligible patients will be randomized to 1 of 3 groups to receive once weekly subcutaneous (SC) injections 
of:  placebo (Sterile Saline for Injection, United States Pharmacopeia [USP]/European Pharmacopeia [EP]) or 
0.6 mg/kg or 1.8 mg/kg of IMO-8400 and will be stratified by baseline Cutaneous Dermatomyositis Disease Area 
and Severity Index (CDASI)v2-Activity score (15 to 20 vs. ≥21). 
Screening evaluations will be completed at Visit 1 or within 28 days prior to administering the first dose of study 
drug. On scheduled site visits (which will occur at least every 4 weeks) study drug will be administered at the study 
site along with all scheduled assessments. At the discretion of the Investigator, a visiting nurse who has been trained 
in the protocol and approved by the Sponsor may conduct the intervening weekly study visits outside of the clinic 
(e.g., at the patient’s home or workplace); the visiting nurse may administer intervening doses of study drug, collect 
vital signs, and assess for adverse events (AEs) and concomitant medications.  
Adverse events and concomitant medications will be monitored continuously; the timing and frequency of all other 
scheduled assessments is specified in the Schedule of Events (SOE). 


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Based on results from a 39-week nonclinical toxicology study in cynomolgus monkeys showing that adverse effects 
were reliably preceded by changes in complement and markers of acute phase reactions, serum levels of 
complement component 3 (C3), complement component 4 (C4), hemolytic complement activity (CH50), albumin, 
globulin, and albumin:globulin (A:G) ratio will be regularly monitored during this study and the following safety 
monitoring/stopping rules will apply: 
• 
If either the C3 or C4 level and the A:G ratio are below the lower limit of normal (LLN), study drug 
administration will be discontinued. 
• 
If either the C3 or C4 level or the A:G ratio are below the LLN, a Patient Safety Committee (PSC) 
consisting of the Investigator, Sponsor Medical Monitor, and Clinical Research Organization (CRO) 
Medical Monitor will convene within 7 days of abnormal laboratory report and review all available safety 
data for the patient; the outcome of the meeting may be to discontinue study drug, to conduct additional 
safety assessments, or to continue study drug without modification of the planned safety assessments. 
Another oligonucleotide investigational product has been associated with clinically significant AEs of 
thrombocytopenia and renal abnormalities as well as injection site reactions (ISRs) in human clinical studies (FDA 
2015). Given IMO-8400 is also an oligonucleotide investigational product, platelet counts, anti-platelet antibodies, 
urine protein, and renal function will be regularly monitored and the following safety monitoring rules will apply: 
• 
If urinalysis results indicate urine protein is greater than + 2, or estimated glomerular filtration rate (eGFR) 
is below 50% of baseline, or platelet count is below 75,000/µL, study drug administration will be 
interrupted and a PSC consisting of the Investigator, Sponsor Medical Monitor, and CRO Medical Monitor 
will convene within 7 days of the abnormal laboratory report and review all available safety data for the 
patient. The outcome of the meeting may be to discontinue study drug, to conduct additional safety 
assessments, or to continue study drug without modification of the planned safety assessments. 
To further ensure the safety of study participants, study drug administration will be discontinued in any patient who 
experiences a serious adverse event (SAE) that is assessed by the Investigator as possibly related or probably related 
to study drug.  
In addition to the role of the PSC, a Data Monitoring Committee (DMC) will review unblinded safety data as 
outlined in the DMC charter. The DMC may also increase or alter safety monitoring, or recommend other 
modifications to ensure patient safety. 
Because SC administration of IMO-8400 has been associated with potentially unblinding ISRs, skin activity 
assessments, manual muscle testing (MMT), and timed function tests will be performed by qualified and trained 
raters who will be blinded to treatment assignment and study drug injection sites and who will have no other role or 
responsibility in the study beyond administering efficacy assessments. Patients will also be asked to wear clothing 
that covers injection sites whenever attending study site visits. 
All patients will complete End-of-Treatment (EOT) assessments at Visit 26/Week 25 (7 days ± 2 from the last dose 
of study drug). For patients who discontinue study drug prematurely, an Early Termination (ET) Visit is required 
within 5 days of the notification of withdrawal; EOT and ET assessments are the same. With Investigator approval, 
patients who successfully complete the EOT assessments may continue receiving treatment with IMO-8400 (or for 
patients randomized to placebo in this study, initiate treatment with IMO-8400) if an extension study for this trial is 
initiated. Additional information regarding procedures to consent patients for participation will be provided if an 
extension study is initiated. 
To protect patient safety and facilitate assessment of treatment effects, patients will be prohibited from receiving 
other investigational agents during the study. Moreover, pre-existing immunomodulatory regimens should be kept 
stable throughout the study. 
Inclusion / Exclusion Criteria: 
The eligibility criteria are designed to include only those patients with an established diagnosis of DM and 
documented skin involvement who are able to safely participate in all study procedures. Patients who do not qualify 
for enrollment at the Screening Visit based on these criteria may be further assessed for eligibility at any time during 
the Screening Period (within 28 days prior to Visit 2/Week 1, Day 1). Under some circumstances, patients who fail 
to meet eligibility criteria during the Screening Period may be rescreened for study entry following discussion with 
the CRO Medical Monitor. 
 


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Inclusion Criteria 
A patient who meets all of the following criteria will be eligible for this study. 
1. Has signed the current, approved Informed Consent Form (ICF). 
2. Is 18 to 75 years of age (inclusive) at the time of consent. 
3. Has definite or probable DM based on the criteria of Bohan and Peter (Appendix 3; 1975a, 1975b) 
OR those patients who have all other definite or probable Bohan and Peter criteria but do not have 
heliotrope rash and Gottron’s signs/papules may still be included if they have one or more of the 
following: 
a) DM autoantibody (anti-Mi-2, anti-MDA5, anti-TIF1-gamma, anti-NXP-2, anti-Jo-1, 
anti-PL-12, anti-PL-7, anti-EJ, anti-KS, anti-OJ); at least 1 autoantibody must be present 
and documented in the patient’s medical record  
b) A classic DM associated skin change including at least one of the following: malar rash 
without sparing nasolabial folds, Shawl sign, V neck rash, periungal erythema, or 
mechanic’s hands; documented in the patient’s medical record 
4. Has a CDASIv2-Activity score ≥15 at Visit 2 (Baseline). 
5. Patients with muscle weakness are eligible; however, having muscle weakness is not mandatory. 
These patients have  documented assessment of active muscle involvement as indicated by clinical 
evidence of symmetrical proximal muscle weakness involving limb-girdle and/or anterior neck 
flexors within 16 weeks prior to Baseline and one or more of the following: 
a) Elevation of serum creatine kinase (CK) or serum aldolase (ALD) levels >1.5 times the 
upper limit of normal (ULN) during Screening or >1.5 times increase compared to a 
documented within normal limits (WNL) level obtained prior to disease onset or while in 
prior remission 
b) Electromyography (EMG) demonstrating one or more of the following within 16 weeks 
prior to Baseline: 
i. Fibrillation potentials (increased insertional irritability and spontaneous activity) 
ii. Positive sharp waves and complex repetitive discharges 
iii. Short duration, small amplitude motor unit action potentials 
c) Muscle biopsy demonstrating one or more of the following within 16 weeks prior to 
Baseline: 
i. Perimysial and/or perivascular infiltration of mononuclear cells 
ii. Perifascicular atrophy 
iii. Note: Patients with a muscle biopsy demonstrating rimmed vacuoles or other 
histologic findings of Inclusion Body Myositis (IBM) are excluded 
d) Magnetic resonance imaging (MRI) demonstrating evidence of disease activity and 
inflammation on the short τ inversion recovery (STIR) image within 16 weeks prior to 
Baseline.  
6. If on permitted concomitant medications at Screening, the therapy regimen can include one or 
more of the following: 
a) Stable dose of prednisone (or other oral equivalent) ≤20 mg/day (or ≤140 mg/week) for 
≥4 weeks 
b) Stable regimen that does not exceed the approved dosages for ≥12 weeks of no more than 
1 of the following non-steroidal immunomodulatory medication(s): intravenous 
immunoglobulin (IVIG), mycophenolate mofetil, cyclophosphamide, cyclosporine, 
leflunomide, tacrolimus, methotrexate, azathioprine 
c) Stable regimen of topical treatments for scalp involvement for ≥3 weeks 
 
 


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7. Study participants must have a diagnostic evaluation for cancer if the diagnosis of DM was within 
2 years prior to the Screening Visit. The evaluation should include either: 
a) All age- and gender-appropriate screening tests and a computed tomography (CT) of the 
chest, abdomen, and pelvis; OR 
b) Positron emission tomography and computed tomography (PET/CT) of the chest, 
abdomen, and pelvis. 
 
Note: If a diagnostic evaluation for cancer has not been performed within 2 years prior to 
the Screening Visit in patients for whom it is required, either a CT of the chest, abdomen, 
and pelvis should be performed, OR a PET/CT of the chest, abdomen, and pelvis if this is 
standard practice in the particular center. The diagnostic evaluation for cancer must be 
normal for a patient to meet this inclusion criterion. 
8. Study participants must have no evidence of active or latent tuberculosis (TB) after a diagnostic 
evaluation with a chest x-ray (CXR) OR chest CT and 1 of the following: a) a purified protein 
derivative (PPD) skin test, b) a QuantiFERON blood test, or c) T-SPOT.TB blood test.  
 
If the diagnostic evaluation has not been performed within 12 weeks of the Screening Visit, it may 
be performed during the Screening Period (performed per Center for Disease Control [CDC] 
guidelines [http://www.cdc.gov/tb/topic/testing/default.htm]).  
 
For the patient to be eligible, the result of the diagnostic evaluation should include a negative chest 
image and 1 of the following: a) a PPD skin test with ≤5-mm induration, b) a negative (not 
detected) QuantiFERON result, or c) a negative T-SPOT.TB blood test. If the QuantiFERON 
result is indeterminate, the test may be repeated once. If the repeat QuantiFERON test result is 
indeterminate, then a PPD skin test result may be used to confirm patient eligibility. The PPD skin 
test is not an acceptable method of TB testing in Sweden.  
9. Women of childbearing potential and men must agree to use effective contraceptive methods from 
Screening throughout the study and until at least 4 weeks after the last dose of study drug. 
Non-childbearing potential is defined as a female who meets either of the following criteria: 
a) postmenopausal state defined as no menses for 12 months without an alternative medical cause 
or b) documented hysterectomy, bilateral tubal ligation, or bilateral oophorectomy.  
Effective contraception methods that can achieve a failure rate of <1% per year when used 
consistently and correctly are considered highly effective birth control methods. Such methods are 
defined as 1 of the following: 
a) True abstinence, defined as refraining from heterosexual intercourse, when this is in line 
with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, 
ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the 
duration of a trial, and withdrawal are not acceptable methods of contraception. 
b) Vasectomized partner (if that vasectomized partner is the sole sexual partner of the 
woman of childbearing potential and has received medical assessment of the surgical 
success of the vasectomy) 
c) An intrauterine hormone-releasing system (IUS) 
d) Oral, intravaginal or transdermal  combined (estrogen and progesterone) implanted 
hormonal contraceptive  
e) NOTE: For patients in Sweden, low dose oral contraceptives are not permitted 
f) 
An intra uterine device (IUD) 
10. Agrees to use a broad-spectrum (UVA/UVB) sunscreen with an SPF ≥15 daily (or a 
water-resistant, broad spectrum sunscreen with an SPF ≥30 for extended outdoor activity), and to 
not increase their normal sun exposure during the course of this study. 
11. Is willing and able to comply with this protocol. 
 


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PROPRIETARY AND CONFIDENTIAL 
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Exclusion Criteria 
A patient who meets any of the following criteria will be excluded from this study. 
1. Has ongoing severe dysphagia (e.g., requires a feeding tube) for the 3 months prior to Screening 
2. Has known hypersensitivity to any oligodeoxynucleotide 
3. Has a history of drug abuse within one year of screening, or evidence of drug abuse by urine drug screening 
4. Has a history of alcohol abuse within one year of screening 
5. Is pregnant (or intends to become pregnant within 6 months of last dose of study medication) or nursing 
6. Has body weight >140 kg 
7. Has any one of the following hepatitis serologic test results: 
a) Positive hepatitis B surface antigen test (HBsAg), or 
b) Positive hepatitis B core antibody test (anti-HBc) AND negative hepatitis B surface antibody 
(anti-HBs), or 
c) Positive hepatitis C virus antibody test (anti-HCV) 
8. Has evidence of seropositive test in the patient’s medical records or is currently receiving treatment for 
human immunodeficiency virus (HIV)-1 or HIV-2  
9. Has screening safety laboratory test meeting any of the following criteria: 
a) Hemoglobin <10.5 g/dL 
b) White blood cell (WBC) count <3000/mm3 
c) Absolute neutrophil count (ANC) <1.5 x 109/L (1500/mm3) 
d) Platelet count <100,000/mm3 
e) Serum creatinine >1.2 mg/dL in female patients and >1.5 mg/dL in male patients. Patients with 
serum creatinine values exceeding limits may be eligible for the study if their eGFRs are 
>60 mL/min 
f) 
Serum aspartate transaminase (AST) or serum alanine transaminase (ALT) >5 times ULN (unless 
considered consistent with muscle origin and accompanied by gamma-glutamyl transferase (GGT) 
<1.5 times ULN) 
g) Total bilirubin >1.5 times ULN 
h) Prothrombin time (PT) >1.5 times ULN 
i) 
C3 or C4 <LLN 
j) 
A:G ratio <LLN 
k) Urinalysis with proteinuria >1+ 
10. Has a diagnosis of Juvenile DM, IBM, drug-induced toxic myopathy, metabolic myopathy, dystrophy, 
cancer-associated DM , or connective tissue disease-associated DM (e.g., overlap syndrome) 
11. Has received one or more of following prohibited treatments within the interval noted prior to Screening 
(Visit 1): 
a) Rituximab within 24 weeks (Note: patients who received rituximab are only eligible for inclusion 
if B-cell counts are confirmed to be within normal limits) 
b) Intravenous corticosteroids within 12 weeks 
c) Intravenous immunosuppressive drugs within 12 weeks 
d) Any other monoclonal antibody, biologic agent, or investigational agent within 12 weeks or 
5 half-lives (whichever is longer) 
e) Antimalarials (e.g., hydroxychloroquine) within 36 weeks 
f) 
Topical corticosteroids (excluding scalp) within 2 weeks 
12. Has evidence of or has required treatment for cancer (except for treated, non-invasive carcinoma of the skin 
or cured carcinoma-in-situ following discussion with Medical Monitor) within 5 years 
13. Has other chronic or active significant medical conditions within 6 months prior to Screening including but 


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PROPRIETARY AND CONFIDENTIAL 
PROTOCOL VERSION 6.0 
not limited to: allogeneic organ transplant (e.g., solid organ, bone marrow, or stem cells); cardiac disease 
(e.g., unstable angina, myocardial infarction, ventricular arrhythmia); congestive heart failure; liver disease; 
neurological disease; hematological disease; kidney disease; uncontrolled seizure disorder; uncontrolled 
pulmonary disease; uncontrolled gastrointestinal disease; uncontrolled endocrinological disease; 
uncontrolled psychiatric disease; or uncontrolled diabetes mellitus  
14. Has interstitial lung disease requiring the use of supplemental oxygen 
15. Has received or is expected to receive any live viral or bacterial vaccination within 3 months prior to 
Screening 
16. Has received a Bacille Calmette-Guerin (BCG) vaccination within 12 months of Screening or is expected to 
receive it during the course of the study  
17. Has a history of or ongoing active, chronic, or recurrent infection (including bacterial, viral, parasitic, 
protozoal, and/or fungal/granulomatous infections [e.g., histoplasmosis, coccidioidomycosis, aspergillosis]) 
requiring treatment with systemic antimicrobials, antivirals, antiparasitics, antiprotozoals, or antifungals 
within 12 weeks prior to Screening, or serious infection (including but not limited to pneumonia, sepsis, 
bone or joint infection) requiring hospitalization or treatment with IV antibiotics within 12 weeks prior to 
Screening 
18. Has a history of opportunistic infection or non-tuberculosis mycobacterial infection within 9 months prior 
to Screening 
19. Has any other condition that would, in the opinion of the Investigator, potentially compromise the safety or 
compliance of the patient or preclude the patient’s successful completion of the study 
Number of Patients: 
Approximately 36 patients will be randomized to the three following cohorts in a 1:1:1 ratio: 
• 
Once weekly SC injections of placebo (Sterile Saline for Injection, USP/EP) 
• 
Once weekly SC injections of IMO-8400 at 0.6 mg/kg 
• 
Once weekly SC injections of IMO-8400 at 1.8 mg/kg 
Investigational Product, Dosage and Mode of Administration: 
IMO-8400 for Injection will be supplied as a sterile, lyophilized powder for reconstitution using Sterile Saline for 
Injection, USP/EP or Sterile Water for Injection USP/EP. Details of the dose preparation procedure are provided in the 
Pharmacy Manual. The assigned dose of IMO-8400 will be administered as a single SC injection in the 4 quadrants of the 
abdomen. Injection site will be rotated with each injection. Injection volume will be based on patient weight with a 
maximum volume of 1.4 mL. 
Duration of Treatment: 
The approximate duration of each patient’s participation in the study is approximately 32 weeks, including 28 days 
of Screening, 24 weeks of study drug, an EOT Visit at 1 week after the last dose of study drug, and an End-of-Study 
(EOS) Visit for safety follow-up 4 weeks after the EOT Visit. 
Reference Therapy, Dosage and Mode of Administration: 
Placebo will be Sterile Saline for Injection, USP/EP, which will be indistinguishable in appearance to 
IMO-8400 injection solution and will be administered in the same manner. 
Assessments 
Safety: 
• 
AEs, reported and observed 
• 
Physical examination findings, including vital signs 
• 
Standard laboratory safety tests including hematology, chemistry, coagulation and urinalysis 
• 
Assessment of ISRs 
• 
Electrocardiograms (ECG) 
• 
Laboratory safety assessments including CH50, C3, C4, troponin, C-reactive protein (CRP), A:G ratio, 
proteinuria, eGFR, and platelet count 


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PROTOCOL VERSION 6.0 
Efficacy: 
• 
CDASI-Activity score (modified CDASI version 2, mCDASIv2) 
• 
International Myositis Assessment Clinical Study (IMACS) “Core Set Measures” (CSMs): 
o 
Manual muscle testing-8 (MMT8) 
o 
Serum CK, ALD, lactate dehydrogenase (LDH), ALT, and AST 
• 
Timed Function Tests 
o 
10-meter walk-run test (10MWR) 
o 
Timed up and go test (TUG) 
o 
4 stair climb test 
• 
Short Form-36 Health Survey (SF-36) 
• 
5-D Itch Scale (5-D Pruritis Scale) 
Pharmacokinetic: 
• 
Blood samples for determination of IMO-8400 plasma concentrations (pre-dose and 2 hours [± 15 minutes] 
post-dose) 
Pharmacodynamic: 
• 
Skin biopsies (2 punch biopsies at each scheduled assessment) for: 1) Type 1 and Type 2 Interferon (IFN) 
gene expression signature, and 2) histology testing 
• 
Whole blood samples for Type 1 and Type 2 IFN gene expression signature 
• 
Serum samples for cytokines/chemokines panel 
Disease-specific Autoantibodies : 
• 
Serum samples for presence of autoantibodies associated with idiopathic inflammatory myopathies, 
including, but not necessarily limited to, the following: anti-MDA-5, anti-Mi-2, anti-TIF1γ, anti-NXP2, 
anti-SAE1, anti-SAA 60, anti-Ro/SSA 52, anti-SSB/La, anti-Sm, anti-RNP, anti-Scl-70, anti-ribosomal-P, 
anti-chromatin, anti-Jo-1, anti-PL-7, and anti-PL-12. 
Immunogenicity: 
• 
Serum samples for antibodies to IMO-8400 and antibodies to double-stranded deoxyribonucleic acid 
(dsDNA) 
Statistical Methods 
Determination of Sample Size 
This study has approximately 80% power to detect a difference of 7 points in change from baseline on the 
mCDASIv2-Activity score at Week 25 using a 1-sided test with an alpha of 0.05. 
Randomization  
Randomization will be performed centrally in a 1:1:1 ratio (placebo or IMO-8400 at 0.6 mg/kg or 1.8 mg/kg) and 
will be stratified by baseline CDASIv2-Activity score (15 to 20 vs. ≥21). 
Analysis Populations 
• 
Safety Population and Intent-to-Treat Population (ITT): All patients who received at least 1 injection of 
study medication 
• 
Per Protocol Population (PP): All patients who received at least 20 doses of study drug as assigned, 
completed the EOT Visit 26/Week 25, and had no major protocol violations that would potentially 
influence treatment effect (as determined by review by Idera prior to unblinding) 
Safety analyses will be performed using the Safety Population. The efficacy, PD, disease-specific autoantibodies, 
and immunogenicity assessments will be analyzed for the ITT population; key endpoints may be also analyzed for 
the PP Population as specified in the Statistical Analysis Plan (SAP).  
Primary Safety and Tolerability Endpoints 
• 
Number of patients discontinuing treatment due to AEs 


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PROPRIETARY AND CONFIDENTIAL 
PROTOCOL VERSION 6.0 
• 
Frequency and severity of AEs 
• 
Physical examination findings, including vital signs 
• 
Standard laboratory safety tests including hematology, chemistry, coagulation and urinalysis 
• 
Assessment of ISRs 
• 
ECG findings 
• 
Laboratory safety assessments including CH50, C3, C4, troponin, CRP, albumin, globulin, A:G ratio, 
proteinuria, eGFR, and platelet count 
Primary Efficacy Endpoint 
• 
Change from baseline in mCDASIv2-Activity score 
Safety Analyses 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) and tabulated by 
event, grade, and relationship to study therapy. Safety analyses will be descriptive in nature; no statistical hypothesis 
testing will be performed. 
Efficacy Analyses 
The primary endpoint will be assessed via a repeated measures mixed model (RMMM). An appropriate covariance 
structure for repeated measures will be used. The difference between each IMO-8400 treatment group and placebo at 
Week 25 will be assessed. The overall alpha level will be controlled using the Bonferroni-Holm step-down method. 
Further details of this analysis will be described in the SAP. A sensitivity analysis to test the effect of important 
covariates on the effect of IMO-8400 will be performed using a RMMM. Differences in response rate between the 
IMO-8400 treatment groups and placebo will be assessed via logistic regression. 
The MMT8, TUG, 4 stair climb test, timed 10MWR test, serum CK, ALD, LDH, AST, ALT, SF-36, and 5-D Itch 
Scale will be analyzed in a similar manner to the primary endpoint. 
Continuous endpoints will be summarized descriptively. Categorical endpoints will be summarized by the number 
and percentage of patients in each category, and 95% confidence intervals for the proportion. 
For the proportion of patients who meet the IMACS 2004 definition of improvement (DOI) (Rider 2004) at EOT, 
logistic regression will be performed. Other exploratory and sensitivity analyses will be specified in the SAP in 
addition to further details regarding the statistical methodology. 
Pharmacokinetic Analyses 
Plasma concentrations of IMO-8400 will be determined pre-dose and 2 hours (± 15 minutes) post-dosing to confirm 
systemic exposure. Pre- and post-dose plasma concentrations may be used to evaluate/interpret time-dependent trends. 
Pharmacodynamic, Disease-specific Autoantibodies, and Immunogenicity Analyses 
Pharmacodynamic, disease-specific autoantibodies, and immunogenicity study parameters will be summarized using 
descriptive statistics. 


