Conditions: Prostate Cancer Metastatic Castrate-Resistant Prostate Cancer PSA
Keywords: OGX-427 Abiraterone Acetate
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 72
Healthy volunteers: no

Brief summary:
This Phase II study has been designed to evaluate the anti-tumor effects of adding OGX-427 to continuing abiraterone acetate and prednisone treatment in men with metastatic castrate-resistant prostate cancer (MCRPC) who have prostate-specific antigen (PSA) progression

Detailed description:
OUTLINE: This is a multi-center study.

This is an open-label, randomized, Phase II clinical trial designed to evaluate the anti-tumor effects of OGX-427 and continuing abiraterone acetate and prednisone versus continuing abiraterone acetate and prednisone alone in men with MCRPC who have evidence of PSA progression but no evidence of symptomatic or radiographic progression that would require alternative therapy (e.g., needing radiation therapy for pain or significant progression of visceral metastases).

Patients on the control arm will be allowed to cross-over to receive OGX-427 following documented disease progression. Patients will be randomized with equal probability to one of the following arms:

EXPERIMENTAL ARM (Arm A):

OGX-427 Starting within 7 days of randomization, three loading doses of 600 mg intravenously (IV) within Week 1 if possible (up to 10 days of initiating treatment), followed by weekly doses of 800 mg IV

Continuation of standard therapy with abiraterone acetate 1000 mg by mouth (PO) daily and prednisone 10-20 mg PO daily

CONTROL ARM (Arm B):

Continuation of standard therapy with abiraterone acetate 1000 mg PO daily and prednisone 10-20 mg PO daily

After documented disease progression, patients on Arm B may opt to receive OGX-427 treatment (according to the Arm A schedule) following a screening evaluation (i.e., all inclusion and exclusion criteria have been met)

Both Arms:

Evaluations at 4 week-intervals. Disease assessments required at the milestone Day 60 assessment (expected to occur after 8 weeks of treatment and prior to Day 1, Week 9) and at 16, 24, 32, 40, and 48 weeks (if applicable) or until documented disease progression. Patients who are withdrawn from the study for a reason other than documented disease progression or patient withdrawal of consent will be followed every 4 weeks in the Off-Treatment Follow-up Period until documented disease progression.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Life Expectancy: Not Specified

Hematopoietic:

* Absolute neutrophil count (ANC) ≥ 1.5 x 109 cells /L, platelet count ≥ 100 x 109 /L, and hemoglobin ≥ 9 g/dL without transfusion

Hepatic:

* Total bilirubin ≤ 1.1 x upper limit of normal (ULN) unless elevated secondary to conditions such as Gilbert's disease, in which case a direct bilirubin ≤ ULN is required
* Serum glutamic pyruvic transaminase (SGPT), alanine transaminase (ALT) and alanine transaminase (SGOT) aspartate transaminase (AST) ≤ 3.0 x ULN

Renal:

* Creatinine ≤ 1.3 x ULN

Cardiac:

* Known left ventricular ejection fraction (LVEF) \<50% or New York Heart Association (NYHA) Functional Classification Class III or IV heart failure

Other:

* Castrate serum testosterone level (\< 50 ng/dL or \< 1.7 nmol/L)
* Potassium within normal limits

Arms:
arm 1: OGX-427 + continuation of standard therapy with abiraterone acetate and prednisone arm 2: Continuation of standard therapy with abiraterone acetate and prednisone

Interventions: intervention 1: OGX-427 intervention 2: Abiraterone Acetate intervention 3: Prednisone
Intervention descriptions: intervention 1: OGX-427 started within 7 days of randomization, three loading doses of 600 mg IV within Week 1 if possible (up to 10 days of initiating treatment), followed by weekly doses of 800 mg IV intervention 2: Standard therapy: Abiraterone Acetate 1000 mg PO daily intervention 3: Standard therapy: Prednisone 10-20 mg PO daily

Protocol document:
Prot_SAP_000.pdf: 
 
 
 
 
 
Protocol Number: GU12-159 
PR-02/Pacific 
 
A Randomized Phase II Study Evaluating OGX-427 in 
Patients with Metastatic Castrate-Resistant Prostate Cancer 
Who Have PSA Progression While Receiving Abiraterone 
 
July 21, 2014 
Version 3.0 
 
CONFIDENTIAL 
 
 
Investigator Sponsors: 
Costantine Albany, MD 
Assistant Professor of Clinical Medicine 
Medical Oncologist, Indiana University 
School of  Medicine 
 535 Barnhill Drive, RT 445 
Indianapolis, IN 46202 
Phone: (317) 278-1711 
Fax: 317-944-3684 
email: calbany@iu.edu 
 
 
 
Christopher Sweeney, MBBS 
Dana Farber Cancer Institute  
Associate Professor of Medicine 
Harvard Medical School 
450 Brookline Ave, D1230 
Boston, MA 02215 
Phone: 617-632-4524 
Fax: 617-632-2165 
email: 
christopher_sweeney@dfci.harvard.edu 
 
 
Trial Support and (OGX-427) Provided By: 
OncoGenex Technologies Inc. 
1522 217th Place, Suite 100 
Bothell, WA 98021 
Phone: 425-686-1571 
Fax: 425-489-0926 
 
IND Application #: 116,523


Protocol Number: PR-02/Pacific 
July 21, 2014, Ver 3.0 
OGX-427 
 
Confidential 
2
 
PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
Protocol Number 
PR-02/Pacific 
Protocol Title 
A Randomized Phase II Study Evaluating OGX-427 in Patients 
with Metastatic Castrate-Resistant Prostate Cancer Who Have 
PSA Progression While Receiving Abiraterone 
Protocol Date 
July 21, 2014 
 
 
Approvals: 
 
 
 
Costantine Albany, MD 
Assistant Professor of Clinical Medicine 
Medical Oncologist, Indiana University 
School of  Medicine 
535 Barnhill Drive 
RT 445 
Indianapolis, IN 46202 
 
Date 
 
 
 
Christopher Sweeney, MBBS 
Dana Farber Cancer Institute 
Associate Professor of Medicine 
Harvard Medical School 
450 Brookline Ave, D1230 
Boston, MA 02215 
 
 
Date 
 


Protocol Number: PR-02/Pacific 
July 21, 2014, Ver 3.0 
OGX-427 
 
Confidential 
3
 
 
 
INVESTIGATOR SIGNATURE PAGE 
Protocol Number 
PR-02/Pacific 
Protocol Title 
A Randomized Phase II Study Evaluating OGX-427 in Patients 
with Metastatic Castrate-Resistant Prostate Cancer Who Have 
PSA Progression While Receiving Abiraterone  
Protocol Date 
July 21, 2014 
 
AGREEMENT 
 
This document is a confidential protocol based on the provision of study drug by 
OncoGenex Technologies Inc. The recipient agrees that no unpublished information 
contained herein will be published or disclosed without the prior written approval of 
OncoGenex Technologies Inc. However, this protocol may be disclosed to appropriate 
Research Ethics Boards (REBs), Institutional Review Boards (IRBs) or authorized 
representatives of OncoGenex, the Sponsor, Investigator, or Boards of Health under the 
condition that they are requested to respect the confidentiality of this document and the 
information herein.  
The signature of the Investigator below constitutes his/her agreement to comply with the 
contents of this protocol. 
 
 
 
 
 
 
 
 
 
 
Investigator’s Name and Title 
 
 
 
 
 
 
 
 
 
 
Investigator’s Signature 
 
 
 
 
 
 
 
 
 
 
Date 


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SYNOPSIS. 
Protocol Number: PR-02/Pacific 
Title of Study: A Randomized Phase II Study Evaluating OGX-427 in Patients with Metastatic Castrate-Resistant Prostate 
Cancer Who Have PSA Progression While Receiving Abiraterone 
Study Population: Men with metastatic castrate resistant prostate cancer (CRPC) who are currently receiving abiraterone 
therapy and have documented PSA progression 
Rationale: Prostate cancer is the most commonly diagnosed cancer and the second most common cause of cancer death in 
men in North America.1 Patients with metastatic disease have a poor prognosis, and although hormonal therapy in the 
form of medical or surgical castration can induce significant long-term remission, development of androgen-independent 
disease is inevitable.  The current standard of care for CRPC is mainly palliative in its intent, with proven treatment 
options currently including analgesia, radiation, bisphosphonates, chemotherapy such as mitoxantrone or docetaxel, and 
abiraterone acetate.  
Abiraterone acetate inhibits cytochrome P450 17α-hydroxylase/C17,20-lyase (CYP17a), a key enzyme involved in de 
novo androgen biosynthesis, thereby broadly decreasing the levels of androgens in both non-castrate and castrate patients. 
Abiraterone acetate with prednisone has been demonstrated in a phase III study to improve overall survival in patients 
with metastatic CRPC who have previously been treated with docetaxel chemotherapy, and it is now considered a standard 
of care. Median duration of treatment on the study was 8 months, although median progression-free survival was 5.6 
months. PSA response rates were only 29%, and median PSA progression-free survival was 10.2 months, but the PSA 
analyses are difficult to interpret as PSA testing was only performed every 3 months on study. In the phase III study, 
patients were continued on study protocol unless they met all three criteria for progression (PSA, objective disease, 
symptoms); this study currently forms the basis for the duration of therapy as standard of care treatment with abiraterone 
acetate. Phase II studies of abiraterone acetate in the post-docetaxel patient population have demonstrated PSA declines of 
>50% occurring in approximately 50% of patients and median PSA progression-free survival in the range of 5-6 months.  
Given that patients on abiraterone acetate can first progress with PSA without symptoms or objective disease progression, 
this provides an opportunity to evaluate novel agents that target potential mechanisms of CRPC resistance in combination 
with abiraterone acetate. 
Heat shock protein (Hsp) family members, including Hsp27, have attracted attention as new therapeutic targets for cancer. 
Hsp27 is a small, ATP-independent Hsp which is highly conserved across species. Hsp27 is expressed in prostate cancer 
and other malignancies. Expression of Hsp27 is induced by cell stress, including cytotoxic chemotherapy, radiation 
therapy, and hormone therapy. Overexpression of Hsp27 confers a resistant phenotype and is implicated in castration 
resistant progression of prostate cancer through multiple mechanisms including apoptosis, growth factor signaling, and 
ligand-dependent and -independent activation of the androgen receptor.  
OGX-427 is a second generation antisense oligonucleotide (ASO) that inhibits expression of Hsp27. A number of in vitro 
and in vivo pharmacological studies have demonstrated that OGX-427 (or an Hsp27 ASO) has single-agent activity in 
reducing Hsp27 mRNA and protein, inhibiting cell proliferation, and inducing apoptosis in several human cancer cell 
lines. In a completed Phase I trial, OGX-427 has been administered as a single agent in doses from 200 to 1000 mg with 
weekly infusions occurring after a loading dose period of three infusions within the first 10 days of initiating treatment. 
OGX-427 treatment has been well tolerated, with the majority of the adverse events and laboratory toxicities reported 
being Grade 1 or Grade 2, although a symptom complex of rigors, pruritus, and erythema during or shortly after infusion 
of drug have required steroid prophylaxis and/or treatment in some patients at higher doses. No maximum tolerated dose 
has been identified based on toxicity. OGX-427 was also administered in combination with docetaxel in the above-


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mentioned phase I study.  
OGX-427 is also in testing in an ongoing randomized phase II study in patients with metastatic CRPC who are 
chemotherapy naïve with minimal symptoms. In this study, patients are being randomized to receive either OGX-427 with 
prednisone or prednisone alone. Preliminary results in the first 32 patients suggest interesting activity, with 59% of OGX-
427-treated patients achieving a PSA decline of >30% and 50% having a circulating tumour cell (CTC) count conversion 
(≥5 to <5 CTC/7.5 mL), while 33% of prednisone-only treated patients had a PSA decline of >30% and 31% had a CTC 
conversion.  Treatment has been well tolerated with infusion reactions (e.g., chills, flushing, diarrhea, nausea, vomiting) 
occurring in 47% of patients receiving OGX-427. One patient developed hemolytic uremic syndrome after week 7, 
probably related to OGX-427. 
This Phase II study has been designed to evaluate the anti-tumor effects of adding OGX-427 to continuing abiraterone 
acetate and prednisone treatment in men with metastatic CRPC who have PSA progression.   
Objectives:  
Patients will be randomized with equal probability to one of two arms, designated as the Experimental Arm (A) and the 
Control Arm (B). The intended intervention in Arm A is continued use of abiraterone/prednisone plus the addition of 
OGX-427. The intended intervention in Arm B is continued use of abiraterone/prednisone.  
Primary:  
 
Progression-Free Survival at the milestone Day 60 assessment: To ascertain whether Arm A has a greater proportion of 
patients observed to be alive without progression at Day 60 (±7 days) as compared to Arm B. 
Secondary:  The secondary objectives are based on comparing the arms with respect to the following outcomes:  
 
1. The proportion of patients who have a PSA response (≥ 30% decline) and any PSA decline post-randomization  
2. Objective response 
3. Progression-free survival (PFS) 
4. Time to disease progression (see Section 6.4.1) 
5. Circulating tumor cell (CTC) counts at baseline and on study 
6. Levels of Hsp27, clusterin, and other relevant proteins at baseline and during study 
7. PTEN deletion status in original pathology specimens correlated with clinical outcomes 


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Study Design: This is an open-label, randomized, Phase II clinical trial designed to evaluate the anti-tumor effects of 
OGX-427 and continuing abiraterone acetate and prednisone versus continuing abiraterone acetate and prednisone alone in 
men with metastatic CRPC who have evidence of PSA progression but no evidence of symptomatic or radiographic 
progression that would require alternative therapy (e.g., needing radiation therapy for pain or significant progression of 
visceral metastases).  
Patients on the control arm will be allowed to cross-over to receive OGX-427 following documented disease progression. 
This study will be conducted at approximately 12-15 sites in Canada and the United States. Patients will be randomized 
with equal probability to one of the following arms:  
Screening Period 
Day – 28 to Randomization 
Randomization 
Experimental Arm (Arm A):  
OGX-427 Starting within 7 days of 
randomization, three loading doses 
of 600 mg IV within Week 1 if 
possible (up to 10 days of initiating 
treatment), followed by weekly 
doses of 800 mg IV 
Continuation of standard therapy 
with abiraterone acetate 1000 mg 
PO daily and prednisone 10-20 
mg PO daily  
Both Arms: 
Evaluations at 4 week-intervals. Disease 
assessments required at the milestone Day 60 
assessment (expected to occur after 8 weeks of 
treatment and prior to Day 1, Week 9) and at 16, 
24, 32, 40, and 48 weeks (if applicable) or until 
documented disease progression. Patients who are 
withdrawn from the study for a reason other than 
documented disease progression (Section 6.4.1) or 
patient withdrawal of consent will be followed 
every 4 weeks in the Off-Treatment Follow-up 
Period until documented disease progression. 
 
  
End of Study Treatment 
Off-Treatment Follow Up Period for disease progression (if 
applicable)  
Control Arm (Arm B):  
Continuation of standard therapy 
with abiraterone acetate 1000 mg 
PO daily and prednisone 10-20 
mg PO daily  
 
After documented disease 
progression, patients on Arm B 
may opt to receive OGX-427 
treatment (according to the Arm A 
schedule) following a screening 
evaluation (i.e. all inclusion and 
exclusion criteria have been met). 
Eligible patients will be stratified by prior chemotherapy (yes versus no) and prior PSA response >30% to abiraterone 
acetate (yes versus no) prior to randomization. Abiraterone acetate and prednisone therapy will continue, with or without 
OGX-427, until disease progression is documented (Section 6.4.1) or another End of Study Treatment criterion is met 
(Section 5.5). Arm A patients with PSA progression in the absence of other indicators for progression (by bone scan, CT 
scan, or need for palliative radiation therapy) may continue therapy until disease progression by bone scan, CT, or need for 
palliative radiation therapy, or until disease related deterioration in ECOG performance status to Grade 3 or higher or 
initiation of other treatments (see Section 6.4.1.2), whichever comes first. All patients will be followed for the date of 
documented disease progression. 
Number of Patients: A total of 74 patients will be randomized to the study.  
Study Agent, Dose and Mode of Administration:  
Study Agent: OGX-427 
Dose and Mode of Administration: 600 mg intravenous (IV) infusion over 2 hours for three loading doses within Week 1 
if possible (up to the first 10 days of initiating treatment), followed by weekly 800 mg IV infusions given over 2 hours 
Premedications Required:  


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Patients on the Experimental Arm should be premedicated with an H2 antagonist, e.g. Ranitidine (150 mg PO or 50 mg 
IV) and an antihistamine, e.g., diphenhydramine (25-50 mg).  It is recommended that these premedications be 
administered 30-90 minutes prior to infusion unless there is a medical reason they cannot receive one or more of the drugs 
(see Section 6.7.3). 
Standard Treatment Agents, Doses and Mode of Administration:  
Abiraterone acetate: 
Dose and Mode of Administration: 1000 mg orally once daily, to be given along with prednisone 
Prednisone:  
Dose and Mode of Administration: 10-20 mg/day orally 
Duration of Treatment: Study treatment for both arms will continue until disease progression or another End of Study 
Treatment criterion is met (see Section 5.5). Patients who are withdrawn from study treatment for a reason other than 
documented disease progression or patient withdrawal of consent to participate in the study will be followed every 4 
weeks in the Off-Treatment Follow-up Period until documented disease progression.  
Definition for Primary Endpoint: 
Progression-Free Survival at the milestone Day 60 assessment: the proportion of patients alive without disease 
progression at the milestone Day 60 assessment 
Disease progression is defined on the basis of PSA progression, measurable or non-measurable disease progression,  ≥2 
new lesions on bone scan, disease-related deterioration in ECOG performance status to Grade 3 or higher, requiring 
palliative radiation therapy, systemic anti-cancer therapy, surgery for disease-related complication, or cancer pain 
requiring either initiation of chronic opiate analgesia (oral or parenteral) or a consistent increase >33% in daily opioid use 
from baseline (see Section 6.4.1.2). 
Statistical Considerations:  
The study is designed to assess the primary endpoint as defined in the objectives. Overall study success is defined as 
meeting statistical criterion on the primary endpoint. The primary endpoint will be tested at a one-sided 10% significance 
level in an intention-to-treat analysis using Fisher’s exact test. Seventy-four patients are required for a hypothesized Arm 
A probability of success that is 25%-points superior than that for Arm B. Given the Arm B probability of success at 5%, 
there will be 90% power. A conservative statement of the overall study type I error probability is 20%.  


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TABLE OF CONTENTS 
SYNOPSIS. ..................................................................................................................................... 4 
TABLE OF CONTENTS ................................................................................................................ 8 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ............................................... 14 
1. 
INTRODUCTION AND BACKGROUND .............................................................. 17 
1.1. 
Treatment of Castrate Resistant Prostate Cancer ....................................................... 17 
1.2. 
Antisense Technology Platform ................................................................................. 17 
1.3. 
Apoptosis Inhibitors ................................................................................................... 18 
1.4. 
Hsp27 as a Therapeutic Target for Cancer ................................................................ 18 
1.5. 
OGX-427 as a Therapeutic Agent.............................................................................. 20 
1.5.1. 
Preclinical Studies ...................................................................................................... 20 
1.5.2. 
Nonclinical Drug Disposition and Toxicity Evaluation of OGX-427 ....................... 25 
1.6. 
Phase I Clinical Study OGX-427-01.......................................................................... 26 
1.6.1. 
Patient Demographics, Number of Cycles Received, and Reasons for 
Discontinuation of Therapy ....................................................................................... 27 
1.6.2. 
Adverse Events .......................................................................................................... 27 
1.6.3. 
Cardiac Repolarization............................................................................................... 30 
1.6.4. 
Complement ............................................................................................................... 30 
1.6.5. 
Efficacy Outcome Measures ...................................................................................... 30 
1.6.6. 
Pharmacokinetics ....................................................................................................... 32 
1.7. 
Phase II Clinical Study PR-01 ................................................................................... 32 
1.7.1. 
Patient Disposition and Demographics ...................................................................... 33 
1.7.2. 
Adverse Events .......................................................................................................... 34 
1.7.3. 
Efficacy Evaluations .................................................................................................. 36 
2. 
RATIONALE ............................................................................................................. 37 
2.1. 
Rationale for the Study .............................................................................................. 37 
2.2. 
Rationale Supporting Drug Dose Selection and Duration ......................................... 38 
2.3. 
Rationale Supporting Evaluation of Other Relevant Proteins ................................... 38 
3. 
STUDY OBJECTIVES .............................................................................................. 39 
3.1. 
Primary Objective ...................................................................................................... 39 
3.2. 
Secondary Objectives................................................................................................. 39 
4. 
STUDY DESIGN OVERVIEW ................................................................................ 40 


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4.1. 
Study Design .............................................................................................................. 40 
4.2. 
Study Treatment ......................................................................................................... 41 
4.2.1. 
Experimental Arm: OGX-427 plus Abiraterone Acetate and 
Prednisone Continuation ............................................................................................ 41 
4.2.2. 
Control Arm: Abiraterone Acetate and Prednisone Continuation ............................. 42 
4.3. 
Number of Patients .................................................................................................... 43 
4.4. 
Number of Clinical Sites ............................................................................................ 43 
4.5. 
Estimated Duration/Completion of Study .................................................................. 43 
5. 
SELECTION AND WITHDRAWAL OF PATIENTS ............................................. 43 
5.1. 
Enrollment of Patients................................................................................................ 43 
5.2. 
Registration Procedures ............................................................................................. 43 
5.3. 
Inclusion Criteria ....................................................................................................... 44 
5.4. 
Exclusion Criteria ...................................................................................................... 45 
5.5. 
End of Study Treatment/Criteria for Withdrawal ...................................................... 46 
6. 
STUDY EVALUATIONS AND PROCEDURES .................................................... 48 
6.1. 
Schedule for Evaluations and Procedures .................................................................. 48 
6.2. 
Detailed Description of Study Visits ......................................................................... 52 
6.2.1. 
Screening Visit for Both Arms ................................................................................... 52 
6.2.2. 
Assignment of Patient Number, Stratification, and Randomization .......................... 54 
6.2.3. 
Study Procedures During Week 1 .............................................................................. 54 
6.2.4. 
Experimental Arm Only: Administration of Weekly OGX-427................................ 56 
6.2.5. 
Study Procedures During Week 3 .............................................................................. 57 
6.2.6. 
Both Study Arms: General Study Procedures at Day 1, Week 5 and 
Every 4 Weeks Thereafter During Study Treatment ................................................. 57 
6.2.7. 
Milestone Day 60 Disease Assessment...................................................................... 58 
6.2.8. 
End of Treatment (EOT) Visit [21 days (± 7 days) Following 
Withdrawal from Study Treatment] ........................................................................... 59 
6.2.9. 
Off Treatment Follow-up Period [Every 4 weeks (± 5 days)] ................................... 61 
6.3. 
Cross-over OGX-427 Treatment for Control Patients ............................................... 61 
6.3.1. 
Procedures for Control Patients to be Eligible for Cross-over 
Treatment ................................................................................................................... 61 
6.3.2. 
Eligibility Criteria for Cross-over Treatment ............................................................ 62 
6.3.3. 
Screening Procedures for Cross-over Treatment ....................................................... 63 
6.4. 
Study Outcome Definitions........................................................................................ 65 


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6.4.1. 
Disease Progression ................................................................................................... 65 
6.4.2. 
Response Definitions ................................................................................................. 67 
6.5. 
Protocol-Specific Samples for Correlative Studies .................................................... 68 
6.5.1. 
Blood Collection for Assays Evaluating Hsp27, Clusterin, and Other 
Relevant Proteins ....................................................................................................... 68 
6.5.2. 
Circulating Tumor Cells ............................................................................................ 68 
6.5.3. 
Tissue for PTEN ........................................................................................................ 68 
6.6. 
Dose Modifications for Toxicity ................................................................................ 68 
6.6.1. 
Dose Modifications for OGX-427 ............................................................................. 69 
6.6.2. 
Dose Modifications for Abiraterone Acetate ............................................................. 69 
6.6.3. 
Hepatic Toxicity for OGX-427 and Abiraterone Acetate .......................................... 70 
6.6.4. 
Hematological Toxicity for OGX-427 ....................................................................... 71 
6.6.5. 
Renal Toxicity for OGX-427 ..................................................................................... 72 
6.6.6. 
Acute Infusion Reactions: Dose Modifications for OGX-427 .................................. 72 
6.6.7. 
Management of Hypertension .................................................................................... 74 
6.6.8. 
Management of Hypokalemia .................................................................................... 75 
6.6.9. 
Management of Rash ................................................................................................. 75 
6.6.10. 
Grade 3 or 4 Non-Hematological Toxicities for OGX-427 and 
Abiraterone Acetate Not Discussed Above ............................................................... 76 
6.6.11. 
Onset of either >Grade 2 Motor Neuropathy or >Grade 2 Muscle 
Weakness ................................................................................................................... 76 
6.6.12. 
Dose Modifications for Prednisone ........................................................................... 76 
6.7. 
Concomitant Medications/Therapy ............................................................................ 76 
6.7.1. 
Bisphosphonates and Bone Protecting Agents .......................................................... 76 
6.7.2. 
Corticosteroids ........................................................................................................... 77 
6.7.3. 
Premedication for OGX-427 Infusion-Related Adverse Events ................................ 77 
6.7.4. 
Anti-emetics ............................................................................................................... 77 
6.7.5. 
Anticoagulation Therapy ........................................................................................... 77 
6.7.6. 
Growth Factors and Transfusions .............................................................................. 77 
6.7.7. 
Anticancer Therapies ................................................................................................. 78 
6.7.8. 
Palliative Radiation Therapy ...................................................................................... 78 
7. 
STUDY AGENTS ..................................................................................................... 78 
7.1. 
OGX-427.................................................................................................................... 78 
7.1.1. 
Risks and Precautions ................................................................................................ 78 


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7.1.2. 
Supply, Packaging, Labeling, Storage of OGX-427 .................................................. 80 
7.1.3. 
Administration ........................................................................................................... 81 
7.1.4. 
Accountability ............................................................................................................ 81 
7.2. 
Abiraterone Acetate ................................................................................................... 81 
7.2.1. 
Risks and Precautions ................................................................................................ 82 
7.2.2. 
Supply, Packaging, Labeling, Storage ....................................................................... 82 
7.2.3. 
Administration ........................................................................................................... 82 
7.2.4. 
Accountability ............................................................................................................ 82 
7.3. 
Prednisone Treatment ................................................................................................ 83 
7.3.1. 
Risks and Precautions ................................................................................................ 83 
7.3.2. 
Supply, Packaging, Labeling, Storage ....................................................................... 83 
7.3.3. 
Administration ........................................................................................................... 83 
7.3.4. 
Accountability ............................................................................................................ 83 
7.4. 
Other Risks and Precautions from Study Procedures ................................................ 84 
8. 
ADVERSE EVENTS ................................................................................................. 84 
8.1. 
Definitions.................................................................................................................. 84 
8.2. 
Reporting of Adverse Events ..................................................................................... 85 
8.3. 
Reporting of Serious Adverse Events ........................................................................ 85 
8.4. 
Hoosier Cancer Research Network Requirements for Reporting SAEs .................... 86 
8.5. 
Assessment of Causality ............................................................................................ 87 
9. 
SAFETY MONITORING .......................................................................................... 88 
9.1. 
Data Safety Monitor ................................................................................................... 88 
Safety monitoring will be performed by an independent data safety monitor (DSM) 
who will be appointed for this study. ......................................................................... 88 
9.2. 
Study Monitoring ....................................................................................................... 88 
9.3. 
Data and Safety Monitoring Plan ............................................................................... 89 
9.4. 
Data/Safety Monitoring and Reporting Guidelines ................................................... 89 
10. 
STATISTICAL CONSIDERATIONS....................................................................... 90 
10.1. 
Sample Size ................................................................................................................ 90 
10.2. 
Analysis Sets .............................................................................................................. 90 
10.3. 
Efficacy Endpoints ..................................................................................................... 90 
10.3.1. 
Primary Endpoint ....................................................................................................... 90 
10.3.2. 
Secondary Endpoints ................................................................................................. 91 


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10.4. 
Safety Summaries ...................................................................................................... 93 
11. 
REGULATORY AND ETHICS CONSIDERATIONS ............................................ 94 
11.1. 
Informed Consent....................................................................................................... 94 
11.2. 
Institutional Review Board (IRB)/Research Ethics Board (REB) ............................. 94 
11.3. 
Patient Confidentiality ............................................................................................... 95 
12. 
ADMINISTRATIVE PROCEDURES ...................................................................... 95 
12.1. 
Drug Provider Responsibilities .................................................................................. 95 
12.2. 
Investigator Responsibilities ...................................................................................... 96 
12.3. 
Regulatory Compliance ............................................................................................. 96 
12.4. 
Ethical Conduct of the Trial / Good Clinical Practice ............................................... 97 
12.5. 
Protocol Modification or Premature Termination ...................................................... 97 
13. 
REFERENCES .......................................................................................................... 98 
14. 
APPENDICES ......................................................................................................... 103 
14.1. 
Drug Formulation / Pharmacy Guideline for OGX-427 .......................................... 103 
14.2. 
Toxicity Grading Scale: NCI CTCAE Version 4.0 ................................................. 106 
14.3. 
Processing and Shipping of Study Samples ............................................................. 107 
14.4. 
Guidelines to Evaluate the Response to Treatment in Solid Tumors 
(RECIST 1.1) ........................................................................................................... 110 
14.5. 
ECOG Performance Status ...................................................................................... 111 


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LIST OF TABLES 
Table 1: 
Incidence of Non-laboratory Grade 3 or 4 AEs Observed in More than 
One Patient Receiving OGX-427 Monotherapy ........................................................ 28 
Table 2: 
Number (%) of Patients with at Least One Grade 3 or 4 Laboratory 
Value on Study: Safety Population of Patients Receiving OGX-427 
Monotherapy .............................................................................................................. 29 
Table 3: 
Baseline Patient Characteristics ................................................................................. 33 
Table 4: 
Evaluations and Procedures Schedule ....................................................................... 49 
Table 5: 
Dose Level Modifications for OGX-427 ................................................................... 69 
Table 6: 
Dose Modifications of OGX-427 for Hepatic Toxicity ............................................. 70 
Table 7: 
Dose Modifications of Abiraterone Acetate for Hepatic Toxicity ............................. 71 
Table 8: 
Dose Modifications for Hematologic Toxicity .......................................................... 71 
Table 9: 
Dose Modifications of OGX-427 for Renal Toxicity ................................................ 72 
Table 10: Dose Modifications for Acute Infusion Reactions with OGX-427 ........................... 74 
Table 11: Dose Modifications of Abiraterone Acetate for Hypertension .................................. 74 
Table 12: Dose Modifications of Abiraterone Acetate for Hypokalemia .................................. 75 
 
LIST OF FIGURES 
Figure 1: 
Hsp27 Concentrations in PC-3 Human Prostate Cancer Cells 
Following Treatment With Control ASO or Hsp27 ASO .......................................... 20 
Figure 2: 
Hsp27 ASO Inhibits Human Prostate Cancer Cell Growth ....................................... 21 
Figure 3: 
Hsp27 ASO Induces Apoptosis in Prostate Cancer Cells .......................................... 21 
Figure 4: 
Androgen Induced Rapid Phosphorylation of Hsp27 on Both Ser 78 
and Ser 82 Residues in a Dose- and Time-Dependent Manner ................................. 22 
Figure 5: 
Androgen-induced Hsp27 Phosphorylation is Androgen-Receptor 
Dependent .................................................................................................................. 23 
Figure 6: 
Effect of Hsp27 on Transcriptional Activity of Androgen Receptors ....................... 24 
Figure 7: 
Effect of Hsp27 ASO Treatment on PC-3 Tumor Growth and 
Chemosensitivity In Vivo ........................................................................................... 25 
Figure 8: 
Best Change in Hsp27+CTCs* by Disease Category & Cohort (in %) ..................... 32 
Figure 9: 
Study Design .............................................................................................................. 40 
  
 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ABBREVIATION/TERM 
DEFINITION 
ACTH 
Adrenocorticotropic Hormone 
AE 
Adverse Event(s) 
AI 
Androgen Independent 
AKT 
Serine/threonine Kinase (Protein Kinase B) 
ALT 
Alanine Aminotransferase 
ANC 
Absolute Neutrophil Count 
AR 
Androgen Receptor 
ARAS 
All Randomized Analysis Set 
ASCO 
American Society of Clinical Oncology  
ASO 
Antisense Oligonucleotide(s) 
AST 
Aspartate Aminotransferase 
ATP  
Adenosine 5'-triphosphate 
AUC  
Area Under the Curve 
BAD 
Bcl-2/Bcl-XL-associated death promoter 
Bb  
Blood marker-complement split products 
Bcl-2/Bcl-XL 
Prototypes for a family of mammalian genes and the proteins that govern 
mitochondrial outer membrane permeabilisation (MOMP) apoptosis  
BID  
Twice Daily 
BP 
Blood Pressure (Vital sign) 
BSA 
Body Surface Area 
°C 
Centigrade, Celsius 
C3a  
Blood marker-complement split products 
CBC 
Complete Blood Count 
CD45- 
Absence of this Protein Tyrosine Phosphatase (CD45)  
CGE 
Capillary Gel Electrophoresis 
cGy 
Centi Gray (unit of radiation) 
CK+ 
Cytokeratin positive cells 
Cl 
Chloride 
CO2 
Carbon Dioxide 
CR 
Complete Response 
CRPC 
Castrate Resistant Prostate Cancer 
CRF 
Case Report Form 
CT 
Computerized Tomography 
CTC 
Circulating Tumor Cell(s) 
CTCAE  
Common Toxicity Criteria for Adverse Events 
Cmax 
Maximum Concentration 
D5W 
5% Dextrose in Water 
Daxx 
Death associated protein 6 
DAPI+ 
4',6-diamidino-2-phenylindole positive (fluorescent stain that binds to DNA) 
dL 
Deciliter 
DNA 
Deoxyribonucleic Acid 
DSM 
Data Safety Monitor 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
EDTA 
Ethylenediaminetetraacetate 
EOT 
End of Treatment 
Fas 
Apoptosis antigen ligand 1 
FDA 
Food and Drug Administration (USA) 
FISH 
Fluorescence in situ hybridization  
GCP 
Good Clinical Practice 
G-CSF 
Granulocyte Colony Stimulating Factor 
GI 
Gastrointestinal 
H2 
Histamine-2 Receptor 


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ABBREVIATION/TERM 
DEFINITION 
hERG 
Human ERG gene  (ether à go go related) 
HR 
Heart Rate (Vital sign) 
Hsp 
Heat Shock Protein 
HUS 
Hemolytic Uremic Syndrome 
I-κBα 
Main apoptosis inhibitor 
ICH 
International Conference on Harmonization 
I.D. 
Identification (number) 
IGF 
Insulin-like growth factor 
INR 
International Normalized Ratio (anticoagulant monitoring) 
IP 
Intraperitoneal(ly) 
IRB 
Institutional Review Board 
IV 
Intravenous(ly) 
K 
Potassium 
Kb 
Kilobases 
kg 
Kilogram 
L 
Liter 
LDH 
Lactate Dehydrogenase 
LHRH 
Luteinizing Hormone-releasing Hormone 
LNCaP 
Androgen-sensitive Prostate Cancer Cells 
MAP 
Mitogen-Activating-Protein 
MAPKAP 
Mitogen-Activating-Protein Kinases 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram(s) 
mL 
Milliliter(s) 
mm 
Millimeter 
MOE 
Methoxyethyl 
mRNA 
Messenger Ribonucleic Acid 
MTD 
Maximum Tolerated Dose 
N or n 
Number of 
Na 
Sodium 
NCI  
National Cancer Institute  
NE 
Not Evaluable 
NF-κB 
Nuclear Factor kappa-light-chain-enhancer of activated B cells 
ng 
Nanogram 
nM (nmol) 
Nanomole or Nanomolar 
NOAEL 
No Observed Adverse Effect Level 
OGX-427 
2’-Methoxy-Ethyl-Phosphorothioate Antisense to Heat Shock Protein-27 
p90Rsk 
Ribosomal s6 kinase 
PC-3 
Human Caucasian Prostate Adenocarcinoma Cell Line 
PD 
Progressive Disease 
PFS 
Progression-free Survival 
pH 
Hydrogen-ion Concentration (acid / alkaline) 
PI 
Principal Investigator 
PO or po 
By Mouth 
PR 
Partial Response and PR Interval 
PSA 
Prostate Specific Antigen 
PTEN 
Phosphatase and tensin homolog (Tumor Suppressor Gene) 
PTT 
Partial Thromboplastin Time 
QT/QTc 
Interval of time between the start of the Q wave and the end of the T wave in the 
heart's electrical cycle 
REB 
Research Ethics Board 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RNA and RNase H 
Ribonucleic Acid (RNA) and enzyme that cleaves RNA (RNase H) 
RPM 
Revolutions per Minute 
SAE 
Serious Adverse Event(s) 
SD 
Stable Disease 
SGOT 
Serum glutamic-oxalacetic transaminase (see AST) 


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ABBREVIATION/TERM 
DEFINITION 
SGPT 
Serum glutamic-pyruvate transaminase (see ALT) 
SI 
Standard international 
SPM 
Study Procedures Manual 
ssDNA 
Single strand DNA 
TNM 
T=size and extent of primary tumor; N=degree of regional lymph node 
involvement; M=presence or absence of distant metastases 
TDF 
Task Delegation Form (for delegation of study responsibilities) 
TPD 
Therapeutic Products Directorate (Canada) 
TPR 
Tetratricopeptide repeat 
ULN 
Upper Limit of Normal 
USP 
United States Pharmacopeia 
µm 
Micrometer  
vs 
Versus 
WBC 
White Blood Cell 
WT 
Wild Type 
 


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1. 
INTRODUCTION AND BACKGROUND 
1.1. 
Treatment of Castrate Resistant Prostate Cancer  
Prostate cancer is the most commonly diagnosed cancer and the second most common 
cause of cancer death in men in North America.1 Patients with metastatic disease have a 
poor prognosis, and although hormonal therapy in the form of medical or surgical 
castration can induce significant long-term remissions, development of androgen-
independent disease is inevitable. The current standard of care for castrate resistant 
prostate cancer (CRPC) is mainly palliative in its intent, with proven treatment options 
currently including analgesia, radiation, bisphosphonates, chemotherapy, and abiraterone 
acetate. Abiraterone acetate inhibits cytochrome P450 17α-hydroxylase/C17,20-lyase 
(CYP17a), a key enzyme involved in de novo androgen biosynthesis, thereby broadly 
decreasing the levels of androgens in both non-castrate and castrate patients. Abiraterone 
acetate with prednisone has been demonstrated in a phase III study to improve overall 
survival in patients with metastatic CRPC who have previously been treated with docetaxel 
chemotherapy,2 and is now considered a standard of care. Median duration of treatment on 
the study was 8 months, although median progression-free survival was 5.6 months. 
Prostate-specific antigen (PSA) response rates were only 29%, and median PSA 
progression-free survival was 10.2 months; however, the PSA analyses are difficult to 
interpret as PSA testing was only performed every 3 months on the study. In the phase III 
study, patients were continued on study protocol unless they met all three criteria for 
progression (PSA, objective disease, symptoms); this study currently forms the basis for 
duration of therapy as standard of care treatment with abiraterone acetate. Phase II studies 
of abiraterone acetate in the post-docetaxel patient population have demonstrated PSA 
declines of >50% occurring in approximately 50% of patients, and median PSA 
progression-free survival in the range of 5-6 months.  Given that patients on abiraterone 
acetate can first progress with PSA (indicating androgen receptor [AR] signaling 
activation) without symptoms or objective disease progression, this provides an 
opportunity to evaluate novel agents that target potential mechanisms of CRPC resistance 
in combination with abiraterone acetate, particularly those that target AR signaling. 
1.2. 
Antisense Technology Platform 
Antisense therapeutics are based on the premise that sequences of single-stranded nucleic 
acids (antisense oligonucleotides, or ASOs) will bind to complementary strands of nucleic 
acids through hybridization. A cancer cell with overexpression of a specific protein 
produces an abundance of messenger RNA that is translated into excess protein.3 The 
introduction of a specific complementary or “antisense” strand of single-stranded DNA can 
bind to the abundant mRNA strands, leading to degradation before translation can occur 
and reduction in protein levels of the target gene.4  
Various antisense chemistries have been evaluated to generate potential drug candidates 
for cancer therapy. Over the last ten years, considerable effort has been made by numerous 
groups to improve the in vivo potency of ASOs by modifications of the phosphodiester-
linkage and heterocyclic structure of the sugar. Advances in modified nucleic acid 
chemistry5-7 have yielded “second-generation” ASO modifications which improve both 


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RNA binding affinity and resistance to nuclease degradation, thereby increasing its half-
life and resulting in increased potency.  
Second-generation chemistry, used by OGX-427, applies 2´-O-(2-methoxyethyl) (2´-MOE 
modification) at the 2′ position of the carbohydrate moiety on both ends of the 
oligonucleotide, resulting in increased target binding affinity, resistance to degradation, 
and substantially better tissue pharmacokinetics. The improved affinity of a second-
generation drug is primarily attributable to its design and composition. In particular, 
second-generation drugs are composed of both RNA-like and DNA-like nucleotides, while 
first-generation drugs are entirely DNA-like. Because RNA hybridizes more tightly to 
RNA than to DNA, the second-generation drugs have a greater affinity for RNA targets 
and therefore greater potency, as demonstrated by the improved antisense potency 
observed in cell culture systems and in animals. In addition, the 2´-MOE modification 
results in decreased binding affinity to RNase H, the principal nuclease that cleaves ASO-
bound RNA, which results in significantly improved tissue half-life in vivo.8 This produces 
a longer duration of action, allowing less frequent dosing.6 Finally, 2´-MOE ASOs have 
been reported to have a more attractive safety profile than unmodified phosphorothioate 
ASOs.5 
Recent technology developments have opened new avenues to identify and validate target 
genes involved in oncogenesis and disease progression, especially in the area of treatment 
resistance. A number of genes have been identified as possible targets for the antisense 
approach. Antisense strategies have demonstrated an ability to specifically inhibit the 
expression of these genes in animal models, resulting in clear antitumor activity.4,9-14 
Antisense therapeutics are particularly well suited for inhibiting targets that are considered 
not amenable to small molecule or monoclonal antibody inhibition. 
1.3. 
Apoptosis Inhibitors 
As mentioned above, one of the main obstacles in the treatment of advanced prostate 
cancer by androgen ablation is androgen-independent (AI) progression and development of 
treatment-resistant disease. AI progression is a complex process involving: adaptive 
upregulation of anti-apoptotic survival genes; variable combinations of clonal selection; 
androgen receptor transactivation in the absence of androgen from mutations or increased 
levels of co-activators; and alternative growth factor pathways. Research during the past 
decade has identified several proteins that may promote progression and resistance by 
inhibiting apoptosis. Laboratory studies at the Prostate Centre at Vancouver General 
Hospital have identified and functionally characterized several survival proteins that 
increase after castration and appear to function to accelerate time to AI recurrence and 
resistance by inhibiting apoptosis. These include clusterin,15 Bcl-2 family members,16 
insulin-like growth factor (IGF) binding proteins17 and heat shock protein 27 (Hsp27).18,19 
Agents targeting Bcl-2,20,21 clusterin20,21 and Hsp27 (abstract) have been successfully 
translated from the lab into the clinic. Human clinical trials are underway for several 
phosphorothioate ASOs.4,22  
1.4. 
Hsp27 as a Therapeutic Target for Cancer 
Heat shock proteins (Hsps) are a family of highly conserved proteins whose expression is 
induced by cell stressors such as hyperthermia, oxidative stress, activation of the Fas death 


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receptor, and cytotoxic drugs.23-25 Hsps have attracted attention as new therapeutic targets 
for cancer, especially since the discovery and characterization of geldanamycin as an 
inhibitor of Hsp9026,27 and the targeting of the clusterin gene,28 whose product has small 
heat shock protein-like function. Molecules inhibiting both these targets have entered into 
clinical trials. Hsp27 is classified among the small heat shock proteins (15-30 kDa) and 
functions as an ATP-independent molecular chaperone. Depending on the phosphorylation 
status and cell stresses, Hsp27 can form oligomers which allow it to have affinity for client 
proteins, preventing their precipitation and aggregation.23-25 Phosphorylation is catalyzed 
by MAPKAP kinase-2, which is downstream of the p38 MAP kinase.29 Increased 
expression of Hsp27 increases tumorigenic and metastatic potential and inhibits apoptotic 
cell death from a variety of causes.30-34  
Hsp27 can inhibit apoptotic cell death by a variety of mechanisms. It prevents formation of 
the apoptosome, apparently doing so by either preventing release of mitochondrial 
cytochrome-c or directly sequestering cytochrome-c in the cytosol after mitochondrial 
release.34 Also, as interference to the intrinsic pathway, Hsp27 may directly interact with 
caspase-3, although this is still of some debate.35,36 It may also interfere with the extrinsic 
pathway and has been shown to inhibit Daxx, a mediator of Fas-induced caspase-
independent apoptosis.37 Furthermore, Hsp27 has been shown to inhibit apoptosis by 
decreasing reactive oxygen species within cells by increasing glutathione and reducing the 
toxic effect of oxidized proteins.38-41 In addition, it can act early during cell stress to 
stabilize and accelerate recovery of actin filaments, thus preventing disruption of the 
cytoskeleton.42-44 Hsp27 is also involved in regulation of the serine/threonine kinase AKT 
(Protein Kinase B), an important signaling molecule for cell survival and proliferation 
downstream of growth factor stimulation.45,46 Furthermore, AKT is constitutively activated 
by loss of the PTEN tumour suppressor gene, one of the most frequently mutated genes in 
cancer including prostate cancer. Hsp27 can also exert its anti-apoptotic effects through 
enhancement of NF-κB activity, by increasing degradation of its main inhibitor I-κBα. 
Recently, Hsp27 has been shown to promote IGF-I survival signaling via p90Rsk 
(Ribosomal s6 kinase) dependent phosphorylation and inactivation of BAD (Bcl-2/Bcl-
XL-associated death promoter).47 
Many malignancies have been shown to express Hsp27, including breast, ovarian, prostate, 
lung, endometrial, gastric, hepatic, and bladder cancers plus leukemia and osteosarcoma.48 
Increased expression of Hsp27 increases tumorigenicity and metastatic potential and 
inhibits apoptotic cell death from a variety of causes.30-34 In prostate cancer, increased 
expression has been associated with increasing Gleason score, poor outcome, and 
development of AI progression.49-51 Over-expression of Hsp27 in the androgen-dependent 
LNCaP prostate cancer cell line suppressed castration-induced apoptosis and conferred 
castration resistance.19 Hsp27 knockdown using ASO potently decreased Hsp27 levels, 
increased caspase-3 cleavage and apoptosis, enhanced paclitaxel chemosensitivity, and 
delayed tumor progression in vivo.18,19 It has also been recently identified that a feed-
forward loop whereby androgen bound AR induced rapid Hsp27 phosphorylation that in 
turn cooperatively facilitated genomic activity of the AR, thereby enhancing prostate 
cancer cell survival.52 OGX-427-induced knockdown of Hsp27, destabilized the AR, 
enhanced ubiquitination and degradation, and, thus, implicated Hsp27 in castration 
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Therefore, targeting Hsp27 as a therapy is very attractive as it would affect multiple 
pathways implicated in cancer progression and resistance, as well as CRPC specifically 
through the AR, as opposed to the targeting of a single pathway, which might be expected 
to have limited benefits in the face of the heterogeneity and redundancy that exists in 
cancer cells.  
1.5. 
OGX-427 as a Therapeutic Agent 
OGX-427 is a 4-12-4 2´-MOE gapmer oligonucleotide with phosphorothiolated 
internucleotide linkages designed to bind to Hsp27 mRNA, resulting in the inhibition of 
the production of Hsp27 protein. OGX-427 is similar to endogenous DNA, but contains 
second-generation ASO chemical modifications intended to optimize its pharmacological 
potency, pharmacokinetics, and safety profile. A number of in vitro and in vivo 
pharmacological studies have demonstrated that OGX-427 (or an Hsp27ASO) has single-
agent activity in reducing Hsp27 mRNA, inhibiting cell growth, and inducing apoptosis in 
several human cancer cell lines. OGX-427 has also demonstrated chemosensitizing activity 
both in vitro and in vivo in combination with several cytotoxic drugs, including docetaxel.  
1.5.1. 
Preclinical Studies  
In preclinical studies, OGX-427 (or a sequence equivalent Hsp27 ASO) was tested alone 
or in combination with other drugs in various animal tumor models. Experimental evidence 
in vitro suggests that Hsp27 plays a role in mediating cell growth and acts as a prosurvival 
protein in Hsp27-expressing human malignancies, including prostate, breast, ovarian, and 
lung. OGX-427, or an Hsp27 ASO, can ameliorate these effects by down-regulation of 
Hsp27. In addition, Hsp27 ASOs have been shown to enhance the effect of chemotherapy. 
All studies were conducted with a control group administered a mismatched-sequence 
control ASO to the target mRNA.  
1.5.1.1. 
In vitro Studies in Prostate Cancer 
Figure 1 represents an example of Hsp27 down-regulation in the human PC-3 prostate cell 
line by an Hsp27 ASO. Vinculin demonstrated equal protein loading for each sample. 
Figure 1: 
Hsp27 Concentrations in PC-3 Human Prostate Cancer Cells Following 
Treatment With Control ASO or Hsp27 ASO 
 
 
PC-3 cells were incubated with Hsp27 ASO or scrambled ASO control at 10, 20, 30, 40, or 
50 nM concentrations.  


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Figure 2 and Figure 3 demonstrate that an Hsp27 ASO can both inhibit cell growth and 
induce apoptosis in the human prostate cancer PC-3 cell line. In Figure 2, PC-3 cells were 
treated for 2 days with 30 nmol/L Hsp27 ASO or scrambled ASO control. Growth rates of 
PC-3 cells were examined daily for 4 days using a non-radioactive cell proliferation assay. 
Compared to a scrambled ASO control, an 87% reduction in PC-3 cell growth 4 days after 
treatment with Hsp27 ASO 30 nM was observed.18 
Figure 2: 
Hsp27 ASO Inhibits Human Prostate Cancer Cell Growth 
 
In addition, treatment of the PC-3 cells with the Hsp27 ASO for 2 days induced 
morphological changes characteristic of apoptosis. Haematoxylin and eosin staining 
showed nuclear shrinkage with chromatin condensation and fragmentation, indicative of 
apoptotic cell death. Apoptosis detected by ssDNA nuclear staining increased 2.5-fold in 
PC-3 cells treated with Hsp27 ASO compared to those treated with scrambled ASO 
control.  
Figure 3: 
Hsp27 ASO Induces Apoptosis in Prostate Cancer Cells 
 
Induction of apoptosis by Hsp27 ASO was also demonstrated by flow cytometry, with the 
fraction of cells undergoing apoptosis (sub G1-G0 fraction) being significantly higher after 


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treatment with 30 nM Hsp27 ASO compared with control (33.8 vs. 9.04 %; respectively; 
p  0.01).  
Molecular chaperones are involved in processes of folding, activation, trafficking, and 
transcriptional activity of most steroid receptors, including AR. In the absence of ligand, 
steroid receptors are predominately cytoplasmic, maintained in an inactive but highly 
responsive state by a large dynamic heterocomplex composed of Hsp, co-chaperones and 
tetratricopeptide repeat (TPR)-containing proteins.53-55 Gleave and colleagues have 
identified a novel feed-forward loop involving cooperative interactions between ligand-
activated AR and Hsp27 phospho-activation that facilitate AR stability, shuttling, and 
transcriptional activity.56 Recently identified non-genomic effects of ARs include 
activation of Src, PI3 Kinase, and AKT. Androgen induced rapid phosphorylation of 
Hsp27 on both Ser 78 and Ser 82 residues in a dose- and time-dependent manner as shown 
in Figure 4. Ser 78 and Ser 82 phosphorylation levels increased 3.2- and 5.3-fold, 
respectively, after 15 minutes of incubation with the synthetic androgen R1881.  
Figure 4: 
Androgen Induced Rapid Phosphorylation of Hsp27 on Both Ser 78 
and Ser 82 Residues in a Dose- and Time-Dependent Manner 
 
 
 
 
 
 
AR is required for androgen-induced phosphorylation of Hsp27, since the anti-androgen 
bicalutamide inhibited R1881-induced Hsp27 phosphorylation (see Figure 5A). To further 
support the data, PC3 cells, which do not express endogenous ARs, were transfected with 
increasing amounts of AR or empty vector with or without R1881. As shown in Figure 5B, 
Hsp27 phosphorylation levels at both Ser 78 and Ser 82 sites increased with increasing 
androgen receptor levels after R1881 treatment. 
0
5
15
30
60
Ti
0
0.5
1
1.5
2
2.5
3
3.5
4
1
2
3
4
5
6
Hsp27 phosphorylation (fold/control)
Ser 78
Ser 82
0
1
2
3
4
5
6
1
2
3
4
5
Hsp27 phosphorylation 
(f old/control)
Ser 78
Ser 82
    0          5         15        30        60    Min 
TIME 
     0       1.5       2.5       5       7.5      10 
DOSE (nM R1881) 


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Figure 5: 
Androgen-induced Hsp27 Phosphorylation is Androgen-Receptor 
Dependent 
 
A 
Casodex
R1881
-
-
+
-
+       +
pHsp27 (S-78)
pHsp27 (S-82)
Total Hsp27
Casodex
R1881
-
-
+
-
+       +
pHsp27 (S-78)
pHsp27 (S-82)
Total Hsp27
 
 
 
 
Hsp27 co-localizes with and shuttles ligand-activated AR during nuclear translocation and 
enhances AR transcriptional activity. PSA transactivation assays were performed using 
LNCaP cells transiently transfected with the PSA (6.1 Kb)-luciferase reported plasmid in 
the presence or absence of increasing amount of wild type (WT) Hsp27. As shown in 
Figure 6A, R1881 treatment induced a 34-fold increase in AR reporter gene expression. 
WT Hsp27 overexpression increases androgen-stimulated transcriptional activity of PSA a 
further 3-fold. Conversely, Hsp27 knockdown using OGX-427 decreased PSA 
transactivation in a dose-dependent manner (Figure 6B). Moreover, Hsp27 knockdown by 
OGX-427 inhibited androgen-induced PSA expression in a dose dependent manner (Figure 
6C). These results indicate that Hsp27 expression enhances androgen-stimulated 
transactivation of ARs. 
B
+R1881
Androgen Receptor
AR
pHsp27 (S-78)
pHsp27 (S-82)
Total Hsp27
0   100   200   300    500
-R1881
0    100   200   300  500  (ng) 
B
+R1881
Androgen Receptor
AR
pHsp27 (S-78)
pHsp27 (S-82)
Total Hsp27
0   100   200   300    500
-R1881
0    100   200   300  500  (ng) 
+R1881
Androgen Receptor
AR
pHsp27 (S-78)
pHsp27 (S-82)
Total Hsp27
0   100   200   300    500
-R1881
0    100   200   300  500  (ng) 


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Figure 6: 
Effect of Hsp27 on Transcriptional Activity of Androgen Receptors 
0
2 0
4 0
6 0
8 0
1 0 0
1 2 0
1 4 0
1
2
3
4
5
L u cife ra se  Activity
(F o ld /co n tro l)
Empty vector (ug)        1      1     0.75   0.5     0
Hsp27 WT (ug)            0      0     0.25   0.5     1
R1881                          -
+        +       +       +
LuciferaseActivity 
(Fold/control)
0
5
10
15
20
25
30
35
40
1
2
3
4
5
Luciferase Activity
(fold/control)
MM (uM)                   50      50       0      0       0
Hsp27 ASO (nM)       0        0       30    50     70 
R1881                         -
+        +      +       +
0
5
10
15
20
25
30
35
40
1
2
3
4
5
Luciferase Activity
(fold/control)
MM (uM)                   50      50       0      0       0
Hsp27 ASO (nM)       0        0       30    50     70 
R1881                         -
+        +      +       +
LuciferaseActivity 
(Fold/control)
A
B
 
C 
Oligo  10    50  100   10    50   100   (nM)
MM
Hsp27 ASO
Hsp27
PSA
GAPDH   
 
1.5.1.2. 
In vivo Studies in Prostate Cancer 
The effects of Hsp27 ASO on the growth of human tumors have been examined. Male 
nude mice bearing PC-3 tumors (200 mm3) were randomly selected for Hsp27 ASO versus 
scrambled ASO control. Ten mg/kg of ASO were administrated once daily by 
intraperitoneal (IP) injection for 91 days. No adverse events were observed in the animals. 
As shown in Figure 7A, Hsp27 ASO administration as a monotherapy significantly 
reduced PC-3 tumor volume by at least 50% from weeks 4 through 6.  
Synergy between Hsp27 ASO and chemotherapy has also been demonstrated. Male nude 
mice bearing PC-3 tumors (200 mm3) were randomly selected for Hsp27 ASO versus 
scrambled ASO control. Similarly, 10 mg/kg of Hsp27 ASO were administrated once daily 
by IP injection for 91 days. From days 7 to 14 and 21 to 28, 0.5 mg of micellar paclitaxel 
was administrated intravenously (IV) once daily. Mean tumor volume was similar in all 
groups before therapy. As shown in Figure 7B, treatment with Hsp27 ASO significantly 
enhanced the apoptotic effects of paclitaxel in vivo, reducing mean PC-3 tumor volume by 
>70% by 13 weeks after initiation of treatment, compared with scrambled ASO control. 
Under the experimental conditions described above, no adverse effects were observed. 