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PROPRIETARY AND CONFIDENTIAL 
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3 
SCHEDULE OF EVENTS 
Event / Period 
Screen1 Baseline 
Treatment 
EOT 
/ ET2 
EOS
3 
Week4 
 
Wk 1/ 
D12 
Wk 
2 
Wk 
3 
Wk 
4  
Wk 
5 
Wk 
6 
Wk 
7 
Wk 
8 
Wk 
9 
Wk 
10 
Wk 
11 
Wk 
12 
Wk 
13 
Wk 
14 
Wk 
15 
Wk 
16  
Wk 
17 
Wk 
18 
Wk 
19 
Wk 
20  
Wk 
21 
Wk 
22 
Wk 
23 
Wk 
24  
Wk 
25 
Wk 
29 
Visits5 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 V10 V11 V12 V13 V14 V15 V16 V17 V18 V19 V20 V21 V22 V23 V24 
V25 
V26 
V27 
Informed Consent6 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion / Exclusion 
Criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination7 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
Skin Photography8 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
CDASIv29 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
Skin Biopsy10  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X10 
 
MMT8 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
Muscle enzymes11 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
SF-36 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
Timed Function Tests12 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
5-D Itch Scale 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
Safety Labs13 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
12-Lead ECG14 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
Pregnancy Test15 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
IMO-8400 Plasma 
Concentration16 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
Auto-Antibodies 17 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
Anti-platelet 
antibodies18 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
IFN Gene Expression 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
Serum Cytokines 19 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
Immunogenicity 20 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
Vital Signs 21 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess Injection 
Site(s)22 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study Drug Admin 23, 24 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Assess AEs25 & Con 
Meds26 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Abbreviations: Admin. = administer; AE = adverse event; C3 = complement component 3; C4 = complement component 4; CDASI = Cutaneous Disease and Activity Severity Index; Con Med = 
concomitant medication; CH50 = hemolytic complement activity; CRP = C-reactive protein; CT = computed tomography; D = day; dsDNA = double-stranded deoxyribonucleic acid; 
ECG = electrocardiogram; eCRF = electronic case report form; EOS = End-of-Study; EOT = End-of-Treatment; ET = Early Termination; IFN = Type 1 and Type 2 interferon; Lab. = laboratory; 
MMT8 = manual muscle testing; PK = pharmacokinetic; PPD = purified protein derivative; SF-36 = 36-Item Short Form Health Survey; TB = tuberculosis; Wk = Week. 
Note: Shaded columns in the Schedule of Events indicate study visits that may be performed by a visiting nurse outside of the clinic (e.g., patient’s home or workplace), at the discretion of the 
Investigator. 
Note: At Baseline, all assessments must be performed before study drug administration. 
1 Screening will be performed within 28 days prior to Week 1/Day 1. 
2 If treatment is terminated prematurely for any reason, the ET Visit will be performed within 5 days of the notification of withdrawal. The ET Visit assessments are the same as the EOT assessments 
(i.e., following 24 weeks of treatment). 
3 The EOS Visit will be performed 4 weeks (± 4 days) after completion of the EOT assessments or the ET assessments. 
4 All days are relative to the day of the prior visit. 
5 Each visit has a window of ± 2 days. 
6 Informed consent must be signed prior to conducting any study-specific procedures. 
7 Physical examinations will include examination of general appearance, head, eyes, ears, nose, and throat (HEENT), heart, lungs, chest, abdomen, skin, lymph nodes, musculoskeletal, and neurological 
systems. Physical examination includes body weight with each exam and, at screening only, height. 
8 Skin photography procedures are provided in the Study Reference Manual.  
9 Full CDASIv2 assessment at Screening and Baseline and modified CDASIv2 (mCDASIv2; i.e., no abdominal skin activity) assessment post-Baseline. 
10 Two 4 mm punch biopsies will be taken at each of the Baseline Visit and the EOT Visit. Biopsies will be taken side by side on the upper back or upper arm of patients (whichever the Investigator 
feels has the most active skin disease at baseline) at the Baseline Visit and in an adjacent area at the EOT Visit. Sites where the baseline biopsy samples were taken should be photographed. Skin 
biopsies are not required for an ET Visit. 
11 Serum muscle enzymes measured include creatine kinase, aldolase, lactate dehydrogenase, alanine transaminase, and aspartate transaminase. 
12 Timed Function Tests include 10-meter walk-run test, timed up and go test, and 4 stair climb test 
13 Routine safety laboratory tests include hematology, chemistry, coagulation, urinalysis, and a urine drug screen; safety laboratory assessments include CH50, C3, C4, CRP, troponin, albumin/globulin 
ratio. The urine drug screen and hepatitis B and C testing will be performed during the Screening Period only. Testing for TB should include a negative chest x-ray or chest CT and 1 of the following: 
a) a PPD skin test with ≤5-mm induration, b) a negative (not detected) QuantiFERON result, or c) T-SPOT.  The PPD skin test is not an acceptable method of TB testing in Sweden. 
14 ECGs will be performed only after the patient is positioned supine, resting, and quiet for a minimum of 5 minutes. 
15 Urine pregnancy testing for women of child-bearing potential. 
16 Sample for analysis of IMO-8400 plasma concentrations should be collected prior to dosing and 2 hours (± 15 minutes) post-dose at Visits 2 (Week 1), 6 (Week 5), 14 (Week 13), and 22 (Week 21). 
An additional sample will be collected as part of the EOT assessments (Visit 26/Week 25). If, at the EOT Visit, the patient is eligible for enrolment into an extension study, the EOT PK sampling will 
be done prior to extension study dosing at the EOT Visit, which will be the same as Visit 1/Week 1 of the extension study, if the extension study is initiated.  
17 Serum samples for assay of autoantibodies.  
18 Serum samples for anti-platelet antibodies. 
19 Serum samples for assay of cytokines/chemokines. 
20 Serum samples for immunogenicity assay (antibodies to IMO-8400 and dsDNA). 
21 Vital signs include heart rate, respiration rate, blood pressure, and temperature and will be measured prior to study drug administration. 
22 Assessment of all prior injection site(s). In addition, on dosing days, the planned injection site will be assessed to confirm it is appropriate for use. 
23 ALL SCHEDULED ASSESSMENTS SHOULD BE PERFORMED PRIOR TO DOSING UNLESS OTHERWISE SPECIFIED. Patients will be monitored for approximately 4 hours after the 
first dose at the Baseline Visit. 
24 THERE CAN NOT BE FEWER THAN 5 DAYS BETWEEN DOSES. 
25 All AEs from the time the informed consent is signed through the EOS Visit 27/Week 29 will be recorded on the eCRF. 
26 Stable regimens and washout periods for permitted concomitant medications are provided in Table 4 and Table 5, respectively. The washout period for prohibited concomitant medications is 
provided in Table 6. 


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4 
BACKGROUND 
 
Purpose of Study 
The purpose of this Phase 2, randomized, double blind, placebo-controlled trial is to assess the 
efficacy, safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), disease-specific 
autoantibodies, and immunogenicity of IMO-8400 in adult patients with dermatomyositis (DM). 
Eligible patients will have confirmed skin involvement.  Muscle involvement will be assessed 
but is not required.  Enrolled patients will receive subcutaneous (SC) injections of 0.6 or 
1.8 mg/kg of IMO-8400 or placebo (Sterile Saline for Injection, United States Pharmacopeia 
[USP]/European Pharmacopeia [EP]) once a week for 24 weeks. If an extension study for this 
trial is initiated, with Investigator approval, patients who successfully complete this study may 
be eligible to continue receiving treatment with IMO-8400 (or for patients randomized to 
placebo in this study, initiate treatment with IMO-8400).  
 
Dermatomyositis Overview 
Dermatomyositis is a rare, progressively debilitating, idiopathic inflammatory myopathy 
associated with significant morbidity and an increased risk of premature death. Affecting less 
than 70,000 people in the United States (US), it is approximately twice as common in women as 
men, with an age of onset that typically peaks between 45 to 65 years in adults, and 5 to 15 years 
in children (Prieto 2010). 
Dermatomyositis is a multisystem disorder with a wide variety of clinical manifestations 
including lung, joint, esophageal, and cardiac findings; however, its hallmark features include the 
characteristic skin manifestations of Gottron’s papules, Gottron’s sign, and heliotrope rash, and 
progressive, symmetrical weakening of proximal muscles. Additional cutaneous symptoms may 
include photodistributed erythema, poikiloderma, nailfold changes, scalp involvement, and 
calcinosis cutis. Proximal muscle weakness, especially in the deltoids, hip flexors and neck 
flexors, may be associated with contractures and elevations in muscle enzymes, and often cause 
significant limitations on activities of daily living, such as difficulty climbing stairs, getting up 
from a chair, carrying heavy groceries, or picking up children. In more severe cases, respiratory 
and oropharyngeal muscle involvement can cause dysphagia, respiratory difficulties and ab 
ingestis pneumonia. Other symptoms of DM include fever, malaise, weight loss and arthralgias, 
heart failure, left ventricular diastolic dysfunction, hyperkinetic left ventricular contraction, and 
interstitial lung disease (Iaccarino 2014). While outcome studies in DM have primarily focused 
on the associated symptoms affecting the muscles in DM patients, the skin manifestations of DM 
can be a very active component of the disease. The skin manifestations of DM can be quite 
challenging to treat, and are often equally devastating to patients (Robinson 2015). 
The diagnosis of DM is often based on its skin manifestations, which are easy to recognize upon 
physical examination. Moreover, Gottron and heliotrope rashes are DM-specific and usually do 
not require histological confirmation. The diagnostic criteria of Bohan and Peter, initially 
proposed in 1975, require a combination of skin and muscle symptoms to establish a diagnosis of 
DM and are still widely accepted today (Appendix 3; Bohan 1975a, Bohan 1975b). 
Treatment for DM usually involves a combination of approaches with a focus on controlling the 
skin and muscle disease. Currently, there are only 2 drugs approved for the treatment of DM, 
Acthar gel (a highly purified sterile preparation of adrenocorticotropic hormone [ACTH]) and 


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prednisone; all other pharmacologic interventions are used off-label. Skin disease may be treated 
by avoiding sun exposure (as the cutaneous manifestations are extremely photosensitive) and/or 
with topical corticosteroids, antimalarial agents, immunomodulatory medications and 
intravenous immunoglobulin (IVIG) (Ang 2005, Levine 2012). Muscle weakness is also most 
commonly treated with corticosteroids, typically in conjunction with an immunosuppressive 
agent. Patients may also require assistive devices for ambulation, as well as adaptive strategies to 
minimize gastrointestinal complications secondary to esophageal muscle weakness, e.g., 
elevation of head of bed, avoidance of eating before bedtime. 
Unfortunately, many patients do not achieve full control of symptoms with prednisone and/or 
experience intolerable side effects, including infection, weight gain, mood/behavioral changes, 
osteoporosis, Cushing’s disease, and diabetes (Harris 2015). Glucocorticoids have also been 
associated with myopathy, which is a serious concern for patients with DM (Schakman 2009). 
Thus, there is an unmet medical need for safe and effective treatments for patients with DM. 
 
IMO-8400 as a Potential Therapy for the Treatment of DM 
While the initial cause of DM is not known, once inflammation is established, injured cells 
release nucleic acids, which in turn activate specific intracellular Toll-like receptors (TLRs 7, 8, 
and 9) expressed on the regenerating muscle cells, keratinocytes, and B-cells. Toll-like receptor 
activation in turn amplifies the inflammatory response, resulting in further damage to skin and 
muscle. Thus, blocking TLR activation represents a potential mechanism for interrupting the 
inflammatory cycle and offers a novel treatment approach for patients with DM. 
Idera Pharmaceuticals, Inc. (Idera; Sponsor) is developing a SC formulation of IMO-8400, a 
novel synthetic phosphorothioate oligonucleotide antagonist to TLRs 7, 8, and 9, as a potential 
treatment for diseases in which TLR-mediated responses contribute to disease pathophysiology, 
including DM. Nonclinical studies using immune cells from mice, monkeys, and humans have 
confirmed IMO-8400’s ability to selectively block the induction of pro-inflammatory cytokines 
and chemokines caused by administration of synthetic TLR7, TLR8, and TLR9 agonists.  
Moreover, in vivo studies have demonstrated IMO-8400’s therapeutic potential in animal models 
for several autoimmune diseases including systemic lupus erythematosus, arthritis, psoriasis, and 
dermal inflammation. 
 
 


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5 
STUDY OBJECTIVES 
 
Primary 
The primary objectives of this study are: 
• To assess the safety and tolerability of IMO-8400 in adult patients with active DM  
• To assess the effect of IMO-8400 on the cutaneous manifestations of DM  
 
Exploratory 
The exploratory objectives of this study are: 
• To investigate associations between the treatment effect of IMO-8400 on indices of 
disease activity, patient-reported outcomes, and PD measures 
• To assess plasma concentrations of IMO-8400 over time 
• To characterize the enrolled population based on disease-specific autoantibody 
profiles for potential subgroup analyses 
• To assess the immunogenicity of IMO-8400 
 
 


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6 
STUDY ENDPOINTS AND DESIGN 
 
Study Endpoints 
6.1.1 
Primary Endpoints 
6.1.1.1 
Primary Safety and Tolerability Endpoints 
• Number of patients discontinuing treatment due to adverse event (AE) 
• AEs, reported and observed 
• Physical examination findings, including vital signs 
• Standard laboratory safety tests including hematology, chemistry, coagulation and 
urinalysis 
• Assessment of injection site reactions (ISRs) 
• Electrocardiograms (ECG) 
• Laboratory safety assessments including hemolytic complement activity (CH50), 
complement component 3 (C3), complement component 4 (C4), troponin, C-reactive 
protein (CRP), albumin:globulin (A:G) ratio, proteinuria, estimated glomerular 
filtration rate (eGFR), and platelet count 
6.1.1.2 
Primary Efficacy Endpoint 
• Change from baseline in Cutaneous Dermatomyositis Disease Area and Severity 
Index (CDASI)-Activity score (modified CDASI version 2 [mCDASIv2]) 
6.1.2 
Exploratory Endpoints 
6.1.2.1 
Exploratory Efficacy Endpoints 
• Change from baseline in the following International Myositis Assessment Clinical 
Study (IMACS) “Core Set Measures” (CSMs). Improvement will be assessed using 
the IMACS group definitions of improvement (DOIs) (2004 DOI [Rider 2004]): 
o Manual muscle testing-8 (MMT8) 
o Serum creatine kinase (CK), aldolase (ALD), lactate dehydrogenase (LDH), 
alanine transaminase (ALT) and aspartate transaminase (AST) 
• Change from baseline in the following Timed Function Tests: 
o 10-meter walk-run test (10MWR) 
o Timed up and go test (TUG) 
o 4 stair climb test 
• Change from baseline in the Short Form-36 Health Survey (SF-36) 
• Change from baseline in the 5-D Itch Scale 


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6.1.2.2 
Pharmacokinetic Endpoints  
• IMO-8400 plasma concentrations pre-dose and 2 hours (± 15 minutes) post-dose to 
confirm systemic exposure 
6.1.2.3 
Pharmacodynamic Endpoints 
Note: the following analyses may be reported separately from the final Clinical Study Report 
(CSR). 
• Change from baseline in Type 1 and Type 2 Interferon (IFN) gene expression 
signature using (a) whole blood and (b) skin biopsy 
• Change from baseline in histology results, using skin biopsies. 
• Change from baseline in DM relevant cytokines/chemokine levels, including 
interleukin (IL) 6, IL-8, IP-10, I-TAC, MCP-1, MCP-2, and tumor necrosis factor 
alpha (TNFα); additional or alternative cytokines or chemokines may be assessed. 
6.1.2.4 
Disease-specific Autoantibody Endpoint 
• Presence of disease-specific autoantibodies at baseline and change from baseline in 
presence of autoantibodies associated with idiopathic inflammatory myopathies 
including, but not necessarily limited to, the following: anti-MDA-5, anti-Mi-2, 
anti-TIF1γ, anti-NXP2, anti-SAE1, anti-SAA 60, anti-Ro/SSA 52, anti-SSB/La, 
anti-Sm, anti-RNP, anti-Scl-70, anti-ribosomal-P, anti-chromatin, anti-Jo-1, 
anti-PL-7, and anti-PL-12 
Note: only baseline autoantibody results will be reported in the CSR. 
6.1.2.5 
Immunogenicity Endpoint 
• Change from baseline in presence of antibodies to IMO-8400 and 
anti-double-stranded deoxyribonucleic acid (dsDNA) 
 
Study Design 
This is a 24-week, Phase 2, randomized, double-blind, placebo-controlled trial of IMO-8400 in 
adult patients with DM with documented active skin disease. The trial is designed to assess the 
safety, tolerability, and treatment effect of IMO-8400 in these patients. The study scheme is 
shown in Figure 1. 


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Figure 1: Study Schematic 
 
Eligible patients will be randomized to 1 of 3 treatment groups to receive once weekly 
SC injections of 0.6 or 1.8 mg/kg of IMO-8400 or placebo (Sterile Saline for Injection, USP/EP) 
and will be stratified by baseline CDASIv2-Activity score (15 to 20 vs. ≥21). 
Screening evaluations will be completed at Visit 1 or within 28 days prior to the first dose of 
study drug at Visit 2/Week 1, Day 1. Study drug will be administered SC once a week. At 
scheduled site visits (which will occur at least every 4 weeks, i.e., at study Weeks 1, 5, 9, 13, 17, 
and 21) study drug will be administered at the study site along with all scheduled assessments. 
At the discretion of the Investigator, a visiting nurse who has been trained in the protocol and 
approved by the Sponsor may conduct the intervening weekly study visits outside of the clinic 
(e.g., at the patient’s home or workplace); the visiting nurse may administer intervening doses of 
study drug, collect vital signs, and assess for AEs and concomitant medications. 
Adverse events and concomitant medications will be monitored continuously; the timing and 
frequency of all other scheduled assessments is specified in the Schedule of Events (SOE) in 
Section 3. 
Rand.
N = 12
N = 12
Placebo
0.60 mg/kg weekly
1.80 mg/kg weekly
N = 12


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Based on results from the 39-week nonclinical toxicology study in cynomolgus monkeys 
showing that adverse effects were reliably preceded by changes in complement and markers of 
acute phase reactions, serum levels of C3, C4, albumin, globulin, and A:G ratio will be regularly 
monitored during this study, and the following safety monitoring/stopping rules (fully defined in 
Section 8.3.2) will apply:  
• If either the C3 or C4 level and the A:G ratio are below the lower limit of normal (LLN), 
study drug administration will be discontinued. 
• If either the C3 or C4 level or the A:G ratio are below the LLN, a Patient Safety 
Committee (PSC) consisting of the Investigator, Idera Medical Monitor, and Clinical 
Research Organization (CRO) Medical Monitor will convene within 7 days of the 
abnormal laboratory test report and review all available safety data for the patient; the 
outcome of the meeting may be to discontinue study drug, to conduct additional safety 
assessments, or to continue study drug without modification of the planned safety 
assessments.  
Another oligonucleotide investigational product has been associated with clinically significant 
AEs of thrombocytopenia and renal abnormalities as well as ISRs in human clinical studies 
(FDA 2015). Given IMO-8400 is also an oligonucleotide investigational product, platelet counts, 
anti-platelet antibodies, urine protein, and renal function will be regularly monitored and the 
following safety monitoring rules will apply: 
• If urinalysis results indicate urine protein is greater than + 2, or eGFR is below 50% of 
baseline, or platelet count is below 75,000/µL, study drug administration will be 
interrupted and a PSC consisting of the Investigator, Sponsor Medical Monitor, and CRO 
Medical Monitor will convene within 7 days of the abnormal laboratory report and 
review all available safety data for the patient. The outcome of the meeting may be to 
discontinue study drug, to conduct additional safety assessments, or to continue study 
drug without modification of the planned safety assessments. 
To further ensure the safety of study participants, study drug administration will be discontinued 
in any patient who experiences an serious adverse event (SAE) that is assessed by the 
Investigator as possibly related or probably related to study drug (see Section 8.3.5). 
In addition to the PSC, a Data Monitoring Committee (DMC) will review unblinded safety data 
as outlined in the DMC charter. The DMC may also increase or alter safety monitoring, or 
recommend other modifications to ensure patient safety. 
Because SC administration of IMO-8400 has been associated with potentially unblinding ISRs, 
the mCDASIv2, MMT8, and timed function tests (10MWR, TUG and 4 stair climb tests) will be 
performed by qualified and trained raters who will be blinded to treatment assignment and study 
drug injection sites and who will have no other role or responsibility in the study other than 
administering the efficacy assessments. Patients will also be asked to wear clothing that covers 
injection sites when attending site visits. 


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All patients will complete End-of-Treatment (EOT) assessments at Visit 26/Week 25; 
(7 days ± 2 from the last dose of study drug). For patients who discontinue study drug 
prematurely, an Early Termination (ET) Visit is required within 5 days of the notification of 
withdrawal; EOT and ET assessments are the same.  
If an extension study for this trial is initiated, with Investigator approval, patients who 
successfully complete this study may be eligible to continue receiving treatment with IMO-8400 
(or for patients randomized to placebo in this study, initiate treatment with IMO-8400). Signed 
informed consent for participation in any extension study will be obtained prior to assessments 
and prior to any extension study dosing at the EOT Visit 26/Week 25 (i.e., Visit 1/Week 1 of the 
extension study. All patients who discontinue study drug prematurely or decline participation in 
an extension study will undergo safety follow-up at the End-of-Study (EOS) Visit 27/Week 29, 
4 weeks after completing EOT/ET assessments. 
Study patients, Investigators, and other site personnel will remain blinded to treatment 
assignment until the last patient to complete the study has either completed their EOS 
assessments for Study 8400-211, and the database is locked, or has enrolled in an extension 
study if one is initiated. 
To protect patient safety and facilitate assessment of treatment effects, patients will be prohibited 
from receiving other investigational agents during the study. Moreover, pre-existing 
immunomodulatory regimens should be kept stable throughout the study (see Section 9.2 for 
additional guidance).  
6.2.1 
Benefits and Risk Assessment 
Dermatomyositis is a rare, progressively debilitating, idiopathic inflammatory myopathy 
associated with significant morbidity and an increased risk of premature death. Unfortunately, 
many patients do not achieve full control of symptoms with prednisone and/or experience 
intolerable side effects, including infection, weight gain, mood/behavioral changes, osteoporosis, 
Cushing’s disease, and diabetes (Harris 2015). Glucocorticoids have also been associated with 
myopathy, which is a serious concern for patients with DM (Schakman 2009). While the initial 
cause of DM is not known, once inflammation is established, injured cells release nucleic acids, 
which in turn activate specific intracellular TLRs (TLRs 7, 8, and 9) expressed on the 
regenerating muscle cells, keratinocytes, and B-cells. Toll-like receptor activation in turn 
amplifies the inflammatory response, resulting in further damage to skin and muscle. Thus, 
blocking TLR activation represents a potential mechanism for interrupting the inflammatory 
cycle and offers a novel treatment approach for patients with DM. 
Toll-like receptors are a family of host sensors for “foreign” constituents (e.g., nucleic acids, 
lipopolysaccharides, peptidoglycans from viruses, bacteria, fungi) that “sound the alarm” and 
activate host immune defenses. The natural ligands for TLRs 7 and 8 are single-stranded 
ribonucleic acid from viruses, and for TLR9, unmethylated cytosine-guanine dinucleotide motifs, 
which are characteristic of bacterial DNA. Binding of the nucleic acid ligands to the cognate 
TLR results in intracellular signaling, generation of nuclear factor kappa-light-chain-enhancer of 
activated B-cells (NF-κB), and production of pro-inflammatory (T helper 1) chemokines and 
cytokines, including IFN-α, TNF-α, and IL-12. Toll-like receptors 7, 8, and 9 are located in the 
endosome whereas, most other TLRs are located on the host cell surface. In man, the endosomal 
TLRs are expressed primarily on dendritic cells and B-cells. 


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IMO-8400 is a selective antagonist of the endosomal TLRs 7, 8, and 9. The pharmacology of 
IMO-8400 has been examined using in vitro assays of mouse, monkey, and human cells; in vivo 
studies in healthy mice and monkeys; murine models of autoimmune disease; and in studies 
using human B-cell lymphoma lines both in vitro and in murine xenograft models. These studies 
demonstrate that IMO-8400 specifically inhibits the activity of TLRs 7, 8, and 9 agonists, and 
directly support the hypothesis that this effect has therapeutic potential in multiple autoimmune 
diseases and in B-cell malignancies characterized by the myeloid differentiation primary 
response gene 88 L265P oncogenic mutation.  
The only secondary pharmacologic effect of IMO-8400 identified was activation of the 
complement pathway in non-human primates. Activation of the alternative complement pathway 
in non-human primates is a well-described effect of phosphorothioate oligonucleotides. This 
process has been related to the polyanionic nature of this class of agents and is independent of 
the intended pharmacological mechanism of action. IMO-8400 and other phosphorothioate 
oligonucleotides also activate the classical complement pathway in long-term toxicity studies in 
monkeys (39 weeks), which has been correlated with adverse treatment-related histological 
changes in this species. As of 01 February 2016, complement activation has not been seen in the 
42 patients treated to date. 
IMO-8400 is being developed as an immune modulator for the potential treatment of DM and 
other disorders. It offers multiple potential advantages:   
• A novel target and mechanism of action 
• Broader activity than currently available agents such as monoclonal antibodies to IFN-α 
or TNF-α, which block only 1 of the multiple cytokines induced by TLR activation 
(Celhar 2012, Means 2005) 
• Greater specificity than such agents — the induction of those cytokines as critical host 
defenses is blocked only when the response is induced through TLRs 7, 8, or 9 
• Could serve as an alternative or dose-sparing adjunct to currently available therapies 
Overall, the adverse observations in nonclinical toxicity studies with IMO-8400 have been 
reported with other oligonucleotides. Adverse pathological findings of myocardial 
degeneration/necrosis, glomerulonephritis, and/or hepatocellular necrosis that were noted in 
non-human primates are thought to be the result of treatment-related vascular inflammation that 
was preceded by IMO-8400 treatment effects on serum complement (most notably C4) and acute 
phase response markers (most notably globulin and C-reactive protein) in affected animals. Such 
observations are reported in chronic toxicity studies in monkeys with other phosphorothioate 
oligonucleotides and have not been observed in humans or other species. 
Frequent monitoring of serum complement (C3, C4, and CH50) and albumin:globulin ratio is 
included in clinical trials with IMO-8400 in order to determine the relevance of these findings to 
humans. Appropriate safety parameters are included in the PIONEER (8400-211) protocol (see 
Section 8.3.2). IMO-8400 was not mutagenic, clastogenic, or genotoxic in standard genotoxicity 
models.  


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Clinical studies of IMO-8400 have been completed in healthy subjects and patients with 
moderate to severe plaque psoriasis, and are currently ongoing in patients with Waldenström’s 
macroglobulinemia (WM) and in patients with diffuse large B-cell lymphoma (DLBCL).  
As of 22 November 2016, 104 subjects/patients have been exposed to IMO-8400, including 
30 healthy subjects, 35 patients with psoriasis, 2 patients with DM, 31 patients with WM, and 
6 patients with DLBCL. Subjects/patients have been exposed to doses ranging from 
0.075 mg/kg/week to 2.4 mg/kg/week with a maximum duration of exposure of 91 weeks.  
Data analyses in patients with psoriasis and WM have demonstrated clinical activity but no 
statistically significant treatment differences have been demonstrated. While statistical 
significance has not been demonstrated, these data do support the hypothesis that there is 
therapeutic potential for IMO-8400 where TLRs are implicated in the pathogenesis of the 
disease. 
The safety profile in the 86 subjects exposed to repeat dosing of IMO-8400 at any dosage 
indicates that IMO-8400 has been generally well tolerated. There have been no treatment-related 
deaths and 3 drug-related SAEs were reported, which were a probable flare of pre-existing 
arthritis, arthralgia, and sepsis in Study 8400-401. Four subjects have discontinued treatment 
with IMO-8400 due to the following treatment-related AEs: chills, arthralgia, arthritis, and rash 
maculo-papular. There have been no other discontinuations due to drug-related 
treatment-emergent AEs. The most common adverse reactions seen with IMO-8400 include:  
• Injection site reactions (e.g., erythema, induration, pruritus, tenderness, and pain). No 
blistering, ulceration, or necrosis have been observed.  
• Non-specific, low grade symptoms (e.g., fever, chills, myalgias, headache, diarrhea, 
fatigue, and nausea). These typically had an onset approximately 8 hours post-injection 
and generally resolved in 1 to 2 days.  
These events have been reported in most patients and are typically mild to moderate in intensity. 
The systemic symptoms have been readily managed with non-steroidal anti-inflammatory drugs. 
The ISRs have not required specific treatment; some subjects have reported benefit from ice 
packs.  
No clinically relevant changes in laboratory values, vital signs, or ECGs have been noted in the 
completed studies, and based upon review of data from ongoing studies, no irreversible or 
unmanageable toxicities have been seen.  
In summary, IMO-8400 has demonstrated biological and clinical activity supporting proof of 
mechanism and the adverse observations in nonclinical toxicity studies with IMO-8400 have 
been reported with other oligonucleotides. Safety parameters associated with toxicities identified 
in the nonclinical program can and will be monitored in the clinic. Further, IMO-8400 has been 
well tolerated to date with identified adverse reactions being reversible and manageable.  
In summary, when the totality of the data are taken into account, the risk-benefit profile is 
acceptable. Refer to the IB for further information about IMO-8400. 


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Patient Study Participation and Study Completion  
6.3.1 
Patient Participation 
The length of a patient’s participation will be from the time the informed consent form (ICF) is 
signed until their last visit is complete and will be approximately 32 weeks, including screening 
up to 28 days prior to treatment, 24 weeks of study drug, an EOT Visit at 7 days ± 2 days after 
the last dose of study drug, and an EOS Visit for safety follow-up 4 weeks after the EOT Visit. 
Regardless of whether they have completed study treatment, a patient will be considered to have 
completed the study when they have either: 
• Completed their EOT assessments at Visit 26 (Week 25) and enrolled in an extension 
study (if initiated) 
• Completed EOT and EOS assessments at Visits 26 and 27 (Week 29), respectively 
6.3.2 
Premature Patient Discontinuation or Treatment Discontinuation 
Patients are free to withdraw consent and/or discontinue participation in the study at any time, 
without prejudice to further medical care. Patients can also be withdrawn for the reasons 
specified in Section 11.5. Patients withdrawn from the study complete the EOT/ET 
Visit 26/Week 25 assessments (Section 10.1.4) and the EOS Visit 27/Week 29 assessments 
(Section 10.1.5) 4 weeks later.  
6.3.3 
Overall Study Completion 
The study will be considered to be complete when the last patient has completed their EOT 
Visit 26/Week 25 assessments and has either enrolled in the extension study (if initiated) or has 
completed the EOS Visit 27/Week 29) assessments, whichever is last. 
 
 


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7 
PATIENT POPULATION AND SELECTION 
The eligibility criteria are designed to include only those patients with an established diagnosis 
of DM and documented skin involvement who are able to safely participate in all study 
procedures. Patients who do not qualify for enrollment at the actual Screening Visit based on 
these criteria may be further assessed for eligibility at any time during the Screening Period 
(within 28 days prior to Week 1, Day 1). Under some circumstances, patients who fail to meet 
eligibility criteria during the Screening period may be rescreened for study entry following 
discussion with the CRO Medical Monitor. 
 
Inclusion Criteria 
A patient who meets all of the following criteria will be eligible for this study. 
1. Has signed the current, approved ICF. 
2. Is 18 to 75 years of age (inclusive) at the time of consent. 
3. Has definite or probable DM based on the criteria of Bohan and Peter (Appendix 3; 
1975a, 1975b) OR those patients who have all other definite or probable Bohan and Peter 
criteria but do not have heliotrope rash and Gottron’s signs/papules may still be included 
if they have one or more of the following: 
a) DM autoantibody (anti-Mi-2, anti-MDA5, anti-TIF1-gamma, anti-NXP-2, anti-Jo-1, 
anti-PL-12, anti-PL-7, anti-EJ, anti-KS, anti-OJ); at least 1 autoantibody must be 
present and documented in the patient’s medical record 
b) A classic DM associated skin change including at least one of the following: malar 
rash without sparing nasolabial folds, Shawl sign, V neck rash, periungal erythema, or 
mechanic’s hands; documented in the patient’s medical record 
4. Has a CDASIv2-Activity score ≥15 at Visit 2 (Baseline). 
5. Patients with muscle weakness are eligible; however, having muscle weakness is not 
mandatory. These patients have documented assessment of active muscle involvement as 
indicated by clinical evidence of symmetrical proximal muscle weakness involving 
limb-girdle and/or anterior neck flexors within 16 weeks prior to Baseline and one or 
more of the following: 
a) Elevation of serum CK or serum ALD levels >1.5 times the upper limit of normal 
(ULN) during Screening or >1.5 times increase compared to a documented within 
normal limits (WNL) level obtained prior to disease onset or while in prior remission 
b) Electromyography (EMG) demonstrating one or more of the following within 
16 weeks prior to Baseline: 
i. 
Fibrillation potentials (increased insertional irritability and spontaneous 
activity) 


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ii. 
Positive sharp waves and complex repetitive discharges 
iii. 
Short duration, small amplitude motor unit action potentials 
c) Muscle biopsy demonstrating one or more of the following within 16 weeks prior to 
Baseline: 
i. 
Perimysial and/or perivascular infiltration of mononuclear cells 
ii. 
Perifascicular atrophy 
iii. 
Note: Patients with a muscle biopsy demonstrating rimmed vacuoles or other 
histologic findings of Inclusion Body Myositis (IBM) are excluded 
d) Magnetic resonance imaging (MRI) demonstrating evidence of disease activity and 
inflammation on the short τ inversion recovery (STIR) image within 16 weeks prior 
to Baseline. 
6. If on permitted concomitant medications at Screening, the therapy regimen can include 
one or more of the following: 
a) Stable dose of prednisone (or other oral equivalent) ≤20 mg/day (or ≤140 mg/week) 
for ≥4 weeks 
b) Stable regimen that does not exceed the approved dosages for ≥12 weeks of no more 
than 1 of the following non-steroidal immunomodulatory medication(s): IVIG, 
mycophenolate mofetil, cyclophosphamide, cyclosporine, leflunomide, tacrolimus, 
methotrexate, azathioprine (see Table 4) 
c) Stable regimen of topical treatments for scalp involvement for ≥3 weeks 
7. Study participants must have a diagnostic evaluation for cancer if the diagnosis of DM 
was within 2 years of the Screening Visit. The evaluation should include either: 
a) All age- and gender-appropriate screening tests and computed tomography (CT) of 
the chest, abdomen, and pelvis; OR 
b) Positron emission tomography and computed tomography (PET/CT) of the chest, 
abdomen, and pelvis. 
Note: If a diagnostic evaluation for cancer has not been performed within 2 years 
prior to the Screening Visit in patients for whom it is required, either a CT of the 
chest, abdomen, and pelvis should be performed, OR a PET/CT of the chest, 
abdomen, and pelvis if this is standard practice in the particular center. The diagnostic 
evaluation for cancer must be normal for a patient to meet this inclusion criterion. 
Note: See Appendix 1 and Appendix 2 for guidelines on age and gender-appropriate 
workup. 


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8. Study participants must have no evidence of active or latent TB after a diagnostic 
evaluation with a chest x-ray (CXR) OR chest CT and 1 of the following: a) a purified 
protein derivative (PPD) skin test, b) a QuantiFERON blood test, or c) T-SPOT.TB blood 
test. 
 
If the diagnostic evaluation has not been performed within 12 weeks of the Screening 
Visit, it may be performed during the Screening Period (performed per Center for Disease 
Control [CDC] guidelines [http://www.cdc.gov/tb/topic/testing/default.htm]). 
 
For the patient to be eligible, the result of the diagnostic evaluation should include a 
negative chest image and 1 of the following: a) a PPD skin test with ≤5-mm induration, 
b) a negative (not detected) QuantiFERON result, or c) a negative T-SPOT.TB blood test. 
If the QuantiFERON result is indeterminate, the test may be repeated once. If the repeat 
QuantiFERON test is indeterminate, then a PPD skin test may be used to confirm patient 
eligibility. The PPD skin test is not an acceptable method of TB testing in Sweden. 
9. Women of childbearing potential and men must agree to use effective contraceptive 
methods from Screening throughout the study and until at least 4 weeks after the last dose 
of study drug.  
Non-childbearing potential is defined as a female who meets either of the following 
criteria: a) postmenopausal state defined as no menses for 12 months without an 
alternative medical cause or b) documented hysterectomy, bilateral tubal ligation, or 
bilateral oophorectomy.  
Effective contraception methods that can achieve a failure rate of <1% per year when 
used consistently and correctly are considered highly effective birth control methods. 
Such methods are defined as 1 of the following: 
a) True abstinence, defined as refraining from heterosexual intercourse, when this is in 
line with the preferred and usual lifestyle of the subject. Periodic abstinence 
(e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of 
abstinence for the duration of a trial, and withdrawal are not acceptable methods of 
contraception. 
b) Vasectomized partner (if that vasectomized partner is the sole sexual partner of the 
woman of childbearing potential and has received medical assessment of the surgical 
success of the vasectomy) 
c) An intrauterine hormone-releasing system (IUS) 
d) Oral, intravaginal, or transdermal combined (estrogen and progesterone) implanted 
hormonal contraceptive  
e) NOTE: For patients in Sweden, low dose oral contraceptives are not permitted 
f) An intra-uterine device (IUD) 


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10. Agrees to use a broad-spectrum (UVA/UVB) sunscreen with an SPF ≥15 daily (or a 
water-resistant, broad spectrum sunscreen with an SPF ≥30 for extended outdoor 
activity), and agrees to not increase their normal sun exposure during the course of this 
study. 
11. Is willing and able to comply with this protocol. 
 
Exclusion Criteria 
A patient who meets any of the following criteria will be excluded from this study. 
1. Has ongoing severe dysphagia (e.g., requires a feeding tube) for the 3 months prior to 
screening 
2. Has known hypersensitivity to any oligodeoxynucleotide 
3. Has a history of drug abuse within one year of screening, or evidence of drug abuse by 
urine drug screening 
4. Has a history of alcohol abuse within one year of screening 
5. Is pregnant (or intend to become pregnant within 6 months of last dose of study 
medication) or nursing 
6. Has body weight >140 kg 
7. Has any one of the following hepatitis serologic test results: 
a) Positive hepatitis B surface antigen test (HBsAg), or 
b) Positive hepatitis B core antibody test (anti-HBc) AND negative hepatitis B surface 
antibody (anti-HBs), or 
c) Positive hepatitis C virus antibody test (anti-HCV) 
8. Has evidence of seropositive test in the patient’s medical records or is currently receiving 
treatment for human immunodeficiency virus (HIV)-1 or HIV-2  
9. Has screening safety laboratory test meeting any of the following criteria: 
a) Hemoglobin <10.5 g/dL 
b) White blood cell (WBC) count <3000/mm3 
c) Absolute neutrophil count (ANC) <1.5 x 109/L (1500/mm3) 
d) Platelet count <100,000/mm3 


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e) Serum creatinine >1.2 mg/dL in female patients and >1.5 mg/dL in male patients. 
Patients with serum creatinine values exceeding limits may be eligible for the study if 
their eGFR are >60 mL/min. 
f) Serum AST or serum ALT >5 x ULN (unless considered consistent with muscle 
origin and accompanied by gamma-glutamyl transferase [GGT] <1.5 x ULN) 
g) Total bilirubin >1.5 x ULN 
h) Prothrombin time (PT) >1.5 x ULN 
i) C3 or C4 <LLN 
j) A:G ratio <LLN 
k) Urinalysis with proteinuria >1+ 
10. Has a diagnosis of Juvenile DM, IBM, drug-induced toxic myopathy, metabolic 
myopathy, dystrophy, cancer-associated DM , or connective tissue disease-associated 
DM (e.g., overlap syndrome) 
11. Has received one or more of following prohibited treatments within the interval noted 
prior to Screening (Visit 1): 
a) Rituximab within 24 weeks (Note: patients who received rituximab are only eligible 
for inclusion if B-cell counts are confirmed to be within normal limits) 
b) Intravenous corticosteroids within 12 weeks  
c) Intravenous immunosuppressive drugs within 12 weeks  
d) Any other monoclonal antibody, biologic agent, or investigational agent within 
12 weeks or 5 half-lives (whichever is longer) 
e) Antimalarials (e.g., hydroxychloroquine) within 36 weeks 
f) Topical corticosteroids (excluding scalp) within 2 weeks 
12. Has evidence of or has required treatment for cancer (except for treated, non-invasive 
carcinoma of the skin or cured carcinoma-in-situ following discussion with Medical 
Monitor) within 5 years 
13. Has other chronic or active significant medical conditions within 6 months prior to 
Screening, including but not limited to: allogeneic organ transplant (e.g., solid organ, 
bone marrow, or stem cells); cardiac disease (e.g., unstable angina, myocardial infarction, 
ventricular arrhythmia); congestive heart failure; liver disease; neurological disease; 
hematological disease; kidney disease; uncontrolled seizure disorder; uncontrolled 


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pulmonary disease; uncontrolled gastrointestinal disease; uncontrolled endocrinological 
disease; uncontrolled psychiatric disease; or uncontrolled diabetes mellitus 
14. Has interstitial lung disease requiring the use of supplemental oxygen 
15. Has received or is expected to receive any live viral or bacterial vaccination within 
3 months prior to Screening 
16. Has received a Bacille Calmette-Guerin (BCG) vaccination within 12 months of 
Screening or is expected to receive it during the course of the study 
17. Has a history of or ongoing active, chronic, or recurrent infection (including bacterial, 
viral, parasitic, protozoal, and/or fungal/granulomatous infections [e.g., histoplasmosis, 
coccidioidomycosis, aspergillosis]) requiring treatment with systemic antibiotics 
antimicrobials, antivirals, antiparasitics, antiprotozoals, or antifungals within 12 weeks 
prior to Screening, or serious infection (including but not limited to pneumonia, sepsis, 
bone or joint infection) requiring hospitalization or treatment with IV antibiotics within 
12 weeks prior to Screening 
18. Has a history of opportunistic infection or non-tuberculosis mycobacterial infection 
within 9 months prior to Screening 
19. Has any other condition that would, in the opinion of the Investigator, potentially 
compromise the safety or compliance of the patient or preclude the patient’s successful 
completion of the study 
 
Patient Rescreening 
Patients who do not qualify for enrollment at the actual Screening Visit based on the 
Inclusion/Exclusion criteria may be further assessed for eligibility at any time during the 
Screening Period (within 28 days prior to Visit 2/Week 1, Day 1). Under some circumstances, 
patients who fail to meet eligibility criteria during the Screening period may be rescreened for 
study entry following discussion with the CRO’s Medical Monitor. 


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8 
STUDY DRUG ADMINISTRATION 
 
Treatments Administered 
All patients will receive the investigational study drug, IMO-8400, at the dose level (total weekly 
exposure) of 0.6 or 1.8 mg/kg, or placebo once a week for 24 weeks. Patients will be randomized 
to one of the following groups in a 1:1:1 ratio. 
• Once weekly SC injections of IMO-8400 at 0.6 mg/kg 
• Once weekly SC injections of IMO-8400 at 1.8 mg/kg 
• Once weekly SC injections of placebo (Sterile Saline for Injection, USP/EP) 
 
Investigational Product(s) 
IMO-8400 for Injection is supplied as sterile, lyophilized powder for reconstitution with Sterile 
Saline for Injection, USP/EP or Sterile Water for Injection USP/EP. Table 2 summarizes the 
physical and chemical properties of IMO-8400. 
Table 2. 
Physical and Chemical Properties of Active Ingredient (Drug Substance) 
Name 
IMO-8400  
Drug Class 
Oligonucleotide antagonist of TLRs 7, 8 and 9 
Molecular Formula C179H216N52Na17O101P17S17 (sodium salt) 
Molecular Weight 
6174 (sodium salt) 
Appearance 
Hygroscopic white to off-white amorphous solid obtained by lyophilization 
Solubility 
Freely soluble in aqueous media 
Melting Point 
Amorphous powder, decomposes on heating without a defined melting point 
Excipients 
Each vial contains nitrogen (National Formulary) 
 
8.2.1 
Packaging and Labeling 
The IMO-8400 drug product will be supplied as 25 mg/vial or 150 mg/vial lyophilized powder 
for reconstitution in a clear, round 5 mL glass vial with a rubber stopper and aluminum overseal. 
Each 5 mL glass vial contains IMO-8400 sodium salt equivalent to 25 or 150 mg/vial of free 
acid. All manufacturing, packaging, and labeling operations will be performed according to 
Good Manufacturing Practice (GMP) and Good Clinical Practice (GCP) guidelines, as well as 
local regulations.  
Sterile Water for Injection, USP/EP and/or Sterile Saline for Injection, USP/EP will be supplied 
by the study site. 