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Figure 7: 
Effect of Hsp27 ASO Treatment on PC-3 Tumor Growth and 
Chemosensitivity In Vivo 
 
(** = P 0.01) 
1.5.2. 
Nonclinical Drug Disposition and Toxicity Evaluation of OGX-427 
1.5.2.1. 
Drug Disposition 
Characterization of plasma kinetics, tissue distribution, excretion and metabolism of 
OGX-427 was accomplished by applying “cold” bioanalytical methods to numerous 
plasma, tissue and urine samples collected during 4-week toxicity studies in monkeys and 
mice, as well as plasma samples obtained from a safety pharmacology study conducted in 
monkeys. In both mice and monkeys, the total dosing period was four weeks, beginning 
with a loading dose period followed by once-weekly maintenance doses thereafter to 28 
days (i.e., dosing on Days 1, 3, 5, 7, 14, 21, and 28). 
The results demonstrated that the disposition of OGX-427 following single or repeated 
intravenous infusion is generally similar to that reported for numerous other 
phosphorothioate oligonucleotides.57-59 Specifically, plasma levels of OGX-427 were 
maximal at the end of infusion (monkeys) or shortly following injection (mice), and the 
Cmax and AUC values were generally dose-proportional and not influenced by gender. The 
mean values for clearance and volume of distribution were not highly variable across dose 
levels or over time for both species. In monkeys, the initial half-life, reflecting distribution 
into tissues, was on the order of 0.5 to 1 hours. The terminal half-life in monkeys was 
estimated to range from approximately 50 to 190 hours, and this component most likely 
reflects the rate of clearance of the intact OGX-427 oligonucleotide from tissues. 
The pattern of tissue distribution of OGX-427 was similar between mice and monkeys. At 
all dose levels, the highest tissue concentrations of OGX-427 were observed in the kidney, 
liver and spleen, with substantially lower levels in all other tissues. The levels of OGX-427 
in the brain and testes were exceptionally low (near or below the limits of detection), 
consistent with the inability of oligonucleotides to cross the blood-brain or blood-testes 


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barriers. For both species, tissue concentrations were maximal at the earliest collection 
time-point following a single dose (Day 2), and tissue concentrations decreased slowly 
thereafter such that OGX-427 was detectable in most tissues (excluding brain) two months 
after a single dose. As expected from this long tissue retention, OGX-427 levels 
accumulated substantially (several fold, relative to Day 2 data) during the every-other-day 
dosing phase (doses on Days 1, 3, 5 and 7). However, tissue accumulation was generally 
observed only up to Day 8, with a maintenance of tissue levels during the weekly dosing 
period in the 4-week studies (i.e., between Days 8 and 29).  
Up to approximately 35% of the total dose of OGX-427 was eliminated as intact drug over 
a 24-hour period, although this excretion occurred relatively slowly. Therefore, the initial 
rapid multi-log decline in plasma concentrations (over the first few hours after dosing) was 
considered a reflection of mainly rapid distribution to tissues and not elimination in urine.  
Greater than 90% of the circulating oligonucleotide detectable by capillary gel 
electrophoresis (CGE) was in the form of intact OGX-427, consistent with the dramatic 
nuclease resistance imparted by the dual chemical modifications in OGX-427, as a second-
generation ASO. The data indicate that clearance from tissues largely occurs via egress of 
intact oligonucleotide, rather than by metabolism. These observations suggest that the 
terminal elimination half-life in plasma likely reflects the rate of clearance from tissues. 
Published information on this relationship for closely related oligonucleotides was the 
basis for selecting the dosing schedules employed in the 4-week toxicity studies.58,59 
1.5.2.2. 
Nonclinical Toxicity Studies 
A comprehensive series of nonclinical toxicity studies were conducted with OGX-427. The 
primary toxicity studies were the 4-week studies in mice and monkeys. These studies were 
supplemented with a series of investigations to assess the cardiovascular safety of 
OGX-427. The first of these studies to be conducted was the standard hERG assay. A 
positive response was obtained in this assay, which prompted a follow-up study in a rabbit 
Purkinje fiber system, as well as a cardiovascular safety study in cynomolgus monkeys. 
The results of these studies indicated no risk of adverse effects on cardiac conductance or 
other forms of myocardial injury. 
The no-adverse effect levels (NOAEL) established in monkeys and mice were, respectively 
10 mg/kg and >50 mg/kg. The proximal tubule degeneration in the kidneys of monkeys 
observed at the 40 mg/kg dose level appears to be the dose-limiting toxicity. The most 
salient effect observed at the 10 mg/kg and 40 mg/kg dose-level in monkeys was the 
increase in complement split products (i.e., Bb and C3a), which was indicative of mild 
activation of the alternative complement pathway. This increase in complement split 
products in monkeys was observed at the end of infusion (absent by 6 hours post-infusion) 
and was not associated with deleterious sequelae at doses up to 40 mg/kg.  
1.6. 
Phase I Clinical Study OGX-427-01 
OGX-427-01 was the first open-label, dose-escalation, Phase I clinical study designed to 
evaluate the safety profile, determine the maximum tolerated dose (up to a maximum dose 
of 1000 mg), characterize the pharmacokinetic profile, and document objective responses 
or disease stabilization for OGX-427 when administered weekly as a single agent and 


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when administered in combination with chemotherapy (docetaxel). The study also assessed 
the potential for OGX-427 to delay cardiac repolarization (QT/QTc interval) and levels of 
specific complement split products following OGX-427 infusion. All patients enrolled had 
cancers that have been shown to overexpress Hsp27 (breast, ovarian, prostate, non-small 
cell lung, and bladder). Patients had to have metastatic disease and have failed all therapies 
felt to be curative or for which no curative therapy existed. Refer to the Investigator’s 
Brochure for more detailed information. 
OGX-427 was administered to patients in 7 cohorts. In Cohorts 1 to 5, OGX-427 was 
administered weekly as a single agent per dose-level in 3-week cycles starting at a dose of 
200 mg OGX-427 in Cohort 1. Dose escalations of 200 mg each occurred within cohorts 
up to 1000 mg of OGX-427 in Cohort 5. Weekly OGX-427 plus docetaxel was 
administered to two subsequent cohorts, Cohorts 6 and 7, at 800 mg and 1000 mg, 
respectively. Intra-patient dose escalation was not allowed. 
The study was initiated in June of 2007 and 65 patients were enrolled. One patient was 
consented but not treated. Data are available from 64 patients who received at least one 
dose of OGX-427: 42 treated in the first five cohorts with OGX-427 as a single agent and 
22 treated with OGX-427 plus docetaxel.  
1.6.1. 
Patient Demographics, Number of Cycles Received, and Reasons for 
Discontinuation of Therapy 
The median age of the 64 patients was 64 years; 43 patients (67%) were male. The 
majority of patients (58%) had prostate cancer, followed by breast (19%), ovarian (11%), 
lung (9%), and bladder (3%) cancers. Ten patients (16%) were unable to complete a 
minimum of one cycle of therapy due mainly to adverse events/safety concerns (4 patients) 
or early disease progression/global deterioration (3 patients). The remaining patients 
completed a range of treatment from one to 10 cycles, with a median of 2 cycles.  
As of the data cut-off (January 2012), 56 of 64 (86%) patients had expired, 1 patient was 
lost to follow-up, 1 patient withdrew consent, and 6 patients remained in follow-up. Four 
patients completed ten cycles of therapy, and 60 patients discontinued therapy prior to 
completion of 10 cycles. Forty-six of 60 (77%) patients discontinued for disease 
progression/global deterioration. Fifteen patients discontinued for other reasons, including 
4 patients who discontinued due to toxicity or adverse event, 3 patients for investigator 
decision, 2 patients for treatment delay, 3 patients for withdrawal of consent, and 2 for 
other reasons.  
1.6.2. 
Adverse Events 
A maximum tolerated dose (MTD) was not observed at the highest dose evaluated (1000 
mg) with or without docetaxel treatment; however, there was one dose-limiting toxicity. A 
breast cancer patient in Cohort 3 (600 mg OGX-427 monotherapy) with undiagnosed brain 
metastases experienced cerebral hemorrhage. The protocol was subsequently amended to 
exclude patients with brain metastases.  
All subjects experienced at least one treatment-emergent adverse event. The majority of 
the adverse events (AEs) reported were Grade 1 or Grade 2 (88% of all AEs). Among 
patients receiving OGX-427 monotherapy, the most common non-laboratory adverse 


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events (i.e., occurring in 20% or more of the patients) included: infusion-related reaction 
(64% of patients), chills (55%), fatigue (38%), pruritus (36%), diarrhea (31%), dyspnoea 
(31%), anemia (29%), nausea (26%), flushing (26%), blood creatinine increased (26%), 
back pain (24%), arthralgia (24%), vomiting (24%), hypokalemia (24%), peripheral edema 
(21%), pyrexia (21%), and decreased appetite (21%). There were no clear trends observed 
across the OGX-427 dosing cohorts for the most common non-laboratory adverse events. 
Non-laboratory adverse events observed in patients receiving OGX-427 plus docetaxel are 
detailed in the Investigator’s Brochure. 
During the Loading Dose Period and Cycle 1, the most common adverse events observed 
in patients receiving OGX-427 monotherapy were similar to those for the treatment period 
as a whole. Events that occurred during the Loading Dose Period and Cycle 1 in 20% or 
more of patients receiving OGX-427 monotherapy were: infusion-related reactions (60% 
of patients), chills (52%), pruritus (33%), fatigue (26%), flushing (24%), anemia (24%), 
diarrhea (21%), nausea (21%), and blood creatinine increased (21%). Prophylaxis with 
ibuprofen or acetaminophen was required per protocol for a 24-hour period on infusion 
days during the Loading Dose Period only in an attempt to decrease the rigors and fevers 
often associated with administration of ASOs. All infusion related reactions (infusion 
reactions plus cytokine release syndrome) during the loading doses and Cycle 1 were 
Grade 1 or 2, except for Grade 3 events experienced by three patients (two treated with 600 
mg OGX-427 monotherapy and one treated with 800 mg OGX-427 monotherapy).  
The incidence of Grade 3 or higher non-laboratory adverse events observed is summarized 
by cohort below (sorted by overall decreased frequency). Among patients receiving OGX-
427 monotherapy, there were 11 non-laboratory Grade 4 events: 3 reports of dyspnea and 
one report each of: dehydration, hyponatremia, hypoglycemia, anemia, neutropenia, 
lymphopenia, cardio-respiratory arrest; one Grade 4 event was reported as not coded.  
Table 1: 
Incidence of Non-laboratory Grade 3 or 4 AEs Observed in More than 
One Patient Receiving OGX-427 Monotherapy 
 
 OGX-427 Monotherapy 
Event 
200 mg 
(N=6) 
400 mg 
(N=7) 
600 mg 
(N=7) 
800 mg 
(N=8) 
1000 mg 
(N=14) 
Any Grade 3 or Higher 
2 (33%) 6 (86%) 
5 (71%) 
5 (63%) 
8 (57%) 
Dyspnoea 
1 (17%) 2 (29%) 
3 (43%) 
0 ( 0%) 
3 (21%) 
Anemia 
0 ( 0%) 
0 ( 0%) 
0 ( 0%) 
2 ( 25%) 
4 ( 29%) 
Fatigue 
0 ( 0%) 
0 ( 0%) 
2 (29%) 
1 (13%) 
2 (14%) 
Hypoxia 
1 (17%) 1 (14%) 
2 (29%) 
0 ( 0%) 
1 ( 7%) 
Chills 
0 ( 0%) 
0 ( 0%) 
1 (14%) 
1 (13%) 
1 ( 7%) 
Back pain 
0 ( 0%) 1 (14%) 
0 ( 0%) 
1 (13%) 
0 ( 0%) 
Infusion related reaction 
0 ( 0%) 
0 ( 0%) 
1 (14%) 
0 ( 0%) 
1 ( 7%) 
Cytokine release syndrome 
0 ( 0%) 
0 ( 0%) 
1 (14%) 
1 (13%) 
0 ( 0%) 
Platelet count decreased 
0 ( 0%) 
0 ( 0%) 
1 (14%) 
1 ( 13%) 
0 ( 0%) 
Pneumonia 
0 ( 0%) 
0 ( 0%) 
0 ( 0%) 
0 ( 0%) 
2 (14%) 
Hypokalemia 
0 ( 0%) 
0 ( 0%) 
1 ( 14%) 
0 ( 0%) 
2 ( 14%) 
Blood creatinine increased 
0 ( 0%) 
0 ( 0%) 
0 ( 0%) 
1 ( 13%) 
1 ( 7%) 
Hyponatremia 
1 ( 17%) 1 ( 14%) 
0 ( 0%) 
0 ( 0%) 
1 ( 7%) 


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Among patients receiving OGX-427 monotherapy, 13 events of laboratory toxicities (31%) 
were Grade 1 or Grade 2; 26 events (62%) were Grade 3. Three laboratory toxicities (7%) 
were Grade 4. The most common laboratory events (i.e., occurring in 25% or more of all 
monotherapy patients) included: transient prolongation of PTT (100% of patients), 
lymphopenia (93%), anemia (88%), elevated AST (50%), hypokalemia (50%), 
hyponatremia (48%), elevated alkaline phosphatase (45%), elevated serum creatinine 
(43%), thrombocytopenia (38%), elevated ALT (36%), elevated INR (33%), and 
leukopenia (33%). 
Transient prolongation of PTT is a known class effect of ASOs. The prolongation of PTT 
stems from interaction of phosphorothioate oligonucleotides with thrombin.60 This effect is 
highly blood-level related; hence, it is typically maximal at the end of a short infusion 
(e.g., 2-hour infusion) and during the Loading Dose Period (three infusions in 5-9 days), 
when high levels of ASOs can be attained. The PTT prolongation diminished in parallel 
with the decline in plasma levels, such that it was largely recovered by 24 hours after the 
infusion. There was no evidence of an increase in bleeding events.  
Lymphopenia, also a known class effect of ASOs, was seen in 93% of patients receiving 
OGX-427 as monotherapy and was Grade 3 or 4 in 36% of the patients. There were no 
clinical sequelae.  
The incidence of all Grade 3 or higher laboratory AEs by cohort is shown in Table 2. Three 
patients in the monotherapy cohorts had Grade 4 AEs, including hyponatremia and 
lymphopenia (Cohort 1: two patients), and thrombocytopenia and neutropenia (Cohort 3: 
one patient).  
Table 2: 
Number (%) of Patients with at Least One Grade 3 or 4 Laboratory 
Value on Study: Safety Population of Patients Receiving OGX-427 
Monotherapy 
 
 OGX-427 Monotherapy 
Event 
200 mg 
(N=6) 
400 mg 
(N=7) 
600 mg 
(N=7) 
800 mg 
(N=8) 
1000 mg 
(N=14) 
Overall 
2 ( 33%) 
4 ( 57%) 
5 ( 71%) 
8 (100%) 
10 ( 71%) 
Hematology 
2 ( 33%) 
2 ( 29%) 
4 ( 57%) 
6 ( 75%) 
7 ( 50%) 
Lymphopenia 
2 ( 33%) 
2 ( 29%) 
2 ( 29%) 
5 ( 63%) 
4 ( 29%) 
Leukopenia 
0 (  0%) 
0 (  0%) 
2 ( 29%) 
0 (  0%) 
0 (  0%) 
Neutropenia 
0 (  0%) 
0 (  0%) 
1 ( 14%) 
0 (  0%) 
0 (  0%) 
Anemia 
0 (  0%) 
0 (  0%) 
0 (  0%) 
2 ( 25%) 
4 ( 29%) 
Thrombocytopenia 
0 (  0%) 
0 (  0%) 
1 ( 14%) 
1 ( 13%) 
1 (  7%) 
Coagulation 
1 ( 17%) 
2 ( 29%) 
2 ( 29%) 
5 ( 63%) 
6 ( 43%) 
Prolonged PTT 
0 (  0%) 
1 ( 14%) 
2 ( 29%) 
5 ( 63%) 
6 ( 43%) 
Elevated INR 
1 ( 17%) 
1 ( 14%) 
0 (  0%) 
0 (  0%) 
0 (  0%) 
Serum Chemistry 
1 ( 17%) 
1 ( 14%) 
3 ( 43%) 
3 ( 38%) 
6 ( 43%) 
Hyponatremia 
1 ( 17%) 
1 ( 14%) 
1 ( 14%) 
2 ( 25%) 
1 (  7%) 
Hypokalemia 
0 (  0%) 
0 (  0%) 
1 ( 14%) 
0 (  0%) 
3 ( 21%) 
Elevated Serum 
Creatinine 
0 (  0%) 
0 (  0%) 
1 ( 14%) 
1 ( 13%) 
1 (  7%) 
Elevated Bilirubin 
0 (  0%) 
0 (  0%) 
1 ( 14%) 
0 (  0%) 
1 (  7%) 


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 OGX-427 Monotherapy 
Event 
200 mg 
(N=6) 
400 mg 
(N=7) 
600 mg 
(N=7) 
800 mg 
(N=8) 
1000 mg 
(N=14) 
Elevated Alkaline 
Phosphatase 
0 (  0%) 
0 (  0%) 
0 (  0%) 
0 (  0%) 
2 ( 14%) 
Elevated AST 
0 (  0%) 
0 (  0%) 
1 ( 14%) 
0 (  0%) 
0 (  0%) 
Elevated ALT 
0 (  0%) 
0 (  0%) 
0 (  0%) 
0 (  0%) 
1 (  7%) 
 
Twenty-six serious adverse events (SAEs) were reported among 20 patients treated with 
OGX-427 monotherapy. SAEs were reported for 48% of patients receiving OGX-427 
monotherapy and 45% of patients receiving OGX-427 plus docetaxel. Among patients 
treated with OGX-427 monotherapy, SAEs reported for more than one patient included: 
dyspnea (4 patients), disease progression (4 patients) and blood creatinine increased (2 
patients). All remaining SAEs were reported for 1 subject each. Refer to the Investigator’s 
Brochure for more information about SAEs classified by Medical Dictionary for 
Regulatory Activities (MedDRA) preferred term and for SAEs among patients receiving 
OGX-427 plus docetaxel. 
Within the total study population, 56 patients (88%) have died. The cause of death was 
progressive disease for 52 of the 56 subjects (93%). Four subjects died due to other causes, 
including bilateral upper extremity venous thrombosis, pancreatic cancer, tumor bleeding 
following right hip gamma nail placement for pathological fracture, and cardiopulmonary 
arrest. The Investigators considered these deaths to be unrelated to treatment with 
OGX-427.  
1.6.3. 
Cardiac Repolarization 
There was no evidence for prolongation of the QTcF interval or change in 
electrocardiogram (ECG) morphology. 
1.6.4. 
Complement 
Levels of complement split products (Bb, C3a, and C5a) were evaluated following three 
loading doses and on Day 1 of each cycle immediately following the infusion of OGX-427. 
There was a significant correlation between the pre- and post-time-weighted ratios of all 
three complement fragments and the dose of OGX-427. Activation of the alternative 
pathway/amplification loop of complement (C3a and Bb) was apparent at low doses of 
OGX-427, whereas activation of the terminal pathway (C5a) did not become apparent until 
the highest doses. Cohorts where docetaxel was combined with OGX-427 appeared to 
generate lower levels of complement, presumably due to the concomitant use of steroid 
prophylaxis for docetaxel. There was no apparent relationship between the time-weighted 
ratios of complement and the incidence of infusion reactions. There was no evidence for an 
increase in significant bleeding events. 
1.6.5. 
 Efficacy Outcome Measures 
Biological activity of OGX-427 when used as monotherapy was observed at doses ≥400 
mg by measurable disease response, decrease in tumor markers (prostate and ovarian) and 
decline in circulating tumor cells (CTCs).  


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1.6.5.1. 
Measurable Disease 
Efficacy data are available for 53 of the 59 patients. Forty-eight of the 53 patients had 
measurable disease at baseline. Thirty patients had baseline and at least one post-baseline 
assessment of measurable disease. 
Eight of the 30 patients (27%) had a decrease in measurable disease from baseline of at 
least 15%. For patients treated with OGX-427 monotherapy, three patients had tumor 
reductions: one patient with prostate cancer (Cohort 4) had a reduction of 25%; one with 
breast cancer (Cohort 2) had a reduction of 23%; and one with lung cancer (Cohort 5) had 
a reduction of 21%. For patients treated with OGX-427 plus docetaxel, five patients had 
tumor reductions: one patient with prostate cancer (Cohort 7) met the definition for a 
partial response (35%) and two had reductions of 19% and 23%; two patients with lung 
cancer (Cohort 7) had reductions of 19% and 87%. 
Thirty-three of 36 patients with prostate cancer had at least one post-baseline PSA 
assessment. Three of 21 patients in the monotherapy cohorts had reductions in PSA ≥30% 
as did six of twelve patients in the combination therapy cohorts. 
1.6.5.2. 
Circulating Tumor Cells 
Blood for total CTCs and Hsp27+ CTCs was collected at screening, prior to the first 
loading dose, and prior to drug administration on Cycles 1, 2, 3, and 5. On average, 75% of 
the baseline total CTCs were Hsp27+ CTCs. Total CTC data at baseline and at least once 
post-study drug administration were available for 55 of 59 patients and for 54 of 59 
patients for Hsp27+ CTCs. Fourteen patients had Hsp27+ CTCs ≤5 /7.5 mL at baseline. 
Responses by CTC and Hsp27+ CTC assessment were documented in all diseases 
evaluated and at all dose levels. A best reduction in both total CTCs and Hsp27+ CTCs of 
≥50% was seen in >50% of patients in all cohorts. Eighteen patients had a reduction of 
Hsp27+ CTCs to ≤5 /7.5 mL. There did not appear to be a dose response. 
Figure 8 represents the number of patients in each cohort who demonstrated a decrease in 
Hsp27+ CTCs for each of the five disease categories. 


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Figure 8: 
Best Change in Hsp27+CTCs* by Disease Category & Cohort (in %) 
 
1.6.6. 
Pharmacokinetics  
Over the dose range of 200 mg to 1000 mg, there was a moderate non-proportional 
increase in both Cmax and AUC0-inf, a moderate decrease in plasma clearance, and a minor 
increase in plasma half-life value for OGX-427 with increasing dose. When OGX-427 was 
administered at the 800 mg or 1000 mg doses in combination with docetaxel (75 mg/m2), 
there was no effect on the plasma pharmacokinetic parameters (AUC0-last, volume of 
distribution, Cmax) of OGX-427. 
1.7. 
Phase II Clinical Study PR-01 
Study PR-01 is a Phase 2, open-label, two-stage, randomized cross-over study designed to 
evaluate the anti-tumor effects of OGX-427 plus low-dose prednisone versus low-dose 
prednisone alone in men with CRPC who have not previously received chemotherapy for 
metastatic disease. This study is currently on-going. The primary endpoint is the 
proportion of patients without disease progression at 12 weeks after start of study 
treatment. The study also assesses the proportion of patients with a PSA decline and/or 
stable disease at the 12-week evaluation; measurable disease response; progression-free 
survival; time to disease progression; circulating tumor cells counts pre- and post-study 
drug; levels of Hsp27, clusterin, and other relevant proteins; and PTEN deletion status. 
Patients are randomized to either a Treatment Arm or a Control Arm. Patients randomized 
to the Treatment Arm begin with three loading doses of 600 mg OGX-427 IV within 10 
days, followed by weekly doses of 1000 mg OGX-427 IV along with 5 mg prednisone 
BID; patients randomized to the Control Arm receive 5 mg prednisone BID. Evaluations 
are conducted at 4-week intervals and disease assessments at weeks 12, 24, and 36 or until 


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disease progression. Patients who are withdrawn from study treatment for a reason other 
than disease progression are followed every 4 weeks until disease progression.  
The first stage of the study will accrue 18 subjects per arm. If one patient or more on the 
Treatment Arm has a response or stable disease at 12 weeks, the second stage will enroll 
an additional 14 evaluable patients on each arm (total of 32 subjects per arm), for a total of 
64 evaluable patients in both arms.  Patients on the Treatment Arm with PSA progression 
in the absence of progression by imaging or need for radiotherapy may continue therapy up 
to a maximum of 24 weeks  or until disease progression. Patients on the Treatment Arm 
who have a documented response (not stable disease) at the 24-week evaluation can 
continue to receive an additional 24 weeks of therapy (or until disease progression). 
Patients on the Control Arm with a response or stable disease at the 24-week evaluation 
may continue on treatment until disease progression. After documentation of disease 
progression, patients on the Control Arm have the option to cross-over to receive OGX-
427 plus prednisone per the Treatment Arm. 
1.7.1. 
Patient Disposition and Demographics 
As of the cutoff date of January 17, 2012, 37 patients have been enrolled on the study. 
Safety and efficacy data are available for the first consecutive 32 patients (17 in the 
Treatment Arm and 15 in the Control Arm). Eight patients in each arm have been 
withdrawn from study treatment. In the Treatment Arm, patients have been withdrawn for 
adverse events (4 patients; events include grade 3 thrombocytopenia and grade 1 renal 
insufficiency; grade 3 elevated creatinine due to hemolytic uremic syndrome; grade 2 
dyspnea and grade 3 fatigue; and grade 1 elevated creatinine); withdrawal of consent (2 
patients); disease progression (1 patient); and other (1 patient).  In the Control Arm, 
patients have been withdrawn for disease progression (7 patients) and death (1 patient). 
Five patients on the Control Arm had disease progression and crossed over to the 
Treatment Arm. 
The median age of patients is 67 years on the Treatment Arm and 72 years on the Control 
Arm. All patients had an ECOG status of 0 or 1. Baseline patient characteristics are shown 
in the table below. 
 
Table 3: 
Baseline Patient Characteristics 
Parameter 
OGX-427 + Prednisone 
(N=17) 
Prednisone 
(N=15) 
Age: median (range) 
67 (53-86) 
72 (62-89) 
PSA: median (range) 
66 (6-260) 
58 (6-606) 
Hemoglobin: median (range) 
135 (118-157) 
130 (104-152) 
ECOG 
0 
13 (76%) 
8 (53%) 
1 
4 (24%) 
7 (47%) 
Disease sites: 
Bone 
13 (76%) 
11 (73%) 
Liver 
0 (0%) 
1 (7%) 
Lung 
2 (12%) 
0 (0%) 
Lymph Node 
8 (47%) 
10 (67%) 
Gleason Score: 
≤7 
9 (53%) 
6 (40%) 


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>7 
7 (41%) 
8 (53%) 
Not available 
1 (6%) 
1 (7%) 
Lactate Dehydrogenase >ULN 
6 (35%) 
2 (13%) 
Alkaline Phosphatase >ULN 
5 (29%) 
2 (13%) 
Prior Prednisone Therapy: Yes 
6 (35%) 
4 (27%) 
Circulating Tumour Cells: 
Median, /7.5 mL (Range) 
15 (2-72) 
25 (3-273) 
≥5 /7.5 mL 
14 (82%) 
13 (87%) 
 
1.7.2. 
Adverse Events 
Overall, 94% of patients on Treatment Arm and 80% on the Control Arm experienced at 
least one treatment-emergent AE. The majority of AEs were grade 1 or grade 2, occurring 
in 69% of patients on the Treatment Arm and 75% patients on the Control Arm who 
experienced AEs. Refer to the Investigator’s Brochure for a complete list of all adverse 
events. 
The most frequently reported non-laboratory AEs in the Treatment Arm were chills, 
diarrhea, nausea, and fatigue; in the Control Arm the most frequent non-laboratory AEs 
were back pain, muscle spasm, and decreased appetite. There were 10 grade 3 or 4 non-
laboratory AEs in 5 patients. Three patients in the Treatment Arm experienced 6 grade 3 
non-laboratory AEs [fatigue (2), agitation (1), anxiety (1), hematuria (1), and presyncope 
(1)] and 2 grade 4 AEs (dizziness and pulmonary embolism). Two patients in the Control 
Arm experienced grade 3 or 4 AEs (1 grade 3 AE of cystitis and 1 grade 4 AE of spinal 
cord compression). 
The most common laboratory AEs consisted of lymphopenia, anemia, and hyperglycemia. 
The majority of laboratory toxicities were grade 1 or 2 (76% of laboratory AEs in the 
Treatment Arm and 80% in the Control Arm). Seven Grade 3 or 4 laboratory AEs were 
experienced by patients on the Treatment Arm (lymphopenia [3], and hyperglycemia, 
elevated creatinine, thrombocytopenia, and hyponatremia [1 each]). One patient on the 
Treatment Arm developed grade 4 hemolytic uremic syndrome at week 7. Three Grade 3 
or 4 laboratory AEs were experienced by patients on the Control Arm, including 
lymphopenia (2) and hyperglycemia (1). 
Infusion Reactions 
In the Phase 1 OGX-427-01 study, a high frequency of infusion reactions (>90%) was 
observed when some patients were given loading doses of 800 mg or 1000 mg and the only 
premedication administered was either ibuprofen or acetaminophen (compared to 
approximately 50% among subjects given loading doses ≤600 mg). In this protocol, the 
loading dose was fixed at 600 mg for all patients on the Treatment Arm, and all patients 
are receiving prophylactic premedication with a minimum of an antihistamine and an H2 
blocker. As of January 17, 2012, infusion reactions to OGX-427 have been observed in 8 
of 17 subjects (47%) on the Treatment Arm. The most common reactions were chills, 
flushing, diarrhea, nausea, and vomiting. There have been no treatment delays, and no 
doses of OGX-427 have been withheld. Four subjects (24%) had at least one infusion 
interrupted, and 2 administrations (12%) were discontinued due to infusion reactions.  


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Serious Adverse Events 
As of January 17, 2012, a total of 8 SAEs have been reported in 6 patients treated with 
OGX-427: 7 events in the Treatment Arm and 1 event in a Control Arm patient who had 
crossed over to receive OGX-427 treatment on the Crossover Arm.  
The SAEs in the Treatment Arm consisted of:  
 Hemolytic uremic syndrome (HUS): A patient presented with grade 3 elevated 
creatinine, grade 3 anemia, and grade 1 thrombocytopenia after receiving 3 
loading doses and 7 weekly doses of 1000 mg OGX-427. The diagnosis of 
grade 4 hemolytic uremic syndrome was confirmed by renal biopsy and 
described by the investigator as probably related to OGX-427. The patient 
required hemodialysis which is ongoing. The patient presented with a second 
SAE of gross hematuria on day 144 which was described by the investigator as 
not related to OGX-427. No other cases of HUS have been observed with 
OGX-427. 
 Gross hematuria and recurrent hematuria: A patient with a history of prostate 
cancer and pelvic irradiation prior to study entry presented with grade 3 gross 
hematuria on study day 193 and with recurrent grade 3 hematuria on study day 
288, both described by the investigator as not related to OGX-427. The patient 
remained on study treatment until day 302. The cause of bleeding was later 
confirmed at cystoscopy as diffuse ulcerative and hemorrhagic cystitis 
consistent with radiation cystitis.  
 Atrial fibrillation: A patient presented with grade 2 atrial fibrillation on study 
day 22 with resolution within 24 hours. The patient continued on study 
treatment through day 57.  
 Renal insufficiency due to dehydration and thrombocytopenia: A patient with a 
history of idiopathic vasculitis purpura managed with corticosteroids one year 
prior to study entry received 2 loading doses of OGX-427 and developed skin 
lesions consistent with recurrent vasculitic purpura concurrent with 
thrombocytopenia, peripheral edema, and poor oral intake resulting in 
dehydration. He was started on prednisone with resolution of the skin lesions 
and thrombocytopenia. The events were described by the investigator as 
probably related to OGX-427. 
 Dizziness and shortness of breath: A patient developed grade 4 dizziness and 
grade 2 shortness of breath 10 days after discontinuation of study drug on day 
66 for unacceptable toxicity (grade 1 confusion). The dizziness was described 
by the investigator as possibly related to OGX-427 and prednisone, and the 
shortness of breath was described as unrelated.  
The SAE in the Crossover Arm consisted of: 
 Bladder infection: A patient developed a grade 3 bladder infection on day 14 
which resolved within 72 hours. 


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Deaths 
One subject in the Control Arm has died from disease progression. 
1.7.3. 
Efficacy Evaluations 
The primary endpoint for the study is the proportion of subjects without disease 
progression at 12 weeks after start of study treatment. Disease progression is defined by 
any of the following: an increase in PSA per the Prostate Cancer Working Group 2 
criteria;61 measurable disease per the Response Evaluation Criteria in Solid Tumors 
(RECIST) version 1.162 on CT scans; ≥2 new bone lesions on bone scan; disease-related 
global or severe deterioration of health status; or need for palliative radiation therapy. As 
of January 17, 2012, 14 patients in the Treatment Arm and 12 patients in the Control Arm 
were evaluable for disease progression on or prior to week 12. Ten of 14 (71%, 95% CI: 
42-92%) patients in the Treatment Arm and 4 of 12 (33%, 95% CI: 10-65%) patients in the 
Control Arm had no documented disease progression at 12 weeks. 
PSA Response 
Of the first 32 evaluable patients, all had a baseline and at least one post-baseline PSA 
value. Ten of 17 (59%) patients on the Treatment Arm had at least a 30% decrease in PSA, 
compared to 5 of 15 (33%) patients on the Control Arm.  
Measurable Disease 
Eight patients on the Treatment Arm and 9 patients on the Control Arm had measurable 
disease at baseline. As of January 17, 2012, 3 (38%) patients on the Treatment Arm 
achieved a partial response, 1 (13%) had stable disease, and it was too early to evaluate 
disease progression in 4 (50%) patients. No patient in the Treatment Arm had disease 
progression. Among patients on the Control Arm, 4 (44%) had achieved stable disease and 
2 (22%) had disease progression; it was too early to evaluate the remaining 3 (33%) 
patients. 
Circulating Tumor Cells (CTCs) 
Blood for both total and Hsp27+ CTCs was collected at screening and weeks 1, 5, 9, and 
13. CTCs at baseline and at least once post-study treatment were available for 14 of 17 
patients in the Treatment Arm and 13 of 15 in the Control Arm. Approximately 70% of the 
total CTCs were Hsp27+ at baseline. Among evaluable patients, 7 of 14 (50%) patients on 
the Treatment Arm and 4 of 13 (31%) patients on the Control Arm had a best total CTC 
change from baseline of ≥5 to <5 CTCs/7.5 mL. No patient had a change from <5 to ≥5 
CTC/7.5 mL. 
 