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8.2.2 
Storage 
The sealed vials of drug product (IMO-8400 for Injection) should be stored at 
2 °C to 8 °C (36 °F to 46 °F). See the Pharmacy Manual for further details on dose preparation 
and storage conditions prior to administration. 
8.2.3 
Preparation and Administration of the Product 
Vials of IMO-8400 will be reconstituted using Sterile Saline for Injection USP/EP, or Sterile 
Water for Injection USP/EP, as described in the Pharmacy Manual. The total volume of the 
patient’s dose will be based on their body weight at the most recent prior clinic study visit but 
may not exceed 1.4 mL (upper limit of patient weight is 140 kg). Dose preparation will be done 
by designated unblinded staff. Detailed dose-preparation instructions and flow sheets will be 
provided in the Pharmacy Manual. 
Each dose of IMO-8400 or placebo will be administered as a single SC injection. The injection 
sites should be selected based on the following:  
• Areas for injection are the 4 quadrants of the abdomen (upper and lower on the left 
and right). 
• Injection sites will be rotated.  
Blinded study personnel will administer all doses of study drug. Injections of study drug may be 
administered in 1 of 2 contexts: at the study site or outside of the clinic as described in 
Section 8.2.4. On study days when a physical examination is scheduled (see SOE in Section 3), it 
is expected that study drug will be administered at the study site.  
8.2.4 
Administration of the Product Outside the Clinic 
With the agreement of the patient and the Investigator, doses may be administered outside of the 
clinic (e.g., at the patient’s home or workplace) by a visiting nurse who has been trained in the 
protocol and approved by the Sponsor. In this event, the Sponsor or designee will arrange for a 
Central Pharmacy to prepare and dispense the patient’s study treatment. Requirements for 
preparation of doses intended for shipment to patient’s home will be detailed in the Pharmacy 
Manual. The study drug will be shipped by overnight courier in an appropriate insulated 
container that has been qualified to maintain the required storage condition (2 °C to 8 °C) with 
cooling packs. The used syringe and packaging materials will be disposed of or destroyed per 
policy of the Central Pharmacy. The visiting nurse will maintain appropriate source documents; 
the events will be entered into the electronic data capture (EDC) system and copies of the source 
documents provided to the site. The patient’s vital signs, AEs (including assessment for ISRs), 
and concomitant medications will also be recorded by the visiting nurse. 
8.2.5 
Instructions for Delays in Dosing 
As previously noted, doses must be administered once every 7 days ± 2 days, with at least 5 days 
between each dose administered. In the event of a missed dose, patients should resume once 
weekly injections.  


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Safety Monitoring and Drug Dose Interruption 
Subjects must be monitored closely for AEs, including SAEs, and laboratory abnormalities 
during the course of the study. Patients will be monitored for approximately 4 hours after the 
first dose at the Baseline Visit. 
Certain laboratory parameters have predefined monitoring and action procedures that must be 
followed (see Section 8.3.2, Table 3), and, as specified in Section 8.3.5, the occurrence of an 
SAE that is assessed by the Investigator as possibly or probably related to study drug will require 
discontinuation of study drug. For other AEs and for laboratory abnormalities not listed in 
Table 3, the Investigator should use his/her judgment in determining whether the event or 
abnormality is clinically significant, whether diagnostic evaluation is warranted, and whether 
potential interruption of study drug therapy is appropriate. 
8.3.1 
Laboratory Abnormalities and Adverse Events Requiring Evaluation and 
Potential Drug Interruption or Discontinuation 
While specific monitoring, diagnostic testing, and supportive care measures must be instituted 
based on the clinical judgment of the Investigator, Investigators are encouraged to contact the 
CRO Medical Monitor to obtain guidance and to ascertain whether similar events are being seen 
at other sites. 
The CRO Medical Monitor should be notified of any AE or laboratory abnormality (see 
Section 8.3.2) that leads to dose interruption and should be apprised of ancillary laboratory or 
other diagnostic findings and the evolving data from any work-up of the initial abnormality. The 
CRO Medical Monitor may suggest review of the case with expert consultants (either at the site 
or retained by Idera). 
8.3.2 
Laboratory Abnormalities Requiring Evaluation and Potential Drug 
Interruption or Discontinuation 
Based on the findings of the toxicology program with IMO-8400 serum levels of C3, C4, CH50, 
and A:G ratio will be regularly monitored during this study. These parameters are being 
monitored due to the results from a 39-week nonclinical toxicology study in cynomolgus 
monkeys showing that adverse effects were reliably preceded by changes in complement and 
markers of acute phase reactions. 
Another oligonucleotide investigational product has been associated with clinically significant 
AEs of thrombocytopenia and renal abnormalities as well as ISRs in human clinical studies 
(FDA 2015). Given IMO-8400 is also an oligonucleotide investigational product, platelet counts, 
anti-platelet antibodies, urine protein, and renal function will be regularly monitored. 
A PSC consisting of the Investigator, CRO Medical Monitor, and Idera Medical Monitor will be 
formed to monitor abnormal laboratory test values as defined in Table 3, with information on 
actions to be taken in the event that abnormalities are noted in specified laboratory parameters. 
If the PSC determines that it is in the patient’s best interest to discontinue study drug because of 
a safety laboratory abnormality (Table 3) or because of a follow-up investigation, this would 
constitute a “withdrawal due to an AE of interest”. For withdrawal due to abnormally low C3, C4 
or A:G ratio, the Investigator must provide a narrative describing the history and reason for 
withdrawal (see Section 11.1.1). 


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Table 3. 
Safety Monitoring Parameters and Actions  
Laboratory Values 
Action to be Taken 
Follow up Required (PSC Action) 
C3 OR C4 below LLN 
AND 
A:G ratio below LLN 
• 
Stop study drug immediately 
• 
Confirm C3, C4 and A:G ratio 
values 
• 
Then start early termination 
process 
C3 OR C4 below LLN 
OR 
A:G ratio below LLN 
• 
Continue study drug 
• 
Convene PSC within 7 days of 
abnormal laboratory test report 
• 
Confirm C3, C4 and A:G ratio 
values 
Missing values on  
C3 OR C4  
OR  
A:G ratio 
• 
Continue study drug, for 
1 additional week of dosing 
while missing value is being 
retrieved 
• 
If missing value is not retrieved 
within 2 weeks, the subsequent 
scheduled dose cannot be 
administered. For example: if there 
is a missing value from Visit 6, the 
Visit 7 dose can be given, but the 
Visit 8 dose must be held until 
safety laboratory testing is 
completed 
Urine protein above + 2 
• 
Interrupt study drug 
administration 
• 
Convene PSC within 7 days of 
abnormal laboratory test report 
• 
Review changes in serum 
creatinine and eGFR 
eGFRa below 50% of 
baseline 
• 
Interrupt study drug 
administration 
• 
Convene PSC within 7 days of 
abnormal laboratory test report 
• 
Review changes in serum 
creatinine and urine protein 
Platelet count below 
75,000/µL 
• 
Interrupt study drug 
administration 
• 
Convene PSC within 7 days of 
abnormal laboratory test report 
• 
Review additional hematology 
laboratory values 
A:G = albumin:globulin ratio; C = complement component; CRP = C-reactive protein; eGFR = estimated 
glomerular filtration rate; LLN = lower limit of normal; PSC = Patient Safety Committee 
a eGFR (mL/min/1.73 m2) = 175 x (Scr, std)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African Ethnicity) 
(FDA 2010) 
8.3.3 
Instructions for Resuming Study Drug Administration after an Interruption 
for Safety Concerns Due to General Laboratory Abnormalities or Adverse 
Events 
To decide about resuming study drug administration after a dose interruption for any clinically 
significant safety concern not related to the specified safety laboratories in Section 8.3.2, the 
Investigator, CRO Medical Monitor, and Idera Medical Monitor will together consider factors 
such as the type and severity of the AE or laboratory abnormality, the potential causal 


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relationship of study drug therapy, the patient’s status in terms of DM or other health conditions, 
and the ability to monitor for recurrence of the event. Instructions for resuming study drug 
administration after an interruption for safety concerns due to the safety laboratory abnormalities 
noted in Section 8.3.2 are provided below in Section 8.3.4. 
If study drug is re-initiated, it must be at the dose and at the same visit schedule to which the 
patient was randomized; no dose reductions are allowed. 
8.3.4 
Instructions for Resuming Study Drug Administration after an Interruption 
for Safety Concerns Due to Safety Laboratory Abnormalities  
After a dose interruption due to an abnormality in safety laboratories as specified in 
Section 8.3.2, the PSC will together consider factors such as the type and severity of the AE or 
laboratory abnormality, the potential causal relationship of study drug therapy, the subject’s 
status in terms of DM or other health conditions, and the ability to monitor for recurrence of the 
event. 
The PSC will use their best judgment in determining whether to restart study drug. If study drug 
is re-initiated it must be at the dose to which the patient was randomized; no dose reductions are 
allowed. 
If the PSC determines that it is in the patient’s best interest to discontinue study drug because of 
a safety laboratory abnormality (Table 3) or because of a follow-up investigation, this would 
constitute a “withdrawal due to an AE of interest.” For withdrawal due to abnormally low C3, C4 
or A:G ratio, the Investigator must provide a narrative describing the history and reason for 
withdrawal (see Section 11.1.1). 
8.3.5 
Serious Adverse Events Requiring Discontinuation of Study Drug 
To ensure the safety of study participants, study drug administration will be discontinued in any 
patient who experiences an SAE that is assessed by the Investigator as possibly related or 
probably related to study drug; the Investigator will assess if study drug administration will be 
discontinued in any patient who experiences an SAE that is assessed as not related to study drug. 
The procedures for discontinuation of study drug and necessary follow-up and documentation are 
summarized in Section 8.3.6 and Section 11.5; also refer to Section 11.4 for instructions for 
completing the follow-up SAE form.  
In addition, when a patient discontinues study drug secondary to the occurrence of a possibly 
related or probably related SAE, this is considered a “withdrawal due to an AE of interest”, and 
the Investigator must provide a narrative describing the history and reason for withdrawal (see 
Section 11.1.1). 
8.3.6 
Instructions for Discontinuation of Study Drug Administration for Safety 
Concerns 
See Section 11.5 for instructions upon a decision to permanently discontinue administration of 
study drug due to an AE, laboratory abnormality, or SAE. If permanent discontinuation of study 
drug is due to a reported SAE, a follow-up SAE report form should be completed (see 
Section 11.4). 


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Method of Assigning Patients to Treatment 
8.4.1 
Blinding and Randomization 
8.4.1.1 
Screening Procedures 
All patients who are screened (including screen failures) will be assigned a patient number by the 
Interactive voice/web-Response System (IXRS). The unique patient identification number will 
consist of 6 digits (xxx-xxx), the first segment of the number represents the study site and the 
second segment of the number represents the patient at that study site. Any patient identification 
number that is assigned will not be reused even if the patient is not randomized. 
8.4.1.2 
Randomization 
Randomization will take place using IXRS. Patients will be randomized after the Investigator has 
verified that they are eligible per criteria in Section 7. Patients will be randomized to receive 
either IMO-8400 at a dose of 0.6 or 1.8 mg/kg/week or placebo once a week for 24 weeks. 
Randomization will be performed centrally in a 1:1:1 ratio and will be stratified by baseline 
CDASIv2-Activity score (15 to 20 vs ≥21). A permuted block randomization schedule will be 
employed. Blocks will be pre-allocated to the two CDASIv2-Activity strata (15 to 20 vs. ≥21) to 
achieve a balanced distribution of treatment assignments within those groups. 
8.4.1.3 
Blinding 
Every attempt should be made to preserve the integrity of study drug blinding. Except for cases 
of emergency unblinding as described in Section 8.4.2, the randomization code will remain 
unbroken for patients, parents/caregivers, and study personnel until the database has been locked. 
Because SC administration of IMO-8400 has been associated with potentially unblinding ISRs, 
the mCDASIv2, MMT8, and timed function tests (10MWR, TUG, and 4 stair climb tests) will be 
performed by qualified and trained raters who will be blinded to treatment assignment and study 
drug injection sites and who will have no other role or responsibility in the study other than 
administration of these efficacy assessments. In addition, patients will be asked to wear clothing 
that covers all injection sites whenever they visit the study site.  
8.4.2 
Emergency Unblinding 
In the event of a medical emergency, laboratory abnormalities or SAE requiring cessation of 
treatment, unblinding is not required to provide effective medical intervention and support. 
In the exceptional circumstance that knowledge of the study drug assignment appears essential 
for providing appropriate medical management and in cases where an immediate need for 
unblinding exists for reasons of patient safety, the Investigator can unblind the patient’s data at 
his/her discretion. When possible, the Investigator should consult the CRO Medical Monitor 
prior to unblinding to discuss the rationale for breaking the blind and the adverse consequences 
of the unblinding for the patient’s continued participation in the study. The treatment assignment 
for that patient will be provided to the Investigator via the IXRS as described in the Study 
Reference Manual (SRM). No randomization lists or other unblinding information will be 
provided to the site. 


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After breaking the blind, the site staff should record details regarding the reasons for breaking 
the blind and any AEs leading to the breaking of the blind in the source documents and the 
appropriate electronic case report form (eCRF). 
 
Treatment Compliance 
Treatment compliance will be assessed via compliance with scheduled weekly injections and 
documented on appropriate pages of the eCRF. 
 
 


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9 
PRIOR AND CONCOMITANT MEDICATIONS 
Investigators may prescribe concomitant medications or treatments deemed necessary to provide 
adequate supportive care. Information regarding any prior and concomitant medications will be 
collected and documented in the eCRF and in the source documents by the clinic staff as 
described in the explanation of study procedures. 
 
Permitted Concomitant Medications 
The following therapies are permitted for use during the 24 weeks of study drug treatment as 
detailed in Table 4: 
• Corticosteroids  
• Non-steroidal immunomodulatory medications - no more than 1 of the following: 
IVIG, mycophenolate mofetil, cyclophosphamide, cyclosporine, leflunomide, 
tacrolimus, methotrexate, azathioprine 
• Topical corticosteroids for use on the scalp only 
Any other treatments (including prescription drugs, non-prescription drugs, and herbal 
remedies), except those listed in the prohibited concomitant medications section (Section 9.3) 
should be taken as prescribed, per Investigator judgment. 
 
Stabilization and Washout Period for Permitted Concomitant Medications  
For patients who are on corticosteroids or non-steroidal immunomodulatory medications, a stable 
regimen should be established as described in Table 4 prior to Screening and maintained during 
the 24 weeks of study drug treatment. Adjustments in dosage for increases in body weight are 
permitted but are not mandatory.  


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Table 4. 
Stable Regimens of Permitted Concomitant Medications 
Category 
Medication 
Dose 
Duration of Stable 
Regimen Prior to 
Screening 
Corticosteroids 
Oral prednisone or 
equivalent 
≤20 mg per day (or 
≤140 mg/week) 
≥4 weeks 
Corticosteroids 
Topical for scalp only 
Limit to 2 
applications per day 
≥3 weeks 
Non-steroidal 
immunomodulatory 
(limited to one) 
Intravenous 
immunoglobulin 
2 g/kg per month 
≥12 weeks 
Oral mycophenolate 
mofetil  
3 g per day 
≥12 weeks 
Oral cyclophosphamide  
5 mg/kg per day 
≥12 weeks 
Oral cyclosporine 
3 mg/kg per day 
≥12 weeks 
Oral leflunomide 
20 mg per day 
≥12 weeks 
Oral tacrolimus 
4 mg per day 
≥12 weeks 
Oral or intramuscular 
methotrexate 
25 mg per week 
≥12 weeks 
Oral azathioprine  
3 mg/kg per day 
≥12 weeks 
Interventions or potential dosage adjustments may be considered if a patient experiences a 
concerning AE related to the medications in Table 4. 
Upward adjustments in dose for reasons other than for change in body weight, or downward 
adjustments to prevent toxicities should be discussed with the CRO Medical Monitor. Patients 
who require interruption, dose modification, or re-initiation of the therapies in Table 4 may 
remain on blinded study drug therapy. 
If a patient had been on more than one non-steroidal immunomodulatory medication, they must 
have stopped administration of the additional non-steroidal immunomodulatory medications for 
at least the washout periods listed in Table 5. Start and stop dates and dose/regimen for washout 
of these medications prior to Screening must be recorded on source documentation and eCRF. 


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Table 5. 
Washout Period for Prohibited Concomitant Medications 
Prohibited Medication 
Washout Period Prior to Screeninga 
Methotrexate 
At least 4 weeks 
Leflunomide, cyclophosphamide, intravenous 
immunoglobulin 
At least 12 weeks 
Any other non-steroidal immunosuppressive 
agent including azathioprine, cyclosporine, 
mycophenolate mofetil, tacrolimus,  
At least 8 weeks 
a Medications are prohibited for at least the specified washout period immediately prior to screening  
 
 
Prohibited Concomitant Medications 
The use of the following concomitant medications is prohibited during the 24 weeks of study 
drug treatment due to the possibility that they might confound interpretation of study results. 
• Rituximab  
• Intravenous corticosteroids 
• Intravenous immunosuppressive drugs 
• Any other monoclonal antibody, biologic agent, or investigational agent  
• Antimalarial agent(s) 
• Topical corticosteroids (excluding scalp)  
• Live viral or bacterial (including BCG) vaccination during the course of the study or 
within 3 months after the last dose of study medication 
9.3.1 
Washout Period for Prohibited Medications 
Medications listed in Table 6 are prohibited within the indicated washout period immediately 
prior to Screening. Start and stop dates and dose/regimen for use of prohibited medications 
during the year prior to Screening (Visit 1) must be recorded on source documentation and 
eCRF. 


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Table 6. 
Washout Period for Prohibited Concomitant Medications 
Prohibited Medication 
Washout Period Prior to Screeninga 
Rituximab  
At least 24 weeks 
AND 
B-cell counts (local testing) that are 
confirmed to be within normal limits 
Intravenous corticosteroids 
At least 12 weeks 
Intravenous immunosuppressives 
At least 12 weeks 
Any other monoclonal antibody, biologic 
agent, or investigational agent  
At least 12 weeks or 5 half-lives 
(whichever is longer) 
Antimalarial agent(s) 
At least 36 weeks 
Topical corticosteroids (excluding scalp)  
At least 2 weeks 
a Medications are prohibited for at least the specified washout period immediately prior to screening  
 


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10 
EXPLANATION OF STUDY PROCEDURES 
 
Pretreatment, Treatment and Follow-up Periods 
No study-related procedures should be performed prior to the signature of the informed consent 
document(s). After a patient has completed the necessary screening assessments and has been 
confirmed to be eligible by the Investigator, the Baseline Visit (Visit 2/Week 1, Day 1) for the 
patient can be scheduled. 
10.1.1 
Screening Visit (Visit 1) and Screening Period 
Once written informed consent is obtained, patients will be screened for eligibility for entry into 
the study based on the inclusion and exclusion criteria detailed in Section 7. Screening includes, 
as indicated in the SOE in Section 3, a full medical/surgical history, including information 
relating to any prior or existing medical conditions/surgical procedures that may be relevant to 
the patient’s experience in the study. Demographic data and DM-specific medical history 
information will also be recorded. Patients will also undergo a full physical examination, vital 
signs and a 12-lead ECG tracing will be obtained, and height and body weight will be measured. 
In addition, the full CDASIv2 will be performed and skin photographs will be taken. Blood and 
urine will be collected for standard safety laboratory assessments as well as pregnancy testing, 
hepatitis B and C screening, and other safety laboratory assessments (Section 8.3.2). 
As part of the patient’s medical history, documented evidence of cancer and TB screening are 
required. Study participants must have a diagnostic evaluation for cancer if the diagnosis of DM 
was within 2 years prior to the Screening Visit. The evaluation should include all age- and 
gender-appropriate screening tests and either a CT of the chest, abdomen, and pelvis OR, 
alternatively, a PET/CT of the chest, abdomen, and pelvis if this is standard practice in the 
particular center. If a diagnostic evaluation for cancer has not been performed in patients for 
whom it is required, a PET/CT (chest, abdomen, and pelvis) should be performed during the 
Screening Period. The diagnostic evaluation for cancer must be normal for a patient to meet this 
inclusion criterion. Study participants also must have no evidence of active or latent TB after a 
diagnostic evaluation with a CXR OR chest CT and 1 of the following: a) a PPD skin test, b) a 
QuantiFERON blood test, or c) T-SPOT.TB blood test. If the diagnostic TB evaluation has not 
been performed within 12 weeks prior to the Screening Visit, it may be performed during the 
Screening Period. For the patient to be eligible, the results of the diagnostic TB evaluation 
should include a negative chest image and 1 of the following: a) a PPD skin test with ≤5-mm 
induration, b) a negative (not detected) QuantiFERON result, or c) a negative T-SPOT.TB test. If 
the QuantiFERON result is indeterminate, the test may be repeated once. If the repeat 
QuantiFERON test is indeterminate, then a PPD skin test may be used to confirm patient 
eligibility. The PPD skin test is not an acceptable method of TB testing in Sweden. 
Once a patient has met all eligibility criteria the site representative should access the IXRS 
system and supply the necessary information to obtain a patient treatment assignment (see 
Section 8.4) in anticipation of administration of the first dose of study drug at the Baseline 
Visit 2/Week 1, Day 1. 


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10.1.2 
Baseline Visit (Visit 2, Day 1) 
Before initiating treatment, each study participant will report to the clinic to complete study 
related procedures as outlined in the SOE in Section 3. Study drug will not be administered until 
all baseline assessments have been completed and collection of the pre-dose sample for 
determination of IMO-8400 plasma concentrations and baseline laboratory samples have been 
obtained. Baseline assessments include physical examination, vital signs, the full CDASIv2, 
IMACS CSMs, SF-36, Timed Function Tests, 5-D Itch Scale, 12-lead ECG, and skin biopsy. In 
addition, skin photographs will be taken. Subsequently the patient will receive the first dose of 
study drug, and the patient will have a 2-hour post-dose blood sample for determination of 
IMO-8400 plasma concentration. The patient will remain at the clinic until released by the 
Investigator approximately 4 hours after the first dose administration.  
10.1.3 
Treatment Period (Visit 2/Week 1 through Visit 25/Week 24) 
The Baseline Visit 2/Week 1 is also Day 1 of the Treatment Period; patients will receive the first 
dose of study drug that day as described in Section 10.1.2. During the treatment period, each 
patient will return to the clinical research facility for Visit 6/Week 5, Visit 10/Week 9, 
Visit 14/Week 13, Visit 18/Week 17, and Visit 22/Week 21. During these visits patients will 
complete the assessments indicated in the SOE in Section 3. All scheduled assessments should 
be performed prior to dosing, unless otherwise specified. All CDASI assessments performed 
after the first dose of study drug will be done using the mCDASIv2. 
With the agreement of the patient and the Investigator, doses during weeks not requiring clinic 
visits may be administered outside of the clinic (e.g., at the patient’s home or workplace) by a 
visiting nurse who has been trained in the protocol and approved by Idera (Section 8.2.4). The 
patient’s vital signs, AEs (including assessment for ISRs), and concomitant medications will be 
recorded by the visiting nurse during administration of study drug.  
On dosing days, the planned injection site will be assessed for the presence of any ISRs to 
confirm the injection site is appropriate for use. All visits during the treatment period of the 
study have a visit window of ± 2 days. There must be at least 5 days between doses. 
10.1.4 
End-of-Treatment Visit (Visit 26) and Early Termination Visit  
The patient will return to the clinical research facility at Week 25 ± 2 days (Visit 26) for the 
EOT Visit. If the patient discontinues prematurely (i.e., before Week 25) the procedures that 
would normally be performed at the Week 25 EOT Visit should be performed as an ET Visit 
before the patient leaves the study. Any patient who withdraws or is withdrawn from the study 
prematurely will be asked to complete the ET assessments (which are the same as the EOT 
Visit 26 assessments) within 5 days of the notification of withdrawal; these patients will also be 
asked to complete the EOS assessments (Visit 27/Week 29) 4 weeks (± 4 days) after completing 
the ET assessments. 
It is intended that with Investigator approval, patients who successfully complete the EOT 
(Visit 26/Week 25 assessments may initiate receiving open-label IMO-8400 treatment upon 
signature of the informed consent document(s) if a separate open-label extension study is 
initiated. Signed informed consent for participation in any extension study must be obtained 
prior to assessments and extension study dosing at Visit 26/Week 25. Patients who do not enroll 


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in an extension study, including patients who withdraw from this study prematurely, will 
complete safety follow-up assessments at the EOS Visit (Visit 27/Week 29), 4 weeks (± 4 days) 
after completing EOT assessments. 
10.1.5 
End-of-Study Visit (Visit 27/Week 29) 
All patients who discontinue study drug prematurely or decline participation in an open-label 
IMO-8400 extension study must return for an EOS Visit at the investigational site 4 weeks 
(± 4 days) after the last dose of study drug for final study-related evaluations.  
10.1.6 
Unscheduled Visits 
Unscheduled visits and assessments may be conducted at Investigator discretion in response to 
new clinical observations or as follow-up to AEs. 
 