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2. 
RATIONALE 
2.1. 
Rationale for the Study 
Many cancers, including prostate cancer, result in the increased expression of Hsp27, one 
of the heat shock proteins that are highly conserved and whose expression is induced by 
cell stress, including cytotoxic chemotherapy, radiation therapy and hormone therapy. 
Hsp27 has been shown to interact with key apoptosis-associated proteins and functions to 
inhibit apoptotic cell death through multiple pathways by a variety of mechanisms. In 
particular for prostate cancer, Hsp27 has been implicated in both ligand-dependent and 
-independent androgen receptor signaling. Given the redundancy that exists in cancers and 
their heterogeneity, targeting Hsp27 is attractive as a cancer therapy as it should result in 
down-regulation of multiple pathways implicated in cancer progression and development 
of resistance.  
OGX-427 is a second-generation ASO that inhibits expression of Hsp27. A number of in 
vitro and in vivo pharmacological studies have demonstrated that OGX-427 (or a sequence 
equivalent Hsp27 ASO) has single agent activity in reducing Hsp27 mRNA, inhibiting cell 
growth and inducing apoptosis in several human cancer cell lines. OGX-427 has also 
demonstrated chemosensitizing activity both in vitro and in vivo in combination with 
several cytotoxic drugs, including docetaxel. In preclinical studies, OGX-427 or the first-
generation Hsp27 ASO was tested alone or in combination with other drugs in various 
animal tumor models. Nonclinical toxicology results indicated that OGX-427 has a 
reasonable safety profile. 
The Phase 1 clinical study was developed to evaluate the safety profile, determine the 
maximum tolerated dose, characterize the pharmacokinetic profile, and evaluate the 
efficacy of OGX-427 when administered as a single agent and when administered in 
combination with taxane chemotherapy (i.e., docetaxel). Enrollment into cohorts 
evaluating the combination of OGX-427 and docetaxel was also performed. Findings from 
this study support that OGX-427 has a reasonable safety profile in humans. A maximum 
tolerated dose was not reached. The highest dose of 1000 mg OGX-427 was well tolerated; 
however, prophylactic medications for potential infusion reactions appear to be indicated, 
at least for some patients, due to infusion reactions requiring treatment and subsequent 
prophylaxis with high-dose steroids at OGX-427 doses ≥800 mg. 
As patients on abiraterone acetate without clinical progression continue treatment even in 
the event of PSA progression, this presents an opportunity to assess novel combinations 
with abiraterone acetate. This clinical study was designed as an open label, randomized 
Phase II clinical study to evaluate the effect of adding OGX-427 to ongoing standard 
therapy with abiraterone acetate and prednisone in men with metastatic CRPC who have 
evidence of PSA progression but no clinical evidence of symptomatic or radiographic 
progression. Given the variability of outcomes in different populations and the lack of 
consistent historical data on progression-free survival rates in this clinical situation, 
randomization to a control arm where patients continue standard therapy with abiraterone 
acetate and prednisone alone is required in order to put the results of the experimental arm 
into context. Patients in the control arm will be allowed to cross over to receive OGX-427 


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at disease progression, if eligible after a re-screening evaluation (i.e., all inclusion and 
exclusion criteria have been met). 
2.2. 
Rationale Supporting Drug Dose Selection and Duration 
A maximum tolerated dose for administering OGX-427 as a single agent was not reached 
in the Phase I trial (OGX-427-01) that evaluated doses up to a maximum of 1000 mg. 
OGX-427 appears to have an acceptable safety profile as a single agent up to a 1000 mg 
dose, which is the dose selected to be utilized in this Phase II study. The major non-
laboratory toxicities among patients receiving OGX-427 monotherapy in the Phase I trial 
were infusion reactions (hypertension, influenza-like illness, rigors, pruritus, flushing, 
pyrexia, and erythema), observed in 76% of patients, with increased frequency and severity 
at the highest doses (800 mg and 1000 mg). Almost all infusion reactions (>95%) were 
Grade 1 or 2 and mainly occurred during the loading doses and Cycle 1. Only 6.3% of 
infusions were interrupted and 2.8% of infusions were delayed or discontinued due to 
reactions. Prophylaxis with ibuprofen or acetaminophen was required per protocol for a 
24-hour period on infusion days during the loading dose period only, in an attempt to 
decrease the rigors and fevers often associated with administration of ASOs. However, 
despite this, many reactions required treatment with antihistamines, H2 antagonist and 
steroids, and some patients required steroid prophylaxis for repeated infusion reactions.  
In the Phase II study (Study PR-01), the three loading doses of OGX-427 were decreased 
to 600 mg in an attempt to decrease the incidence and severity of infusion reactions. 
Thereafter, weekly dosing of OGX-427 was at the 1000 mg dose. In addition, prophylactic 
premedications (an antihistamine and H2 antagonist) were administered prior to each dose 
of OGX-427.  
Results available from Study PR-01, based on 37 randomized patients, suggest that the 600 
mg loading dose is better tolerated than higher doses when accompanied by premedication 
with a minimum of an antihistamine and an H2 blocker. As of January 17, 2012, infusion 
reactions to OGX-427 have been observed in 8 of 17 subjects (47%) on the Treatment 
Arm. The most common reactions were chills, flushing, diarrhea, nausea, and vomiting. 
There have been no treatment delays, and no doses of OGX-427 have been withheld. Four 
subjects (24%) had at least one infusion interrupted, and 2 administrations (12%) were 
discontinued due to infusion reactions. 
The “mechanism of action” for OGX-427 is in part through effects on androgen receptor 
(AR) signaling, and measures of PSA, as an AR-regulated gene, would reflect OGX-427 
efficacy. However, since PSA is an imperfect marker of disease progression, patients with 
PSA progression as best response will be allowed up to 24 weeks of this experimental 
therapy in the absence of other indicators of clinical progression to evaluate for a late 
response or for slowed progression. Due to limited drug supply at this time, responders 
will be limited to 48 weeks (12 cycles) of therapy. 
2.3. 
Rationale Supporting Evaluation of Other Relevant Proteins 
The purpose of the serum and plasma samples is to assess changes in Hsp27 and clusterin 
levels and to explore other proteins (e.g., other Hsp family members and their client 
proteins) and cancer-associated microRNA (e.g., miR-141, miR-126) to explore as 


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biomarkers that may emerge as prognostic or predictive factors in prostate cancer. 
Germline DNA will not be evaluated. 
3. 
STUDY OBJECTIVES 
Patients will be randomized with equal probability to one of two arms, designated as the 
Experimental Arm (A) and the Control Arm (B). The intended intervention in Arm A is 
continued use of abiraterone and prednisone plus the addition of OGX-427.The intended 
intervention in Arm B is continued use of abiraterone and prednisone.  
3.1. 
Primary Objective 
The primary objective for this study is progression-free survival at the milestone Day 60 
assessment: to ascertain whether Arm A has a greater proportion of patients observed to be 
alive without progression as compared to Arm B. 
3.2. 
Secondary Objectives 
The secondary objectives are based on comparing the arms with respect to the following 
outcomes: 
1. The proportion of patients who have a PSA response (≥30% decline) and any PSA 
decline post-randomization  
2. Objective response 
3. Progression-free survival (PFS) 
4. Time to disease progression (see Section 6.4.1) 
5. Circulating tumor cell (CTC) counts at baseline and on study 
6. Levels of Hsp27, clusterin, and other relevant proteins at baseline and during study 
7. PTEN deletion status in original pathology specimens correlated with clinical 
outcomes 
 


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4. 
STUDY DESIGN OVERVIEW 
4.1. 
Study Design  
This is an open-label, randomized, Phase II clinical trial designed to evaluate the anti-
tumor effects of OGX-427 and continuing abiraterone acetate and prednisone versus 
continuing abiraterone acetate and prednisone alone in men with metastatic CRPC who 
have evidence of PSA progression but no evidence of symptomatic or radiographic 
progression that would require alternative therapy (e.g., needing radiation therapy for pain 
or significant progression of visceral metastases).  
Stratified randomization will be used in order to minimize between-arm imbalance using 
the following stratification factors: prior chemotherapy (yes versus no), and prior PSA 
response >30% to abiraterone acetate (yes versus no). Individuals in the Control Arm will 
have the option to cross-over to receive OGX-427 as per the Experimental Arm schedule 
after documented disease progression if they continue to meet eligibility criteria. 
 
Figure 9: 
Study Design 
Screening Period  
Day – 28 to Randomization 
Randomization 
Experimental Arm (Arm A):  
OGX-427 Starting within 7 days 
of randomization, three loading 
doses at 600 mg IV within 
Week 1 if possible (up to the 
first 10 days of initiating 
treatment), followed by weekly 
doses of 800 mg IV 
Continuation of standard 
therapy with abiraterone 
acetate 1000 mg PO daily and 
prednisone 10-20 mg PO daily 
  
Both Arms: 
Evaluations at 4 week-intervals. Disease 
assessments required at the milestone 
Day 60 assessment (expected to occur 
after 8 weeks of treatment and prior to 
Day 1, Week 9) and at 16, 24, 32, 40, 
and 48 weeks (if applicable) or until 
documented disease progression. 
Patients who are withdrawn from the 
study for a reason other than 
documented disease progression 
(Section 6.4.1) or patient withdrawal of 
consent will be followed every 4 weeks 
in the Off-Treatment Follow-up Period 
until documented disease progression. 
 
 
End of Study Treatment 
Off-Treatment Follow Up Period for disease progression (if applicable) 
Control Arm (Arm B):  
Continuation of standard 
therapy with abiraterone 
acetate 1000 mg PO daily and 
prednisone 10-20 mg PO daily  
 
After documented disease 
progression, patients on the Arm 
B may opt to receive OGX-427 
treatment (according to the Arm 
A schedule) following a 
screening evaluation (i.e., all 
inclusion and exclusion criteria 
have been met). 


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4.2. 
Study Treatment 
The term, “Study Treatment,” as used throughout the protocol, refers to general study-
related procedures including the administration of abiraterone and prednisone (for patients 
on both study arms) and OGX-427 (for patients on the Experimental Arm only). Control 
Arm patients who ”cross-over” to Experimental Arm intervention will follow the 
Experimental Arm schedule as outlined in this protocol. Regardless of study arm, all 
patients must begin study-related procedures within 7 days following randomization. 
4.2.1. 
Experimental Arm: OGX-427 plus Abiraterone Acetate and Prednisone 
Continuation 
4.2.1.1. 
Abiraterone acetate 
Per inclusion criteria, patients should already be receiving abiraterone acetate at 1000 mg 
orally on a daily schedule. Abiraterone should be continued throughout the study unless 
discontinuation is required for toxicity or documented disease progression. Abiraterone 
usage must be adequately documented.  
4.2.1.2. 
Prednisone 
Per inclusion criteria, patients should already be receiving prednisone (10-20 mg PO/day). 
Prednisone should be administered at the same dose throughout the study unless dose 
modification or discontinuation is required for toxicity. Prednisone usage must be 
adequately documented.  
4.2.1.3. 
OGX-427 
OGX-427 Loading Dose Period  
Patients randomized to the Experimental Arm will receive OGX-427 in addition to 
abiraterone and prednisone. The schedule of administration of OGX-427 begins with three 
loading doses. The first loading dose of OGX-427 should be administered within 7 days 
following randomization. The day on which the first loading dose is given will be 
considered Day 1, Week 1. 
The three loading doses of 600 mg of OGX-427 will be administered IV over 2 hours 
during Week 1, if possible (up to 10 days of initiating treatment). There must be at least 
one “non-infusion” day between each administration of OGX-427 (i.e., every other day) 
during the Loading Dose week and between the third loading dose of OGX-427 and the 
Day 1, Week 2 dose of OGX-427 that initiates weekly OGX-427 administration. Note: If 
the third loading dose or the Day 1, Week 2 dose is delayed, subsequent weekly 
administration will continue based on the actual Day 1, Week 2 administration date. 
Weekly Administration of OGX-427 
Following completion of the Loading Dose Period, 800 mg OGX-427 will be administered 
weekly (IV over 2 hours, every 7 days +/- 2 days) during the OGX-427 Treatment Period. 
The day on which the first weekly dose of OGX-427 is given will be considered Day 1, 
Week 2. Patients will be evaluated in the clinic every 4 weeks. Disease assessments will 


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occur every 8 weeks or as indicated. Treatment with OGX-427 and abiraterone/prednisone 
will continue until disease progression is documented or another End of Study Treatment 
Criterion is met (Section 5.5). Patients who fulfill the criteria for either PSA response (per 
Section 6.4.2.2,  ≥30% decline) or objective disease response (not stable disease) at Week 
24 will receive 600 mg OGX-427 (rather than 800 mg) from Week 25 through Week 48 or 
until meeting an End of Study Treatment Criterion. 
Patients who are removed from study treatment for a reason other than documented disease 
progression or patient withdrawal of consent to participate in the study will be followed 
every 4 weeks in the Off Treatment Follow-Up Period until the date of documented disease 
progression.  
4.2.1.4. 
Premedications for OGX-427 
Patients on the Experimental Arm should be premedicated with an H2 antagonist, e.g., 
Ranitidine (150 mg PO or 50 mg IV) and an antihistamine, e.g., diphenhydramine (25-50 
mg) It is recommended that these premedications be administered 30-90 minutes prior to 
infusion unless there is a medical reason they cannot receive one or more of the drugs (see 
Section 6.7.3).  
If a patient manifests a Grade 2 or greater adverse event(s) during or subsequent to 
an infusion of OGX-427, despite the above premedications, treatment should follow 
Institutional Guidelines; recommendations, including the use of steroids, are 
available in Section 6.6.6/Table 11.  
Following treatment with steroids (i.e., 8 mg of dexamethasone) on more than one 
occasion for a Grade 2 or greater adverse event associated with an infusion, the patient 
should receive 8 mg dexamethasone as prophylaxis in addition to continued premedication 
with an H2 antagonist and an antihistamine for a minimum of 12 weeks, or longer if 
necessary. 
4.2.2. 
Control Arm: Abiraterone Acetate and Prednisone Continuation 
4.2.2.1. 
Abiraterone acetate 
Patients will continue on abiraterone acetate as per package insert and standard of care. 
Approved dosing of abiraterone acetate is 1000 mg orally daily on an empty stomach (1 
hour before or 2 hours after a meal). Abiraterone should be continued throughout the study 
unless discontinuation is required for toxicity or documented disease progression. 
Abiraterone usage must be adequately documented. 
4.2.2.2. 
Prednisone 
Prednisone must be given with abiraterone acetate. The standard dosing of prednisone with 
abiraterone acetate is a total daily dose of 10-20 mg/day orally. Prednisone should be 
administered at the same dose throughout the study unless dose modification or 
discontinuation is required for toxicity. Prednisone usage must be adequately documented.  
Patients who are withdrawn from study treatment for a reason other than documented 
disease progression or patient withdrawal of consent to participate in the study will be 


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followed every 4 weeks until documented disease progression during the Off-Treatment 
Follow-up Period.  
4.2.2.3  Missed or Delayed Evaluations (Control Arm) 
If an every 4 week evaluation is  missed or delayed, the next evaluation should continue on 
the original schedule.  For example, patient misses their week 9 evaluation and comes in 
on week 10 for week 9 assessment, the next evaluation will occur in 3 weeks in order to 
keep on the original scheduled timeline.    
4.3. 
Number of Patients 
Approximately 80 patients will be screened in order to randomize 74 patients to the study 
(37 patients per arm).  
4.4. 
Number of Clinical Sites 
Approximately 12-15 sites will participate in Canada and the United States. 
4.5. 
Estimated Duration/Completion of Study 
Completion of accrual is projected for ≤18 months after all sites are activated, based on an 
accrual rate of approximately 4 patients per year per site.  
5. 
SELECTION AND WITHDRAWAL OF PATIENTS 
5.1. 
Enrollment of Patients  
Each potential patient will be provided with an informed consent form that has been 
reviewed and approved by the site’s governing Institutional Review Board (IRB) or 
Research Ethics Board (REB). In accordance with the International Conference on 
Harmonization (ICH) guidelines on informed consent, the Principal Investigator (or 
designee) will provide potential patients with a verbal description of the study including, 
but not limited to, study purpose, study procedures, risks, and benefits. Potential patients 
will be asked to read the consent form and to sign and date it once all of their questions 
have been answered and they voluntarily agree to participate in the study. A copy of the 
signed informed consent form will be provided to the patient. 
Upon obtaining signed informed consent, each patient will undergo the screening 
procedures outlined in Section 6.2.1. A screening log will be maintained by the site and 
will include documentation of screening failures. Patients meeting all inclusion/exclusion 
criteria will then be randomized to have OGX-427 added to their abiraterone/prednisone 
therapy or to continue abiraterone/prednisone therapy alone (see Section 6.2.2). All 
patients are considered enrolled once randomized.  
5.2. 
Registration Procedures 
All patients must be registered through Hoosier Cancer Research Network’s Electronic 
Data Capture (EDC) system. 


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Detailed guidelines for patient registration and electronic case report form (eCRF) 
completion can be found in the Study Procedures Manual (SPM) associated with this 
protocol.   
Patients must be registered prior to starting protocol therapy and begin protocol therapy 
within 7 calendar days after randomization.   
Randomization will occur immediately after registering a patient.  
5.3. 
Inclusion Criteria 
Subjects must meet ALL of the following criteria to be eligible for inclusion into 
the study. 
1. ECOG performance status of 0 or 1 
2. Histological or cytological diagnosis of adenocarcinoma of the prostate 
3. Metastatic disease on chest, abdominal, or pelvic CT scan and/or bone scan  
4. Currently receiving abiraterone acetate and prednisone and meeting the following 
criteria:  
a. Any PSA decline within 12 weeks from initiation of abiraterone 
b. Currently tolerating abiraterone acetate (1000 mg oral daily) and prednisone 
(10-20 mg oral daily) 
c. PSA progression, defined as an increase in PSA which is ≥25% above the nadir 
and an absolute value of ≥2 ng/mL, which is confirmed by a second value ≥2 
weeks later.  
d. No evidence of symptomatic or radiographic progression that would require 
alternative therapy (e.g., needing radiation therapy for pain or significant 
progression of visceral metastases or >33% increase in daily opioid use within 
2 weeks prior to randomization)  
5. All patients who have not had a surgical orchiectomy must continue treatment with 
LHRH agonist or antagonist to maintain a castrate level of testosterone.  
6. Patient must fulfill “Prior Therapy” criteria as follows:  
a. Chemotherapy: no more than 1 prior chemotherapy regimen for CRPC is 
permitted; a minimum of at least 28 days must have passed since the last dose 
of chemotherapy. 
b. Hormone therapy: hormonal androgen ablation therapy prior to abiraterone is 
required.  
c. Experimental therapy: prior non-cytotoxic experimental therapy is permitted 
provided a minimum of at least 14 days has passed since completing therapy. 
Prior treatment with MDV3100 is allowed. 
d. Radiation: prior external beam radiation is permitted provided a minimum of at 
least 14 days have passed since completing radiotherapy (exception for 
radiotherapy: at least 7 days since completing a single fraction of ≤800 cGy to a 
restricted field or limited-field radiotherapy to non-marrow bearing area such as 
an extremity or orbit) at the time of randomization 


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7. Baseline laboratory values as stated below: 
a. ANC  1.5 x 109 cells /L, platelet count  100 x 109 /L, and hemoglobin  9 
g/dL without transfusion 
b. Creatinine  1.3 x upper limit of normal (ULN) 
c. Total bilirubin  1.1 x ULN (unless elevated secondary to conditions such as 
Gilbert’s disease, in which case a direct bilirubin ≤ ULN is required) 
d. SGPT (ALT) and SGOT (AST)  3.0 x ULN 
e. Castrate serum testosterone level ( 50 ng/dL or  1.7 nmol/L) 
f. Potassium within normal limits 
8. Must be willing to use effective contraception throughout study treatment and for 3 
months after completion of study treatment if able to father a child. 
9. Must be willing not to change (add or subtract) bone protecting therapy 
(bisphosphonates and/or denosumab) during the study unless changed for toxicity. 
10. Written informed consent must be obtained prior to any protocol-specific 
procedures being performed. 
11. At least 14 days has passed since any major surgery and 5 days for minor surgery 
(i.e. port placement), 
 
5.4. 
Exclusion Criteria 
Subjects meeting ANY of the following exclusion criteria will NOT be eligible for 
inclusion into the study: 
1. Currently receiving abiraterone acetate in combination with any other anti-cancer 
agent (except prednisone) 
2. Documented brain metastases, or carcinomatous meningitis, treated or untreated 
(Brain imaging for asymptomatic patients is not required.) 
3. Cord compression requiring surgery or radiation therapy while on abiraterone 
treatment 
4. Active second malignancy (including lymphoid malignancies such as chronic 
lymphocytic leukemia or low grade lymphoma) defined, in general, as requiring 
anticancer therapy or at high risk of recurrence during the study; not including 
adequately treated non-melanomatous skin cancer or other solid tumors curatively 
treated with no evidence of disease in > 3 years 
5. History of allergic reactions to therapeutic antisense oligonucleotides  
6. Active autoimmune disease requiring treatment 
7. Participated in a prior Phase 3 clinical study evaluating custirsen regardless of 
study arm assignment (i.e., either control or investigational arm), or prior exposure 
to OGX-427  
8. Known LVEF <50% or NYHA Class III or IV heart failure 


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9. Uncontrolled medical conditions such as myocardial infarction, uncontrolled 
hypertension, stroke or treatment of a major active infection within 3 months of 
randomization, as well as any significant concurrent medical illness that in the 
opinion of the Investigator would preclude protocol therapy 
10. Planned concomitant participation in another clinical trial of an experimental agent, 
vaccine, or device. Concomitant participation in observational studies is acceptable. 
5.5. 
End of Study Treatment/Criteria for Withdrawal 
Patients on the study should receive study treatment until disease progression or another 
End of Study Treatment criterion is documented. Patients should be withdrawn from study 
treatment only for the following reasons:  
1. Documented progression of disease (Section 6.4.1)  
Note: Patients on the OGX-427 Experimental Arm with only PSA progression in 
the absence of other indicators for progression (by bone scan, CT, deterioration in 
ECOG performance status to Grade 3 or higher, or initiation of other treatments) 
may continue therapy up to a maximum of 24 weeks or until disease progression as 
defined in Section 6.4.1.2.  
Note: Patients on the Control Arm will be withdrawn from study if they are unable 
or unwilling to cross-over to receive OGX-427 after documented disease 
progression. 
2. Unacceptable toxicity (toxicity that requires stopping study treatment) 
3. Study treatment administration missed for more than 3 weeks (i.e., more than 4 
weeks without study treatment)  
4. Patient withdrawal of consent to continue participating in the study. Patients may 
withdraw from the study at any time, for any reason, without jeopardy to their 
current and future care. 
5. Non-cancer related illness that in the view of the Investigator prevents continuation 
of study treatment 
6. Completion of study treatment:  
a. Patients who have completed 24 weeks on the Experimental Arm and have 
stable disease or PSA only progression 
b. Patients who fulfill the criteria for disease response (not stable disease) and 
have completed 48 weeks on the Experimental Arm 
c. Patients on the Control Arm who have completed 48 weeks of treatment 
7. Termination of study or of study drug supply by OncoGenex 
Any patient withdrawn from study treatment for any reason must have the procedures 
outlined in the End of Treatment Visit (Section 6.2.7). The reason(s) for withdrawal from 
study treatment must be recorded on the End of Treatment electronic case report form 
(eCRF). Patients from the Control Arm who are crossing-over to the Experimental Arm 
will have a repeat Screening Visit at the time of cross-over instead of an End of Treatment 
Visit. 


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Note: Only patients on the Control Arm who remain on study treatment until disease 
progression will be allowed to cross-over to receive OGX-427 treatment. If disease 
progression is by PSA or bone scan only, confirmation of progression must be 
documented.  
All patients will be followed for disease progression.  
 


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6. 
STUDY EVALUATIONS AND PROCEDURES 
6.1. 
Schedule for Evaluations and Procedures  
Table 4 provides a summary of required evaluations and procedures. The 28-day interval 
for screening can be extended by 1-3 working days. Patients on the Experimental Arm 
should receive the first loading dose of OGX-427 within 7 calendar days following 
randomization. All patients in the Treatment and Control Arms should continue 
abiraterone acetate and prednisone therapies uninterrupted. Patients crossing over from the 
Control Arm to the Experimental Arm must begin treatment with OGX-427 within 8 
weeks of documented disease progression.


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Table 4: 
Evaluations and Procedures Schedule 
 
Screening 
period (up 
to 28 days + 
1-3 days) 
Randomization Perioda 
Week 1 Study Evaluations 
Subsequent Weekly Study Evaluations 
Milestone 
Disease 
Assessment 
Disease 
Assessments 
End of 
Treatment 
Visit 
(EOT)b 
Off Treatment 
Follow up 
Period (until 
disease 
progression) 
Procedure 
Screening 
Visit(s)a  
All three OGX-427 loading 
doses should occur  
during Week 1 
Study evaluations will occur on Day 1 (-/+ 2 days) 
and will be repeated every 4 weeks for both arms 
unless otherwise indicated  
Obtain CT 
and bone 
scans and 
PSA at 
Day 60 (±7 
days) 
Obtain CT 
and bone 
scans at 
16, 24, 32, 
40, and 48 
wks (if 
applicable) 
or as 
indicated 
Within 
21 (±7) 
days of 
meeting 
EOT 
criteria 
Every 4 weeks 
(±5 days) 
Day 1 
Week 1 
Both 
Arms 
Treat
-ment 
Arm 
Dose 
2 
Treat-
ment 
Arm 
Dose 3 
 
Week 
2 
Week  
3 
Week  
4 
Week  
5 
Signed/dated informed consent 
● 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics, disease/medical 
history, concurrent illnesses 
● 
●c 
 
 
 
 
 
 
 
 
 
 
 
Physical exam including weightd 
● 
 
 
 
 
 
 
 
● 
 
 
● 
● 
Vital signs: temp, HR, BPe 
● 
● 
● 
● 
 
 
 
 
● 
 
 
● 
 
ECOG performance score 
● 
● 
 
 
 
 
 
 
● 
 
 
● 
● 
Chest/abdomen/pelvic CT scans and 
bone scanf  
●g 
 
 
 
 
 
 
 
 
● 
● 
 ●h 
●h 
Concomitant medicationse 
● 
● 
 
 
 
 
 
 
● 
● 
 
  ●i 
●i 
Safety evaluation/ AE recordinge 
 
● 
● 
● 
 
 
 
 
 
 
● 
 
 
 
  ●i 
●i 
CBC and serum chemistryj 
● 
●k 
 
 
 
 
●j 
 
● 
 
 
● 
 
LDH and Testosterone  
● 
 
 
 
 
 
 
 
 
 
 
 
 
PSAl 
● 
●k 
 
 
 
 
 
 
● 
● 
 
● 
● 
Original pathology report and 
specimen or slidesm 
● 
 
 
 
 
 
 
 
 
 
 
 
 
Blood for Hsp27/clusterin/other 
relevant proteinsn 
●   
● 
 
 
 
 
 
 
● 
 
 
● 
● 
Blood for CTC assessmento 
●   
● 
 
 
 
 
 
 
● 
 
 
 
 
OGX-427 
Experimental 
Arm 
Pre-dose: anti-
histamine, H2 
antagonistp 
 
● 
● 
● 
 
● 
● 
● 
● 
 
 
 
 
OGX-427 infusion 
(every 7 ± 2 days 
starting Week 2) 
 
● 
● 
● 
 
● 
● 
● 
● 
 
 
 
 
Both Arms 
Abiraterone 
(1000 mg) and 
Prednisone (10-
20 mg PO daily ) q 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Note:  
Control Arm: Patients will begin study evaluations within 7 days after randomization (considered Day 1 of Week 1). Evaluations on Day 1 of Week 1 and every 4 weeks 
thereafter include: vital signs (temp, HR, BP), ECOG performance score, recording of concomitant medications and adverse events, safety evaluation, and blood for PSA, Hsp27, 
clusterin, other relevant proteins, CBC, and chemistry. Disease assessments are completed every 8 weeks (at the milestone Day 60 assessment and at weeks 16, 24, 32, 40, and 
48) until disease progression or another End of Study Treatment criterion is met (Section 6.4.1). Blood for CTCs will be collected during screening and at Weeks 1, 5, 9, and 13 
only. Patients who have disease-related deterioration in ECOG performance status to Grade 2 or higher are not eligible to cross-over.  Control Arm patients will be allowed to 
cross over to receive OGX-427 treatment identical to the schedule in the Experimental Arm only after documented disease progression and if within 48 weeks from study 
randomization; these patients must continue to meet inclusion/exclusion criteria and obtain sponsor (or delegate) approval. For patients eligible to cross over, the first Loading 
Dose of OGX-427 must be administered within 8 weeks of the date of progression. Patients who are crossed over can continue to receive OGX-427 treatment until an End of 
Study Treatment criterion is met (Section 5.5). Patients who are withdrawn from study treatment for a reason other than documented disease progression or patient withdrawal of 
consent to participate in the study will be followed every 4 weeks and have disease assessments every 8 weeks in the Off-Treatment Follow-up Period until documented disease 
progression. (Cross-over to the Experimental Arm is not allowed for Control Arm patients who progress in the Follow Up Period.) If a Control Arm patient does not cross-over to 
receive OGX-427 treatment, an EOT visit is needed.  
Experimental Arm: The first loading dose of OGX-427 (600 mg) will begin within 7 days following randomization and is considered Week 1, Day 1. Loading doses must be 
completed within Week 1 if possible (up to the first 10 days of initiating treatment). Following the three loading doses, OGX-427 (800 mg) is administered once weekly. Weekly 
treatment (every 7 days ±2 days) will continue until disease progression is documented or another End of Study Treatment criterion is met (Section 5.5). Patients who are 
withdrawn from study treatment for a reason other than documented disease progression or patient withdrawal of consent to participate in study will be followed every 4 weeks 
and have disease assessments every 8 weeks in the Off-Treatment Follow-up Period until documented disease progression. Experimental Arm patients (including cross-over 
patients) with PSA progression in the absence of other indicators for progression may continue therapy up to a maximum of 24 weeks, or until disease progression by imaging, 
need for alternative or additional therapy, or deterioration in ECOG performance status to Grade 3 or higher, whichever comes first (see Section 6.4.1.2). Note: Patients treated 
with OGX-427 who fulfill the criteria for PSA response (per Section 6.4.2.2., ≥ 30% decline) or objective disease response (not stable disease) at the 24-week will receive 600 
mg of OGX-427 (rather than 800mg) from Week 25 through Week 48 for an additional 24 weeks or until meeting an End of Study Treatment Criterion.. All patients will be 
followed every 4 weeks for date of documented disease progression. 
 
a All patients will have an initial screening visit. Control Arm patients who are being screened for cross-over to receive OGX-427 will need to repeat the physical exam, vital 
signs, weight, ECOG performance status, disease assessment, CBC, chemistries, PSA, blood sampling for Hsp27, clusterin, and other relevant proteins, and CTCs after 
documented disease progression. Eligibility worksheets must be submitted to the study sponsor (or delegate), forms can be found in the Study Procedures Manual. 
b EOT visit indicated for patients who received OGX-427 per the Experimental Arm schedule and patients who were randomized to the Control Arm and will not cross-over to the 
Experimental Arm. 
c Current health status and concurrent illnesses only 
d Conduct a complete physical exam at screening (including weight). Physical exams done at 4 week evaluations and at the End of Treatment and Off Treatment Follow Up visits 
are limited to weight, signs and symptoms of disease or toxicity.  
e Vital signs are required at the 4-week evaluation visits and at the EOT Visit. For Arm A patients, vital signs will also be required pre and post loading doses during the Loading 
Dose Period. Additional vitals, recording of AEs, and recording of any concomitant medications administered will be required if any signs and symptoms of an infusion reaction 
arise (e.g., chills, flushing, itching) during or immediately after OGX-427 infusion. 
f If new clinical signs and symptoms of disease progression: repeat chest/abdominal/pelvic CT scans and bone scan. Disease progression is defined as one or more of the 
following:  1) PSA: If a decline from baseline: an increase of ≥ 25% and ≥ 2 ng/ml above the nadir confirmed by a second value 3 or more weeks later. If no decline from 
baseline: an increase of ≥ 25% and ≥ 2 ng/ml from baseline confirmed by a second value 3 or more weeks later (Disease progression based on an increase in PSA cannot be 
documented prior to Day 60 (8 weeks). Patients may continue therapy, at the discretion of the Investigator, if there is only progression by PSA and there are no other indicators 
of progression); 2) Measurable disease progression per RECIST 1.1; 3) Bone scan: ≥ 2 new lesions (if the first on study bone scan (at Day 60) shows ≥ 2 new lesions, this 
requires confirmation on a second scan ≥ 4 weeks later); 4) Non-measurable disease: unequivocal progression of existing non-target lesions on CT scan; 5) Disease related 
deterioration in ECOG performance status to Grade 3 or higher; 6) Need for palliative radiation therapy; 7) initiation of any cytotoxic, systemic anti-cancer therapy; 8) surgery 
for any complication due to disease progression; 9) Cancer pain requiring chronic administration of opiate analgesia (oral or parenteral) or a consistent increase >33% in daily 
opioid use from baseline.  
g Chest/abdominal/pelvic CT scans and bone scans performed at the facility where subsequent scans will be performed are acceptable within 28 days prior to randomization and do 
not need to be repeated for inclusion/exclusion unless patient has developed new signs and symptoms of disease. 


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h For Experimental Arm patients: obtain chest/abdomen/pelvic CT scans and a bone scan at Day 60, weeks 16, 24, 32, 40, and 48, if applicable and within two weeks of the EOT 
Visit (if not performed within the last 8 weeks). If disease progression is not documented at EOT, perform chest/abdomen/pelvic CT scans and a bone scan every 8 weeks during 
the Off-Treatment Follow-Up Period until disease progression is documented. 
i Concomitant medications and adverse events (graded using the CTCAE v.4.0) should continue to be collected for 30 days after last dose of OGX-427 or until event resolves to 
≤Grade 2 or is assessed as chronic, or until the EOT visit for patients who did not receive OGX-427. Subsequent anti-cancer therapy administered during Off Treatment Follow-
Up Period should also be recorded. 
j CBC includes: WBC, ANC, lymphocytes, platelets, and hemoglobin. Serum Chemistry includes: electrolytes (Na, K, Cl, and CO2), serum creatinine, AST, ALT, alkaline 
phosphatase, total bilirubin, and glucose. CBC and serum chemistries are to be performed at screening, prior to the first loading dose (see note k below), on Week 1, Day 1 of the 
Treatment Period (7 days after randomization for patients on both Arms), at Week 3, Day 1 (of the first Treatment Period only), at every 4-week interval evaluation during the 
treatment period, and at the EOT visit (not required in Off Treatment Follow Up). Patients on Experimental Arm: CBC and serum chemistry samples can be collected 24 
hours prior to Day 1 to assure that no new safety concerns have arisen since the last assessment.  
k PSA, CBC, and serum chemistries are not required at Week 1 if previously performed at screening ≤14 days prior to visit.  
l PSA will be obtained at screening (one time within 14 days prior to randomization or cross-over), at Week 1, Day 1 (not required if performed within 14 days prior to visit), at 
the milestone Day 60 (±7 days) assessment, at every 4-week interval evaluation visit, at EOT, and at 4-week intervals in the Off-Treatment Follow-up Period (if indicated). Note 
that PSA assessments should be conducted at the same time points as CT and bone scans. For patients on Experimental Arm (including patients who cross-over): blood for PSA 
is to be drawn prior to receiving OGX-427. 
m Obtain and redact a copy of the original prostate cancer pathology report to be placed in the patient’s medical record. Once the patient has been randomized, arrange for a 
paraffin block (block preferred but unstained slides are acceptable) of their primary tumor diagnostic specimen to be sent to the address specified in Section 14.3. This is 
required for participation in the study, if available. Tissue will be returned if requested. Slides will not be returned.  
 n Blood for assays for Hsp27, clusterin, and other relevant proteins is to be drawn during screening  for both arms, at Week 1, Day 1 and at every 4-week interval evaluation visit, 
at the EOT visit, and in the Off-Treatment Follow Up Period (if indicated) (See Section 14.3 for details). For patients on Experimental Arm (including patients who cross-over): 
blood for evaluating Hsp27, clusterin and other relevant proteins is to be drawn prior to receiving OGX-427. 
o Blood for CTCs is to be drawn during screening for both arms and at Weeks 1, 5, 9, and 13 only. CTC samples must be collected and shipped on the same day. For patients on 
Experimental Arm (including patients who cross-over): blood for CTCs is to be drawn prior to receiving OGX-427.  
p Premedications include: an H2 antagonist, e.g., Ranitidine (150 mg PO or 50 mg IV); and an antihistamine, e.g., diphenhydramine (25-50 mg). It is recommended that these 
premedications be administered 30-90 minutes prior to infusion unless there is a medical reason they cannot receive one or more of the drugs. Following the need for treatment 
with steroids (8 g of dexamethasone) on more than one occasion for a Grade 2 or greater adverse event associated with an infusion, the patient should receive dexamethasone (8 
mg) in addition to premedication with an H2 antagonist and an antihistamine for a minimum of 12 weeks, or longer if necessary. 
q Both Arms: abiraterone acetate (1000 mg daily) and oral prednisone (10-20 mg/day total dose) must be continued until the End of Treatment Visit unless discontinued for 
toxicity. Missed doses are not made up. 
 


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6.2. 
Detailed Description of Study Visits 
6.2.1. 
Screening Visit for Both Arms 
Screening evaluations must be completed in up to a 28-day period (i.e. from the first 
screening evaluation to randomization) unless otherwise specified. The 28 day interval for 
screening can be extended by 1-3 working days. The purpose of the screening period is to 
ensure that patients meet all enrollment criteria and adequately comprehend the protocol 
and its requirements. A screening log at each site will document all patients who provide 
informed consent and are evaluated for the study. More than one clinic visit may be 
required in order to complete all screening evaluations. 
Prior to the conduct of any study-related procedures, the Investigator (or designee) will 
explain the study, answer all questions to the patient’s satisfaction, and obtain a signed, 
IRB/REB approved, informed consent form. A copy of the signed informed consent form 
will be given to the patient.  
Note: Patients on the Control Arm of the study who have documented disease 
progression and are undergoing screening to receive OGX-427 will need to repeat 
screening procedures as detailed in Section 6.3.3 to ensure they meet eligibility 
criteria. Only patients on the Control Arm who remain in the study until disease 
progression will be allowed to cross-over to receive OGX-427 treatment.  
The screening will include the following: 
1. Collect a signed and dated informed consent form. 
2. Collect demographics. 
3. Document histological (or cytological) diagnosis. 
4. Document TNM stage at diagnosis. 
5. Document Gleason score. 
6. Document prior administration of all cancer therapies, including adjuvant therapy, 
surgery, radiation therapy, hormonal therapy, and chemotherapy. 
7. Document date of metastatic disease. 
8. Document medical history to include: significant historical events or findings, 
including pre-existing conditions and concurrent illnesses. 
9. Obtain and redact a copy of the original prostate cancer pathology report to be 
placed in the patient’s medical record. (If the patient is randomized, a paraffin 
block or unstained slides from the primary diagnostic tumor specimen is required, 
if available, for PTEN analysis.)  
10. Perform a complete physical examination. 
11. Assess vital signs (temperature, heart rate, blood pressure). 
12. Document weight. 
13. Record ECOG performance status. 


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14. Obtain chest/abdomen/pelvic CT scans and a bone scan for disease assessment if 
not obtained within 28 days. Patients with scans performed as standard of care prior 
to consent for this study within 28 days of study enrollment that are available at the 
same facility where subsequent scans will be performed will NOT be required to 
have repeat scans unless they have developed new signs or symptoms of disease. 
CT scans should be performed per RECIST 1.1 criteria (see Section 6.4). 
15. Record concomitant medications, including any pain analgesics. 
16. At least 14 days has passed since any major surgery and 5 days for minor surgery 
(i.e. port placement), 
17. Collect approximately 34.5 mL blood as follows: (all CBCs, serum chemistries, 
and PSA assays will be performed in the local laboratory; the remaining assays will 
be performed at the Central Laboratory). 
5 mL of anticoagulated blood for a CBC to include: 
 white blood cell (WBC) count  
 absolute neutrophil and lymphocyte count 
 platelet count 
 hemoglobin 
5 mL of blood for serum chemistry testing:  
 electrolytes (Na, K, Cl, and CO2) 
 serum creatinine 
 SGOT (AST)  
 SGPT (ALT) 
 alkaline phosphatase 
 bilirubin (total) 
 glucose 
 LDH  
 
serum testosterone 3 mL of blood for PSA within 14 days prior to 
randomization 
A separate blood draw of approximately 21.5 mL for Hsp27, clusterin, other 
relevant proteins, and CTCs is to be obtained during screening to better assess the 
baseline levels.  
7 mL of blood (red topped tube) and 7 mL of blood (EDTA tube) for assays 
evaluating Hsp27, clusterin, and other relevant proteins (see Section 14.3). Serum 
and plasma will be divided into three aliquots and sent to a Central Laboratory.  


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7.5 mL of blood for CTCs must be collected in a CellSave Preservative Tube™ 
supplied by the Sponsor (see Section 14.3) and shipped to the Central Laboratory 
on the same day.  
6.2.2. 
Assignment of Patient Number, Stratification, and Randomization 
Following completion of the screening evaluations, patients meeting all 
inclusion/exclusion criteria will be assigned a unique patient number during the 
registration through the Hoosier Cancer Research Network’s Electronic Data Capture 
(EDC) system.  
Randomization will take place immediately following registration. The stratification 
factors of prior chemotherapy (yes versus no) and prior PSA response >30% to abiraterone 
acetate (yes versus no) will be employed in randomization in order to minimize between-
arm assignment imbalance. Within the strata, patients will be randomly assigned with 
equal probability to either the Experimental Arm: OGX-427 plus abiraterone/prednisone or 
the Control Arm: abiraterone/prednisone. 
Patients on the Control Arm who cross over to receive OGX-427 therapy will NOT require 
further randomization. However, Sponsor (or delegate) approval of eligibility is required. 
(See section 6.3).  
Once the patient has been randomized, arrange for a paraffin block (block preferred but 
slides are acceptable) of their primary tumor diagnostic specimen to be sent to the address 
specified in Section 14.3. This is required for participation in the study, if tissue is 
available. A redacted copy of the pathology report should accompany the tissue sample or 
slides.  
All patients should continue their ongoing abiraterone and prednisone daily dosing 
uninterrupted during the study.  
Patients on the Experimental Arm should initiate infusion of the first loading dose of 
OGX-427 within 7 days following randomization.  All three loading doses should be 
completed within Week 1 if possible (within up to 10 days of initiating treatment) (Section 
6.2.3). Patients crossing over from the Control Arm to receive OGX-427 must initiate the 
first loading dose within 8 weeks of documented disease progression. 
6.2.3. 
Study Procedures During Week 1 
For the Control Arm: Study procedures for Day 1, Week 1 should begin within 7 days 
following randomization. Study visits, evaluations, and procedures for the Control Arm 
will occur on Day 1 of Week 1 and then every 4 weeks, +/-2 days (28 days) unless 
otherwise indicated. 
For the Experimental Arm: Study procedures for Day 1, Week 1 should begin within 7 
days following randomization. OGX-427 loading dose infusions will be administered on 
three days beginning on Day 1, Week 1. Loading dose infusions must be a minimum of 36 
hours apart (i.e., every other day). All three loading doses should occur during Week 1, 
if possible. Note: If the third loading dose or the Day 1, Week 2 dose is delayed, 
subsequent weekly administration will continue based on the Day 1, Week 2 
administration date. Study visits, evaluations, and procedures for the Experimental Arm 


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will occur starting on Day 1 of Week 1 and then every 4 weeks, +/-2 days (28 days) unless 
otherwise indicated.  
For both study arms, the following study procedures should be performed on Day 1, 
Week 1. Note: Procedures in the Experimental Arm should be performed prior to the first 
OGX-427 loading dose infusion unless otherwise specified. 
 Assess vital signs (temperature, heart rate, blood pressure) 
 Record ECOG score (see Section 14.5) 
 Record concomitant medications 
 Evaluate current health status and document concurrent illnesses 
 Collect approximately 13 mL blood as follows: (Note: not required prior to 
Day 1 Week 1 if previously performed within 14 days prior to study visit)  
5 mL of anticoagulated blood for a CBC to include: 
 WBC count 
 absolute neutrophil and lymphocyte count 
 platelet count 
 hemoglobin 
5 mL of blood for serum chemistry testing:  
 electrolytes (Na, K, Cl, and CO2) 
 serum creatinine 
 SGOT (AST)  
 SGPT (ALT) 
 alkaline phosphatase 
 bilirubin (total) 
 glucose 
3 mL of blood for PSA (sent to Local Laboratory)  
 Collect approximately 21.5 mL blood as follows: 
7 mL of blood (red topped tube) for serum and 7 mL of blood (EDTA) for 
plasma for assays evaluating Hsp27, clusterin, and other relevant proteins (see 
Section 14.3). Serum and plasma will be divided into three aliquots and sent to 
a Central Laboratory.  
7.5 mL of blood for CTCs must be collected in a CellSave Preservative Tube™ 
supplied by Sponsor and shipped to the Central Laboratory on the same day 
(see Section 14.3).  


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6.2.3.1. 
Administration of Loading Dose Infusions of OGX-427 
1. Administer premedication with an H2 antagonist, e.g., Ranitidine (150 mg PO or 
50 mg IV) and an antihistamine, e.g., diphenhydramine (25-50 mg). It is 
recommended that these premedications be administered 30-90 minutes prior to 
each loading dose infusion unless there is a medical reason the patient cannot 
receive one or more of the drugs. See Section 6.7.3 treatment recommendations for 
repeated infusion reactions. 
2. Administer 600 mg OGX-427 over 2 hours using an infusion pump on each of the 
three non-sequential days starting on Day 1 of Week 1. Assess vital signs 
(temperature, heart rate, blood pressure) pre and post each infusion. There must be 
a minimum of one non-treatment day between each of the three loading dose 
infusion days (i.e. every other day). There must also be at least one but no more 
than 3  non-treatment day(s) between the last (third) loading dose infusion and the 
first weekly dose of OGX-427 (considered to be Week 2, Day 1) An example of a 
dosing schedule would be to give the three loading dose administrations of 
OGX-427 on Monday, Wednesday and Friday with the first weekly dose of OGX-
427 (Week 2, Day 1) on the following Monday. The day prior to Day 1 of weekly 
OGX-427 administration must be a non-treatment day (i.e., Sunday in the above 
example).  
3. If any signs or symptoms of an infusion reaction (i.e. chills, flushing, itching) occur 
during or immediately after any infusion, the following should be performed: 
 Record additional vital signs 
 Record AEs 
 Record any concomitant medications administered  
6.2.4. 
Experimental Arm Only: Administration of Weekly OGX-427  
1. Administer premedication with an H2 antagonist, e.g., Ranitidine (150 mg PO or 
50 mg IV) and an antihistamine, e.g. diphenhydramine (25-50 mg). It is 
recommended that these premedications be administered 30-90 minutes prior to 
each infusion of OGX-427 unless there is a medical reason the patient cannot 
receive one or more of the drugs.  
2. Administer 800 mg OGX-427 by infusion over 2 hours. Patients who fulfill the 
criteria for disease response (not stable disease) at Week 24 will receive 600 mg 
OGX-427 (rather than 800 mg) from Week 25 through Week 48 or until meeting an 
End of Study Treatment Criterion. After the Loading Dose Period, vital signs are 
only required at the 4-week evaluation visits and at the EOT visit.  
3. If any signs or symptoms of an infusion reaction (i.e. chills, flushing, itching) occur 
during or immediately after any infusion, the following should be performed: 
 Record additional vital signs 
 Record any AEs 
 Record any concomitant medications administered  


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6.2.5. 
Study Procedures During Week 3 
For both study arms, the following study procedures should be performed on Day 1 of 
Week 3:  
 Collect approximately 10 mL blood as follows:  
5 mL of anticoagulated blood for a CBC to include: 
 WBC count 
 absolute neutrophil and lymphocyte count 
 platelet count 
 hemoglobin 
5 mL of blood for serum chemistry testing:  
 electrolytes (Na, K, Cl, and CO2) 
 serum creatinine 
 SGOT (AST)  
 SGPT (ALT) 
 alkaline phosphatase 
 bilirubin (total) 
 glucose 
6.2.6. 
Both Study Arms: General Study Procedures at Day 1, Week 5 and Every 
4 Weeks Thereafter During Study Treatment 
For patients on the Experimental Arm: All study procedures must be completed prior to the 
OGX-427 infusion. The CBC and serum chemistry samples may be collected 24 hours 
prior the OGX-427 infusion.  
For both study arms, the following study procedures should be performed: 
 Conduct brief physical examination limited to signs and symptoms of disease or 
toxicity.  
 Assess vital signs. 
 Record weight. 
 Record ECOG score (see Section 14.5). 
 Update and record adverse events that occurred since the last visit. 
 Update and record concomitant medications taken since the last visit. 
 Collect approximately 27 mL blood as follows:  
5 mL of anticoagulated blood for a CBC to include: 
 WBC count 


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 absolute neutrophil and lymphocyte count 
 platelet count 
 hemoglobin 
5 mL of blood for serum chemistry to include:  
 electrolytes (Na, K, Cl, and CO2) 
 serum creatinine 
 SGOT (AST)  
 SGPT (ALT) 
 alkaline phosphatase 
 bilirubin (total) 
 glucose 
3 mL of blood for PSA (sent to Local Laboratory) 
7 mL of blood (red topped tube) and 7 mL of blood (EDTA tube) for assays 
evaluating Hsp27, clusterin, and other relevant protein levels (see Section 14.3) 
Serum and plasma will be divided into three aliquots and sent to a Central 
Laboratory.  
6.2.6.1. 
CTCs for Both Arms at Weeks 1, 5, 9, 13 only (Day 1 of each) 
7.5 mL of blood for CTCs must be collected in a CellSave Preservative Tube™ supplied 
by Sponsor and shipped on the same day (see Section 14.3).  
For patients on the Experimental Arm, blood samples for CTC assessment must be 
collected prior to the infusion of OGX-427. 
6.2.6.2. 
Disease Assessments for Both Arms 
For this study, disease will be assessed according to criteria in Section 6.4.1 and Section 
6.4.2.  
Any patient who develops new clinical signs or symptoms of disease progression at any 
time should have a chest, abdominal, and pelvic CT scan and a bone scan to assess for 
disease progression.  
All patients will be assessed for disease status with a chest, abdominal, and pelvic CT scan 
and a bone scan at the milestone Day 60 assessment (expected to occur at the end of Week 
8, prior to Week 9), and at 16, 24, 32, 40, and 48 weeks (i.e., every 8 weeks) until disease 
progression.  
6.2.7. 
Milestone Day 60 Disease Assessment 
The objective of the milestone Day 60 disease assessment will be to evaluate for any 
previously undiscovered evidence of progression. This assessment will be conducted 
approximately 60 calendar days following randomization and is expected to occur after 
Week 8 and prior to Day 1, Week 9. The milestone Day 60 disease assessment must be 


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completed within the inclusive window of Day 53 to Day 67 post-randomization, 
regardless of the timing of Week 8 treatment (i.e., whether treatment scheduling at any 
time has been delayed). All living patients who have not had documented disease 
progression prior to the milestone Day 60 disease assessment will be assessed for evidence 
of disease progression. For patients who had criteria possibly indicating disease 
progression on or after Week 4 (i.e., appearance of 2 or more new bone lesions), the 
milestone Day 60 disease assessment will be the confirmation scan that disease 
progression has occurred (see Section 6.4.1.2). 
The milestone Day 60 disease assessment must be scheduled in the inclusive window of 
Days 53 to 67 following randomization. This assessment may be conducted in conjunction 
with procedures scheduled for Day 1, Week 9 (as detailed in 6.2.6) if that visit occurs 
within the specified timeframe (Days 53 to 67). Milestone Day 60 disease assessments 
done outside of this window are protocol violations. Please note that the rules for 
scheduling the milestone Day 60 disease assessments apply even if the patient was 
recently evaluated according to the study calendar just prior to Day 53, or would be 
evaluated according to the study calendar shortly after Day 67. Clinical site personnel 
are encouraged to contact the Sponsor (or a designated representative) to discuss options 
for scheduling of the milestone Day 60 disease assessment in cases where other 
evaluations would precede or follow closely.  
For the milestone Day 60 disease assessment, the following evaluations must be 
completed: 
1. Record bisphosphonate or denosumab usage. 
2. Obtain chest, abdomen and pelvic CT scans (MRI, if appropriate) and a bone scan. 
Note: MRI should only be performed if disease assessment at screening was 
assessed by MRI. 
3. Collect approximately 3 mL of blood for PSA (sent to Local Laboratory).  
Refer to Section 6.4.1 for disease progression criteria. 
6.2.8. 
End of Treatment (EOT) Visit [21 days (± 7 days) Following Withdrawal 
from Study Treatment] 
The following patients who are withdrawing from study treatment for any reason (see 
Section 5.5) must have an EOT Visit: 
 Patients who were randomized to the Experimental Arm  
 Patients who were randomized to the Control Arm and will not cross-over to 
receive OGX-427  
 Patients who have crossed over from the Control Arm and have received OGX-
427 
Note: Patients on the Control Arm who have disease progression and wish to cross over on 
the study to receive OGX-427 per the Experimental Arm Procedures will have a Screening 
Visit in the same time period rather than an EOT Visit (see Section 6.3.3).  
The following will be documented/evaluated at the EOT Visit: 


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1. Record the reason for withdrawal from further treatment for patients on the 
Experimental Arm or from the study for patients on the Control Arm who are not 
eligible to cross-over or do not wish to cross-over to receive OGX-427 treatment.  
2. Conduct physical exam limited to signs and symptoms of disease or toxicity. 
3. Assess vital signs. 
4. Document weight. 
5. Record ECOG score (see Section 14.5).  
6. Any patient who does not have documented disease progression must have a repeat 
chest, abdominal and pelvic CT scan and bone scan if not performed within the last 
8 weeks. 
7. Collect approximately 27 mL of blood as follows:  
5 mL anticoagulated blood for CBC to include: 
 WBC count 
 absolute neutrophil and lymphocyte count 
 platelet count 
 hemoglobin 
5 mL blood for serum chemistry to include:  
 electrolytes (Na, Cl, K, and CO2) 
 serum creatinine 
 SGOT (AST) 
 SGPT (ALT) 
 alkaline phosphatase 
 bilirubin (total) 
 glucose 
3 mL of blood for PSA (sent to Local Laboratory) 
7 mL of blood (red topped tube) and 7 mL of blood (EDTA) for assays for 
evaluating Hsp27, clusterin, and other relevant protein levels (see Section 14.3). 
Serum and plasma will be divided into three aliquots and sent to a Central 
Laboratory.  
9. Update and record adverse events since last assessment. All previous and new 
adverse events are to be followed to at least 30 days following last dose of OGX-
427 (for Experimental Arm, including cross-over patients) or until the End of 
Treatment Visit for the Control Arm. All SAEs and Grade 3 or higher adverse 
events that are ongoing must be followed until each event resolves or is assessed as 
chronic. Follow-up can be accomplished via an additional clinic visit or telephone 
contact with patient. 


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10. Update and record concomitant medications since last assessment. All concomitant 
medications are to be followed for at least 30 days following last dose of OGX-427 
(for Experimental Arm, including cross-over patients) or until the End of Treatment 
Visit for patients on the Control Arm. Follow-up can be accomplished via an 
additional clinic visit or telephone contact with the patient.   
6.2.9. 
Off Treatment Follow-up Period [Every 4 weeks (± 5 days)] 
Patients will have study visits and evaluations every 4 weeks after the End of Treatment 
Visit, and continuing until disease progression is documented.  
The following evaluations will be performed unless otherwise specified: 
1. Physical exam limited to signs and symptoms of disease or toxicity. 
2. Record weight. 
3. Record ECOG score (see Section 14.5). 
4. Collect approximately 3 mL of blood for PSA (sent to Local Laboratory).  
5. Collect approximately 7 mL of blood (red topped tube) and 7 mL of blood (EDTA 
tube) for assays for evaluating Hsp27, clusterin, and other relevant protein levels 
(see Section 14.3). Serum and plasma will be divided into three aliquots and sent to 
a Central Laboratory.  
6. Update and record all adverse events for 30 days following last dose of OGX-427 
or until the End of Treatment Visit for the Control Arm. All SAEs and grade 3 or 
higher adverse events that are ongoing need to be followed until each event 
resolves or is assessed as chronic. 
7. Repeat chest, abdominal and pelvic CT scans, and bone scan every 8 weeks. (Note: 
Patients who develop new clinical signs or symptoms of disease progression at any 
time should have a repeat chest, abdominal, and pelvic CT scan and a bone scan).  
After 30 days following the last dose of OGX-427 or End of Treatment Visit for the 
Control Arm, record only concomitant medications associated with SAEs and grade 3 or 
higher adverse events that have not resolved or have not been assessed as chronic. 
Subsequent anti-cancer therapy administered during the Off-Treatment Follow-up Period 
should be recorded.  
6.3. 
Cross-over OGX-427 Treatment for Control Patients  
6.3.1. 
Procedures for Control Patients to be Eligible for Cross-over Treatment 
Patients in the Control Arm with documented disease progression will be allowed to cross-
over to receive OGX-427 treatment per the Experimental Arm schedule, providing the 
patient is eligible for treatment with OGX-427 (i.e., fulfills all inclusion and exclusion 
criteria below) and continues to receive abiraterone acetate and prednisone.  Note: 
Crossover must occur within 48 weeks of study randomization. 


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Only patients on the Control Arm who remain on study treatment until documented disease 
progression will be allowed to cross-over. Control Arm patients who have disease-related 
deterioration in ECOG performance status to Grade 2 or higher are not eligible to cross-
over. Sponsor (or delegate) approval of eligibility for cross-over is required.  
Screening for eligibility criteria will begin following the date of documented disease 
progression (see Section 6.3.3). The first loading dose of OGX-427 must be administered 
within 8 weeks of the date of documented disease progression and will be considered 
Day 1, Week 1 for OGX-427 treatment.  
OGX-427 treatment, study evaluations, and disease assessments will occur in the same 
manner as defined for the Experimental Arm in Sections 6.2.3 through 6.2.7 until further 
disease progression is documented or the patient meets another End of Study Treatment 
criterion for withdrawal (see Section 5.5). Patients who are withdrawn from study 
treatment for a reason other than documented disease progression or patient withdrawal of 
consent to participate in the study should be followed until further disease progression is 
documented, if possible. 
6.3.2. 
Eligibility Criteria for Cross-over Treatment 
To be eligible for cross-over treatment, subjects must meet ALL of the following 
inclusion criteria and not meet any of the exclusion criteria. 
Inclusion criteria: 
1. Has met one or more of the criteria for disease progression as outlined in Section 
6.4.1.2 (other than disease related deterioration in ECOG performance status to 
Grade 3 or higher; initiation of any cytotoxic, systemic anti-cancer therapy; or 
cancer pain requiring initiation of chronic opiate analgesia (oral or parenteral) or a 
consistent increase >33% in daily opioid use from baseline) within 48 weeks from 
study randomization 
Note: If disease progression is by PSA or bone scan only, confirmation of 
progression must be documented prior to first dose of OGX-427. 
2. ECOG performance status of 0 or 1 
3. Currently receiving and tolerating abiraterone acetate (1000 mg oral daily) and 
prednisone (10-20 mg oral daily)  
4. No evidence of other symptomatic or radiographic progression that would require 
alternative therapy  
5. All patients who have not had a surgical orchiectomy must continue treatment with 
LHRH agonist or antagonist to maintain a castrate level of testosterone.  
6. Prior radiation therapy for disease progression is permitted if a minimum of at least 
14 days have passed since completing radiotherapy at the time of the first dose of 
OGX-427 (exception for radiotherapy: at least 7 days since completing a single 
fraction of ≤800 cGy to a restricted field or limited-field radiotherapy to non-
marrow bearing area such as an extremity or orbit) 


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7. At least 14 days has passed since any major surgery and 5 days for minor surgery 
(i.e. port placement)  
8. Baseline laboratory values as stated below: 
a. ANC  1.5 x 109 cells /L, platelet count  100 x 109 /L, and hemoglobin  9 
g/dL without transfusion 
b. Creatinine  1.3 x upper limit of normal (ULN) 
c. Total bilirubin  1.1 x ULN (unless elevated secondary to conditions such as 
Gilbert’s disease, in which case a direct bilirubin ≤ ULN is required) 
d. SGPT (ALT) and SGOT (AST)  3.0 x ULN 
e. Castrate serum testosterone level ( 50 ng/dL or  1.7 nmol/L) 
f. Potassium within normal limits 
9. Recovery from all toxicities of prior therapy to ≤grade 2 by NCI CTCAE, version 
4.0 
10. Must be willing to continue use of effective contraception throughout study 
treatment and for 3 months after completion of study treatment if able to father a 
child. 
11. Must continue to be willing not to change (add or subtract) bone protecting therapy 
(bisphosphonates and/or denosumab) during the study unless changed for toxicity. 
Exclusion criteria: 
Subjects meeting ANY of the following exclusion criteria will NOT be eligible for 
cross-over treatment: 
1. Documented brain metastases or carcinomatous meningitis while on abiraterone 
treatment, treated or untreated (Brain imaging for asymptomatic patients is not 
required.) 
2. Cord compression requiring surgery or radiation therapy while on abiraterone 
treatment 
3. Any new uncontrolled medical condition that would preclude protocol therapy 
4. Active second malignancy (including lymphoid malignancies such as chronic 
lymphocytic leukemia or low grade lymphoma) defined, in general, as requiring 
anticancer therapy or at high risk of recurrence during the study; not including 
adequately treated non-melanomatous skin cancer or other solid tumors curatively 
treated with no evidence of disease in > 3 years 
5. Active autoimmune disease requiring treatment 
6. Known LVEF <50% or NYHA Class III or IV heart failure 
6.3.3. 
Screening Procedures for Cross-over Treatment 
 Note: The date of cross over is considered the last day all screening procedures are 
confirmed completed and the patient is deemed eligible to cross over. The Day 60 
evaluation should be scheduled for 60 days after the date of cross over. 
 


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Screening for cross-over patients will include: 
1. Record the reason for ending Control Arm treatment. 
2. Perform a complete physical examination. 
3. Assess vital signs (temperature, heart rate, blood pressure). 
4. Document weight. 
5. Record ECOG performance status. 
6. Obtain chest/abdomen/pelvic CT scans and a bone scan for disease assessment if 
not obtained within 28 days. CT scans should be performed per RECIST 1.1 
criteria (see Section 6.4). 
7. Record concomitant medications. 
8. Collect approximately 34.5 mL blood as follows: (all CBCs, serum chemistries, 
and PSA assays will be performed in the local laboratory; the remaining assays will 
be performed at the Central Laboratory). 
5 mL of anticoagulated blood for a CBC to include: 
 white blood cell (WBC) count  
 absolute neutrophil and lymphocyte count 
 platelet count 
 hemoglobin 
5 mL of blood for serum chemistry testing:  
 electrolytes (Na, K, Cl, and CO2) 
 serum creatinine 
 SGOT (AST)  
 SGPT (ALT) 
 alkaline phosphatase 
 bilirubin (total) 
 glucose 
  
 
3 mL of blood for PSA within 14 days prior to cross-over 
A separate blood draw of approximately 21.5 mL for Hsp27, clusterin, other 
relevant proteins, and CTCs is to be obtained during screening to better assess the 
levels at time of cross-over. It is preferred that this blood draw occur within 14 
days of cross-over, i.e., close to the time of OGX-427 treatment.  