Description of Assessments 
The following sections describe the assessments that are necessary during the study. Rational for 
the appropriateness of selected assessments are provided in Section 17. 
10.2.1 
Informed Consent 
The Investigator must inform each prospective patient of the nature of the study, explain the 
potential risks, and obtain written informed consent from the patient prior to performing any 
study-related screening procedures.  
10.2.2 
Inclusion/Exclusion Criteria 
All patients must meet all of the inclusion criteria specified in Section 7.1 and none of the 
exclusion criteria specified in Section 7.2 to be enrolled in this study. As noted in Section 7.3, 
under some circumstances, patients who fail to meet eligibility criteria during the Screening 
Period may be rescreened for study entry following discussion with the CRO’s Medical Monitor. 
10.2.3 
Demographic Information and Medical History 
Basic demographic information (e.g., date of birth, age, sex, race) will be collected and a detailed 
medical history, including review of past and ongoing medications and therapies, history of 
alcohol use, and smoking history will be obtained at the Screening Visit as specified in the SOE 
in Section 3. 
The Investigator should review the study candidate’s medical history, including details relating 
to DM and any other medical conditions. As part of the patient’s medical history, documented 
evidence of cancer and TB screening are required. Information regarding current medications 
must be captured on the eCRF. Details regarding any medication received within 3 months prior 
to screening will be collected on the eCRF. Information on permitted and prohibited 
medications, doses, and regimens are provided in Section 9. 
10.2.4 
Physical Examination Including Weight and Height 
Physical examinations will be conducted at the time points specified in the SOE provided in 
Section 3. Physical examinations will be performed by the Investigator, an MD Sub-Investigator, 
a Nurse Practitioner, or a Physician’s assistant (if licensed in the state to perform physical 


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examinations); if possible, the same person should perform all examinations for a given patient. 
Physical examinations will include examination of general appearance, head, eyes, ears, nose, 
and throat (HEENT), heart, lungs, chest, abdomen, skin, lymph nodes, musculoskeletal, and 
neurological systems.  
Height is measured in centimeters, without shoes, at the Screening Visit only. Weight should be 
recorded in kg and will be measured during all physical examinations. 
10.2.5 
Skin Photography 
Photography of the areas of the skin assessed in the CDASIv2 will be taken at Screening 
(Visit 1), Baseline (Visit 2/Week 1, prior to initiation of study drug treatment), and at the 
EOT/ET Visit 26/Week 25 as described in the SRM. Permission to perform photography will be 
requested in the informed consent document(s). Subjects who refuse being photographed may 
still participate in the study.  
The SRM and additional documents will provide instructions on skin photography procedures. 
10.2.6 
Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) 
The full CDASI version 2 (CDASIv2) assessment will be performed at the Screening and 
Baseline Visits. Subsequent CDASI assessments will be performed using the mCDASIv2, which 
eliminates the abdominal skin assessments post-injection. The mCDASIv2 will be performed by 
trained raters blinded to treatment assignment at the time points specified in the SOE in 
Section 3. To further decrease the risk of unblinding, patients will be provided with an 
abdominal covering to mask injection sites when the mCDASIv2 is performed  
The CDASIv2 is a clinician administered, one-page instrument designed to evaluate the 
cutaneous manifestations of DM (see Appendix 4). Developed by leading academic 
dermatologists and rheumatologists with an expertise in DM, it takes approximately 5 minutes to 
complete and its validity and reliability have been demonstrated in multiple studies of DM 
patients (Klein 2008, Yassaee 2010, Goreshi 2012). 
The CDASI includes separate measurements for disease activity and damage and yields a Total 
Score that captures overall disease state, an Activity Score that reflects the current inflammatory 
state of disease, and a Damage Score. Decreases in CDASI scores are indicative of improvement. 
10.2.7 
Skin Biopsy  
Skin biopsies will be performed at the Baseline Visit 2/Week 1, Day 1, and at the EOT 
Visit 26/Week 25. Two 4 mm punch biopsies will be taken side by side on the upper back or 
upper arm of patients (whichever the Investigator feels has the most active skin disease at 
baseline) at baseline and in an adjacent area at the EOT biopsy. Sites where the baseline biopsy 
samples were taken should be photographed PRIOR to the baseline biopsy (no photographs will 
be taken after the biopsy) to document the disease activity and to guide the EOT biopsy site. 
Biopsies can be performed with or without local anesthesia, as considered appropriate for a 
specific patient or study site. The skin samples should be prepared for analyses as per the 
procedures described in the Laboratory Manual. The skin biopsy is not required for a premature 
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10.2.8 
International Myositis Assessment Clinical Study (IMACS) Core Set 
Measures 
The IMACS Group, which includes more than 100 adult and pediatric rheumatologists, 
neurologists, dermatologists, rehabilitation medicine physicians, statisticians, nurses, and others 
with expertise in myositis, was founded in 2000 to facilitate clinical research for the idiopathic 
inflammatory myopathies including DM. The IMACS Group has identified a core set of outcome 
measures (the CSMs) to comprehensively describe myositis disease activity in juveniles and 
adults. The IMACS Group has also identified preliminary DOIs in disease activity (Rider 2004), 
which reflect clinically meaningful change in each of the CSMs. The subset of the CSMs 
identified by IMACS that will be used in this study are briefly described in Sections 10.2.8.1 and 
Section 10.2.8.2. 
10.2.8.1 
Manual Muscle Testing (MMT8) 
Manual muscle testing will be performed by trained raters blinded to treatment assignment and 
who will have no other role or responsibility beyond administering efficacy assessments in the 
study at the time points specified in the SOE in Section 3. 
Manual muscle testing assesses the function and strength of individual muscles and muscle 
groups based on the effective performance of a movement against gravity or manual resistance. 
A particular muscle or muscle group is first isolated, then an external force is applied and the 
patient’s ability to complete the movement is graded by a trained therapist or clinician. This 
study will use an abbreviated MMT, the MMT8 (see Appendix 5), which was developed and 
validated by IMACS (Rider 2010). In the MMT8, 8 proximal, distal, and axial muscles including 
the deltoid, biceps, wrist extensors, quadriceps, ankle dorsiflexors, neck flexors, gluteus 
maximus, and gluteus medius, are evaluated unilaterally. Of note, the 8 muscle groups selected 
by expert consensus for inclusion in the MMT8 include 4 of the 5 weakest muscles in patients 
with idiopathic inflammatory myopathies (i.e., the neck flexor, deltoid, gluteus maximus, and 
gluteus medius) (Harris-Love 2009). 
10.2.8.2 
Muscle Enzymes 
The activity of serum enzymes derived from muscle in myositis patients has long been used as an 
indicator of myositis disease activity in clinical practice. Collection of blood samples for testing 
of muscle enzyme levels including CK, ALD, LDH, ALT and AST will be performed at the time 
points specified in the SOE in Section 3 (see Appendix 6). 
10.2.9 
Short Form-36 Health Survey 
The SF-36 will be completed by the patient at the time points specified in the SOE in Section 3. 
The SF-36 is an extensively validated and widely used measure of quality of life that assesses 
patients’ perceptions of health status and its impact on their lives (Ware 1992). It consists of 
36 items organized into 8 scales (physical functioning, social functioning, role limitations 
physical, bodily pain, general medical health, mental health, role limitations emotional, and 
vitality). Two summary measures of physical and mental health, the Physical Component 
Summary and Mental Component Summary, respectively, are derived from scale aggregates. 
Higher scores are associated with better quality of life (see Appendix 7).  


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10.2.10 
Timed Function Tests 
The timed function tests will be performed by qualified and trained raters who will be blinded to 
treatment assignment and study drug injection sites and who will have no other role or 
responsibility in the study assignment beyond administering these efficacy assessments (see 
Section 8.4.1) at the time points specified in the SOE in Section 3. 
Timed function tests will include time taken to walk/run 10 meters, time taken to stand from a 
seated position, and time taken to climb 4 standard-sized stairs (Mendell 1989, Griggs 1991, 
Beenakker 2005, Pradhan 2006, Podsiadlo 1991, Rao 2009) (see the SRM). These tests provide 
additional measures of muscle strength and functional capability in patients with DM. Decreases 
in time taken to complete these tasks are considered to be indicative of patient improvement. 
10.2.10.1 
Timed 10-meter Walk-run Test (10MWR) 
This test measures, in seconds, the time it takes a patient to walk as quickly as they can along a 
marked path without assistance for 10 meters. The time taken to complete the task is measured 
with a stopwatch. 
10.2.10.2 
Timed Up and Go (TUG) 
This test measures, in seconds, the time taken by an individual to stand up from a standard arm 
chair, walk a distance of 3 meters, turn, walk back to the chair, and sit down. The time taken to 
complete the task is measured with a stopwatch. 
10.2.10.3 
4 Stair Climb Test 
This test measures, in seconds, the time it takes the subject to climb up 4 standard-sized steps. 
The time taken to complete the task is measured with a stopwatch. 
10.2.11 
5-D Itch Scale (5D Pruritis Scale) 
The 5-D Itch Scale will be completed by the patient at the time points specified in the SOE in 
Section 3. 
The 5-D Itch Scale is a brief multidimensional questionnaire for use in clinical trials (see 
Appendix 8). The five dimensions of itch include degree, duration, direction, disability, and 
distribution. The duration, degree and direction domains each include one item, while the 
disability domain has 4 items. All items of these first 4 domains are measured on a 5-point Likert 
scale. The distribution domain includes 16 potential locations of itch, including 15 body part 
items and one point of contact with clothing or bandages. The scores of each of the 5 domains 
are achieved separately and then summed together to obtain a total 5-D score. 5-D scores can 
potentially range between 5 (no pruritus) and 25 (most severe pruritus). 
10.2.12 
Clinical Laboratory Tests 
Blood and urine samples for routine (Table 7) and safety laboratory (Table 8) tests will be 
collected at the time points specified in the SOE in Section 3 and analyzed by an accredited 
central laboratory selected by Idera. The appropriate Laboratory Manual should be referenced for 
procedures on sample collection, handling, storage, and shipping. 


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Any value outside of the current reference ranges for the laboratory performing the test will be 
flagged on the laboratory results. The Investigator will score all abnormal assessment results as 
either clinically significant (CS), or not clinically significant (NCS). See Section 8.3.2 for 
guidelines on actions for safety laboratory results. 


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10.2.12.1 
Routine Safety Laboratory Assessments 
Table 7. 
Routine Safety Laboratory Assessments 
Category 
Analyte 
Hematology 
CBC: RBC, WBC, hemoglobin, hematocrit, platelet count 
Differential WBC count: neutrophils, monocytes, 
lymphocytes, eosinophils, basophils, abnormal cells 
Absolute cell counts: ANC 
Coagulation 
PT, activated partial thromboplastin time (aPTT), international 
normalized ratio (INR) 
Clinical chemistry Panel  
Renal: Serum sodium, potassium, chloride, bicarbonate, 
calcium, magnesium, phosphorus, creatinine, urea nitrogen 
Endocrine: Serum glucose, thyroxine (T4), thyroid stimulating 
hormone (TSH) 
Liver: serum ALT (SGTP), AST (SGOT), LDH, GGT, 
alkaline phosphatase, albumin, total protein, total bilirubin, 
direct bilirubin, indirect bilirubin 
Lipids: Serum cholesterol, LDL, HDL 
Urinalysis 
Routine and microscopic analyses 
Hepatitis screen  
(At Screening Visit only) 
Hepatitis B virus (HBV) screen: HBsAg and anti-HBc 
Hepatitis C virus (HCV) screen: anti-HCV 
TB test (within 3 months 
prior to screening or 
during the Screening 
Period) 
A negative chest x-ray and one of the following: 
a) a PPD skin test with ≤5-mm induration, OR 
b) a negative (not detected) QuantiFERON result, OR 
c) a negative T-SPOT.TB test.  
If the QuantiFERON result is indeterminate, the test may be 
repeated once (local testing), per Center for Disease Control 
(CDC) guidelines  
If the second QuantiFERON test is indeterminate, a PPD skin 
test may be used to confirm eligibility.  
(http://www.cdc.gov/tb/topic/testing/default.htm). 
Drug abuse 
(At Screening Visit only) 
Urine drug screen 
ALT (SGPT) = alanine aminotransferase (serum glutamate-pyruvate transaminase); ANC = absolute neutrophil 
count; aPTT = activated Partial Thromboplastin Time; AST (SGOT) = aspartate transaminase (serum glutamic 
oxaloacetic transaminase); CBC = complete blood count; GGT = gamma-glutamyl transferase; HBsAg = hepatitis B 
surface antigen; HDL = high-density lipoprotein; INR = international normalized ratio; LDH = lactate 
dehydrogenase; LDL = low density lipoprotein; PPD = purified protein derivative; PT = prothrombin time; 
RBC = red blood cells; T4 = thyroxine; TB = tuberculin; TSH = thyroid stimulating hormone; WBC = white blood 
cells 
Note: The PPD skin test is not an acceptable method of TB testing in Sweden. 


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10.2.12.2 
Safety Laboratory Assessments 
Table 8. 
Safety Laboratory Assessments 
Category 
Analyte 
Immune activation 
Serum globulin, serum albumin, A:G ratio, CRP 
Complement activation 
C3, C4, CH50 
Heart 
Troponin 
A:G albumin: globulin; C = complement component; CH50 = hemolytic complement activity; CRP = C-reactive 
protein 
10.2.13 
12-Lead Electrocardiogram (ECG)  
A 12-lead ECG will be obtained at the time points specified in the SOE in Section 3 at the study 
site. ECGs will be performed only after the patient is positioned supine, resting, and quiet for a 
minimum of 5 minutes. The ECG will be reviewed and interpreted by medically qualified 
personnel. The Investigator will review the results of the ECG report, document the 
interpretation and designate the findings as normal or abnormal (CS or NCS), and report changes 
from previous readings. 
10.2.14 
Pregnancy test 
Urine samples for pregnancy testing will be collected on all women of childbearing potential at 
the time points specified in the SOE in Section 3. 
Non-childbearing potential is defined as a female who meets either of the following criteria: 
• Postmenopausal state defined as no menses for 12 months without an alternative medical 
cause. 
• Documented hysterectomy, bilateral tubal ligation or bilateral oophorectomy. 
10.2.15 
IMO-8400 Plasma Concentration 
Blood samples for determination of IMO-8400 plasma concentrations will be collected prior to 
administration of study drug pre-dose and 2 hours (± 15 minutes) post-dose at Visit 2/Week 1, 
Day 1, Visit 6/Week 5, Visit 14/Week 13, and Visit 22/Week 21. An additional sample will be 
collected as part of the EOT Visit 26/Week 25 assessments.  
If an extension study is initiated and the patient is enrolled, the EOT PK sample will be the same 
as the Visit 1/Week 1, Day 1 pre-dose sample for the extension study. The appropriate 
Laboratory Manual should be referenced for procedures on sample collection, handling, storage, 
and shipping. 


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10.2.16 
Autoantibodies 
Blood samples will be collected at the time points specified in the SOE in Section 3 for 
assessment of autoantibodies associated with idiopathic inflammatory myopathies including, but 
not necessarily limited to: anti-MDA-5, anti-Mi-2, anti-TIF1γ, anti-NXP2, anti-SAE1, 
anti-SAA 60, anti-Ro/SSA 52, anti-SSB/La, anti-Sm, anti-RNP, anti-Scl-70, anti-ribosomal-P, 
anti-chromatin, anti-Jo-1, anti-PL-7, and anti-PL-12. Assessment of autoantibodies will help to 
characterize the enrolled population; subgroup analyses may be performed according to the 
autoantibody profile. Additional serum for anti-platelet antibodies will also be collected at the 
time points specified in the SOE in Section 3. The appropriate Laboratory Manual should be 
referenced for procedures on sample collection, handling, storage and shipping. 
10.2.17 
Interferon (IFN) Gene Expression 
Blood samples and a skin biopsy for analysis of Type 1 and Type 2 IFN gene expression profiles 
will be obtained at the time points specified in the SOE in Section 3. Guidance on performing the 
skin biopsy is provided in Section 10.2.7 and in the SRM. 
10.2.18 
Histology 
A second skin biopsy will be obtained for histology analysis at the same time points as the 
IFN skin biopsies, as specified in the SOE in Section 3. Guidance on performing the skin biopsy 
is provided in Section 10.2.7 and in the SRM.  
10.2.19 
Serum Cytokines 
Blood samples for analysis of DM-relevant cytokines/chemokine levels (including IL-6, IL-8, 
IP-10, I-TAC, MCP-1, MCP-2, and TNFα; additional or alternative cytokines or chemokines 
may be assessed) will be obtained at the time points specified in the SOE in Section 3. The 
appropriate Laboratory Manual should be referenced for procedures on sample collection, 
handling, storage and shipping. 
10.2.20 
Immunogenicity  
Blood samples for assessment of antibodies to IMO-8400 and dsDNA will be collected at the 
time points specified in the SOE in Section 3. The appropriate Central Laboratory Manual should 
be referenced for procedures on sample collection, handling, storage and shipping. 
10.2.21 
Vital Signs  
Vital signs (temperature [oral or tympanic], pulse rate, respiratory rate, and blood pressure) will 
be measured at the time points specified in the SOE in Section 3. Vital signs will be measured 
prior to injection. All assessments will be performed after patients have remained seated for 
5 minutes. Temperature should be recorded in degrees Celsius (°C), and pulse rate and 
respiratory rate should be measured over 1 minute. 
10.2.22 
Concomitant Medications/Therapies/Procedures During Treatment 
Review of all concomitant medications, therapies and procedures, and changes in dosage of 
concomitant medications will be assessed at each visit as specified in the SOE in Section 3. Data 
on pharmacological and non-pharmacological treatments will be recorded on an eCRF page. At 


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each study visit, the patient will be asked about any additional treatments or any changes in 
regimen or dosages since the last visit. Indications for any new medications or therapies during 
the study period will be recorded as an AE. Further detail on concomitant medications is 
provided in Section 9. 
10.2.23 
Blood Volume Collection Summary  
An estimated 20 to 55 mL of blood is required to be drawn at clinic visits, with an estimated total 
of 350 mL expected during this study (refer to details in the Laboratory Manual). 


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11 
ADVERSE EVENT REPORTING 
At each study visit, patients will be evaluated for new AEs and the status of existing AEs. All 
AEs from the time the informed consent is signed through the EOS Visit 27/Week 29 will be 
recorded on the eCRF. 
 
Definition of Adverse Events 
11.1.1 
Adverse Event (AE) 
An AE is any untoward medical occurrence in a clinical study patient, whether or not the event is 
considered causally related to the investigational product. An AE can be a new occurrence or an 
existing process that increases significantly in severity or frequency. 
Adverse events include:  
• Symptoms described by the patient or signs observed by the Investigator or medical 
staff  
• Test abnormalities (laboratory tests, ECG, x-rays, etc.) that result in an alteration in 
medical care (diagnostic or therapeutic) 
− Abnormally low values for C3, C4 or A:G ratio may result in discontinuation of 
study treatment. Patients who discontinue due to these laboratory test 
abnormalities will be classified as “withdrawals due to adverse events” and a 
narrative describing their history and reason for withdrawal will be prepared by 
the Investigator. 
− Abnormally low eGFR or platelet count or abnormally high urine protein as 
described in Table 3 may result in discontinuation of study treatment. Patients 
who discontinue due to these laboratory test abnormalities will be classified as 
“withdrawals due to adverse events”.  
• Injury or accidents. Note that if a medical condition is known to have caused the 
injury or accident (a fall secondary to dizziness), the medical condition (dizziness) 
and the accident (fall) should be reported as 2 separate AEs. The outcome of the 
accident (hip fracture secondary to the fall) should be recorded in source documents. 
Abnormalities present at Baseline are considered AEs only if they reoccur after resolution or 
worsen in severity or frequency during the study. 
Each AE is to be classified as serious or nonserious. 
11.1.2 
Serious Adverse Events (SAE)  
An AE is serious when the patient outcome, regardless of whether or not it is considered related 
to the study medication, is one or more of the following: 
• Death  
• Life threatening, per the Investigator, the patient was at immediate risk of death from 
the event at the time that the event occurred. It does not include an event that 
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• Hospitalization, initial or prolonged, meaning that a hospital admission and/or 
prolongation of a hospital stay was required for the treatment of the AE, or occurred 
as a consequence of the event. It does not include a pre-planned elective hospital 
admission for treatment or diagnostic procedures 
• Disability or incapacity that is persistent or significant 
• Congenital anomaly or birth defect that occurs in the offspring of a patient exposed to 
the study drug 
• Important medical event that, although not immediately life-threatening, requires 
intervention in order to prevent one of the other serious outcomes listed above 
11.1.3 
Suspected and Unexpected Serious Adverse Reaction (SUSAR) 
A SUSAR is defined as an SAE that meets both the following criteria with respect to study drug:  
• Suspected — is assessed as related or possibly related to study drug (see 
Section 11.2.3) 
• Unexpected — compared to the study drug-related AEs described in Investigator’s 
Brochure, the event meets any of the following criteria: 
− The event was not previously described;  
− The event is now characterized as more severe (see Section 11.2.4) 
− The event is now characterized more specifically (e.g., an event of “interstitial 
nephritis” in a patient receiving an agent previously described as associated with 
“acute renal failure”). 
 
Evaluation of Adverse Events 
All AEs/SAEs experienced by the patient will be recorded in the eCRF and will include a 
concise description of: the event; date and time of event onset and resolution; relationship to 
study drug; severity; management of study medication; management of the AE/SAE, and 
outcome as described in Sections 11.2.1 through 11.2.7.  
Abnormalities in vital signs, laboratory results, and other safety assessments will be recorded as 
an AE if they meet the definition of an AE (Section 11.1).  
When possible, a diagnosis should be recorded as an AE, rather than symptoms or isolated 
laboratory abnormalities related to that diagnosis.  
A medical or surgical procedure is not an AE; rather the condition leading to the procedure 
should be recorded as the AE. If the condition is not known, the procedure must be reported as 
an AE instead.  
Similarly, death is not an AE, but is rather the outcome of the AE(s) that resulted in death. If the 
AE(s) leading to death are not known, then death must be reported as an AE. 