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 7 mL of blood (red topped tube) and 7 mL of blood (EDTA tube) for assays 
evaluating Hsp27, clusterin, and other relevant proteins (see Section 14.3). 
Serum and plasma will be divided into three aliquots and sent to a Central 
Laboratory.  
 7.5 mL of blood for CTCs collected in a CellSave Preservative Tube™ 
supplied by the Sponsor (see Section 14.3) and shipped to the Central 
Laboratory on the same day. 
6.4. 
Study Outcome Definitions 
6.4.1. 
Disease Progression 
In addition to disease assessments every 8 weeks, all patients should be evaluated for 
disease progression at the time of any new signs or symptoms of cancer during the study. 
Disease progression is defined in Section 6.4.1.2. 
6.4.1.1. 
Evaluation of Baseline Target and Non-Target Lesions 
Measurable Disease (Target Lesions) 
Measurable lesions include all soft-tissue lesions. Visceral lesions must be able to be 
accurately measured in at least one dimension with the longest diameter  10 mm using CT 
scans or MRI. For pathological lymph nodes to be measureable, a node must by ≥ 15 mm 
in the short axis.  
Previously irradiated lesions should not be considered measurable. 
CT scans with contrast (unless contraindicated, i.e., especially for patients with increased 
risk of contrast related nephropathy) should be performed with slice thickness no greater 
than 5 mm. The same method of assessment should be used at baseline and during 
follow-up assessments for each lesion, i.e., conventional vs. spiral CT or MRI. 
At baseline, measurable lesions representing overall tumor burden, up to a maximum of 2 
lesions per organ and 5 lesions in total, should be identified as “target lesions” and 
recorded and measured. Lesions that are unsuitable for accurate, repeated 
measurements should not be selected as target lesions. A sum of the diameters (long 
axis for non-nodal and short axis for nodal lesions) of all target lesions at baseline will be 
calculated and reported as the baseline sum diameter. This will be used as reference to 
characterize disease response. Lesions should be recorded in the same order on sequential 
examinations. 
Non-Measurable Disease (Non-Target Lesions) 
All other lesions or sites of disease (including lesions on bone scan) should be identified 
as “non-target lesions” and should also be recorded at baseline. This includes measurable 
lesions smaller than dimensions defined above or lesions in excess of 2 per organ or 5 in 
total. Worsening (increase in intensity or size of a lesion) of pre-existing non-target 
lesions, including bone lesions, may be difficult to interpret and therefore will not be 
considered evidence of progressive disease. Measurement of these lesions is not required; 


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however the presence or absence of each should be noted. Do not record “increased”, 
“decreased” or “stable.”  
6.4.1.2. 
Criteria for Disease Progression 
Patients will be assessed as having Disease Progression if one or more of the following 
criteria have been met:  
a. PSA: If a decline from baseline: an increase of ≥ 25% and ≥ 2 ng/mL above the 
on-study nadir confirmed by a second value 3 or more weeks later. If no decline 
from baseline: an increase of ≥ 25% and ≥ 2 ng/mL from baseline confirmed by 
a second value 3 or more weeks later 
Note: Disease progression based on PSA cannot be confirmed prior to Day 60 
(8 weeks). 
b. Measurable disease: Progression of measurable disease has occurred if any of 
the criteria below are met on CT scan: 
 The appearance of one or more new lesions 
 At least a 20% increase in the sum of diameters of target lesions, taking as 
reference the smallest sum on study, including the baseline sum. In addition 
to the relative increase of 20%, the sum must also demonstrate an absolute 
increase of at least 5 mm. 
c. Bone scan: ≥ 2 new lesions (if the first on study bone scan at Day 60 shows ≥ 2 
new lesions, this requires confirmation on a second scan ≥ 4 weeks later which 
shows ≥2 additional new lesions) 
d. Non-measurable disease (non-target lesions on CT scan): Progression of disease 
has occurred if the criteria outlined below for “unequivocal progression” of 
existing non-target lesions on CT scan has been met. To achieve unequivocal 
progression on the basis of non-target disease, there must be an overall level of 
substantial worsening in non-target disease such that, even in presence of stable 
disease (SD) or partial response (PR) in measurable disease, the overall tumor 
burden has increased sufficiently to merit discontinuation of therapy. The 
designation of overall progression solely on the basis of change in non-target 
disease in the face of SD or PR of target disease will therefore be extremely 
rare. When the patient has only non-measurable disease, the same general 
concepts apply as noted above, however, in this instance, there is no measurable 
disease assessment to factor into the interpretation of an increase in non-
measurable disease burden. A useful test that can be applied is to consider if the 
increase in overall disease burden based on the change in non-measurable 
disease is comparable in magnitude to the increase that would be required to 
declare PD for measurable disease: i.e., an increase in tumor burden 
representing an additional 73% increase in “volume” (which is equivalent to a 
20% increase diameter in a measurable lesion). 
e. Disease related deterioration in ECOG performance status to Grade 3 or higher. 
Note: Patients whose ECOG performance status decreases to Grade 2 during 
the study should be assessed by the Investigator for their need for systemic 
chemotherapy or other non-study therapies. Note: Patients on the Control Arm 


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with an ECOG Grade 2 or higher are not eligible to cross-over to the 
Experimental Arm. 
f. Need for palliative radiation therapy 
g. Initiation of any cytotoxic, systemic anti-cancer therapy 
h. Surgery for any complication due to disease progression 
i. Cancer pain requiring initiation of chronic opiate analgesia (oral or parenteral) 
or a consistent increase >33% in daily opioid use from baseline. Note: Any 
patients with cancer pain who require increasing narcotics for relief of cancer 
pain should be assessed by the Investigator for the need to initiate systemic 
chemotherapy or other non-study therapies.   
6.4.2. 
Response Definitions 
6.4.2.1. 
Objective Response 
Objective Response takes into account both measurable and non-measurable lesions by CT 
(or MRI, if applicable), bone lesions, and tumor markers. 
Complete Response (CR): Disappearance of all measurable and non-measurable lesions on 
CT scan and bone scan, with no new lesions. All pathological lymph nodes (whether target 
or non-target) must have reduction in short axis to <10 mm. All tumor markers must have 
normalized, as have disease-related symptoms. Confirmatory scans are required. 
Partial Response (PR): At least a 30% decrease in the sum of diameters (long axis for non-
nodal lesions, short axis for nodal lesions) of measurable lesions on CT scan, taking as 
reference the baseline sum diameters, with no “unequivocal progression” of 
non-measurable lesions on CT scan or bone scan and no new lesions. 
Stable Disease (SD): Neither sufficient shrinkage of measurable lesions on CT scan to 
qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest 
sum diameters while on study. There may be persistence of one or more non-target lesions 
on CT scan or bone scan, and/or maintenance of tumor marker level above the normal 
limits. 
Disease Progression (PD): See Section 6.4.1.2 subpoints b, c, and d. 
Not Evaluable (NE): When no imaging/measurement is performed at a particular time 
point, the patient is NE at that time point. If only a subset of lesion measurements are made 
at an assessment, the patient is NE at that time point, unless PD is otherwise determined. 
Every attempt should be made to perform an imaging evaluation prior to initiating any new 
anticancer therapy. 
6.4.2.2. 
PSA Response 
A PSA response is defined as a post-treatment decline in PSA from baseline. The response 
must be confirmed by a second value 3 or more weeks later. 
≥50% response: A PSA decline of 50% or more from baseline, confirmed by a second 
value 3 or more weeks later. 
≥30% response: A PSA decline of 30% or more from baseline, confirmed by a second 
value 3 or more weeks later. 


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PSA progression: See Section 6.4.1.2 subpoint a. 
6.5. 
Protocol-Specific Samples for Correlative Studies 
Details regarding processing, labeling, and shipping of samples can be found in Section 
14.3. Following completion of all correlative analysis, any remaining research samples will 
be destroyed within 3 years following completion of the study. 
 
6.5.1. 
Blood Collection for Assays Evaluating Hsp27, Clusterin, and Other 
Relevant Proteins 
Blood for assays for evaluating Hsp27, clusterin, and other relevant proteins will be 
collected, processed at the local site and shipped to a central laboratory for analysis (see 
Section 14.3). Baseline and changes in Hsp27 protein levels will be explored in relation to 
patient outcomes as a possible prognostic and predictive biomarker for OGX-427 biologic 
activity. Clusterin, a cytoprotective chaperone protein similar to heat shock proteins, will 
be measured as clusterin protein levels may change in response to Hsp27 inhibition.  
6.5.2. 
Circulating Tumor Cells  
Baseline and changes in circulating tumor cells (CTCs) after treatment have been 
correlated with prognosis in CRPC. CTCs will be collected at screening and weeks 1, 5, 9 
and 13. Blood for CTCs will be collected, processed at the local site, and shipped to a 
central laboratory for analysis using the Immunicon/Veridex system (see Section 5.5).  
6.5.3. 
Tissue for PTEN 
Hsp27 is involved in regulation of the serine/threonine kinase AKT, and AKT is 
constitutively activated by loss of the PTEN tumor suppressor gene, which frequently 
occurs in prostate cancer.63 Furthermore, pre-clinical data suggest that loss of PTEN may 
be a potential predictive factor for response to Hsp27 inhibition. Original 
biopsy/prostatectomy specimens (tissue is preferred however unstained slides are 
acceptable) and redacted pathology reports from all patients randomized to study will be 
sent to a central laboratory for evaluation of PTEN deletion status using a FISH assay63 
(see Section 14.3). Tissue will be returned if requested. Slides will not be returned. 
6.6. 
Dose Modifications for Toxicity 
Toxicities will be graded using the National Cancer Institute Common Toxicity Criteria for 
Adverse Events (NCI CTCAE), Version 4.0. In general, the need for dose modifications of 
OGX-427, abiraterone acetate, and/or prednisone will be assessed based on laboratory 
values or physical signs obtained within 48 hours prior to treatment.  
Treatment delays, for experimental arm, for any reason, not made up in the same calendar 
week of the scheduled dose will be considered ‘missed’ doses. Treatment may not be 
missed for more than three weeks (4 missed doses). If treatment must be delayed longer 
than three weeks for any reason, the patient will be removed from protocol treatment but 
will continue to be followed for safety and disease progression.  


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No dose reductions of the 600 mg dose will be performed during the three OGX-427 
loading doses. However, any grade 3 or 4 adverse events occurring during the loading dose 
period must resolve to ≤ Grade 1 before the next loading dose or before the first weekly 
dose of 800 mg OGX-427 can be administered.  
The OGX-427 weekly dose of 800 mg should be administered starting at Week 2. After 
Week 2, dose modifications may occur as indicated in this section. 
The dose of OGX-427 or abiraterone will not be re-escalated once the dose is reduced. If 
more than two dose reductions of OGX-427 or abiraterone are required, the patient should 
be removed from study treatment. If OGX-427 or abiraterone is discontinued due to 
toxicity, the patient will be removed from study treatment. Patients should have an End of 
Treatment Visit and then should enter the Off-Treatment Follow-up Period until disease 
progression. 
If prednisone is reduced due to toxicity, the patient may continue on study treatment with 
abiraterone (with or without OGX-427, dependent on randomization). However, 
abiraterone should not be administered without some form of steroid coverage. If serious 
side effects develop related to mineralocorticoid excess, stress doses of steroids can be 
given. 
Reasons for modifying the dose of OGX-427, abiraterone acetate, or prednisone must be 
recorded in the source documents and the eCRF. 
6.6.1. 
Dose Modifications for OGX-427  
Table 5: 
Dose Level Modifications for OGX-427 
Dose Level 
Study agent 
100% 
800 mg 
First dose reduction 
700 mg 
Second dose reduction* 
600 mg 
* Requirement for a third dose reduction will lead to discontinuation from 
study treatment. 
 
6.6.2. 
Dose Modifications for Abiraterone Acetate 
Dose modifications for abiraterone are noted below. For more information refer to the 
Package Insert for abiraterone acetate provided in the Study Procedure Manual. 
Table 6: 
Dose Level Modifications for Abiraterone Acetate 
Dose Level 
Study Agent 
100% 
1000 mg 
First dose reduction 
750 mg 
Second dose reduction* 
500 mg 
* Requirement for a third dose reduction will lead to discontinuation from 


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study treatment. 
 
6.6.3. 
Hepatic Toxicity for OGX-427 and Abiraterone Acetate 
Modification for hepatic toxicity should be based on AST, ALT, and bilirubin values. The 
dose adjustments are shown in the table below.  
 
Table 7: 
Dose Modifications of OGX-427 for Hepatic Toxicity  
 
Transaminase AST and ALT levels 
 
3.0 x ULN  
(Grade 1) 
>3.0 and 5.0 x ULN 
(Grade 2) 
>5.0 x ULN  
(Grade 3) 
>20 x ULN 
(Grade 4) 
Bilirubin 
1.1 x ULN 
100% of dose 
Hold 
Resume when both 
AST and ALT  
3.0 x ULN 
Hold 
Resume when both 
AST and ALT  
3.0 x ULN; 
Decrease OGX-427 
by 1 dose level 
Remove from 
protocol 
treatment 
 
Bilirubin 
>1.1 x ULN 
Hold 
Resume when 
bilirubin to 
1.1 x ULN 
 
Hold 
Resume when bilirubin to 
1.1 x ULN and  
both AST and ALT 
3.0 x ULN;  
Decrease OGX-427 by 1 
dose level 
Remove from 
protocol treatment 
 
Remove from 
protocol 
treatment 
 
 


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Table 8: 
Dose Modifications of Abiraterone Acetate for Hepatic Toxicity 
 
Transaminase AST and ALT levels 
 
3.0 x ULN  
(Grade 1) 
>3.0 and 5.0 x ULN 
(Grade 2) 
>5.0 x ULN  
(Grade 3) 
>20 x ULN 
(Grade 4) 
Bilirubin 
3.0 x ULN 
100% of dose 
Hold 
Monitor liver tests at 
least weekly 
Resume when bilirubin 
<1.5 x ULN and  
both AST and ALT 
3.0 x ULN 
Hold 
Monitor liver tests at 
least weekly 
Resume when 
bilirubin <1.5 x ULN 
and both AST and 
ALT 3.0 x ULN 
Decrease abiraterone 
by 1 dose level 
Remove from 
protocol 
treatment 
 
Bilirubin 
>3.0 x ULN 
Any 
AST/ALT 
Hold 
Monitor liver tests at least weekly 
Resume when bilirubin 
1.5 x ULN and  
both AST and ALT 3.0 x ULN  
Decrease abiraterone by 1 dose level 
Remove from 
protocol 
treatment 
 
 
 
6.6.4. 
Hematological Toxicity for OGX-427  
Table 9: 
Dose Modifications for Hematologic Toxicity  
Toxicity 
Dose Modification* 
ANC 1.5 x109 cells /L and platelet 
count 100 x 109/L, 
100% of present dose  
 
ANC <1.5 x109 cells /L 
  
AND/OR 
 
 platelet count <100 x 109/L 
Hold OGX-427: Repeat counts weekly 
When ANC 1.5 x109 cells /L and platelet count 100 x 
109/L, resume at 100% of present dose 
If held for more than 1 week, resume but decrease 
OGX-427 by one dose level following the recovery of the 
ANC to 1.5 x109 cells/L and the platelet count to 100 x 
109/L 
Remove patient from protocol treatment if the ANC has 
not recovered to 1.5 x109 cells /L and/or platelet count to 
100 x 109/L within 3 weeks (4 missed doses) 
*Note: Grade 3-4 lymphopenia is a known class effect of ASOs; dose modifications are not required. 
 


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6.6.5. 
Renal Toxicity for OGX-427 
Table 10: 
Dose Modifications of OGX-427 for Renal Toxicity 
Toxicity 
Dose Modification 
Creatinine level increase of  
>0.3 mg/dL above baseline; 
creatinine 1.5 - 2.0 x above baseline 
(Grade 1) 
100% of present dose  
Creatinine 2 - 3 x above baseline 
(Grade 2) 
Hold 
Resume OGX-427 at 100% of present dose when 
creatinine ≤2.0 x above baseline (Grade 1)* 
Creatinine >3 x baseline or  
>4.0 mg/dL; hospitalization 
indicated (Grade 3) 
Hold 
Resume OGX-427 when creatinine ≤2.0 x above baseline 
(Grade 1)*; decrease OGX-427 by 1 dose level 
Life-threatening consequences; 
dialysis indicated (Grade 4) 
Remove from protocol treatment  
*Note: Repeat creatinine assessment at least weekly until resolution to grade 1. 
 
6.6.6. 
Acute Infusion Reactions: Dose Modifications for OGX-427 
In the event of an acute infusion reaction (e.g., flushing, rash, fever, urticaria, dyspnea, 
bronchospasm, and/or hypotension) during the OGX-427 infusion, follow the Institutional 
Guidelines of each site and the recommendations shown in the table below based on the 
grade of the reaction. There will be no dose reductions of OGX-427 during the Loading 
Dose Period, but loading doses must be held until resolution of any toxicity to ≤ Grade 1. 
In addition, dosing of OGX-427 at Cycle 1, Day 1, will be held until resolution of any 
infusion reactions to ≤ grade 1 following the last loading dose.  
To identify the grade of a reaction, refer to the list below adapted from the NCI CTCAE 
Version 4.0 dated May 28, 2009 (under the terms “Infusion related reaction” and 
“Cytokine release syndrome”): 
 Grade 1: Mild reaction; infusion interruption not indicated; intervention not 
indicated.  
 Grade 2: Therapy or infusion interruption indicated but responds promptly to 
symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV fluids); 
prophylactic medications indicated for ≤24 hrs.  
 Grade 3: Prolonged (e.g., not rapidly responsive to symptomatic medication 
and/or brief interruption of infusion); recurrence of symptoms following initial 
improvement; hospitalization indicated for clinical sequelae. Note: any infusion 
that is interrupted and not resumed within the visit will be considered a Grade 3 
reaction. 
 Grade 4: Life-threatening consequences; urgent intervention indicated 


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Table 11: 
Dose Modifications for Acute Infusion Reactions with OGX-427  
Toxicity 
Dose Modification 
Any Grade 1 infusion reaction 
Slow the rate of infusion of the drug until resolution of symptoms, 
then resume at the planned infusion rate. 
First Grade 2 infusion reaction 
Stop the infusion. Give dexamethasone 8 mg IV, diphenhydramine 50 
mg IV, and/or an H2 antagonist (e.g. Ranitidine 50 mg IV), after 
consultation with the attendant physician. Resume infusion after 
recovery of symptoms to grade ≤1 at a slower rate and increase 
incrementally toward the initial rate. If the reaction recurs, stop the 
infusion and do not administer the remaining volume. 
Second Grade 2 infusion 
reaction, or first Grade 3 
infusion reaction 
Stop the infusion. Give dexamethasone 8 mg IV, diphenhydramine 50 
mg IV, and/or an H2 antagonist (e.g. Ranitidine 50 mg IV), after 
consultation with the attendant physician. Resume accordingly after 
recovery of symptoms to grade ≤1. 
Add 8 mg dexamethasone to the premedication regimen (H2 
antagonist and antihistamine) for a minimum of 12 weeks. 
Grade 2 or Grade 3 infusion 
reaction in the presence of 
steroid prophylaxis 
Stop the infusion. Give dexamethasone 8 mg IV, diphenhydramine 50 
mg IV, and/or an H2 antagonist (e.g. Ranitidine 50 mg IV), after 
consultation with the attendant physician.  
Grade 2 or 3 infusion reaction in the presence of steroids: reduce 
subsequent administration of OGX-427 by one dose level (a 
maximum of two dose reductions are allowed after Week 2). Any 
patient experiencing a second grade 3 infusion reaction to OGX-
427 despite adequate steroid prophylaxis will be discontinued 
from study treatment. 
Any Grade 4 infusion reaction  
Discontinue OGX-427 infusion. Follow Institutional Guidelines for 
treatment. Discontinue all study treatment. 
 
6.6.7. 
Management of Hypertension 
Table 12: 
Dose Modifications of Abiraterone Acetate for Hypertension 
Toxicity 
Dose Modification 
Grade 1 or 2 hypertension 
Institute or increase anti-hypertensive measures while continuing 
abiraterone 
Grade 3 hypertension for >24 
hours (BP≥160/100 or, if 
previously normal, symptomatic 
increase by >20 mm Hg 
[diastolic] or BP>160/100) or, 
requires more than one drug than 
previously used 
Hold abiraterone 
Institute or increase anti-hypertensive measures 
Abiraterone may be restarted when blood pressure values on 
hypertensive therapy return to ≤grade 1 (140/90) 
Resume abiraterone at the same dose 
If grade 3 toxicity recurs in spite 
of adequate antihypertensive 
Hold abiraterone 


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regimen 
Continue medical management for hypertension 
Abiraterone may be restarted when blood pressure values return to  
≤grade 1 (140/90) 
Reduce the dose of abiraterone by one dose level 
Grade 4 (life-threatening, 
malignant hypertension, or any 
hypertension with a  neurologic 
deficit) 
Patient should be removed from study therapy. 
 
6.6.8. 
Management of Hypokalemia 
Table 613: 
Dose Modifications of Abiraterone Acetate for Hypokalemia 
Toxicity 
Dose Modification 
Grade 1 asymptomatic  
hypokalemia (<LLN to 3.0 
mmol/L) 
Hold abiraterone; initiate oral K+ supplement or increase dose up to a 
maximum oral dose of 80 mEq/day.  Abiraterone can be reinstituted at 
the same dose once the K+ is normal. 
Grade 2 hypokalemia 
(symptomatic <LLN to 3.0 
mmol/L) or grade 3 hypokalemia 
(<3.0-2.5 mmol/L) 
Hold abiraterone; initiate oral K+ supplement or increase dose up to a 
maximum oral dose of 80 mEq/day. Resume abiraterone when three 
consecutive  K+ are normal; decrease abiraterone by one dose level.  
If serum K+ cannot be corrected 
with 80 mEq of daily K+ dosing 
by oral supplementation 
Administer IV K+. Resume abiraterone when three consecutive  K+ 
are normal; decreased abiraterone by one dose level. 
Grade 4 hypokalemia 
(<2.5 mmol/L)  
Remove patient from protocol therapy. 
Note: While making changes to potassium supplementation, the K+ should be repeated at 
least weekly (or more frequently per investigator) until three consecutive values are in the 
normal range. 
 
6.6.9. 
Management of Rash 
 For any grade 3 rash covering >30% body surface area (BSA), abiraterone 
should be held until resolution to grade 1 and the dose of abiraterone should be 
reduced by one dose level.  Weekly OGX-427 infusions may continue. 
 If grade 3 rash does not resolve to grade 1 within 3 weeks, the patient will be 
removed from protocol therapy. 
 


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6.6.10. 
Grade 3 or 4 Non-Hematological Toxicities for OGX-427 and Abiraterone 
Acetate Not Discussed Above  
Discontinue OGX-427 and abiraterone therapy for the following reasons: 
 Any Grade 4 non-hematological AE with the following exceptions: alopecia, 
anemia, pain, fatigue (asthenia, lethargy, malaise), insomnia, nail changes, 
arthralgia and myalgia. 
 Any Grade 3 non-hematological AE which is felt by the principal investigator 
(PI) to be clinically relevant and which does not resolve to  Grade 2 within 48 
hours of the initiation of standard therapy or supportive care, (e.g. antiemetics 
for nausea or vomiting, antidiarrheal for diarrhea, insulin for hyperglycemia or 
IV fluids for renal compromise secondary to dehydration).  
Decrease the dose of OGX-427 and abiraterone by one dose-level for the following 
reasons: 
 Grade 4 fatigue (asthenia, lethargy, malaise), arthralgia and myalgia occurring 
for more than 3 weeks. 
 Any Grade 3 non-hematological AE which is felt by the PI to be clinically 
relevant and which resolves to  Grade 2 within 48 hours of standard therapy or 
supportive care but reoccurs. 
6.6.11. 
Onset of either >Grade 2 Motor Neuropathy or >Grade 2 Muscle 
Weakness 
Any onset of >grade 2 motor neuropathy or >grade 2 muscle weakness should be evaluated 
by EMG to rule out the possibility of chronic inflammatory demyelinating polyneuropathy 
(CIDP). With a diagnosis of CIDP the patient should be discontinued from study treatment.  
6.6.12. 
Dose Modifications for Prednisone 
Prednisone can be held or decreased for adverse events per investigator standard of care. 
Examples of prednisone side effects that an investigator may consider decreasing or 
discontinuing prednisone dosing include onset or exacerbation of diabetes mellitus, 
hypertension, gastrointestinal ulceration or bleeding, severe neurological side effects, or 
other serious adverse events. Prednisone may be reinstituted with the resolution of the 
adverse event at the discretion of the Investigator. The reason for altering the dose or 
discontinuing prednisone should be documented on the eCRF. Abiraterone should not be 
administered without some form of steroid coverage. If serious side effects develop related 
to mineralocorticoid excess, stress doses of steroids can be given. 
6.7. 
Concomitant Medications/Therapy 
6.7.1. 
Bisphosphonates and Bone Protecting Agents 
Changes in bisphosphonate usage and/or bone protecting agents such as denosumab should 
not occur during the study treatment (unless the deletion or change is for toxicity 
associated with the baseline usage of these drugs). If the patient is not on a bisphosphonate 
or denosumab at study entry, they should not be initiated during study treatment. All 


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administration of bisphosphonates or denosumab (or any change in usage) during study 
treatment must be documented on the eCRF (including the reason for change if indicated).  
6.7.2. 
Corticosteroids 
Patients on both arms of the protocol will continue receiving prednisone, 10-20 mg/day 
PO. Patients who are intolerant of prednisone at a dose of 10 mg/day will not be eligible 
for the protocol. Changes in corticosteroid usage (except as premedication for infusion 
reactions [Section 6.7.3]) should not occur during the study treatment unless the deletion or 
change is for toxicity associated with the baseline usage. All administration of 
corticosteroids during study treatment, including premedications or treatment for infusion 
reactions, must be documented on the eCRF.  
6.7.3. 
Premedication for OGX-427 Infusion-Related Adverse Events  
All patients should be premedicated before each dose of OGX-427 with an H2 antagonist, 
e.g., ranitidine (Zantac) (50 mg IV or 150 mg PO) and an antihistamine e.g. 
diphenhydramine (25-50 mg IV or PO). It is recommended that these premedications be 
administered30-90 minutes prior to the infusion unless there is a medical reason the patient 
cannot receive one or more of the drugs. The type of H2 antagonist and antihistamine 
administered is at the discretion of the Investigator. For example, cimetidine (Tagament) 
could be substituted for ranitidine and/or loratadine (Claritin) for diphenhydramine 
(Benadryl).  
Should a patient manifest a Grade 2 or greater adverse event(s) during or subsequent to an 
infusion of OGX-427 despite the above premedications, treatment should follow 
Institutional guidelines, however recommendations, including use of steroids, are available 
in Section 6.6.6/Table 11. 
Following the need for treatment with steroids (8 mg of dexamethasone) on more than one 
occasion for a Grade 2 or greater adverse event associated with an infusion, the patient 
should receive prophylaxis with dexamethasone, 8 mg, in addition to continued 
premedication with an H2 antagonist and an antihistamine, for a minimum of 12 weeks, or 
longer if necessary. 
6.7.4. 
Anti-emetics  
Prophylactic or therapeutic treatment will be at the discretion of the Investigator. 
6.7.5. 
Anticoagulation Therapy 
Anticoagulation therapy for thrombosis with warfarin (Coumadin) is allowed, if required, 
during the study. The INR should be followed closely. In addition, low molecular weight 
heparins in a therapeutic dose are allowed, if clinically required, during the study. Platelets 
should be followed closely. 
6.7.6. 
Growth Factors and Transfusions 
Granulocyte-colony stimulating factor (G-CSF) is allowed. It is recommended that 
treatment with G-CSF follow the guidelines of the American Society of Clinical Oncology 
(ASCO), unless otherwise specified by Institutional standards. All other growth factors and 


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all transfusions will be at the discretion of the Investigator. Administration of all growth 
factors and transfusions must be documented on the Concomitant Medications eCRF.  
6.7.7. 
Anticancer Therapies 
Treatment with any other anticancer therapy (except steroids) is not allowed and is 
considered a protocol violation unless the patient has documented disease progression or 
has withdrawn from all further study evaluations. Anticancer therapies include, but are not 
limited to, other chemotherapy, immunotherapy, experimental therapy, or radiation therapy 
(except as indicated below). Patients who discontinue study treatment for disease 
progression should have documentation of any anticancer therapy administered.  
6.7.8. 
Palliative Radiation Therapy 
Patients will be removed from study treatment and will be considered to have disease 
progression for any cancer-related radiation therapy while on study. Lesions which are 
symptomatic or cause unstable bone should be irradiated before the start of study 
treatment. Previously irradiated lesions should not be considered measurable.  
All radiation therapy must be completed at least 14 days before randomization (or 
following disease progression and prior to receiving OGX-427 therapy at the time of cross-
over). Exception for radiotherapy: at least 7 days must have passed since completing single 
fraction of  800 cGy to a restricted field or limited-field radiotherapy to non-marrow 
bearing area such as an extremity or orbit) at the time of randomization.  
7. 
STUDY AGENTS 
7.1. 
OGX-427 
OGX-427 will be supplied by OncoGenex Technologies Inc. OGX-427 Drug Product, 25 
mg/mL injection is formulated as a mannitol-phosphate buffer solution (pH 7.4) for IV 
administration and is supplied as an 8-mL solution containing 200 mg OGX-427 in a 
single vial. The drug substance and active ingredient of OGX-427 is an antisense 
oligonucleotide (ASO). 
Further information with regard to the drug product and drug substance may be found in 
the Investigator’s Brochure for OGX-427 Injection, 25 mg/mL, and the Study Procedure 
Manual provided for this study. 
7.1.1. 
Risks and Precautions  
Safety data for OGX-427 have been compiled from the completed Phase I study OGX-
427-01 and from the ongoing open-label Phase II study PR-01. Safety data from the 
ongoing placebo-controlled Phase II study OGX-427-02 is not included in this summary 
because these data are currently blinded. Only data on side effects experienced by the 76 
patients receiving OGX-427 monotherapy (plus prednisone) are reported. Also included in 
these data is the one reported sudden unexpected serious adverse reaction (SUSAR) in the 
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High levels of infusion reactions were observed in study OGX-427-01, especially at the 
highest doses tested (800 mg and 1000 mg) and during in the loading dose period and first 
weekly infusions, when OGX-427 concentrations are the highest. This observation 
prompted a reduction in the three loading doses from 1000 mg in study OGX-427-01 to 
600 mg in study PR-01 and the addition of premedications (H2 antagonist and 
antihistamine). Because this study and subsequent studies will use the 600 mg loading 
dose, data on infusion-related reactions reported below reflect those observed among 
subjects in study PR-01, who received the 600 mg loading dose and prophylactic 
medications as outlined above. 
The risks and side effects documented in patients who have been treated with OGX-427 
plus prednisone only that have been identified as possibly, probably, or definitely related 
to study drug are defined below:  
Very likely (>20% of patients): 
 Anemia (83%) which can cause tiredness, shortness of breath, and a possible 
need for red blood cell transfusions  
 Lymphopenia (79%) which in rare circumstances could lead to uncommon but 
serious infections  
 Transient prolongation of PTT (55%) which in rare circumstances could lead to 
serious bleeding  
 Infusion reactions during or soon after the infusion of OGX-427 have occurred 
in approximately 52% of patients. The most common symptoms have been 
chills (33%), flushing (19%), diarrhea (15%), nausea (11%), and vomiting 
(11%). The majority of the reactions occurred during the first three loading 
doses and during the first weekly infusions of therapy. However, reactions have 
continued to occur with further infusions in some patients. 
 Decrease in kidney function (41%), which could require dialysis  
 Decrease in liver function (reversible) (37%)  
 Hyponatremia (37%) which could cause a seizure  
 Thrombocytopenia (36%) which in rare situations could lead to an increased 
risk of bleeding and/or need for platelet transfusions  
 Hypokalemia (36%)  
 Hyperglycemia (26%) 
 Diarrhea (24%) 
 Fatigue (21%) 
Less likely (5-20% of patients): 
 Elevated international normalized ratio (INR; 20%) 
 Nausea (20%) 
 Pyrexia (16%)  


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 Decreased appetite (13%) 
 Vomiting (13%) 
 Blood creatinine increased (12%) 
 Numbness, tingling, stabbing pains in the hands and/or feet (10%) 
 Arthralgia (9%) 
 Dizziness (9%) 
 Hypertension (9%) 
 Neutropenia (9%) 
 Hyperkalemia (9%) 
 Cytokine release syndrome (8%) 
 Headache (8%) 
 Myalgia (8%) 
 Elevated bilirubin (8%) 
 Difficulty walking and/or weakness of the arms and/or legs (8%) 
 Hematuria (7%) 
 Influenza like illness (7%) 
 Urticaria (7%) 
 Dyspnea (5%) 
 Abdominal pain (5%) 
 Erythema (5%) 
 Chest pain (5%) 
 Rash (5%) 
Rarely (but may be serious) (< 5% of patients): 
 Cerebral hemorrhage 
 Thrombosis which in rare cases can lead to a pulmonary embolus  
 Vascular purpura 
 Hemolytic uremic syndrome (HUS) 
 Chronic Inflammatory Demyelenating Polyneuropathy (CIDP), which has led 
to the inability to walk 
7.1.2. 
Supply, Packaging, Labeling, Storage of OGX-427 
All clinical trial material will be labeled in accordance with local and federal regulations, 
stipulating that the product is for investigational use only. The drug product OGX-427 is 


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provided at a concentration of 200 mg/vial (25 mg/mL in 8 mL) in a USP Type 1 glass vial 
with a coated butyl rubber closure and aluminum seal with plastic flip-off button. The vials 
containing OGX-427 are to be stored in a secure, temperature monitored refrigerator at 
2-8 °C until the time of use. OGX-427 vials require withdrawal and injection into an IV 
diluent solution (Dextrose in Water: D5W) using aseptic technique. Each vial will contain 
at least 8 mL fill volume. The contents of each vial will be a clear, colorless to slightly 
yellow liquid by visual inspection. OGX-427 diluted in D5W is stable for 24 hours when 
stored at room temperature.  
At the completion of the study, all unused vials of OGX-427 must be returned to the 
Sponsor, unless there is a written Institutional procedure that calls for immediate disposal 
of unused drug product vials or the site is instructed otherwise by the Sponsor. All 
materials released for human clinical trials will be periodically tested and monitored for 
their acceptable shelf life for at least the duration of the study. Any material that fails to 
comply with the manufactured specifications will be promptly removed from the 
Investigative site and replaced with new clinical supplies by the Sponsor.  
7.1.3. 
Administration 
OGX-427 should be added to 250 mL 5% Dextrose in Water (D5W) as close to the time of 
administration as possible (see Pharmacy Manual for more details). The dose will be 
administered using either a peripheral or central indwelling catheter intravenously as an 
infusion over 2 hours. An infusion pump should be used. (See 14.1 for more detailed 
instructions).  
7.1.4. 
Accountability 
The Investigator or designee will maintain records of product delivery to the trial site, 
product inventory at the site, the dose given to each patient and the return of unused doses 
to OncoGenex (or where otherwise mandated, the destruction of unused doses).  
7.2. 
Abiraterone Acetate 
Abiraterone acetate is a CYP17 inhibitor indicated for use in combination with prednisone 
for the treatment of patients with metastatic castration-resistant prostate cancer who have 
received prior chemotherapy containing docetaxel. 
Based upon experience from clinical trials, abiraterone acetate is generally well tolerated.  
The most common adverse events related to abiraterone acetate monotherapy include 
fatigue, hypertension, fluid retention, and hypokalemia due to mineralocorticoid excess 
caused by compensatory adrenocorticotropic hormone (ACTH) drive. In this study, the 
concomitant administration of prednisone is expected to mitigate these side effects by 
supplementing cortisol and abrogating ACTH drive. When patients receive abiraterone 
acetate, they will also be prescribed prednisone (10-20 mg daily). If serious side effects 
develop related to mineralocorticoid excess, stress doses of steroids can be given.   
Further information with regard to the drug product and drug substance may be found in 
the Package Insert for abiraterone acetate provided in the Study Procedure Manual for this 
study. 


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7.2.1. 
Risks and Precautions  
Adverse reactions listed below were documented in a Phase 3 trial in patients who have 
been treated with abiraterone acetate plus prednisone (n=791); adverse events shown 
were due to abiraterone and occurred with either a ≥2% absolute increase in frequency 
compared to placebo or were events of special interest. 
 Joint swelling/discomfort (29.5%) 
 Edema (26.7%) 
 Muscle discomfort (26.2%) 
 Hot flush (19.0%) 
 Diarrhea (17.6%) 
 Urinary tract infection (11.5%) 
 Cough (10.6%) 
 Hypertension (8.5%) 
 Arrhythmia (7.2%) 
 Urinary frequency (7.2%) 
 Nocturia (6.2%) 
 Dyspepsia (6.1%) 
 Fractures (5.9%) 
 Upper respiratory tract infection (5.4%) 
 Chest pain or chest discomfort (3.8%) 
 Cardiac failure (2.3%) 
7.2.2. 
Supply, Packaging, Labeling, Storage  
Abiraterone acetate is commercially available in 250 mg tablets. Store at room 
temperature.  
7.2.3. 
Administration 
Abiraterone acetate will be administered orally at 1000 mg once daily in combination with 
oral prednisone taken twice daily. Abiraterone acetate must be taken on an empty stomach; 
no food should be consumed for at least 2 hours before and 1 hour after the dose. Please 
refer to the Package Insert for complete safety information and for administration 
directions. Missed doses are not made up. 
7.2.4. 
Accountability  
Evidence of prescription(s) as well as ongoing assessment of patient compliance with 
dosing regimen must be present in source documentation. Pill counts will not be conducted 
for this study. 


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7.3. 
Prednisone Treatment 
Prednisone is a corticosteroid used for the treatment of many cancers and is usually given 
along with other anticancer drugs.  
7.3.1. 
Risks and Precautions  
Prednisone should be administered with fluids and food to decrease the risk of 
gastrointestinal complications. Prednisone can exacerbate diabetes mellitus, hypertension 
and chronic and acute infections. Prednisone can mask symptoms of infections.  
Other Toxicities:  
 Cardiovascular: fluid retention (common), hypertension, congestive heart 
failure.  
 Gastrointestinal (GI): pain and/or ulcerations anywhere in the GI tract 
(common), weight increase (common), increased thirst, pancreatitis (rare).  
 Infections: increased risk of acute and chronic infections (common).  
 Metabolic: diabetes mellitus, fluid and electrolyte disturbances.  
 Musculoskeletal: weakness (common), decrease in muscle mass (common), 
osteoporosis.  
 Neurological: mood swings (common), depression, insomnia (common), 
dizziness, headache, confusion (rare), excitement (rare), psychosis (rare), 
seizures (rare).  
 Ophthalmological: visual changes.  
 Urological: increased frequency of urination.  
Withdrawal of prednisone after prolonged therapy may result in symptoms such as fever, 
myalgias, and arthralgia which could be symptoms of adrenal insufficiency. 
7.3.2. 
Supply, Packaging, Labeling, Storage  
Prednisone is commercially available in 2.5 mg, 5 mg, 10 mg, 20 mg and 50 mg tablets. 
Store at room temperature and away from heat, light and moisture.  
7.3.3. 
Administration 
Prednisone will be administered orally at 10-20 mg daily. Please refer to the Package Insert 
for complete safety information and for administration directions. Missed doses are not 
made up. 
7.3.4. 
Accountability  
Evidence of prescription(s) as well as ongoing assessment of patient compliance with 
dosing regimen must be present in source documentation. Pill counts will not be conducted 
for this study.  


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7.4. 
Other Risks and Precautions from Study Procedures  
Other discomforts of this study are those of collecting blood, insertion of intravenous lines 
and lying in radiology machinery. Venipuncture causes transient discomfort and may cause 
temporary hypotension (e.g., fainting) from a vasovagal response. Bruising due to bleeding 
beneath the skin may occur if pressure is not applied long enough. Infection could occur at 
the site of needle insertion or insertion of an intravenous line. Edema, pain and/or phlebitis 
could occur at the site of an infusion if the drug leaks out into tissues. Back discomfort 
could occur when lying on hard tables while undergoing radiology assessments. 
8. 
ADVERSE EVENTS 
Safety will be assessed by consideration of all adverse events reported by or elicited from 
the patient and by abnormalities detected on hematology and serum chemistry tests and 
physical examination. All laboratory values will be separately graded for toxicity by the 
drug provider based on NCI CTCAE Version 4.0. Consequently, laboratory abnormalities 
do not have to be recorded on the Adverse Event eCRF unless they result in a dose 
modification or require treatment. Worsening of other pre-existing medical conditions and 
any changes to concomitant medications/treatments will also be taken into account in this 
evaluation.  
All adverse events (serious and non-serious) beginning at the time of randomization and 
ending 30 days following the last dose of OGX-427 or at the End of Treatment Visit for 
the Control Arm will be recorded on the Adverse Event eCRF. Serious adverse events and 
grade 3 or higher adverse events that are ongoing at the end of study will be followed until 
each event resolves or is assessed as chronic.  
8.1. 
Definitions 
An adverse event (AE) is any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom or disease temporally associated with the administration, at 
any dose, of a medicinal or therapeutic product whether or not considered related to that 
product. 
Serious and severe are not synonymous. The term “severe” is often used to describe the 
intensity (severity) of a specific event (as in mild, moderate, or severe myocardial 
infarction); the event itself, however, may be of relatively minor medical significance 
(such as severe headache). This is not the same as “serious” which is based on 
patient/event outcome or action criteria usually associated with events that pose a threat to 
a patient's life or functioning. Seriousness, not severity, serves as a guide for defining 
regulatory reporting obligations. 
A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that (at 
any dose): 
 Results in death (death due to progressive disease will not be reported as an 
SAE) 
 Is life-threatening (i.e., the patient was at risk of death at the time of the event) 


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 Requires inpatient hospital admission or prolongs existing hospitalization 
 Results in persistent or significant disability/incapacity 
 Results in congenital anomaly/birth defect 
Medical and scientific judgment should be exercised in deciding whether or not reporting 
an SAE is appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
patient, or may require intervention to prevent one of the outcomes listed above. These 
should usually be considered serious (examples of such events are intensive treatment for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization; or development of drug dependency or drug abuse). 
8.2. 
Reporting of Adverse Events 
All adverse events occurring during the study, whether or not attributable to the study 
treatment, observed by the Investigator or reported by the patient spontaneously or in 
response to a direct question, will be recorded in the patient’s source documents and 
eCRFs. Adverse events will be graded in accordance with NCI CTCAE Version 4.0. (See 
Section 14.2.)  
The nature of each event, start and end date, action taken in response to the event, 
outcome, NCI CTCAE toxicity grade, relationship to OGX-427, relationship to abiraterone 
acetate, relationship to prednisone treatment, and whether the event is serious should be 
established and recorded on the Adverse Event eCRF. All entries must be clearly 
documented in the source documents and the source documentation should be signed and 
dated by an Investigator. 
Adverse events documented in the eCRF without a stop date should be reviewed at 
subsequent visits. Documentation regarding adverse events should be updated as 
necessary. 
Adverse events changing in severity will be recorded as new adverse events. 
Laboratory normal values used for the analyses and laboratory certification accreditation(s) 
will be provided for each site-specific laboratory and updated as required, at least yearly. 
8.3. 
Reporting of Serious Adverse Events 
Any SAE occurring in this study on or after the time of randomization must immediately 
be reported to both the Sponsor-Investigators and OncoGenex Pharmaceuticals Inc and/or 
others as described below.  
The SAE Report Form (see Study Procedure Manual) should be faxed or emailed by the 
study site within 24 hours of initial knowledge of the event at the site. The form should be 
sent to Hoosier Cancer Research Network. Additional details are available in the Study 
Procedure Manual. 
The original copy of the SAE Report and the fax confirmation sheet must be kept within 
the Trial Master File at the study site. 


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All SAEs including those that are ongoing at the end of study will be followed until each 
event resolves or is assessed as chronic. The Investigator should provide conventional 
medical treatment if necessary and monitor the patient’s condition until the event resolves 
or becomes chronic. 
The SAE Report should be completed using standard medical terms and in English, to the 
best extent possible given the time constraints.  
An adequate SAE Report includes the following minimum information: 
 Study number 
 Patient I.D. number and initials 
 Event description including date of onset, outcome and reason for the event to 
be considered serious 
 Name of investigational product including drug dose and administration dates 
 Assessment of causality (none, possible, probable, definite) 
 Person reporting event including site name or number 
A follow-up report with additional information (e.g., duration of event with event outcome 
[resolution, ongoing, fatal], laboratory tests performed, other diagnostic tests performed 
and treatments) should be faxed in a timely manner to Hoosier Cancer Research Network, 
using a new SAE Report form stating this is a follow-up to the previously reported SAE 
and giving the date of the original report. The follow-up information should describe 
whether the event has resolved or continues, if and how it was treated, and whether the 
patient continued or withdrew from study participation. Additional reports should be 
provided as soon as further information becomes available. 
When all information has been obtained, and whenever possible, an SAE should be 
recorded as the diagnosis (e.g., small bowel obstruction) not as a series of signs and 
symptoms (e.g., abdominal pain, fever, vomiting). 
OncoGenex (or delegate) will notify Investigators of other reportable SAEs occurring at 
other sites through “Dear Doctor” letters. The Investigator is responsible for informing the 
local IRB/REB of SAEs that occur at the site and reportable SAEs communicated by the 
Sponsor in compliance with local requirements. 
Detailed instructions for reporting serious adverse events are available in the Study 
Procedures Manual. 
8.4. 
Hoosier Cancer Research Network Requirements for Reporting 
SAEs 
Hoosier Cancer Research Network will report any SAE to OncoGenex within one 
working day of receipt of the SAE Reporting Form and to regulatory authorities (FDA) 
per federal requirements.   
 
Hoosier Cancer Research Network will fax the SAE form to OncoGenex and will provide 
follow-up information as reasonably requested. 


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8.5. 
Assessment of Causality 
The causal relationship between an adverse event and OGX-427, abiraterone acetate, 
and/or prednisone will be determined and documented separately by the responsible 
Investigator, or designee, according to best medical judgment as follows:  
Table 7: 
Assessment of Causal Relationship to OGX-427, Abiraterone Acetate, 
or Prednisone 
Category 
Description 
None 
The event is definitely not associated with the OGX-427, abiraterone, or prednisone. 
Possible 
The event may be related to OGX-427, abiraterone, or prednisone. The event follows a 
reasonable temporal sequence following OGX-427, abiraterone, or prednisone administration 
but could have been produced by the patient’s clinical state or other modes of therapy 
administered to the patient. 
Probable 
The event is likely related to OGX-427, abiraterone, or prednisone. The event follows a 
reasonable temporal sequence following the administration of OGX-427, abiraterone, or 
prednisone, abates upon discontinuation of OGX-427, abiraterone, or prednisone, and cannot 
be reasonably explained by known characteristics of the patient’s clinical state or other modes 
of therapy administered to the patient. 
Definite 
The event is related to OGX-427, abiraterone, or prednisone. The event follows a reasonable 
temporal sequence following OGX-427, abiraterone, or prednisone administration, abates 
upon discontinuation of OGX-427, abiraterone, or prednisone and cannot be explained by 
known characteristics of the patient’s clinical state or other modes of therapy administered to 
the patient.  


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9. 
SAFETY MONITORING 
9.1. 
Data Safety Monitor 
Safety monitoring will be performed by an independent data safety monitor (DSM) who 
will be appointed for this study.  
Although OGX-427 was tolerable at 1000 mg doses in combination with docetaxel and an 
MTD was not reached in the Phase 1 study, this will be the first evaluation of OGX-427 in 
combination with abiraterone acetate. Thus, there will be a scheduled complete DSM 
safety review after the first 20 patients have been enrolled (10 patients per treatment arm) 
and treated for at least one cycle to assess the frequency of ≥ Grade 3 adverse events and 
serious adverse events. In addition, the independent DSM will perform real-time 
monitoring of serious adverse events for the first 20 patients. Frequency of further safety 
reviews will be determined by the DSM based on this early safety review. 
The primary responsibility of the DSM will be overall safety for patients on the protocol. 
The DSM will monitor the safety of individual patients during the entire adverse event 
reporting period (i.e., from the first administration of Study Drug through 30 days after 
completion of study treatment). The DSM will:  
 The sponsor will provide the DSM with a copy of any unexpected Study Drug-
related SAE Report Form within 15 business days of receipt by the sponsor. 
The Medical Monitor will also provide the DSM with copies of all expedited 
SAE reports submitted to regulatory agencies.  
 Perform periodic reviews of all safety data for individual patients. These 
listings would be based on the available safety data in the clinical study 
database and will include: demographic characteristics, general medical history 
(including concurrent illnesses), disease history, Study Drug administration, 
vital signs during infusion, clinical laboratory data (serum chemistry, 
hematology), and reported adverse events. 
 Perform continued monitoring of Grade 3 and higher adverse events and SAEs 
on an ongoing basis for all patients. 
9.2. 
Study Monitoring 
Monitoring visits to the trial sites will be made periodically during the trial, to ensure all 
aspects of the protocol are followed.  Source documents will be reviewed for verification 
of agreement with data as submitted via the data collection system.  The 
investigator/institution guarantees access to source documents by the Sponsor or its 
designee and appropriate regulatory agencies. 
The trial site may also be required to participate in a quality assurance audit by OncoGenex 
or its designee as well as inspection by appropriate regulatory agencies. 
 


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It is important for the investigators and his/her relevant personnel to be available during 
the monitoring visits and possible audits and for sufficient time to be devoted to the 
process. 
9.3. 
Data and Safety Monitoring Plan 
Hoosier Cancer Research Network data safety monitoring activities include: 
 Review of clinical trial conduct for progress and safety 
 Review of all adverse events requiring expedited reporting as defined in the 
protocol 
 Review of reports generated by data quality control review process  
 Notification of the Sponsor Investigator and funding company of recommended 
action 
 Notification of sites coordinated by the Hoosier Cancer Research Network of 
adverse events requiring expedited reporting and subsequent committee 
recommendations for study modifications 
See Section 9.1 for additional details. 
9.4. 
Data/Safety Monitoring and Reporting Guidelines 
Hoosier Cancer Research Network will compile data summary reports for this trial and 
submit these reports monthly to the Sponsor-investigator.  Hoosier Cancer Research 
Network will submit data summary reports a minimum of twice a year to a DSMC for 
review.  


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10. 
STATISTICAL CONSIDERATIONS 
This section describes the sample size calculation and the planned statistical analyses for 
the primary and secondary efficacy endpoints and for safety. 
10.1. 
Sample Size 
The planned sample size is 74 patients. Patients will be randomized with equal probability 
to the two treatment arms. 
Overall study success is defined as the primary endpoint meeting statistical criterion. The 
one-sided type I error probability for the outcome is specified to be 10%, giving an overall 
type I error probability for the primary endpoint of 20%. 
For this endpoint, if it is assumed that the control arm success probability is 5% then there 
will be 90% power to detect a hypothesized 25 %-point increment in the success 
probability, with an increment of 12.9% or more defining the region of success for that 
outcome. If the control arm success probability is greater than 5%, the power will be less. 
For example, for a control arm success probability of 20% the power will be 78%, and for 
a control arm success probability of 40% the power will be 74%. 
10.2. 
Analysis Sets 
The All Randomized Analysis Set (ARAS) is defined as all subjects who are randomized. 
Subjects in the ARAS will be analyzed according to the arm into which they are 
randomized (“intent-to-treat” analysis). 
The Safety Analysis Set is defined as all patients who were randomized and received at 
least one dose of study drug (OGX-427) plus continued treatment with abiraterone and 
prednisone on Arm A or were randomized and continued to receive abiraterone and 
prednisone only on Arm B. Subjects in the Safety Analysis Set will be analyzed according 
to the treatment actually received. 
10.3. 
Efficacy Endpoints 
10.3.1. 
Primary Endpoint 
The primary objective of this study (Section 3.1) is to ascertain whether Arm A has a 
greater proportion of patients observed to be alive without progression at the milestone 
Day 60 assessment as compared to Arm B. The status of each patient at approximately Day 
60 (window of Day 53-67) post-randomization is to be recorded as alive without disease 
progression or not (binary outcome) in order to compute the arm-specific proportion of 
patients who are alive without disease progression at approximately Day 60. This binary 
endpoint is called the milestone Day 60 status. Patients without an event prior to Day 60 
post-randomization are to have a thorough disease assessment at Day 60 (window of Day 
53-67) in order to establish the milestone Day 60 status. Day 60 as measured from the date 
of randomization will normally occur after completion of Week 8 treatment. However, the 
milestone Day 60 disease assessment must be completed within the inclusive window of 
Day 53 to Day 67 post-randomization, regardless of the timing of Week 8 treatment (i.e., if 


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treatment scheduling at any time has been delayed). An event is defined as evidence of 
disease progression on or before Day 60. Patients without events prior to Day 60 but who 
do not have the milestone Day 60 disease assessment (and are therefore protocol 
violations) will be classified as not being alive without disease progression at Day 60 (a 
conservative assumption relative to efficacy and enabling an intent-to-treat analysis for this 
endpoint).  
This alive without disease progression endpoint is being evaluated as a milestone binary 
outcome in order to overcome potential bias associated with unequal between-arm 
progression assessment schedules in an open-label trial. Unequal assessment schedules are 
likely because the planned interventions in the two treatment arms are dissimilar.  
The primary objective will be met if the proportion of patients in Arm A meeting the 
success criterion is significantly greater than the proportion of patients in Arm B meeting 
the success criterion at the milestone Day 60 assessment. 
The primary analysis for this endpoint is Fisher’s exact test for the 2x2 frequency table 
created by the combination of treatment arm (A, B) and endpoint (success, non-success). 
This Fisher’s exact test can be regarded as a one-sided test of the between-arm difference 
in the proportion of successes. The null hypothesis of Arm A having an equal or inferior 
outcome relative to Arm B will be evaluated using the one-sided P value. 
The statistical analyses for the primary efficacy endpoint will be performed for the set of 
all randomized subjects. Efficacy summary tables for the primary efficacy endpoint will be 
provided for both the set of all randomized subjects and the safety analysis set. (See 
Section 10.2 for definitions of analysis sets.)  
10.3.2. 
Secondary Endpoints 
The secondary objectives of the study are described in Section 3.2. Summaries of the 
secondary efficacy endpoints will be provided for the Safety Analysis Set. 
PSA Response 
Baseline PSA is defined as the PSA result at the Day 1 Week 1 visit. If the Day 1 Week 1 
PSA result is missing then baseline PSA is defined as the PSA result at the Screening visit. 
At visits after Day 1 Week 1, the percent change from baseline PSA will be calculated for 
each subject.  Best PSA response is defined as the maximum percent decrease from 
baseline PSA, or the minimum percent increase if there is no decrease. Patients who do not 
have PSA data after baseline will have missing data for best PSA response. 
Best PSA response will be categorized as ‘≥ 30% decline,’ ‘< 30% decline,’ or ‘missing’ 
and the number (%) of patients within each category will be summarized by treatment arm. 
Similar summaries will be provided for best PSA response categories of ‘≥ 50% decline,’ 
‘≥ 90% decline,’ and ‘any decline.’ Best PSA response will be also be summarized by 
treatment arm using descriptive statistics (e.g., number of subjects, mean, standard 
deviation, median, minimum, and maximum). 
Objective Response 
Objective response (see Section 6.4.2.1 for definition) will be assessed at Day 60, Week 
16, Week 24, Week 32, Week 40, Week 48, End of Treatment, and at each visit during the 


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Off-Treatment Follow-Up Period. Best objective response is defined as the best response 
for each subject. The number (%) of patients in each best response category (CR, PR, SD, 
PD, NE) will be summarized by treatment arm. 
For subjects with measurable disease at baseline, the baseline sum of lesion diameters and 
the percent change from baseline at each visit will be calculated.  The best percent change 
from baseline will be summarized by treatment arm. The best percent change from baseline 
will be categorized as CR, PR, SD, PD, or NE and summarized by treatment arm.  The 
definition for each of these categories follows: 
 CR: A 100% decrease in the sum of diameters, taking as reference the baseline sum 
of diameters. 
 PR: At least a 30% decrease (but < 100% decrease) in the sum of diameters, taking 
as reference the baseline sum of diameters. 
 SD: Best percent change from baseline is defined, but does not meet criteria for 
CR, PR or PD. 
 PD: At least a 20% increase in the sum of diameters of target lesions, taking as 
reference the smallest sum on study, including the baseline sum. In addition to the 
relative increase of 20%, the sum must also demonstrate an absolute increase of at 
least 5 mm.  
 NE: No scans after baseline, or scans after baseline are not evaluable due to 
missing lesion measurements. 
Progression-free Survival 
Progression-free survival is defined as the time (weeks) from randomization to 
documented disease progression (see Section 6.4.1.2  for definition) or death from any 
cause. The following censoring rules will be applied to PFS: 
 If there is no documentation of disease progression or death by the time of data 
cutoff, then PFS will be censored at the date of the last disease assessment before 
the data cutoff.  
 Subjects who do not have any post-baseline disease assessments will be censored 
for PFS at the date of randomization.  
 Subjects who initiate a new anticancer therapy will be censored for PFS at the date 
of the last disease assessment before the start of new anticancer therapy.  
PFS will be summarized by treatment arm using Kaplan-Meier estimates, and Kaplan-
Meier plots will be provided. Estimates of the median PFS and first and third quartiles will 
be provided using the Kaplan-Meier estimates along with two-sided 95% CIs. Estimates 
and 95% CIs will also be provided for the PFS probability at several time points based on 
the Kaplan-Meier estimates. 
Time to Disease Progression 
Time to disease progression will be summarized for the subset of patients who have 
documented disease progression (see Section 6.4.1.2 for definition). Time to disease 
progression will be summarized by treatment arm using Kaplan-Meier estimates, and 


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Kaplan-Meier plots will be provided. Estimates of the median PFS and first and third 
quartiles will be provided using the Kaplan-Meier estimates along with two-sided 95% 
CIs. Estimates and 95% CIs will also be provided for the PFS probability at several time 
points based on the Kaplan-Meier estimates. 
CTC Counts 
The baseline CTC count is defined as the CTC count at the Day 1 Week 1 visit. If the Day 
1 Week 1 CTC count is missing then baseline CTC count is defined as the CTC count at 
the Screening visit.  
The number of CTCs/7.5 mL will be summarized at baseline and at visits after baseline by 
treatment arm. The number (%) of patients with ≤ 5 CTCs/7.5 mL will also be summarized 
by treatment arm at baseline and at visits after baseline.  
Levels of Hsp27 and Clusterin 
The baseline result for each test is defined as the result at the Day 1 Week 1 visit. If the 
Day 1 Week 1 result is missing then the baseline result is defined as the result at the 
Screening visit.  
Hsp27 and clusterin levels will be summarized at baseline and at visits after baseline by 
treatment arm using descriptive statistics (e.g., number of subjects, mean, standard 
deviation, median, minimum, and maximum). Similar summaries will be provided for 
change and percent change from baseline at visits after baseline. 
10.4. 
Safety Summaries 
Safety summaries will be provided for the safety analysis set (see Section 10.2 for 
definition). 
Adverse events that occur multiple times for a subject will be counted only once per 
subject in summary tables.  In tables that enumerate AEs by toxicity grade, only the worst 
toxicity grade for an AE occurring multiple times for a patient will be counted. 
The number (%) of patients with at least one adverse event, at least one serious adverse 
event, and/or at least one Grade 3 or higher adverse event will be summarized by treatment 
arm.  
Laboratory test results will be converted to standard international (SI) units and selected 
laboratory tests (lymphocytes, neutrophils, platelet count, hemoglobin, sodium, potassium, 
creatinine, bilirubin, AST, ALT) will be graded for toxicity using the criteria from CTCAE 
(Version 4.0) and normal ranges from the individual laboratories. If one or more normal 
ranges for a laboratory are missing then a standard normal range will be used to perform 
toxicity grading. The number (%) of patients with at least one laboratory toxicity and at 
least one Grade 3 or higher laboratory toxicity will be summarized by treatment arm and 
laboratory test. The incidence of laboratory toxicity will also be summarized for each 
laboratory test by toxicity grade and treatment arm. In these tables, only the worst toxicity 
grade for a patient will be counted for a toxicity occurring multiple times. 