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11.2.1 
Description of Event  
The diagnosis or description will be as specific and complete as possible (i.e., “lower extremity 
edema”, rather than just “edema”). Whenever possible, signs and symptoms due to a common 
etiology will be reported as an integrated diagnosis; for example, cough, runny nose, sneezing, 
sore throat and head congestion would be reported as “upper respiratory infection”. 
11.2.2 
Date and Time of Onset  
The date and time at which the event was first apparent. The time of onset of symptoms may be 
appreciably earlier than the date and time the Investigator becomes aware of the event. Some 
events may be apparent to the patient and Investigator independently, and information from each 
may contribute to the final report. For example, a patient may report the onset of a rash two days 
before being seen by a physician who makes a diagnosis of herpes zoster based on appearance 
and laboratory confirmation. In that case, there is a single AE, with the date of onset based on the 
date of the initial observation by the patient and a specific description (herpes zoster) based on 
the clinical exam and tests. 
11.2.3 
Relationship to Study Drug 
A causality assessment must be provided for all AEs. This assessment must be made by the 
Investigator and recorded on the eCRF (SAE form, as appropriate). The definitions for the 
causality assessment are provided below. 
• Not related: The AE is clearly not related to study drug 
• Possibly related: There is some evidence supporting the possibility of a causal 
relationship between study drug and the AE, i.e., the event follows a reasonable 
temporal sequence from the time of study drug administration and/or follows a known 
response pattern to the study drug, but could also have been attributed to other 
factors. AEs that are deemed by the Investigator to be possibly related to study drug 
shall be considered related to study drug. 
• Probably Related: There is strong evidence that there is a causal relationship 
between study drug and the AE 
As previously noted in Section 8.3.5, any SAE assessed by the Investigator as possibly related or 
probably related to study drug will require discontinuation of study drug administration 
according to the procedures outlined in Section 11.5; the Investigator will assess if study drug 
administration will be discontinued in any patient who experiences an SAE that is assessed as 
not related to study drug.  
11.2.4 
Severity  
The severity of all AEs will be assessed by the Investigator as mild, moderate, or severe using 
the following criteria: 
• Mild: An AE that is transient, requires minimal or no treatment, and does not 
interfere with the patient’s daily activities 


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• Moderate: An AE that is usually alleviated with specific therapeutic intervention. 
The event interferes with usual activities of daily living, causing discomfort, but 
poses no significant or permanent risk of harm to the research participant 
• Severe: An AE that interrupts usual activities of daily living, or significantly affects 
clinical status, or may require intensive therapeutic intervention 
Changes in the severity of an AE must be recorded in the eCRF to allow an assessment of the 
duration of the event at each level of severity. Adverse events characterized as intermittent 
require documentation of onset and duration of each episode if the severity of the intermittent 
event changes. 
11.2.5 
Action Taken with Study Medication upon Occurrence of an Adverse Event 
For each AE the Investigator will be required to document the action taken regarding study drug 
in response to the AE. Options include: 
• Discontinued (withdrawn): Study drug was stopped permanently due to the AE 
• Dosing Interrupted: Study drug regimen was modified by being temporarily halted, 
i.e., one or more doses were not administered, but drug was not stopped permanently 
• Dose Not Changed (none): No change in the administration of study mediation 
11.2.6 
Actions Taken for Management of AE 
AEs will be followed and managed by the Investigator, including obtaining any supplemental 
studies needed to define the nature and/or cause of the event (e.g., laboratory tests, diagnostic 
procedures, consultation with other health care professionals).  
For each AE the Investigator will categorize the actions taken to manage the AE as follows: 
• Concomitant medication: One or more medications (prescription or 
over-the-counter) were started or increased in dose; non-medication actions may also 
have been ordered 
• Other action: Non-medication action(s) were ordered as management of the AE 
(e.g., bed placed in Trendelenburg position, warm compresses applied to IV access 
site) 
• No action: No actions were ordered for management of the AE 
11.2.7 
Outcome of AEs 
If possible, AEs will be followed until resolved (synonyms: recovered, recuperated, ended) either 
with or without sequelae, or the Investigator assesses them as chronic or stable. 
The outcome of each event (including date and time) will be described using the following 
categories:  
• Recovered: The event resolved and patient returned to baseline 
• Recovered With Sequelae: The event resolved but the patient is left with residual 
problems (e.g., functional deficits, pain) 


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• Not Recovered: At the last observation, the event was unchanged 
• Death (Fatal): To be used for the one AE which, in the judgment of the Investigator, 
was the primary cause of death 
• Unknown: There were no observations after the onset (initial observation or report) 
of the event 
A patient withdrawn from the study because of an AE must be followed by the Investigator until 
clinical recovery is complete and laboratory results have returned to normal, or until progression 
has been stabilized. Follow-up may need to continue after the patient has discontinued from the 
study, and additional investigations may be requested by the Investigator. (see Section 11.4 for 
additional details on AE/SAE follow-up requirements). 
11.2.8 
Injection Site Reactions 
New ISRs will be captured in AE reporting, and assessment of all previously used injection 
site(s) will be made at all clinic and non-clinic visits before and after dosing, and at the EOT and 
EOS Visits. In addition, on dosing days, the planned injection site will be assessed to confirm it 
is appropriate for use. ISRs that are reported by the patient or observed by the Investigator will 
be recorded by verbatim term, onset date, resolution date, anatomical location, and the visit 
number or date of the injection associated with the reaction. The verbatim terms of pain, 
tenderness, pruritis, induration, erythema, blisters, ulceration, and necrosis will be offered in the 
eCRF to simplify data collection and reporting, and Investigators will rate the severity as mild, 
moderate, or severe. An ISR may be composed of more than one AE using more than one 
verbatim term. 
For ISRs of induration, erythema, blisters, ulceration, and necrosis, Investigators will measure 
and record the largest edge-to-edge lesion distance in millimeters. 
 
Reporting Serious Adverse Events 
The Investigator will review each SAE and evaluate the severity and the causal relationship of 
the event to study drug. All SAEs will be recorded from signing of informed consent until the 
EOS Visit 27/Week 29. Serious AEs occurring after the EOS Visit and coming to the attention of 
the Investigator must be reported only if there is (in the opinion of the Investigator) reasonable 
causal relationship with the study drug. 
The Investigator is responsible for providing notification to the CRO of any SAE, whether 
deemed study drug-related or not, that a patient experiences during their participation in study 
within 24 hours of when he or she became aware of the event. 
As a minimum requirement, the initial notification should provide the following information: 
• 
Study number 
• 
Patient number 
• 
Name of Investigator  
• 
Adverse event 
• 
Criterion for classification as ‘serious’ 


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• 
Study drug name 
• 
Causality assessment (if sufficient information is available to make this 
classification) 
• 
Identifiable reporter of event 
CRO Safety personnel will request clarification of omitted or discrepant information from the 
initial notification. The Investigator or an authorized delegate is responsible for sending the 
requested information within 24 hours. 
Initial reports of SAEs must be followed later with detailed descriptions, including clear 
photocopies of other documents as necessary (e.g., hospital reports, consultant reports, autopsy 
reports), with the study patient’s personal identifiers removed. If a new SAE Report Form is sent, 
then the Investigator must sign and date the form. The CRO may also request additional 
information on the SAE, which the Investigator or an authorized delegate must send to the SAE 
contact information below. 
SERIOUS ADVERSE EVENT REPORTING INSTRUCTIONS 
PAREXEL Clinical Studies Safety Center 
United States (US) Telephone number/SAE Hotline: Durham, NC +1-919-294-5268 
Fax number: +1-919-544-3572 
US Email: NorthAmerica_Medical@parexel.com 
United Kingdom (UK) Telephone number/SAE Hotline: Uxbridge +44 1895 273434 
Fax number: Uxbridge +44 1895 231847 
UK Email: DrugSafety@parexel.com  
Provide the name of the Investigator, your name, the telephone number where you can be 
reached, and the protocol number and title. 
 
Follow Up of Adverse Events/Serious Adverse Events 
All AEs/SAEs documented at a previous visit/contact that are designated as not recovered will be 
reviewed by the Investigator at subsequent visits/contacts. 
All AEs will be followed until the resolution of AE, completion of the patient’s participation, or 
study termination, whichever occurs first.  
Serious AEs will be followed until resolution, the condition stabilizes, or the Investigator and 
Sponsor agree that follow up is no longer necessary. Rules for AE/SAE follow up apply to all 
patients, including those withdrawn from the study prematurely to the extent allowed by the 
patient’s consent. The Investigator will ensure that follow up includes further investigations 
consistent with appropriate medical management and patient consent to determine the nature 
and/or causality of the AE/SAE. 


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Other Reportable Events 
Certain events that occur in the absence of an AE should be reported to the Sponsor. These 
include the following events: 
• Pregnancy exposure (patient becomes pregnant while taking study drug). Should a female 
patient or partner of a male patient become pregnant during the study, the patient will 
inform the Investigator. The patient will be asked to follow up with the study site to 
report the eventual outcome of the pregnancy. The information will be tracked by the 
Sponsor. 
• Overdose of study medication (defined as dosing ≥2 fold above intended weekly dose) 
occurring as a result of dosing amount error or timing error should be reported on the 
eCRF. The CRO Medical Monitor should be contacted if an overdose occurs. Any 
adverse outcomes of overdose should be recorded as AEs/SAEs according to the 
procedures described in Section 11.2. 
• Lactation exposure (subject was taking study drug while nursing an infant) 
• Accidental exposure (someone other than the study subject was exposed to study drug) 
• Other medication errors that potentially place subjects at greater risk of harm than was 
previously known or recognized (e.g., study drug was administered via an incorrect 
route) 


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12 
WITHDRAWAL OF PATIENTS  
All patients who receive study drug should remain in the study whenever possible. However, 
patients are free to withdraw consent and/or discontinue participation in the study at any time, 
without prejudice to further medical care. 
A patient’s treatment and participation in the study may also be discontinued at any time at the 
discretion of the Investigator, CRO Medical Monitor, or Idera. Justifiable reasons to discontinue 
a patient from treatment and the study may include, but are not limited to the following: 
• The patient was erroneously included in the study (i.e., did not meet eligibility 
criteria) 
• The patient experiences an SAE assessed as possibly or probably related to study 
drug 
• The patient is unable to comply with the requirements of the protocol 
• The patient participates in another investigational study 
• The patient withdraws consent 
• The patient becomes pregnant 
• A patient for whom the blind is intentionally broken 
Patients who are withdrawn from treatment should complete the EOT/ET Visit 26/Week 25 
assessments within 5 days of notification of withdrawal and the EOS Visit 27/Week 29 at 
4 weeks (± 4 days) after the ET Visit (see Sections 10.1.4 and 10.1.5 for information regarding 
the EOT/ET and EOS Visits, respectively). A patient who completes the initial portion of the 
study (through the EOT Visit 26/Week 25) and is then lost to follow-up will not be considered to 
have prematurely withdrawn.  
A patient will be considered “discontinued due to an AE” if they withdraw from the study due to 
any AE, regardless of whether or not the AE is considered related to investigational product. If 
the patient withdraws from the study due to an AE, the Investigator should arrange for the patient 
to be followed appropriately until the AE has resolved or stabilized (in the opinion of the 
Investigator). 
The Investigator will document the reason(s) for treatment or study discontinuation on the eCRF. 
Idera and the CRO Medical Monitor should be informed when a patient is withdrawn from the 
study. 
 
 


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13 
DATA COLLECTION, QUALITY ASSURANCE, AND MANAGEMENT 
 
Data Collection and Recording 
The Investigator or personnel designated by the Investigator will perform primary data collection 
based on source document hospital or clinic records or other source documentation. All required 
study information must be recorded on the appropriate eCRF. The study monitor will review 
eCRFs for accuracy and completeness to ensure maximum data integrity. In addition, as the 
person ultimately responsible for the accuracy of all eCRF data, the Investigator will provide 
electronic endorsement that the data on the eCRFs are accurate and complete. Data processed at 
a central laboratory (e.g., safety laboratory tests and bioanalytical data) will be transferred 
electronically. An IXRS will be used to allocate the randomized treatments to patients as they are 
enrolled. The randomized treatment assignments will be transferred electronically for integration 
with the clinical study data at the appropriate time. 
 
Data Quality Assurance 
The eCRFs will be reviewed by a CRO study monitor against the source notes for identification 
and clarification of any discrepancies. Automated quality assurance programs will be in place to 
identify discrepancies, such as missing data, selected protocol violations, out of range data, and 
other data inconsistencies. Requests for data clarification or correction will be documented using 
an electronic data query and forwarded to the Investigator or study coordinator for resolution. All 
changes to the eCRFs will be tracked to provide an audit trail. 
The Investigator must make study data accessible to the study monitor, to other authorized 
representatives of Idera, and to the appropriate regulatory authority inspectors. Audits for quality 
assurance of the database may be performed according to relevant standard operating procedures 
within the CRO or at the request of Idera. 
 
Data Management 
Idera, in close collaboration with any designee, will be responsible for: 
• database creation and validation 
• eCRF review and data validation  
• query resolution 
• data analysis and reporting 
A detailed Data Management Plan will be prepared separately and approved by Idera.  
 
Protocol Violations 
Prior to unblinding the study, Idera will review the protocol violations that occur during the 
study. A determination will be made as to which violations are considered to be major or would 
potentially impact efficacy assessments. Patients with such violations will not be included in the 
Per Protocol analysis, as per Section 14.3. 


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Examples of violations that would be considered to impact efficacy assessments would be: 
• Change in background DM therapy during the study period 
• Wrong study treatment was given 
• Receiving <80% of planned doses of study treatment while on study. 
 
 


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14 
STATISTICAL METHODS AND PLANNED ANALYSES 
 
General Considerations 
Continuous endpoints will be summarized descriptively. Categorical endpoints will be 
summarized by the number and percentage of patients in each category and 95% confidence 
intervals for the proportion. 
 
Determination of Sample Size 
A simulation was conducted in which one of the IMO-8400 groups exhibits a mean decrease of 
7 points in CDASIv2-Activity score over 24 weeks, assuming a baseline mean of 25 and a 
standard deviation of 8.5 and the placebo group exhibits no mean decrease. Correlation between 
baseline CDASIv2-Activity score and Week 25 mCDASIv2-Activity score was assumed to be 
0.4 for IMO-8400 treated patients and 0.7 for placebo treated patients. Using a repeated 
measures mixed model (RMMM) to analyze monthly mCDASIv2-Activity assessments, 
10 patients with complete data yields 81.2% power to detect such a 7-point difference between 
groups at Week 25, using a 1-sided test with an alpha of 0.05. A 20% rate of patient dropout was 
assumed, yielding the final sample size of 12 subjects per treatment group. 
 
Analysis Sets 
Safety Population and Intent-to-Treat Population (ITT) — all patients who received at least 
1 injection of study medication. 
Per Protocol Population (PP) — all patients who received at least 20 doses of study drug as 
assigned, completed the EOT Visit 26/Week 25, and had no major protocol violations that would 
potentially influence treatment effect (as determined by review by Idera prior to unblinding). 
Safety analyses will be performed using the Safety Population. The efficacy, PD, 
disease-specific autoantibody, and immunogenicity assessments will be analyzed for the 
ITT population; key endpoints may be also analyzed for the PP Population as specified in the 
Statistical Analysis Plan (SAP). Analyses will be performed comparing the IMO-8400 treatment 
groups with placebo. Details will be provided in the SAP. 
 
Statistical Analyses 
14.4.1 
Demographic and Baseline Characteristics 
Patient demographics and baseline characteristics will be summarized descriptively by treatment 
group. 
14.4.2 
Study Conduct and Patient Disposition 
The number of patients who enrolled in the study, the number randomized to each group, and the 
number in each analysis set will be summarized descriptively. The number of patients who 
completed the study will be summarized, and for those who terminated study participation before 
study completion, the reason for early termination will be tabulated by treatment group. 


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14.4.3 
Treatment Compliance 
Study drug exposure will be tabulated by the number of doses of study drug received. The 
number of and reason for missed doses will be tabulated categorically by treatment group. 
14.4.4 
Efficacy Analyses 
The primary efficacy endpoint will be assessed via an RMMM. An appropriate covariance 
structure for repeated measures will be used. The difference between each IMO-8400 treatment 
group and placebo at Week 25 will be assessed. The overall alpha level will be controlled using 
the Bonferroni-Holm step-down method. Further details of this analysis will be described in the 
SAP. A sensitivity analysis will be performed to test the effect of important covariates on the 
effect of IMO-8400 using an RMMM. 
Differences in response rate between the IMO-8400 treatment groups and placebo will be 
assessed via logistic regression. 
The MMT8, TUG, 4 stair climb test, timed 10MWR test, serum CK, ALD, LDH, AST, ALT, 
SF-36, and 5-D Itch Scale will be analyzed in a similar manner to the primary endpoint. 
For the proportion of patients who meet the IMACS 2004 DOI (Rider 2004) at EOT, logistic 
regression will be performed. 
All efficacy endpoints will also be summarized descriptively by treatment group and nominal 
visit. Other exploratory and sensitivity analyses will be specified in the SAP in addition to 
further details regarding the statistical methodology. 
14.4.5 
Safety Analyses 
Safety analyses will be descriptive in nature; no statistical hypothesis testing will be performed. 
14.4.5.1 
Physical Examination and Vital Signs 
Physical examination data will list whether changes were noted. Changes in physical 
examination post baseline will be recorded as AEs. The actual value and change from baseline of 
vital signs will be summarized descriptively by treatment group and nominal visit. Graphical 
figures will be produced for each vital sign, showing a box and whisker plot representing the 
maximum absolute change from baseline by dose group. 
14.4.5.2 
Clinical Laboratory Tests 
The actual value and change from baseline of laboratory results for hematology, chemistry, 
urinalysis and coagulation and safety laboratory tests will be summarized using descriptive 
statistics by treatment group and nominal visit. Shift tables will also be produced, comparing the 
category at baseline for each parameter (low, normal, high) to the worst value post-baseline. All 
laboratory test results will be listed, and values will be flagged that are above or below the 
normal range, and those judged by the Investigator to be clinically significant will also be 
flagged. 
14.4.5.3 
Adverse Events 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
and tabulated by event, severity, and relationship to study therapy. Listings of SAEs and AEs 


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leading to study discontinuation will be produced. A listing of verbatim AE terms and the 
MedDRA terms they are mapped to will be produced. 
14.4.5.4 
Electrocardiograms 
The actual value and change from baseline of ECG parameters will be summarized descriptively 
by treatment group and nominal visit. The number of patients experiencing QTC changes greater 
than 30 and 60 ms will be tabulated, as well as the number of patients with a QTC value greater 
than 450 and 500 ms. 
14.4.5.5 
Concomitant Medications and Therapies 
Concomitant medications will be coded using the WHO Drug Dictionary. Results will be 
tabulated by anatomic therapeutic class and preferred term. 
14.4.5.6 
Injection Site Reactions 
The ISR verbatim terms of pain, tenderness, pruritis, induration, erythema, blisters, ulceration, 
and necrosis will be summarized by the greatest post-randomization severity for each symptom. 
14.4.6 
Pharmacokinetic Analyses 
Plasma concentrations of IMO-8400 will be determined pre-dose and 2 hours (± 15 minutes) 
post-dosing to confirm systemic exposure. Pre- and post-dose plasma concentrations may be 
used to evaluate/interpret any time-dependent trends in safety or PD outcomes. 
14.4.7 
Pharmacodynamic, Disease-specific Autoantibodies, and Immunogenicity 
Analyses 
Pharmacodynamic, disease-specific autoantibodies, and immunogenicity study parameters will 
be summarized using descriptive statistics. 
Details of the association between change in PD endpoints, clinical outcome measures, and dose 
received will be described in the SAP. 
Figures presenting the median value of PD endpoints over time will be presented by treatment 
group. 
Note: PD results (IFN gene expression, histology, and cytokine/chemokine results) may be 
reported separately from the final CSR, and only the baseline autoantibody results will be 
reported in the CSR.  
 
Significance Levels 
Statistical analyses will use a 1-sided test with alpha set at 0.05.  
 
Missing or Invalid Data 
No missing data will be imputed. If any data are found to be invalid after database lock, the data 
will be hard-coded and a listing of all hard-coded values will be included in the CSR. 


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15 
STUDY COMMITTEES 
 
Data Monitoring Committee (DMC) 
A DMC, operating autonomously from Idera, will be responsible for providing independent 
recommendations to Idera about evolving risk-benefit observed in the course of the study and 
any modifications required during the course of the study. The DMC will comprise at least 
1 physician experienced in treating DM, and a biostatistician. The DMC will be chaired by one 
of these individuals. DMC members must not be actively involved in study design, conduct, or 
daily management of this study and must not have financial, proprietary, professional, or other 
interests that may affect impartial, independent decision-making. Specialists may be invited to 
participate as non-voting members at any time if additional expertise is desired.  
The DMC will operate under a charter developed as a collaborative document between the DMC 
and Idera. The primary responsibility of the DMC is to protect the safety and welfare of patients 
participating in this clinical study and to ensure the integrity of the clinical study.  
In general, the DMC will be responsible for: 
• Examining accumulated unblinded safety and other relevant data at prespecified 
points during the course of the study in order to make recommendations concerning 
continuation, termination, or modification of the study 
• Reviewing the general progress of the study as regards such issues as patient accrual, 
and protocol violations 
• Providing expert advice to Idera on an ad hoc basis regarding matters such as safety 
concerns or diagnostic evaluations in individual patients 
Based on the results of its deliberations, the DMC can recommend continuation of the study 
unchanged, study interruption, study termination, modification of the study, or alteration in the 
DMC monitoring plan.  
The DMC will review unblinded safety data as outlined in the DMC Charter. The DMC may also 
increase or alter safety monitoring, or recommend other modifications to ensure patient safety. 
The composition and specific responsibilities of the DMC are described in the DMC Charter, 
which is maintained as a separate document. 
 
Patient Safety Committee (PSC) 
A PSC consisting of the Investigator, CRO Medical Monitor and Idera Medical Monitor will be 
formed to monitor abnormal laboratory test values. See Sections 8.3.2 and 8.3.4 for actions to be 
taken in the event that abnormalities are noted in specified laboratory parameters. 
 
 


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16 
SPECIAL REQUIREMENTS AND PROCEDURES 
 
Compliance with Ethical and Regulatory Guidelines 
This study was designed and will be conducted in accordance with the ethical principles that 
have their origins in the Declaration of Helsinki and in conformance with International Council 
for Harmonisation (ICH) GCP E6 guidance documents. The study will comply with the 
requirements that are enunciated in the US Code of Federal Regulations (CFR) related to the 
protection of human subjects (21 CFR Part 50), Institutional Review Boards (IRBs) (21 CFR 
Part 56) and investigational new drug applications (INDs) (21 CFR Part 312), electronic records 
and electronic signatures (21 CFR 11) and financial disclosure (21 CFR 54). 
 
Institutional and Ethics Review 
This protocol and a patient ICF, participant information sheet, and any proposed advertising 
material, must be reviewed and approved by an IRB/independent ethics committee (IRB/IEC), 
applicable regulatory authorities, and host institution(s) for written approval (where applicable) 
before enrollment of patients and release of investigational product. Documentation of IRB/IEC 
approval and the approved consent form must be received by the CRO prior to obtaining the 
patient’s informed consent. Amendments to the original approved documents, where applicable, 
will also be submitted to and approved by the above parties. Investigators will comply with the 
appropriate IRB/IEC reporting requirements. 
 