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11. 
REGULATORY AND ETHICS CONSIDERATIONS 
11.1. 
Informed Consent 
The informed consent forms used for the study must comply with ICH E6 standard Good 
Clinical Practice (GCP), which is consistent with the principles that have their origin the 
Declaration of Helsinki and International Conference on Harmonization (ICH) Guidelines, 
and must have been approved by the Sponsor or Sponsor’s representatives (prior to and 
after review by the site’s IRB/REB) and the Investigator’s IRB/REB. The Investigator or 
an authorized associate, who must be a physician, must explain the nature of the study and 
the treatment in such a manner that the patient is aware of his/her rights and 
responsibilities, as well as potential benefits and risks. The Investigator is also responsible 
for answering any questions the patient may have throughout the study and sharing any 
new information, in a timely manner, that may be relevant to the patient’s willingness to 
continue his/her participation in the trial.  
Patients must also be informed that participation is voluntary and that they may withdraw 
from the study at any time, without prejudice to their current or future care. Documentation 
of the discussion and the date of informed consent should be recorded in the patient’s 
medical record or a study/clinic chart. Once all of their questions have been answered and 
they have voluntarily agreed to participate in the study, patients will be asked to sign and 
date the Informed Consent Form.  
Patients, or their legally authorized representative, must give informed consent in writing 
prior to the performance of any protocol-specific procedure. Patients who cannot give 
informed consent (i.e. mentally incompetent patients or those physically incapacitated such 
as comatose patients) are not to be recruited into the study. Patients who are competent but 
physically unable to sign the consent form may have the document signed by their nearest 
relative or legal guardian. A copy of the signed Informed Consent Form will be provided 
to the patient. 
11.2. 
Institutional Review Board (IRB)/Research Ethics Board (REB) 
Before the investigational product can be shipped to the investigative site and before the 
consenting and screening of patients at the site, the protocol, any protocol amendments, the 
consent form, any advertising materials, any materials to be provided to the subjects for the 
proposed clinical study and any other documents required by the local IRB/REB must be 
submitted by the Investigator for review and approval by the IRB/REB. The Investigator 
must also ensure that the IRB/REB reviews the progress of the study, if necessary, and 
renews its approval of the study on an annual basis. Any member of the IRB/REB who is 
directly affiliated with this study as an Investigator or as site personnel must abstain from 
the IRB/REB vote on the approval of the protocol. 
All amendments or revisions to the protocol must undergo review by appropriate 
IRB/REBs. Amendments/revisions will be circulated to all participating sites with clear 
instructions regarding IRB/REB review. Amendments will be submitted by the Sponsor to 
the Therapeutic Products Directorate (TPD) and/or the Food and Drug Administration 
(FDA) and any other appropriate Regulatory Agencies prior to central implementation to 
the study, and by REBs prior to local implementation, EXCEPT when the amendment 


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eliminates an immediate hazard to clinical trial subjects or is of a purely administrative 
nature. 
A copy of the IRB/REB approval letter must be forwarded to the Sponsor or Sponsor’s 
representative before the study is implemented. The approval letter must clearly state the 
protocol title and version that was reviewed. The Investigator also must forward copies of 
subsequent amendment approval letters to the Sponsor upon receipt. 
11.3. 
Patient Confidentiality 
The Investigator must attempt to assure that the patients’ confidentiality will be maintained 
within the limit of the law. Patients will be identified by patient number and initials (or 
other code) on all documents submitted to the Sponsor. Patients will not be identified by 
name.  
All records will be kept in a secure place in the clinical research site. Computer data entry 
and data review programs will be done using patient numbers and initials (or other code) 
only. Clinical information will not be released without written permission of the patient, as 
outlined in the patient consent form. 
The Investigator must maintain a separate screening log, including screen failures, of 
patient names and identification codes. 
12. 
ADMINISTRATIVE PROCEDURES 
12.1. 
Drug Provider Responsibilities 
Following site initiation each study site will be provided with OGX-427 and study-related 
supplies. Upon completion of the study all unused supplies should be returned to 
OncoGenex or, upon notification from OncoGenex, destroyed according to local standard 
operating procedures, with documentation of the destruction.  
All Investigators and their study personnel will receive training regarding the study 
procedures. This training will take place prior to enrollment of the first patient at each 
study site. Each study site will be provided with information regarding Good Clinical 
Practices and regulations specific to the conduct of clinical trials.  
The study will be monitored by representatives of OncoGenex Technologies Inc. and/or 
designees. Routine monitoring visits will be conducted to:  
 Assure compliance with the study protocol 
 Verify that the research facilities, including laboratories and equipment, are 
adequate to safely and properly conduct the study 
 Verify that the investigational product is stored properly and under the proper 
conditions, is in sufficient supply, and that receipt, use and return of 
investigational product at the study sites are controlled and documented 
adequately 
 Verify that written informed consent was obtained before initiation of any 
screening procedures performed solely for the purpose of determining 


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eligibility for the clinical study and/or prior to the provision of study 
medication 
 Review the patient eCRFs and source documents to ensure that reported study 
data are accurate, complete and verifiable from source documents 
 Ensure that adequate records of clinical trial supplies are maintained 
 Verify that the Investigator and study site personnel are adequately qualified 
throughout the study 
 Verify that the safety information and amendments are submitted to the 
IRB/REBs 
12.2. 
Investigator Responsibilities 
All requested study data must be entered on the eCRFs for the study. For those patients 
who withdraw before completion of their specified treatment regimen, all available 
efficacy and safety data must be entered in the eCRF. The reason for withdrawal must be 
specified. Incomplete or inconsistent data on the eCRFs will result in data queries that will 
be returned to the Investigator for resolution. 
The Investigator must maintain adequate and accurate source documents upon which 
eCRFs for each patient are based. The source documents are to be separate and distinct 
from the eCRF input data. An explanation should be provided for all missing data. The 
documents to be maintained must include, but are not limited to, detailed notes on: 
 The medical history prior to participation in the study. 
 The basic identifying information, such as demographics, that link the patient’s 
source documents with the eCRFs. 
 The results of all diagnostic tests performed, diagnoses made, therapy provided 
and any other data on the condition of the patient. 
 The patient’s exposure to study treatment. 
 All AEs. 
 The patient’s exposure to any concomitant therapy, including dates of 
administration. 
 All relevant observations and data on the condition of the patient throughout the 
study. 
 The oral and written communication with the patient regarding the study 
treatment, including the risks and benefits of the study. The date of informed 
consent must be recorded in the source documentation. 
12.3. 
Regulatory Compliance 
Quality Assurance representatives from OncoGenex or their delegate, the TPD, the FDA, 
and all other regulatory agencies as required will be allowed to periodically visit the 
Investigators/Investigative sites to discuss the conduct of the trial and, upon request, 


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inspect the records of the trial. These reviews are necessary to insure that the study is 
conducted according to standards consistent with the ICH Good Clinical Practice (GCP) 
Guideline. 
The Investigator agrees to discuss and correct, if necessary, any problems or deficiencies 
that are found during the course of these reviews. 
12.4. 
Ethical Conduct of the Trial / Good Clinical Practice 
The Sponsor(s) follows the ICH E6 standard for GCP which is consistent with the 
principles that have their origin in the Declaration of Helsinki. This trial will be conducted 
in accordance with the International Conference on Harmonization (ICH) Guidelines on 
GCP, the US Code of Federal Regulations, the Food and Drugs Act (Health Canada), and 
local requirements regarding IRB/REB committee review, informed consent, and other 
statutes or regulations regarding the protection of the rights and welfare of human subjects 
participating in biomedical research.  
12.5. 
Protocol Modification or Premature Termination 
All protocol amendments must be approved by OncoGenex Technologies Inc. Each 
IRB/REB will review and approve amendments prior to their implementation in the study. 
IRB/REB approval need not be obtained prior to removal of an immediate hazard to 
patients. 
Individual patient protocol modifications may only be made with regard to the following 
and must be well documented: 
 Patient safety (in consultation with the PI) 
 Dose modification as described in Section 6.6 (must be well documented) 
OncoGenex Technologies Inc. may terminate the protocol early for safety or if other issues 
occur. 


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13. 
REFERENCES 
 
1. Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2006. CA Cancer J Clin 56:106-
30, 2006 
 
2. de Bono JS, Logothetis CJ, Molina A, et al: Abiraterone and Increased Survival in 
Metastatic Prostate Cancer. New England Journal of Medicine 364:1995-2005, 2011 
 
3. Chi KN, Gleave ME: Antisense approaches in prostate cancer. Expert Opin Biol 
Ther 4:927-36, 2004 
 
4. Gleave M, Nelson C, Chi K: Antisense targets to enhance hormone and cytotoxic 
therapies in advanced prostate cancer. Curr Drug Targets 4:209-21, 2003 
 
5. Henry S, Stecker K, Brooks D, et al: Chemically modified oligonucleotides exhibit 
decreased immune stimulation in mice. J Pharmacol Exp Ther 292:468-79, 2000 
 
6. Henry SP, Geary RS, Yu R, et al: Drug properties of second-generation antisense 
oligonucleotides: how do they measure up to their predecessors? Curr Opin Investig 
Drugs 2:1444-9, 2001 
 
7. Zellweger T, Miyake H, Cooper S, et al: Antitumor activity of antisense clusterin 
oligonucleotides is improved in vitro and in vivo by incorporation of 2'-O-(2-
methoxy)ethyl chemistry. J Pharmacol Exp Ther 298:934-40, 2001 
 
8. Gleave M, Miyake H, Zangemeister-Wittke U, et al: Antisense therapy: current 
status in prostate cancer and other malignancies. Cancer Metastasis Rev 21:79-92, 
2002 
 
9. Jansen B, Schlagbauer-Wadl H, Brown BD, et al: bcl-2 antisense therapy 
chemosensitizes human melanoma in SCID mice. Nat Med 4:232-4, 1998 
 
10. Jansen B, Wacheck V, Heere-Ress E, et al: Chemosensitisation of malignant 
melanoma by BCL2 antisense therapy. Lancet 356:1728-33, 2000 
 
11. Wacheck V, Heere-Ress E, Halaschek-Wiener J, et al: Bcl-2 antisense 
oligonucleotides chemosensitize human gastric cancer in a SCID mouse 
xenotransplantation model. J Mol Med 79:587-93, 2001 
 
12. Heere-Ress E, Thallinger C, Lucas T, et al: Bcl-X(L) is a chemoresistance factor in 
human melanoma cells that can be inhibited by antisense therapy. Int J Cancer 99:29-
34, 2002 
 
13. Ziegler A, Luedke GH, Fabbro D, et al: Induction of apoptosis in small-cell lung 
cancer cells by an antisense oligodeoxynucleotide targeting the Bcl-2 coding sequence. 
J Natl Cancer Inst 89:1027-36, 1997 
 
14. Monia BP, Johnston JF, Geiger T, et al: Antitumor activity of a phosphorothioate 
antisense oligodeoxynucleotide targeted against C-raf kinase. Nat Med 2:668-75, 1996 
 
15. Miyake H, Nelson C, Rennie PS, et al: Testosterone-repressed prostate message-2 
is an antiapoptotic gene involved in progression to androgen independence in prostate 
cancer. Cancer Res 60:170-6, 2000 


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16. Miayake H, Tolcher A, Gleave ME: Chemosensitization and delayed androgen-
independent recurrence of prostate cancer with the use of antisense Bcl-2 
oligodeoxynucleotides. J Natl Cancer Inst 92:34-41, 2000 
 
17. Kiyama S, Morrison K, Zellweger T, et al: Castration-induced increases in insulin-
like growth factor-binding protein 2 promotes proliferation of androgen-independent 
human prostate LNCaP tumors. Cancer Res 63:3575-84, 2003 
 
18. Rocchi P, So A, Kojima S, et al: Heat shock protein 27 increases after androgen 
ablation and plays a cytoprotective role in hormone-refractory prostate cancer. Cancer 
Res 64:6595-602, 2004 
 
19. Rocchi P, Beraldi E, Ettinger S, et al: Increased Hsp27 after androgen ablation 
facilitates androgen-independent progression in prostate cancer via signal transducers 
and activators of transcription 3-mediated suppression of apoptosis. Cancer Res 
65:11083-93, 2005 
 
20. Chi KN, Gleave ME, Klasa R, et al: A phase I dose-finding study of combined 
treatment with an antisense Bcl-2 oligonucleotide (Genasense) and mitoxantrone in 
patients with metastatic hormone-refractory prostate cancer. Clin Cancer Res 7:3920-7, 
2001 
 
21. Tolcher AW, Chi K, Kuhn J, et al: A phase II, pharmacokinetic, and biological 
correlative study of oblimersen sodium and docetaxel in patients with hormone-
refractory prostate cancer. Clin Cancer Res 11:3854-61, 2005 
 
22. Jansen B, Zangemeister-Wittke U: Antisense therapy for cancer--the time of truth. 
Lancet Oncol 3:672-83, 2002 
 
23. Mosser DD, Morimoto RI: Molecular chaperones and the stress of oncogenesis. 
Oncogene 23:2907-18, 2004 
 
24. Garrido C, Schmitt E, Cande C, et al: HSP27 and HSP70: potentially oncogenic 
apoptosis inhibitors. Cell Cycle 2:579-84, 2003 
 
25. Concannon CG, Gorman AM, Samali A: On the role of Hsp27 in regulating 
apoptosis. Apoptosis 8:61-70, 2003 
 
26. Neckers L, Schulte TW, Mimnaugh E: Geldanamycin as a potential anti-cancer 
agent: its molecular target and biochemical activity. Invest New Drugs 17:361-73, 
1999 
 
27. Neckers L, Mimnaugh E, Schulte TW: Hsp90 as an anti-cancer target. Drug Resist 
Updat 2:165-172, 1999 
 
28. Chi KN, Eisenhauer E, Fazli L, et al: A phase I pharmacokinetic and 
pharmacodynamic study of OGX-011, a 2'-methoxyethyl antisense oligonucleotide to 
clusterin, in patients with localized prostate cancer. J Natl Cancer Inst 97:1287-96, 
2005 
 
29. Landry J, Lambert H, Zhou M, et al: Human HSP27 is phosphorylated at serines 78 
and 82 by heat shock and mitogen-activated kinases that recognize the same amino 
acid motif as S6 kinase II. J Biol Chem 267:794-803, 1992 


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30. Oesterreich S, Weng CN, Qiu M, et al: The small heat shock protein hsp27 is 
correlated with growth and drug resistance in human breast cancer cell lines. Cancer 
Res 53:4443-8, 1993 
 
31. Hansen RK, Parra I, Lemieux P, et al: Hsp27 overexpression inhibits doxorubicin-
induced apoptosis in human breast cancer cells. Breast Cancer Res Treat 56:187-96, 
1999 
 
32. Lemieux P, Oesterreich S, Lawrence JA, et al: The small heat shock protein hsp27 
increases invasiveness but decreases motility of breast cancer cells. Invasion Metastasis 
17:113-23, 1997 
 
33. Garrido C, Fromentin A, Bonnotte B, et al: Heat shock protein 27 enhances the 
tumorigenicity of immunogenic rat colon carcinoma cell clones. Cancer Res 58:5495-
9, 1998 
 
34. Bruey JM, Paul C, Fromentin A, et al: Differential regulation of HSP27 
oligomerization in tumor cells grown in vitro and in vivo. Oncogene 19:4855-63, 2000 
 
35. Pandey P, Farber R, Nakazawa A, et al: Hsp27 functions as a negative regulator of 
cytochrome c-dependent activation of procaspase-3. Oncogene 19:1975-81, 2000 
 
36. Concannon CG, Orrenius S, Samali A: Hsp27 inhibits cytochrome c-mediated 
caspase activation by sequestering both pro-caspase-3 and cytochrome c. Gene Expr 
9:195-201, 2001 
 
37. Charette SJ, Landry J: The interaction of HSP27 with Daxx identifies a potential 
regulatory role of HSP27 in Fas-induced apoptosis. Ann N Y Acad Sci 926:126-31, 
2000 
 
38. Garrido C, Ottavi P, Fromentin A, et al: HSP27 as a mediator of confluence-
dependent resistance to cell death induced by anticancer drugs. Cancer Res 57:2661-7, 
1997 
 
39. Mehlen P, Kretz-Remy C, Preville X, et al: Human hsp27, Drosophila hsp27 and 
human alphaB-crystallin expression-mediated increase in glutathione is essential for 
the protective activity of these proteins against TNFalpha-induced cell death. EMBO J 
15:2695-706, 1996 
 
40. Rogalla T, Ehrnsperger M, Preville X, et al: Regulation of Hsp27 oligomerization, 
chaperone function, and protective activity against oxidative stress/tumor necrosis 
factor alpha by phosphorylation. J Biol Chem 274:18947-56, 1999 
 
41. Wyttenbach A, Sauvageot O, Carmichael J, et al: Heat shock protein 27 prevents 
cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species 
caused by huntingtin. Hum Mol Genet 11:1137-51, 2002 
 
42. Lavoie JN, Hickey E, Weber LA, et al: Modulation of actin microfilament 
dynamics and fluid phase pinocytosis by phosphorylation of heat shock protein 27. J 
Biol Chem 268:24210-4, 1993 
 
43. Huot J, Lambert H, Lavoie JN, et al: Characterization of 45-kDa/54-kDa HSP27 
kinase, a stress-sensitive kinase which may activate the phosphorylation-dependent 


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protective function of mammalian 27-kDa heat-shock protein HSP27. Eur J Biochem 
227:416-27, 1995 
 
44. Guay J, Lambert H, Gingras-Breton G, et al: Regulation of actin filament dynamics 
by p38 map kinase-mediated phosphorylation of heat shock protein 27. J Cell Sci 110 ( 
Pt 3):357-68, 1997 
 
45. Konishi H, Matsuzaki H, Tanaka M, et al: Activation of protein kinase B 
(Akt/RAC-protein kinase) by cellular stress and its association with heat shock protein 
Hsp27. FEBS Lett 410:493-8, 1997 
 
46. Rane MJ, Pan Y, Singh S, et al: Heat shock protein 27 controls apoptosis by 
regulating Akt activation. J Biol Chem 278:27828-35, 2003 
 
47. Zoubeidi A, Zardan A, Wiedmann RM, et al: Hsp27 promotes insulin-like growth 
factor-I survival signaling in prostate cancer via p90Rsk-dependent phosphorylation 
and inactivation of BAD. Cancer Res 70:2307-17, 2010 
 
48. Ciocca DR, Calderwood SK: Heat shock proteins in cancer: diagnostic, prognostic, 
predictive, and treatment implications. Cell Stress Chaperones 10:86-103, 2005 
 
49. Bubendorf L, Kolmer M, Kononen J, et al: Hormone therapy failure in human 
prostate cancer: analysis by complementary DNA and tissue microarrays. J Natl Cancer 
Inst 91:1758-64, 1999 
 
50. Cornford PA, Dodson AR, Parsons KF, et al: Heat shock protein expression 
independently predicts clinical outcome in prostate cancer. Cancer Res 60:7099-105, 
2000 
 
51. Hoang AT, Huang J, Rudra-Ganguly N, et al: A novel association between the 
human heat shock transcription factor 1 (HSF1) and prostate adenocarcinoma. Am J 
Pathol 156:857-64, 2000 
 
52. Zoubeidi A, Zardan A, Beraldi E, et al: Cooperative interactions between androgen 
receptor (AR) and heat-shock protein 27 facilitate AR transcriptional activity. Cancer 
Res 67:10455-65, 2007 
 
53. Smith DF: Chaperones in progesterone receptor complexes. Semin Cell Dev Biol 
11:45-52, 2000 
 
54. Stenoien DL, Cummings CJ, Adams HP, et al: Polyglutamine-expanded androgen 
receptors form aggregates that sequester heat shock proteins, proteasome components 
and SRC-1, and are suppressed by the HDJ-2 chaperone. Hum Mol Genet 8:731-41, 
1999 
 
55. Bertorelli G, Bocchino V, Olivieri D: Heat shock protein interactions with the 
glucocorticoid receptor. Pulm Pharmacol Ther 11:7-12, 1998 
 
56. Gleave M: Unpublished, 2007 
 
57. Geary RS, Leeds JM, Henry SP, et al: Antisense oligonucleotide inhibitors for the 
treatment of cancer: 1. Pharmacokinetic properties of phosphorothioate 
oligodeoxynucleotides. Anticancer Drug Des 12:383-93, 1997 


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58. Geary RS, Yu RZ, Watanabe T, et al: Pharmacokinetics of a tumor necrosis factor-
alpha phosphorothioate 2'-O-(2-methoxyethyl) modified antisense oligonucleotide: 
comparison across species. Drug Metab Dispos 31:1419-28, 2003 
 
59. Yu RZ, Geary RS, Monteith DK, et al: Tissue disposition of 2'-O-(2-methoxy) 
ethyl modified antisense oligonucleotides in monkeys. J Pharm Sci 93:48-59, 2004 
 
60. Sternberg CN, Yagoda A, Scher HI, et al: Methotrexate, vinblastine, doxorubicin, 
and cisplatin for advanced transitional cell carcinoma of the urothelium. Efficacy and 
patterns of response and relapse. Cancer 64:2448-58, 1989 
 
61. Scher HI, Halabi S, Tannock I, et al: Design and end points of clinical trials for 
patients with progressive prostate cancer and castrate levels of testosterone: 
recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 
26:1148-59, 2008 
 
62. Eisenhauer EA, Therasse P, Bogaerts J, et al: New response evaluation criteria in 
solid tumours: revised RECIST guideline (version 1.1). European journal of cancer 
(Oxford, England 45:228-47, 2009 
 
63. Yoshimoto M, Cunha IW, Coudry RA, et al: FISH analysis of 107 prostate cancers 
shows that PTEN genomic deletion is associated with poor clinical outcome. Br J 
Cancer 97:678-85, 2007 
 
 


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14. 
APPENDICES 
14.1. 
Drug Formulation / Pharmacy Guideline for OGX-427 
Drug: OGX-427 which is an Antisense Oligonucleotide (ASO) 
How Supplied: 200 mg per 8 mL solution resulting in a 25 mg/mL concentration for 
OGX-427 in a 10 mL vial. 
Appearance: Clear, colorless to slightly yellow solution. 
Packaging: 10 mL USP Type I glass vial with a coated butyl rubber closure and  
aluminum seal with a plastic flip-off button. Vials are provided in cartons. 
Storage: Undiluted concentrate vials to be refrigerated 2 – 8°C (36 -46°F). Protect from 
heat and direct sunlight. The drug product does not contain a preservative and is intended 
for single use only. 
Handling: Per sterile treatment drug procedures at the study site. 
Diluent/Dilution: Add the specified amount of OGX-427 to 250 mL of 5% Dextrose in 
Water for Injection, USP (D5W). 
Stability: OGX-427 is stable for 24 hours when diluted in D5W. 
Administration Route: Continuous intravenous infusion with infusion pump. 
Dosage: See protocol for study-specific details. 
Treatment Duration: 2 hour intravenous infusion. 
Drug Re-supply: Please refer to the study-specific Clinical Supplies Shipment Request 
and Verification form, found in the Study Procedure Manual. For specific questions 
regarding re-supply, please contact OncoGenex Technologies Inc. 
GENERAL INFORMATION 
Detailed procedures for receipt and reorder of drug can be found in the Pharmacy Manual. 
All shipping and receipt documents found in each shipment should be filed in the 
pharmacy binder along with the accountability records. 
OGX-427 Drug Product, 25 mg/mL, Injection is formulated as a mannitol-phosphate 
buffer solution (pH 7.4) for IV administration and is supplied as an 8 mL solution 
containing 200 mg OGX-427 in a single vial (10 mL clear glass). The drug substance and 
active ingredient of OGX-427 is an ASO. All vials of OGX-427 will be labeled as required 
by the relevant regulatory agencies and must be stored in a secure, temperature monitored 
refrigerator, at a temperature of 2 - 8° C (36-46° F) within the hospital pharmacy until the 
time of use. DO NOT FREEZE. 
OGX-427 dosing solutions will be prepared and dispensed by the pharmacy according to 
the method of preparation described below. All OGX-427 dosing solutions will be 
administered intravenously using an infusion pump (preferably). Once mixed for 
administration, it is recommended that the OGX-427 dosing solution be administered 
within 24 hours if kept at room temperature or in a refrigerator (2-8° C, 36-46° F). The 


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pharmacist must maintain an accurate accountability record documenting the utilization of 
the investigational product at the clinical site. 
DRUG DILUTION PROCEDURE 
The OGX-427 drug dilution procedure should be performed according to the instructions 
below and following proper aseptic technique:  
1. OGX-427 should be stored between 2 - 8° C (36 – 46°F) prior to use. 
2. Once dose instructions have been received from the site Investigator, remove 
OGX-427 from the refrigerator and inspect the vials for particulate matter. Vials 
containing particulate matter should not be used. 
3. Using proper aseptic technique withdraw the correct amount of OGX-427 from 
each vial using a syringe and a needle.  
Dose Period 
Dosage 
# of vials 
Volume of OGX-427 
Loading Doses (Week 1) 
600 mg  
3 
24 mL 
Weekly Doses (Beginning 
Week 2)* 
800 mg 
4 
32 mL 
*Subtract 1 vial (200 mg) if a dose reduction of OGX-427 is required due to toxicity 
(A maximum of 2 dose reductions allowed after Week 2). 
4. Add OGX-427 to 250 mL of intravenous 5% Dextrose in Water (D5W) solution. 
Attach the intravenous tubing to the bag and prime the IV line with the D5W 
solution. 
5. Label the bag with appropriate identification. 
6. OGX-427 can be administered via a central venous line for continuous intravenous 
infusion or a secure peripheral line may be used. This decision is at the discretion 
of the Investigator. The infusion should be administered over 2 hours using an 
infusion pump. 
 
RE-SUPPLY OF INVESTIGATIONAL PRODUCT 
Re-supply of investigational study agent, OGX-427, will be managed by OncoGenex 
Technologies Inc. or a designated drug management vendor. All re-supply requests should 
follow the instructions found in the Study Procedure Manual. Request for re-supply must 
originate with the clinical trial pharmacist at the site.  
ACCOUNTABILITY/DISPOSAL OF INVESTIGATIONAL PRODUCT 
Unless other procedures are agreed upon prior to study start, all used vials of OGX-427 
must be maintained within the pharmacy for ongoing drug accountability, to be performed 
by the study monitor throughout the conduct of the trial. Any discrepancies in drug 
accountability must be explained in writing and filed in the Investigator Study File and 
with OncoGenex Technologies Inc. 


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All used and unused OGX-427 vials will undergo final reconciliation at the pharmacy at 
the end of the trial. Drug accountability and reconciliation will be performed by the 
CRA/monitor prior to the product destruction by the pharmacy. At the end of the study, 
sites will be informed whether unused drug will either be returned to OncoGenex or 
destroyed at the site. All product destruction must be done by incineration in accordance 
with the institution’s Standard Operating Procedures. A copy of the Standard Operating 
Procedure for drug destruction should be collected and on file with the Sponsor. 
 


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14.2. 
Toxicity Grading Scale: NCI CTCAE Version 4.0  
This information is also available on-line at: NCI CTCAE Version 4.0 
 


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14.3. 
Processing and Shipping of Study Samples 
Specimen collection kits (containing all required blood collection tubes, storage vials and 
laboratory order form) will be provided to each of the participating clinical sites.  
Following completion of all correlative analysis, any remaining research samples will be 
destroyed within 3 years following completion of the study. 
Circulating Tumor Cell (CTC) Sampling: 
CTC samples will be collected into a 7.5 mL CellSave® Preservative Tube (provided by the 
Sponsor). The samples must be collected and then shipped on the same day by an 
overnight courier. Samples will be processed on the CellTracks AutoPrep System® with 
the CellSearch Circulating Tumor Cell Kit®. Epithelial cells in the enriched sample will be 
characterized and counted (CK+/DAPI+/CD45-) with the CellTracks Analyzer II®.  
All samples will be sent to:  
Jenny Bazov 
Analytical Pharmacology 
Prostate Centre at Vancouver General Hospital 
The Jack Bell Research Centre 
2660 Oak Street 
Vancouver, BC   V6H 3Z6 
(604) 875-4908 
E-mail notification must be given prior to shipment of any samples addressed to: 
hadomat@prostatecentre.com  
eli@prostatecentre.com 
jbazov@prostatecentre.com  
All CellSave Preservative tubes for CTC analysis must be shipped at ambient 
temperature by express overnight delivery on the same day after they have been 
drawn. Collection of samples in CellSave preservative tubes should be coordinated 
with Jenny Baybik via e-mail or phone (604-875-4111 ext 68661) or Estelle Li via 
email or phone (604-875-4111 extension 63213) prior to sample collection. 
 
Blood Collection for Assays for Evaluating Hsp27, Clusterin, and Other Relevant 
Proteins:  
7 mL of blood for serum (red-top tube or equivalent, no additives) and 7 mL of blood for 
plasma (EDTA) will be collected. For serum, allow the blood to clot at room temperature 
for 20-30 minutes. For both serum and plasma, centrifuge samples at 4°C for 15 minutes at 
3500 RPM. Serum and plasma will be removed and transferred into three polyethylene 
tubes (for a total of three aliquots of serum and three aliquots of plasma). These tubes 
should be labeled as serum or plasma with the date/time of collection and patient number 
indicated.  


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Note: hemolysis and platelets can affect the Hsp27 results. Hemolyzed samples should be 
redrawn. To assure that platelet contamination does not occur, please pipet the Hsp27 
aliquot first (before the clusterin sample) from the upper half of the serum layer, making 
sure that the buffy coat is not disturbed.  
Short term storage (less than 1 week) at -20 °C is acceptable; however, storage at -80 °C is 
recommended for longer storage if batch shipping.  
All samples will be sent to:  
Jenny Bazov 
Analytical Pharmacology 
Prostate Centre at Vancouver General Hospital 
The Jack Bell Research Centre 
2660 Oak Street 
Vancouver, BC   V6H 3Z6 
(604) 875-4908 
E-mail notification must be given prior to shipment of any samples addressed to: 
hadomat@prostatecentre.com  
eli@prostatecentre.com 
jbazov@prostatecentre.com  
 
Original Pathology Sample/Report for Evaluation of PTEN Deletion Status: 
If available, all patients randomized to the study will have representative sections from a 
paraffin block of their primary diagnostic tumor specimen evaluated for PTEN deletion 
status by fluorescence in situ hybridization (FISH). After a patient is randomized to the 
study, obtain a section of the original paraffin tumor block (or unstained slides) and a copy 
of the original (redacted) pathology report. Prepare 3 slides with 6 µm thick sections from 
the archival paraffin blocks (known to contain cancer from prostatectomy or core biopsies) 
and send to the address below. Slide sets should be sent in batches upon notification from 
the sponsor and will not be returned. 
Jenny Bazov 
Analytical Pharmacology 
Prostate Centre at Vancouver General Hospital 
The Jack Bell Research Centre 
2660 Oak Street 
Vancouver, BC   V6H 3Z6 
(604) 875-4908 
 


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Sample Schedule for CTCs and Serum/Plasma for Hsp27, Clusterin, and Other 
Relevant Proteins 
 
Sample Timepoint 
Blood for CTC  
Serum/Plasma for Hsp27, Clusterin, and 
Other Relevant Proteins  
Screening Baseline  
X 
X 
Week 1, Day 1 
X 
X 
Week 5, Day 1 
X 
X 
Week 9, Day 1 
X 
X 
Week 13, Day 1 
X 
X 
After Week 13 
Stop collecting blood 
for CTC 
Collect serum and plasma for Hsp27, clusterin, 
and other relevant proteins every 4 weeks until 
disease progression or Week 21, at EOT visit, 
and every 4 weeks during Off Treatment 
Follow Up until disease progression  
Further details on sample preparation, labeling, storage and shipment will be provided in 
the Study Procedure Manual. 


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14.4. 
Guidelines to Evaluate the Response to Treatment in Solid 
Tumors (RECIST 1.1) 
This information is available online at: Revised RECIST Guideline (Version 1.1) 
  


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14.5. 
ECOG Performance Status 
This information is available at: ECOG Performance Status