Confidentiality 
All information regarding the nature of the proposed investigation that is provided to the 
Investigator by Idera or the CRO with the exception of information that is required by law or 
regulations to be disclosed to the IRB or the appropriate regulatory authority, must be kept in 
confidence by the Investigator in accordance with current Health Insurance Portability and 
Accountability Act standards.  
Research records will be collected and stored in a manner that protects the confidentiality of 
patient information. The names and identities of all research patients will be kept in strict 
confidence and will not appear on eCRFs or other records provided to or retained by Idera (or its 
authorized designee). The names and identities of the patients need not be divulged; however, the 
records must nevertheless be inspected. This will be accomplished by blanking out the patient’s 
name and replacing the name with the patient’s study identification number on any record 
provided to or retained by Idera (or designee). The ICF must include appropriate statements 
explaining these requirements. 
By signing this protocol, the Investigator affirms to Idera that the Investigator will maintain, in 
confidence, information furnished by Idera and will divulge such information to the IRB/IEC 
under an appropriate understanding of confidentiality with such board. 
 
Changes to the Conduct of the Study or Protocol 
Any changes in the study protocol, such as changes in the study design, objectives or endpoints, 
inclusion and exclusion criteria, and/or procedures (except to eliminate an immediate hazard) 
will be implemented only after the mutual agreement of the Investigator and the Sponsor or 
designee. All protocol changes must be documented in protocol amendment(s). Protocol 


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amendment(s) must be signed by the Investigator and approved by the IRB/IEC and Competent 
Authorities (CA), if applicable, prior to implementation. If a protocol amendment requires 
changes in the informed consent documents (if applicable), the revised documents must be 
reviewed and approved by the CRO Medical Monitor before review and approval by the IRB. 
Emergency departures from the protocol that eliminate an apparent immediate hazard to a 
particular patient and that are deemed by the Investigator as crucial for the safety and wellbeing 
of that patient may be instituted for that patient only. The Investigator will contact the CRO 
Medical Monitor as soon as possible regarding such a departure. These departures do not require 
preapproval by the IRB; however, the IRB and CRO Medical Monitor must be notified in writing 
as soon as possible in accordance with the IRB policies after the departure has been made. In 
addition, the Investigator will document the reasons for the protocol deviation and the ensuing 
events in the patient's eCRF. Documentation of IRB approval of any amendments must be 
returned to CRO. 
 
Investigator Responsibilities 
16.5.1 
Patient Informed Consent 
Investigators must adhere to GCP, which includes ethical principles that have their origin in the 
Declaration of Helsinki, when developing the patient ICF and when obtaining consent from the 
patient. By signing the Statement of Investigator (Food and Drug Administration [FDA] Form 
1572), the Investigator assures that informed consent will be obtained from each patient prior to 
study entry and that the informed consent will be obtained in accordance with current 
regulations. 
The Investigator will give each patient full and adequate verbal and written information 
regarding the objectives and procedures of the study and the possible risks involved. An 
informed consent document will be provided to each patient in a language in which the patient is 
fluent. This information must be provided to the patient prior to undertaking any study-related 
procedure. 
It is the responsibility of the Investigator to document the consent process within the source 
documents and obtain consent using an IRB/IEC-approved consent form. 
16.5.2 
Case Report Forms 
The Investigator will make available copies of pertinent records in connection with the study, 
including all source documents, to Idera or the CRO upon request with due precaution towards 
protecting the privacy of the patient. 
Under direction of the Investigator, data will be entered by the site onto the eCRFs in the 
electronic data capture system. Unless explicitly directed, blank data fields are not acceptable. 
Any erroneous entries made on the eCRFs should be corrected. Changes made to the data after 
initial entry into the eCRF will be captured via an electronic audit trail, and should include the 
reason for change. Incomplete entries or entries needing additional explanation will be 
highlighted or queried to the Investigator for clarification. 
After database lock, the Investigator will receive an electronic copy of the patient data for 
archiving at the investigational site. At all times, the Principal Investigator has final 


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responsibility for the accuracy and authenticity of all clinical data entered into the eCRFs and/or 
reported to Idera from the Investigator’s site. 
16.5.3 
Record Retention 
The Principal Investigator(s) must maintain all Essential Documents (as listed in the 
ICH Guideline for GCP) until notified by Idera and in accordance with all local laws regarding 
retention of records. 
The Investigator must obtain written permission from Idera before disposing of any records. In 
order to avoid any possible errors, the Investigator will contact Idera prior to the destruction of 
any study records. The Investigator will promptly notify Idera in the event of accidental loss or 
destruction of any study records. If the Investigator relocates, retires, or for any reason 
withdraws from the study, the study records may be transferred to an acceptable designee, such 
as another Investigator, another institution, or to Idera. 
16.5.4 
Monitoring and Auditing 
An Idera or CRO representative will visit the Investigator periodically at mutually convenient 
times, before, during, and after completion of the study, for the purpose of monitoring the 
progress of this study in accordance with the protocol, GCP, and local regulations. 
Non-compliance with the protocol, GCP, and local regulations will be documented and 
corrective actions implemented, as necessary. It is the responsibility of the Investigator to be 
present or available for consultation during monitoring visits. During these routine visits, all data 
pertaining to a patient’s participation in this clinical investigation must be made available to the 
monitor. 
At any time prior to, during, or after completion of the clinical study, an audit may be performed 
by Idera, CRO, or a representative of a national regulatory agency may choose to inspect a study 
site. Investigators should notify Idera upon notification of inspection by a representative of a 
national regulatory agency. A Sponsor or designee representative will be available to assist in the 
preparation for study site inspections. All pertinent study data should be made available for 
verification, audit, or inspection purposes. 
16.5.5 
Study or Site Termination 
If Idera, the Investigator, or regulatory authorities discover any conditions during the study that 
indicate that the study or study site should be terminated, this action may be taken after 
appropriate consultation between the Sponsor and the Investigator. The Sponsor has the right to 
terminate the participation of either an individual site or the study at any time, for any reason, 
which may include the following: 
• The incidence and severity of AEs in this or other studies indicates a potential health 
hazard to patients 
• Patient enrollment is unsatisfactory 
• Data recording is inaccurate or incomplete 
• Investigator does not adhere to the protocol or applicable regulatory guidelines in 
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• Submission of knowingly false information from the study site to the Sponsor or 
regulatory authorities 
In the event that the study is terminated early, Idera will provide specific guidance to 
investigational sites regarding the EOS procedures. 
16.5.6 
Investigational Product Control 
16.5.6.1 
Accountability of Study Drug  
The study site (under direction of the Investigator) must maintain accurate records demonstrating 
dates and amount of study drug received, to whom dispensed (patient-by-patient accounting), 
any amount returned, and accounts of any study drug accidentally or deliberately destroyed. 
Study drug accountability should be performed for placebo as well. Unless otherwise notified, all 
vials both used and unused, must be saved for study drug accountability. At the end of the study, 
a final reconciliation must be made between the amount of study drug supplied, dispensed, and 
subsequently destroyed or returned to Idera. A written explanation will be provided for any 
discrepancies. The Investigator must ensure that the study drug is maintained in a controlled 
location, with limited access, and under adequate storage conditions. 
16.5.6.2 
Disposition of Unused Study Drug 
All unused investigational products must be maintained under adequate storage conditions in a 
limited-access area. If any unused material is remaining upon completion of the study, the 
Investigator will return unused material to Idera or destroyed after accountability has been 
performed by CRO representative.  
16.5.6.3 
Product Handling and Complaints Reporting 
If there are any issues during the course of the study related to the quality of the investigational 
product, the clinical site pharmacist or pharmacy designee should contact the CRO Medical 
Monitor. 
16.5.7 
Public Notification of Study Conduct 
Consistent with Section 113 of the Food and Drug Modernization Act of 1997 (FDAMA) and 
with requirements of the International Committee of Medical Journal Editors (ICJME) as a 
condition of consideration for publication of study results, Idera will be responsible for ensuring 
that this protocol is listed at the ClinicalTrials.gov website and that information at the website 
relating to study design and conduct is appropriately updated during the course of the study. In 
order to facilitate this process, Investigators will need to supply Idera with appropriate contact 
information for study site personnel. 
16.5.8 
Dissemination of Results 
The information developed during the conduct of this clinical study is considered confidential by 
Idera. This information may be disclosed as deemed necessary by Idera. 
To allow for the use of the information derived from this clinical study and to insure compliance 
with current regulations, the Investigator is obliged to provide Idera with complete test results 
and all data developed in this study. The information obtained during this study may be made 


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available to other physicians who are conducting similar studies and to the FDA or other 
regulatory authorities. Such information may be disclosed as deemed necessary by Idera. 
Idera intends that the data from this study will be presented and published. The Idera staff in 
collaboration with the Investigator will be responsible for writing presentations and manuscripts 
for publication. Investigators will not be allowed to publish or present the data from this study 
without prior agreement with Idera.  
16.5.9 
Clinical Study Report 
A study Investigator will be designated to review and sign the completed CSR(s). 
16.5.10 
Communication with Regulatory Authorities 
Idera and CRO will assume responsibility for regulatory interactions with the FDA, the European 
Medicines Evaluation Agency (EMEA) and/or other regulatory authorities. In this regard, Idera 
will maintain an Investigational New Drug (IND) for IMO-8400 in support of the study. In 
fulfilling this responsibility, Idera and CRO will collect, assemble, and communicate all required 
regulatory documents (e.g., Form FDA 1572, Investigator financial disclosure forms, protocol 
and protocol amendments, investigator brochures, informed consent documents, annual reports) 
as required by regulation. Idera and CRO will also assume responsibility for AE reporting to 
regulatory authorities. 
 
 


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17 
STUDY RATIONALE 
This Phase 2 study was designed to build on prior clinical experience with IMO-8400, and to 
safely and efficiently generate critical dosing, safety, and efficacy data to support continued 
development of IMO-8400 for the treatment of DM and autoimmune diseases in which 
TLR receptors play a pivotal role. 
IMO-8400 is a synthetic oligonucleotide that acts as a specific antagonist for TLRs 7, 8, and 9. It 
inhibits cell activation by agonists of those TLRs, including generation of NF-κB and the 
induction of cytokines and chemokines such as TNFα, IL-12, IL-1β, IP-10, IL-6, and IFN-α. 
IMO-8400 does not interfere with the immune stimulation mediated through other TLRs. 
In murine models of autoimmune disease in which activation of TLRs play a critical pathogenic 
role including psoriasis, lupus, rheumatoid arthritis, and dermal inflammation, IMO-8400 has 
shown potent ability to inhibit the development of disease or to reduce ongoing signs and 
symptoms. Given that there is no animal model of human DM available for testing therapeutic 
agents (Katsumata, 2008) these models serve as surrogate DM mouse models that demonstrate 
the therapeutic effects of IMO-8400 in analogous diseases where inflammation due to TLR 
activation is implicated in pathogenesis. 
Taken together, these studies support the hypothesis that IMO-8400 represents a novel approach 
to the treatment of diseases in which activation of endosomal TLRs is part of the 
pathophysiology, including DM. Current treatment options for DM often have significant 
adverse effects and/or are limited in the extent or duration of their impact. Thus IMO-8400 has 
the potential to address a substantial unmet medical need. 
 
Study Design 
The randomized, double-blind, placebo-controlled nature of the design was intended to eliminate 
bias in treatment assignment, facilitate blinding of study treatment, eliminate placebo effects, and 
ensure the reliability and validity of the study data. Randomization will be stratified by baseline 
CDASIv2 Activity score (15 to 20 vs. ≥21). The inclusion of multiple study sites is intended to 
enhance study accrual from this limited patient population while providing reassurance that the 
results are likely to have general applicability. 
Selection of placebo as the reference arm in the proposed study is clearly appropriate given that 
this is a first-in-class approach to DM and that no approved standard therapy exists. Use of 
placebo provides an opportunity to obtain information regarding the full treatment effect size for 
IMO-8400. Comparison of IMO-8400 to corticosteroids is inappropriate because corticosteroids 
have a different mechanism of action and may have different clinical effects relative to 
IMO-8400. 
Mandating that patients not receive prednisone or oral immunosuppressive therapy is not feasible 
as it would be potentially unethical to withdraw these therapies from patients who are benefiting 
from their use and would also shrink the pool of eligible patients. 
 
Selection of Study Population 
The entry criteria were designed to enroll only those patients with a confirmed diagnosis of 
DM in conjunction with documented evidence of skin involvement that could reasonably be 
expected to safely complete the study and provide interpretable data.  


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Bohan and Peter’s diagnostic criteria, proposed in 1975, are still widely accepted, however, they 
are unable to differentiate DM from inclusion body myopathy or dystrophies for which the 
investigation of myositis specific autoantibodies and MRI must be performed (Iaccarino 2014). 
Therefore, supplemental criteria are provided in the inclusion criteria to ensure that appropriate 
patients with confirmed DM are enrolled. 
17.2.1 
Baseline Disease Activity Assessment 
Baseline CDASI is likely to have prognostic significance for the primary assessment of skin 
activity. Changes in CDASI over 12 and 24 weeks for a convenience sample of 115 patients 
were analyzed by baseline score (unpublished data). Approximately 30% of patients showed 
improvement in CDASI scores by at least 4 points (clinically relevant changes) at both the 
12- and 24-week assessment. Improvements are assumed to result from current standard care, 
although no data on treatments during the 24 weeks were collected. Patients with a high baseline 
CDASI score experienced larger decreases in CDASI at 24 weeks than those with a low baseline 
score. To control for possible effects of baseline disease activity on the results, randomization 
will be stratified by baseline CDASIv2-Activity score (15-20 vs. ≥21), and the study will be 
powered to detect a 7 point treatment effect, a therapeutic effect beyond that of the standard of 
care. 
17.2.2 
Dose Selection 
17.2.2.1 
Estimation of Human Equivalent Dosages from Animal Models of 
Autoimmune Disease 
In the absence of an animal model of DM, the activity of IMO-8400 was tested in murine models 
of autoimmune diseases where, like DM, pathologic products that activate endosomal TLRs are 
formed endogenously. In the NZBW/F1 lupus mouse model, IMO-8400 demonstrated a 
dose-dependent improvement in inflammatory markers and renal impairment. Dose-dependent 
activity in animal models of arthritis, psoriasis, and dermal inflammation has also been seen with 
IMO-8400. Using a data-driven, systemic exposure-based dosage conversion for 
oligonucleotides as described in Yu et al (Yu 2015), the range of IMO-8400 dosages with 
therapeutic response in the NZBW/F1 mouse (3.8 to 7.5 mg/kg/week) extrapolates to a 0.76 to 
1.5 mg/kg/week human equivalent dosage range. An exposure-based comparison between 
humans and mice in clinical and nonclinical studies conducted with IMO-8400 yields a similar 
dosage conversion from mice to humans as that described in Yu et al. The IMO-8400 doses 
being tested in this protocol, 0.6 mg/kg/week and 1.8 mg/kg/week, span the human equivalent 
dose range estimated from the NZBW/F1 lupus mouse model and the 1.8 mg/kg/week dose is 
within the estimated active dose range predicted by the other animal models of autoimmune 
disease. 
17.2.2.2 
Safety Profile of Selected Doses 
Patients with DM in this study will be given IMO-8400 at 0.6 or 1.8 mg/kg/week for 24 weeks. 
In clinical trials as of 22 November 2016, IMO-8400 has been generally well tolerated. There 
were no treatment-related SAEs or fatalities, except 3 patients with WM with SAEs reported as a 
significant exacerbation of the subject’s arthritis, arthralgia, and sepsis. Further description about 
all reported SAEs and AEs can be found in the Investigator’s Brochure. In summary, a total of 


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60 subjects have been exposed to IMO-8400 at dosages ≥0.6 mg/kg/week. As of 22 November 
2016, 32 subjects have been exposed to IMO-8400 at 0.6 mg/kg/week, 6 subjects have been 
exposed to 1.2 mg/kg/week, and 21 subjects have been exposed to 2.4 mg/kg/week Subjects have 
been exposed to IMO-8400 for up to 91 weeks.  
 
Appropriateness of Efficacy Assessments 
Dermatomyositis is a multisystem disorder with a wide variety of clinical manifestations. 
Characteristic skin findings are a hallmark of the disease as well as muscle weakness. Therefore 
endpoints have been selected that have a logical connection to the skin and muscle disease 
symptoms. The effects of IMO-8400 on the skin and muscle manifestations of DM will be 
primarily evaluated using the CDASI, which has been used in other studies of DM and is a 
reliable and valid assessment for these purposes. The blinding of efficacy assessor to potential 
ISRs requires the mCDASIv2, eliminating the abdominal skin assessment from the overall score.  
Most of the other efficacy measures included in this study (including muscle enzyme levels and 
MMT8) were specifically recommended for inclusion in clinical trials of DM by the IMACS 
coalition of health care providers and researchers with experience and interest in the myositis 
syndromes (Rider 2004). Timed function tests, including the 10MWR, TUG and 4 stair climb 
test were added as exploratory endpoints to evaluate the potential effects of IMO-8400 on 
functional outcome measures (as opposed to rating scales) and the 5-D Itch Scale, a reliable and 
validated assessment of pruritis, was added to evaluate the ability of IMO-8400 to address this 
symptom. 
17.3.1 
CDASI 
The CDASI is a one-page instrument designed to evaluate the cutaneous manifestations of DM. 
Developed by leading academic dermatologists and rheumatologists with an expertise in DM, the 
validity and reliability have been demonstrated in multiple studies of DM patients (Klein 2008, 
Yassaee 2010, Goreshi 2012). 
To determine the minimal difference in CDASI scores associated with clinically significant 
change, a 2-center, prospective study of 199 patients with DM was conducted. Patients were 
evaluated with the CDASI, a PGA of disease severity, and a PGA of disease change since the 
last visit (improved, worse, no change) over the course of 12 visits. Clinical response was 
defined as a rating of “improved” on the PGA of disease change or a 3-point/2 cm change on the 
PGA of disease severity. Data were analyzed with logistic regression models using generalized 
estimating equations to account for correlation among patients. Based on the results, an 
improvement (i.e., decrease) in CDASI-Activity scores of 4 or 5 points in the CDASI-Activity 
Score is considered indicative of a clinically significant change (Anyanwu 2013). 
Of note, clinically significant change in cutaneous manifestations of DM, as indicated by 
decreases in CDASI-Activity scores ≥4, were associated with statistically significant increases in 
quality of life as measured by the Skindex-29 and patient-reported itch and pain on a 10-point 
visual analogue scale (Robinson, 2015). 
The CDASI has been used as a clinical endpoint in a least 1 clinical trial, a 52-week randomized, 
double-blind, placebo-controlled trial of etanercept in DM subjects. While treatment with 
etanercept was not associated with statistically significant changes in CDASI-Activity scores, 


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etanercept-treated patients demonstrated mean changes from baseline in CDASI-Activity scores 
of -4.9 after 24 weeks, while placebo-treated controls had a mean change of +1.5, confirming the 
responsiveness of the CDASI to changes in disease activity over time (Amato 2011). 
The original CDASI had 4 activity and 2 damage measures. Yassaee et al (2010) created a 
second version of the CDASI (CDASIv2) and validated the new version in order to simplify and 
improve the tool for clinical research and care. The modified CDASI has 3 activity and 2 damage 
measures, and results of the research efforts by Yassaee et al indicated that all scores of the 
original and the modified CDASI correlated perfectly with each other. 
In this study, the full CDASIv2 assessment will be performed at the Screening and Baseline 
Visits. Subsequent CDASI assessments will be performed using a mCDASIv2, which eliminates 
the abdominal skin assessments post-injection to decrease the risk of unblinding. 
17.3.2 
IMACS 
The IMACS CSMs are validated and reliable clinical outcome measures used to evaluate 
multiple components of disease activity including muscle strength and laboratory enzymes. 
Analyses of the CSMs have been defined as: Change from baseline in the IMACS CSMs. 
Improvement will be assessed using the IMACS group DOIs (2004 DOI [Rider 2004]).  
17.3.2.1 
Manual Muscle Testing (MMT8) 
Manual muscle testing is used to evaluate the function and strength of individual muscles and 
muscle groups based on the effective performance of a movement against gravity or manual 
resistance and is 1 of the IMACS CSMs for DM. The MMT has been widely used in myositis 
therapeutic trials and clinical studies (Feldman 2008, Jain 2006, Amato 2011) and its reliability 
and validity have been demonstrated repeatedly (Cuthbert 2007, Rider 2011). Moreover, the 
IMACS group identified muscle strength assessment as a key measure for clinical trials 
(Miller 2001). 
The MMT8 is less physically and mentally taxing for the patient and clinician, has excellent 
internal and inter-rater reliability, and performs as well as or better than Total MMT in terms of 
responsiveness, content validity, and construct validity, it is expected to be an even more reliable 
indicator of muscle strength than the full MMT and has been incorporated into the IMACS CSM 
(https://www.niehs.nih.gov/research/resources/imacs/diseaseactivity/). While an absolute value 
for the minimal clinically important difference has not been determined for the MMT or MMT8, 
a group of adult and pediatric rheumatologists and neurologists have reached consensus that 
MMT should improve by ≥15% to classify an adult DM/PM patient as improved and should 
improve by ≥18% to classify a juvenile DM/PM patient as improved (Rider 2004). 
17.3.2.2 
Muscle Enzyme Levels 
Muscle enzyme levels are another of the IMACS CSMs. Per IMACS, increases from Baseline in 
at least 2 of the following muscle enzymes is associated with a clinical improvement in DM: CK, 
LDH, AST, ALT, or ALD. Improvement is defined as changes from Baseline in LDH of ≥25%, 
and changes from Baseline in CK, AST, ALT, and ALD of ≥30% (Rider 2004). 


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17.3.3 
Timed Function Tests 
Timed function tests (TFTs) will include time taken to run/walk 10 meters (10MWR), time taken 
to stand from a seated position (Timed Up and Go [TUG]), and time taken to climb 
4 standard-sized stairs. Commonly used in assessment of neuromuscular diseases, these tests are 
relevant to DM in that they assess functional aspects of proximal muscle strength required for 
everyday ambulation (Brooke 1989, Podsiadlo 1991, Rao 2009). TFTs are reproducible, simple 
to administer, and have documented response to therapeutic intervention including corticosteroid 
therapy (Mendell 1989, Griggs 1991, Beenakker 2005). They are easy to perform functional 
assessments that usually take less than 5 minutes and provide adjunct functional assessment to 
the CDASI and IMACS.  
17.3.4 
5-D Itch Scale (5-D Pruritis Scale) 
The 5-D Itch Scale is a validated patient-reported outcome measure that evaluates the 
5 dimensions of itch (degree, duration, direction, disability and distribution) (Elman 2010). The 
evaluation is sensitive and able to measure multidimensional aspects of pruritus, including 
severity and impact on quality of life with demonstrated content validity, test-retest reliability, 
and internal consistency. The test can detect changes over time in patients with chronic pruritus 
and has been shown to have applicability in multiple diseases including skin disease, liver 
disease, kidney disease, HIV/AIDS, and burns (Elman 2010). 
17.3.5 
SF-36 
SF-36 scores can be transformed using general US population norms so that all scales have a 
mean of 50 and a standard deviation of 10 as described in the SF-36 User’s Manual (Ware 2001). 
Therefore, scores can be directly compared across scales, as well as to the general population 
norm of 50. 
 
Safety Monitoring 
The safety measures used in this study are available as standard laboratory tests and reflect 
appropriate monitoring of adult subjects receiving an investigational drug. Although no such 
events have been observed in clinical studies to date, adverse effects of myocardial 
degeneration/necrosis, glomerulonephritis, and/or hepatocellular necrosis were observed in 
cynomolgus monkeys treated with ≥6 mg/kg/week of IMO-8400 for up to 39 weeks (see the 
Investigator’s Brochure for further detail). Changes in serum C3, C4 and the A:G ratio were 
sensitive predictors of toxicity in the 39-week monkey toxicology study, but several animals with 
no pathological changes at necropsy had abnormally low C3, C4, or A:G ratio, indicating a low 
specificity for the individual assays. Combining the data for these assays results in improved 
predictive power; using a compound rule of “low C3 or low C4 AND low A:G ratio” had a 
sensitivity of 100% and specificity of 74% for the prediction of adverse histological findings at 
necropsy. 
All five monkeys with histological evidence of toxicity met the compound rule of abnormally 
low pre-dose C3 or C4 levels AND low A:G ratios several weeks to months prior to their 
unscheduled deaths or necropsy. Six of the animals in the recovery group met the compound rule 
during the dosing period. As five out of the fourteen monkeys (36%) that met the compound rule 
during the dosing period had histological evidence of toxicity at the primary or unscheduled 


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necropsy, it was estimated that two or three of the six monkeys in the recovery group with low 
pre-dose C3 or C4 levels AND low A:G ratios would have been expected to have had 
histological evidence of toxicity at the end of treatment. Because none of the monkeys had 
adverse microscopic findings at the end of their recovery period, it is concluded that the adverse 
histopathological findings would be avoidable or reversible if dosing were interrupted based on 
the compound rule.  
In addition to the usual monitoring of AEs and laboratory data, Idera will monitor C3, C4, and 
the A:G ratio every 4 weeks in an effort to avoid toxicity in study subjects. (Subjects must have 
normal C3, C4 and A:G ratio for inclusion in the study).  
Another oligonucleotide investigational product has been associated with clinically significant 
AEs of thrombocytopenia and renal abnormalities as well as ISRs in human clinical studies 
(FDA 2015). Given IMO-8400 is also an oligonucleotide investigational product, platelet counts, 
anti-platelet antibodies, urine protein, and renal function will be regularly monitored. 
Stopping rules for abnormal safety laboratory test results are defined in Section 8.3.2. In 
addition, a DMC will review unblinded safety and efficacy data as outlined in the DMC Charter. 
 
Overview of Human Safety Experience 
In studies to date, IMO-8400 was safe and well tolerated in adult human subjects/patients at dose 
levels up to 2.4 mg/kg/week. Refer to Section 17.2.2 and the Investigator’s Brochure for more 
detailed safety data. 


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18 
REFERENCES 
Amato AA, Tawil R, Kissel J, Barohn R, McDermott MP, Pandya S, et al. A randomized, 
pilot trial of etanercept in dermatomyositis. Ann of Neurol. 
2011 Sep;70(3):427-36. 
Ang GC and Werth VP. Combination antimalarials in the treatment of cutaneous 
dermatomyositis: a retrospective study. Arch Dermatol. 2005 Jul;141(7): 855-9. 
Anyanwu CO, Cynthia O, Fiorentino D, Chung L, Wang Y, Propert KJ, et al. Validation 
of the cutaneous dermatomyositis disease area and severity index: characterizing 
severity and assessing responsiveness to clinical change. [abstract] Arthritis 
Rheum. 2013;65 Suppl 10:1935 . 
Beenakker AC, Fock JM, Van Toll MJ, Maurits NM, Koopman HM, Brouwer OF, et al. 
Intermittent prednisone therapy in Duchenne muscular dystrophy: a randomized 
controlled trial.. Arch Neurol. 2005 Jan;62:128-32. 
Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 
1975 Feb 13;292(7):344-7. 
Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J 
Med. 1975 Feb 20;292(8):403-7. 
Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley R, Florence J, et al. 
Duchenne muscular dystrophy: Patterns of clinical progression and effects of 
supportive therapy. Neurology. 1989 Apr;39(4):475-81. 
Celhar T, Magalhães R, Fairhurst AM. TLR7 and TLR9 in SLE: when sensing self goes 
wrong. Immunol Res. 2012 Sep;53(1-3):58-77. 
Cuthbert SC,Goodheart GJ. On the reliability and validity of manual muscle testing: a 
literature review. Chiropr Osteopat. 2007 Mar 6;15:4. 
Elman S, Hynan LS, Gabriel V, Mayo MJ. The 5-D itch scale: a new measure of pruritus. 
Br J Dermatol. 2010 Mar;162(3):587-93.  
FDA Draft Guidance: Pharmacokinetics in Patients with Impaired Renal Function – 
Study Design, Data Analysis, and Impact on Dosingn and Labeling. FDA Center 
for Drug Evaluation and Research. Revesion 1, 2010 Mar. 
FDA Briefing Document: Peripheral and Central Nervous System Drugs Advisory 
Committee Meeting. NDA 206031. Drisapersen. 2015 Nov. 
Feldman BM, Rider LG, Reed AM, Pachman LM. Juvenile dermatomyositis and other 
idiopathic inflammatory myopathies of childhood. Lancet. 
2008 Jun 28;371:2201–12. 


IMO-8400 
 
Clinical Study Protocol 8400-211 
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PROTOCOL VERSION 6.0 
Goreshi R, Okawa J, Rose M, Feng R, Lee LA, Hansen CB, et al. Evaluation of 
reliability, validity, and responsiveness of the CDASI and the CAT-BM. J Invest 
Dermat. 2012 Apr;132(4):1117–24. 
Griggs RC, Moxley RT, Mendell JR, Fenichel GM, Brooke MH, Pestronk A, et al. 
Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the 
time course and dose response. Clinical Investigation of Duchenne Dystrophy 
Group. Arch Neurol. 1991 Apr;48:383-8. 
Harris E, Tiganescu A, Tubeuf S, Mackie SL. The prediction and monitoring of toxicity 
associated with long-term systemic glucocorticoid therapy. Curr Rheumatol 
Rep.2015 Jun;17(6):513.  
Harris-Love MO, Shrader JA, Koziol D, Pahlajani N, Jain M, Smith M, et al. Distribution 
and severity of weakness among patients with polymyositis, dermatomyositis and 
juvenile dermatomyositis. Rheumatology (Oxford). 2009 Feb;48(2):134–9. 
Iaccarino, L., A. Ghirardello, Bettio S, Zen M, Gatto M, Punzi L, et al. The clinical 
features, diagnosis and classification of dermatomyositis. J Autoimmun. 
2014 Feb-Mar;48-49:122-7. 
Jain M, Smith M, Cintas H, Koziol D, Wesley R, Harris-Love M, et al. Intra-rater and 
inter-rater reliability of the 10-point Manual Muscle Test (MMT) of strength in 
children with juvenile idiopathic inflammatory myopathies (JIIM). Phys Occup 
Ther Pediatr. 2006;26(3):5-7. 
Katsumata Y, Ascherman DP. Animal models in myositis. Curr Opin Rheumatol. 
2008 Nov;20:681-5. 
Klein RQ, Bangert CA, Costner M, Connolly MK, Tanikawa A, Okawa J, et al. 
Comparison of the reliability and validity of outcome instruments for cutaneous 
dermatomyositis. Br J Dermatol. 2008 Sep;159(4):887–94. 
Levine T. Treating refractory dermatomyositis or polymyositis with adrenocorticotropic 
hormone gel: a retrospective case series. Drug Des Devel Ther. 2012;6:133-9. 
Means TK, Luster AD. Toll-like receptor activation in the pathogenesis of systemic lupus 
erythematosus. Ann NY Acad Sci. 2005 Dec;1062:242-51. 
Mendell JR, Moxley RC, Griggs, Brooke MH, Fenichel GM, Miller JP, et al. 
Randomized, double-blind six–month trial of prednisone in Duchenne’s muscular 
dystrophy. N Engl J Med. 1989 Jun 15;320(24):1592-7. 
Miller FW, Rider LG, Chung YL, Cooper R, Danko K, Farewell V, et al. Proposed 
preliminary core set measures for disease outcome assessment in adult and 
juvenile idiopathic inflammatory myopathies. Rheumatology (Oxford). 
2001 Nov;40(11):1262–73. 


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PROPRIETARY AND CONFIDENTIAL 
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Podsiadlo D, Richardon S. The timed “up and go”: a test of basic functional mobility for 
frail elderly persons. J Am Geriatr Soc. 1991 Feb;39(2):142-8. 
Pradhan S, Ghosh D, Srivastava NJ, Kumar A, Mittal B, Pandey CM, et al. Prednisolone 
in Duchenne muscular dystrophy with imminent loss of ambulation. J Neurol. 
2006 Oct;253(10):1309-16. 
Prieto S, Grau JM. The geoepidemiology of autoimmune muscle disease. Autoimmun 
Rev. 2010 Mar;9(5):A330-4. 
Rao AK, Muratori L, Louis ED, Moskowitz CB, Marder KS, et al. Clinical measurement 
of mobility and balance impairments in Huntington’s disease: validity and 
responsiveness. Gait Posture. 2009 Apr;29:433-6. 
Rider LG, Giannini EH, Brunner HI, Ruperto N, James-Newton L, Reed AM, et al. 
International consensus on preliminary definitions of improvement in adult and 
juvenile myositis. Arthritis Rheum. 2004 Jul;50(7):2281-90. 
Rider LG, Koziol D, Giannini EH, Jain MS, Smith MR, Whitney-Mahoney K, et al. 
Validation of manual muscle testing and a subset of eight muscles (MMT8) for 
adult and juvenile idiopathic inflammatory myopathies. Arthritis Care Res. 
2010 Apr;62(4):465–72. 
Rider LG, Werth VP, Huber AM, Alexanderson H, Rao AP, Ruperto N, et al. Measures 
of adult and juvenile dermatomyositis, polymyositis, and inclusion body myositis: 
Physician and Patient/Parent Global Activity, Manual Muscle Testing (MMT), 
Health Assessment Questionnaire (HAQ)/Childhood Health Assessment 
Questionnaire (C-HAQ), Childhood Myositis Assessment Scale (CMAS), 
Myositis Disease Activity Assessment Tool (MDAAT), Disease Activity Score 
(DAS), Short Form 36 (SF-36), Child Health Questionnaire (CHQ), physician 
global damage, Myositis Damage Index (MDI), Quantitative Muscle Testing 
(QMT), Myositis Functional Index-2 (FI-2), Myositis Activities Profile (MAP), 
Inclusion Body Myositis Functional Rating Scale (IBMFRS), Cutaneous 
Dermatomyositis Disease Area and Severity Index (CDASI), Cutaneous 
Assessment Tool (CAT), Dermatomyositis Skin Severity Index (DSSI), Skindex, 
and Dermatology Life Quality Index (DLQI). Arthritis Care Res. 2011 Nov;63 
Suppl 11):S118–157. 
Robinson ES, Feng R, Okawa J, Werth VP. Improvement in the cutaneous disease 
activity of patients with dermatomyositis is associated with a better quality of life. 
Br J Dermatol. 2015 Jan;172(1):169–74. 
Schakman O, Gilson H, Kalista S, Thissen JP. Mechanisms of muscle atrophy induced by 
glucocorticoids. Horm Res. 2009 Nov;72 Suppl 1:36-41. 
Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. 
Conceptual framework and item selection. Med Care. 1992 Jun;30(6):473-83. 


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Ware JE, Kosinski M. Interpreting SF-36 summary health measures: a response. Qual 
Life Res. 2001;10(5):405-13; discussion 415-20. 
Yassaee M, Fiorentino D, Okawa J, Taylor L, Coley C, Troxel AB, et al. Modification of 
the cutaneous dermatomyositis disease area and severity index, an outcome 
instrument. Br J Dermatol. 2010 Mar;162(3):669–73. 
Yu RZ, Grundy JS, Henry SP, Kim TW, Norris DA, Burkey J, et al. Predictive 
dose-based estimation of systemic exposure multiples in mouse and monkey 
relative to human for antisense oligonucleotides with 2′-O-(2-methoxyethyl) 
modifications. Mol Ther Nucleic Acids. 2015 Jan 20;4:e218. 


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APPENDIX 1. AGE AND GENDER-APPROPRIATE CANCER WORK-UP GUIDELINES FOR 
WOMEN 
Recommended Test & Schedule 
Age (years) 
18-19 
20 
21-29 
30-39 
40-49 
50-54 
55-59 
60-65 
66-69 
70-74 
75 
Periodic health exams, including physical examination for 
signs of cancer of the: 
• Thyroid 
• Oral cavity 
• Skin 
• Lymph nodes 
• Ovaries 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pap test every 3 years 
 
 
X 
 
 
 
 
 
 
 
 
Clinical breast exam every 3 years 
 
 
X 
X 
 
 
 
 
 
 
 
Pap test every 3 years OR 
Pap test and HPV test every 5 years a 
 
 
 
X 
X 
X 
X 
X b 
 
 
 
Clinical breast exam yearly 
 
 
 
 
X 
X 
X 
X 
X 
X 
 
Mammography c yearly or every 2 years 
 
 
 
 
X 
X 
X 
X 
X 
X 
 
Communicate risks and symptoms of endometrial cancer d 
 
 
 
 
---------------Starting at the time of menopause---------------- 
Flexible sigmoidoscopy, double-contrast barium enema, or CT 
colonography every 5 years e, OR 
Colonoscopy every 10 years 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
Guaiac-based fecal occult blood test or fecal immunochemical 
test yearly e,f 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
Low-dose CT (lungs) yearly, if patient 
• Is in fairly good health, and 
• Has a 30 pack per year smoking history, and 
• Is still smoking or has quit within the last 15 years 
 
 
 
 
 
 
X 
X 
X 
X 
 
a A woman who has had her uterus removed (and also her cervix) for reasons not related to cervical cancer and who has no history of cervical cancer or serious pre-cancer should 
not be tested. 
b Women over age 65 who have had regular cervical cancer testing with normal results should not be tested for cervical cancer. Once testing is stopped, it should not be started 
again. Women with a history of a serious cervical pre-cancer should continue to be tested for at least 20 years after that diagnosis, even if testing continues past age 65. 
c Some women – because of family history, a genetic tendency, or certain other factors – should be screened with MRI in addition to mammograms. 
d Women should report any unexpected bleeding or spotting to their doctors. Some women – because of their history – may need to consider having a yearly endometrial biopsy. 
e If the test is positive, a colonoscopy should be done. 
f Highly-sensitive versions of these tests should be used with the take-home multiple sample method. One test done by the doctor in the office is not adequate for testing. 


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CT = computed tomography; HPV = human papilloma virus; MRI = magnetic resonance imaging 
Note: Guidelines are based on recommendations from the American Cancer Society and the US Preventative Services Task Force. This is US guidance only; EU countries should 
follow local guidance. 


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APPENDIX 2. AGE AND GENDER-APPROPRIATE CANCER WORK-UP GUIDELINES FOR MEN 
Recommended Test & Schedule 
Age (years) 
18-19 
20 
21-29 
30-39 
40-49 
50-54 
55-59 
60-65 
66-69 
70-74 
75 
Periodic health exams, including physical 
examination for signs of cancer of the: 
• Thyroid 
• Oral cavity 
• Skin 
• Lymph nodes 
• Testes 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PSA blood test with or without rectal exam a 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
Flexible sigmoidoscopy, double-contrast barium 
enema, or CT colonography every 5 years b OR 
Colonoscopy every 10 years 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
Guaiac-based fecal occult blood test or fecal 
immunochemical test yearly c 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
Low-dose CT yearly, if patient 
• Is in fairly good health, and 
• Has a 30 pack per year smoking history, and 
• Is still smoking or has quit within the last 15 years 
 
 
 
 
 
 
X 
X 
X 
X 
 
a Starting at age 50, men should talk to a doctor about the risks and possible benefits of testing and treatment. If they are African American or have a father or brother who had 
prostate cancer before age 65, men should have this talk with a doctor starting at age 45. For men who decide to be tested, the frequency of testing will depend on PSA level. 
b If the test is positive, a colonoscopy should be done. 
c 
 Highly-sensitive versions of these tests should be used with the take-home multiple sample method. One test done by the doctor in the office is not adequate for testing. 
CT = computed tomography; PSA = prostate-specific antigen 
Note: Guidelines are based on recommendations from the American Cancer Society and the US Preventative Services Task. This is US guidance only; EU countries should follow 
local guidance. 


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APPENDIX 3. BOHAN AND PETER DIAGNOSTIC CRITERIA FOR 
DERMATOMYOSITIS 
A 
Symmetric proximal muscle weakness determined by physical examination 
B 
Elevation of serum skeletal muscle enzymes, including CK, aldolase, serum 
glutamate oxaloacetate and pyruvate transaminases, and lactate dehydrogenase 
C 
The electromyographic triad of short, small, polyphasic motor unit potentials; 
fibrillations, positive sharp waves, and insertional irritability; and bizarre, high-
frequency repetitive discharges 
D 
Muscle biopsy abnormalities of degeneration, regeneration, necrosis, 
phagocytosis, and an interstitial mononuclear infiltrate 
E 
Typical skin rash of DM. Including a heliotrope rash and Gottron’s sign/papules 
Criteria for DM: 
• Definitive: Three criteria (A, B, C or D) + E 
• Probable: Two criteria (A, B, C or D) + E 
• Possible: One criterion (A, B, C or D) + E 
From Bohan 1975a and Bohan 1975b 
 
 


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APPENDIX 4. CUTANEOUS DERMATOMYOSITIS DISEASE AREA 
AND SEVERITY INDEX (CDASI) VERSION 2 
Source: PCI Licensing Group, Perelman School of Medicine 


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NOTE: The CDASIv2 has been modified for this study such that abdominal assessments will not 
be performed after the first injection of study drug, to avoid unblinding the raters. Therefore, 
post-injection score totals will not include scores for the abdomen. 


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APPENDIX 5. IMACS FORM 04: MANUAL MUSCLE TESTING 8 
SCORING SHEET 
Source: http://www.niehs.nih.gov/research/resources/imacs/diseaseactivity/index.cfm 
 
Patient number 
 
 
Assessor 
 
 
Date of Assessment (mm/dd/yy) 
 
 
Visit number 
 
 
 
Function of the Muscle 
Grade 
No Movement 
No contractions felt in the muscle 
0 
Tendon becomes prominent or feeble contraction felt 
in the muscle, but no visible movement of the part 
0 
Test Movement 
MOVEMENT IN HORIZONTAL PLANE 
 
Moves through partial range of motion 
1 
Moves through complete range of motion 
2 
ANTIGRAVITY POSITION 
 
Moves through partial range of motion 
3 
Test Position 
Gradual release from test position 
4 
Holds test position (no added pressure) 
5 
Holds test position against slight pressure 
6 
Holds test position against slight to moderate 
pressure 
7 
Holds test position against moderate pressure 
8 
Holds test position against moderate to strong 
pressure 
9 
Holds test position against strong pressure 
10 
 
MMT8 is a set of 8 designated muscles tested unilaterally (potential score 0 – 80), test on right 
side (use left side if right side cannot be tested). 
 


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Position 
Order of Testing 
Sitting 
 
Deltoid middle (shoulder abductors) 
1 
Biceps brachii (elbow flexors) 
2 
Wrist extensors (extensor carpi ulnaris/radialis) 
3 
Quadriceps femoris (knee extensors) 
4 
Ankle dorsiflexors (tibialis anterior) 
5 
Supine 
 
Neck flexors (scalenes, sternocleidomastoid) 
6 
Deltoid middle (G.E. test if needed) 
- 
Gluteus medius (G.E. test if needed) 
- 
Sidelying (lying on left side-right muscles tested) 
 
Gluteus medius (hip abductors) 
7 
Gluteus maximus (G.E. test if needed) 
- 
Biceps brachii (G.E. test if needed) 
- 
Neck flexors (G.E. test if needed) 
- 
Prone 
 
Gluteus maximus (hip extensors) 
8 
Scoring Area 
Muscle Groups 
Right (0 – 10) 
Left (0 – 10) 
Axial (0 – 10) 
Axial Muscles (0 – 10) 
 
 
 
Neck flexors 
- 
- 
 
Proximal Muscles (0 – 100) 
 
 
 
Deltoid middle 
 
 
- 
Biceps brachii 
 
 
- 
Gluteus maximus 
 
 
- 
Gluteus medius 
 
 
- 
Quadriceps 
 
 
- 
Distal Muscles (0 – 40) 
 
 
 
Wrist extensors 
 
 
- 
Ankle dorsiflexors 
 
 
- 
MMT- 8 score (0 – 80) 
 
 
 
 
 


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APPENDIX 6. IMACS FORM 06: SERUM LEVELS OF MUSCLE 
ENZYMES 
Source: http://www.niehs.nih.gov/research/resources/imacs/diseaseactivity/index.cfm 
 
Patient number 
 
 
Date of Assessment (mm/dd/yy) 
 
 
Visit number 
 
 
 
Blood laboratories: 
Result 
Normal Range 
 
Creatine kinase (IU/L) 
 
 
 
 
 
Aldolase (IU/L) 
 
 
 
 
 
Aspartate transaminase (IU/L) 
 
 
 
 
 
Alanine transaminase (IU/L) 
 
 
 
 
 
Lactate dehydrogenase (IU/L) 
 
 
 
 
 
Creatinine (mg/dL) 
 
 
 
 
 
 
 


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APPENDIX 7. SF-36 HEALTH SURVEY 
Source: Quality Metric: http://www.qualitymetric.com/products/descriptions/sflicenses.shtml 
 


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APPENDIX 8. 5-D ITCH SCALE (ALSO KNOWN AS THE 5-D PRURITIS 
SCALE) 
Source: Elman S, Hynan LS, Gabriel V, Mayo MJ. The 5-D itch scale: a new measure of 
pruritus. Br J Dermatol. 2010 Mar;162(3):587-93. 


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APPENDIX 9. INVESTIGATOR’S AGREEMENT 
I have read the foregoing protocol (Protocol 8400-211) and agree to the following: 
• The protocol contains all necessary details for carrying out this study.  
• I will conduct the study as detailed in the protocol and will abide by all its provisions. 
• I will conduct the study in compliance with ICH Guidelines for Good Clinical Practice, the 
requirements of the IRB and all applicable government regulations. 
• I will train and supervise all individuals delegated to assist me in conducting this study, including 
providing copies of the protocol and all pertinent information and discussing the material with 
them to ensure they are fully informed regarding the investigational drug, the protocol and their 
responsibilities and obligations.  
• I will use only the current informed consent form approved by the Sponsor (or their designee) and 
by the IRB responsible for this study.  
• I will fulfill all requirements for submitting pertinent information to the IRB and to the Sponsor, 
including reportable serious adverse events.  
• I will complete all case report forms, including resolution of queries, in a timely manner.  
• I will provide the Sponsor (or their designee) with access to any source documents from which 
case report form information may have been derived. 
• I will provide the Sponsor with complete, signed statements of financial disclosure as required. 
• I understand that the information in this protocol and the referenced Investigator’s Brochure is 
confidential and that its disclosure to any third parties (other than those approving or conducting 
the study) is prohibited. I will take the necessary precautions to protect this information from loss, 
inadvertent disclosure or access by third parties.  
 
 
Signature of Investigator 
 
Date (dd-mmm-yyyy) 
 
Investigator (printed name): 
 
 
 
 
 
Facility / Site of Investigation:  
 
 
 
 
 

SAP_000.pdf: