Conditions: Idiopathic Pulmonary Fibrosis
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 117
Healthy volunteers: no

Brief summary:
This study will evaulate the long-term safety, efficacy and pharmacokinetics (PK) of recombinant human pentraxin-2 (rhPTX-2; PRM-151) zinpentraxin alfa, administered by intravenous (IV) infusion to participants with idiopathic pulmonary fibrosis (IPF).

Detailed description:
This study is being conducted for the treatment of eligible participants who have taken part in Study PRM-151-202 and received the open-label study drug or completed the Phase III Study WA42293 with PRM-151. Participants who have discontinued treatment from or have completed Study WA42293 and do not want to receive PRM-151 in this study, will be invited to enroll in survival follow-up.

Arms:
arm 1: Corhort A: Participants entering, following participation in study PRM-151-202.

Cohort B: Participants entering, following participation in study WA42293.

Interventions: intervention 1: PRM-151 (Zinpentraxin Alfa)
Intervention descriptions: intervention 1: Cohort A: Participants will receive three loading doses of open-label PRM-151 on days 1, 3, and 5, then one infusion every 4 weeks (Q4W). 10 mg/kg of PRM 151 will be administered by intravenous (IV) infusion over 60 minutes on days 1, 3, and 5, then one infusion every 4 weeks.

Cohort B: Participants previously randomized to the placebo in WA42293 will receive study medication in the three loading doses on days 1, 3 and 5 in a blinded fashion. All three doses will contain PRM-151. Participants previously randomized to the treatment arm in WA42293 will receive study medication in the three loading doses on days 1, 3 and 5 in a blinded fashion. One of the three doses will contain PRM-151, whereas two doses will contain placebo.

Protocol document:
Prot_000.pdf: 
 
Official Title: A Phase III Open-Label Extension Study to Evaluate Long-Term 
Safety and Efficacy of PRM-151 in Patients With Idiopathic Pulmonary 
Fibrosis (IPF) 
NCT Number: NCT04594707 
Document Dates: Protocol Version 4: 28-April-2022 
 
 
 


 
CONFIDENTIAL 
 
This clinical study is being sponsored globally by F. Hoffmann-La Roche Ltd of Basel, 
Switzerland.  However, it may be implemented in individual countries by Roche’s local affiliates, 
including Genentech, Inc. in the United States.  The information contained in this document, 
especially any unpublished data, is the property of F. Hoffmann-La Roche Ltd (or under its 
control) and therefore is provided to you in confidence as an investigator, potential investigator, or 
consultant, for review by you, your staff, and an applicable Ethics Committee or Institutional 
Review Board.  It is understood that this information will not be disclosed to others without written 
authorization from Roche except to the extent necessary to obtain informed consent from persons 
to whom the drug may be administered. 
 
PRM-151 (Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
Protocol WA42294, Version 4 
PROTOCOL 
TITLE: 
A PHASE III OPEN-LABEL EXTENSION STUDY TO 
EVALUATE LONG-TERM SAFETY AND EFFICACY 
OF PRM-151 IN PATIENTS WITH IDIOPATHIC 
PULMONARY FIBROSIS (IPF) 
PROTOCOL NUMBER: WA42294 
VERSION NUMBER: 
4 
EUDRACT NUMBER: 
2020-001429-30 
IND NUMBER: 
110,774 
NCT NUMBER: 
NCT04594707 
TEST PRODUCT: 
Recombinant human pentraxin-2 (rhPTX-2; 
PRM‑151) [Zinpentraxin Alfa] 
MEDICAL MONITOR: 
, MBBS 
SPONSOR NAME AND 
LEGAL REGISTERED 
ADDRESS: 
F. Hoffmann-La Roche Ltd 
Grenzacherstrasse 124 
4070 Basel, Switzerland 
APPROVAL DATE: 
See electronic signature and date stamp on the final 
page of this document. 


PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
2/Protocol WA42294, Version 4 
PROTOCOL HISTORY 
Protocol 
Associated Country-Specific Protocols 
Version 
Date Final 
Country 
Version 
Date Final 
4 
See electronic date stamp 
on the final page. 



3 
1 February 2022 



2 
17 November 2020 
 
 
 
1 
10 July 2020 
VHP 
1 
16 November 2020 
 


PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
3/Protocol WA42294, Version 4 
PROTOCOL AMENDMENT, VERSION 4: 
RATIONALE 
Protocol WA42294 has been amended to incorporate changes made to include new 
information and identified risk of first and second generation PRM-151 drug product.  
Changes to the protocol, along with a rationale for each change, are summarized below. 
 
Text has been added to describe galectin-1 and galectin-3 host cell protein identified 
within first generation PRM-151 drug product.  It has been further clarified that an 
additional purification step will be applied to the second generation PRM‑151 which 
will not contain detectable levels of Chinese hamster ovary cell galectins 
(Sections 1.2 and 4.3.1.1). 
 
Text has been added to describe the sugar galactose-α-1,3-galactose identified in 
first and second generation PRM-151 drug product and on the increased risk of 
anaphylaxis or hypersensitivity reaction in patients with a history of tick bites, red 
meat allergy, or IgE antibodies directed against galactose-α-1,3-galactose 
(Sections 1.2.2 and 5.1.2). 
 
Text has been added on the potential risk of post-implantation fetal loss associated 
with PRM-151 (Sections 5.1 and 5.1.3) 
 
Additional minor changes have been made to improve clarity and consistency.  
Substantive new information appears in italics.  This amendment represents cumulative 
changes to the original protocol.


PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
4/Protocol WA42294, Version 4 
 
TABLE OF CONTENTS 
PROTOCOL AMENDMENT ACCEPTANCE FORM .......................................... 11 
PROTOCOL SYNOPSIS .................................................................................... 12 
1. 
BACKGROUND ............................................................................ 20 
1.1 
Idiopathic Pulmonary Fibrosis .................................................. 20 
1.2 
PRM-151.................................................................................. 21 
1.2.1 
PRM-151 Host Cell Proteins .................................................... 22 
1.2.2 
Galactose--1,3-galactose (α‑Gal) ........................................... 22 
1.3 
Study Rationale and Benefit-Risk Assessment ........................ 23 
1.3.1 
BenefitRisk Assessment ........................................................ 23 
1.3.2 
Risks Associated with Radiologic Imaging ............................... 24 
2. 
OBJECTIVES AND ENDPOINTS ................................................. 25 
2.1 
Safety Objective ....................................................................... 25 
2.2 
Efficacy Objectives .................................................................. 25 
2.3 
Exploratory Efficacy Objective ................................................. 26 
2.4 
Pharmacokinetic Objectives..................................................... 26 
2.5 
Immunogenicity Objectives ...................................................... 26 
2.6 
Biomarker Objective ................................................................ 27 
2.7 
Health Status Utility Objective .................................................. 27 
3. 
STUDY DESIGN ........................................................................... 27 
3.1 
Description of the Study ........................................................... 27 
3.1.1 
Overall Study Design and Plan ................................................ 27 
3.2 
End of Study and Length of Study ........................................... 30 
3.3 
Rationale for Study Design ...................................................... 30 
3.3.1 
Rationale for PRM-151 Dose and Schedule ............................ 30 
3.3.2 
Rationale for the Study Design ................................................ 31 
3.3.3 
Rationale for Collection of Survival Data in Cohort C .............. 32 
3.3.4 
Rationale for Biomarker Assessments ..................................... 32 
4. 
MATERIALS AND METHODS ...................................................... 32 
4.1 
Patients .................................................................................... 32 
4.1.1 
Inclusion Criteria ...................................................................... 32 


PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
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4.1.2
Exclusion Criteria ..................................................................... 34
4.2
Method of Treatment Assignment and Blinding ....................... 34
4.2.1
Treatment Assignment ............................................................. 34
4.3
Study Treatment and Other Treatments Relevant to the 
Study Design ........................................................................... 35
4.3.1
Study Treatment Formulation and Packaging .......................... 35
4.3.1.1
PRM-151 (Zinpentraxin Alfa) ................................................... 35
4.3.1.2
Placebo for Initial Loading Dose .............................................. 36
4.3.2
Study Treatment Dosage, Administration, and Compliance .... 36
4.3.3
Investigational Medicinal Product Handling and 
Accountability ........................................................................... 37
4.3.4
Continued Access to PRM-151 ................................................ 38
4.4
Concomitant Therapy .............................................................. 38
4.4.1
Permitted Therapy ................................................................... 39
4.4.2
Prohibited Therapy .................................................................. 39
4.4.3
Use of Pirfenidone or Nintedanib ............................................. 40
4.5
Study Assessments ................................................................. 40
4.5.1
Informed Consent Forms and Eligibility Assessments ............. 40
4.5.2
Sequence of Assessments ...................................................... 41
4.5.3
Medical History, Baseline Conditions, Concomitant 
Medication, and Demographic Data ......................................... 42
4.5.4
Physical Examinations ............................................................. 43
4.5.5
Vital Signs ................................................................................ 44
4.5.6
Pulmonary Function Tests ....................................................... 44
4.5.7
Six-Minute Walk Test ............................................................... 44
4.5.8
High-Resolution Computed Tomography ................................. 45
4.5.9
Assessment of Acute Exacerbations of IPF, 
Hospitalizations for Respiratory Causes, and Deaths 
(Adjudication Events) ............................................................... 45
4.5.9.1
Acute Exacerbations of IPF and Suspected Acute 
Exacerbations of IPF ............................................................... 46
4.5.9.2
Hospitalizations for Respiratory Causes .................................. 46
4.5.9.3
Deaths Due to Respiratory Causes ......................................... 47
4.5.9.4
Health Care Utilization for Respiratory Events ......................... 47
4.5.10
Laboratory, Biomarker, and Other Biological Samples ............ 47


PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
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4.5.11 
Electrocardiograms .................................................................. 49 
4.5.12 
Clinical Outcome Assessments ............................................... 50 
4.5.12.1 
Data Collection Methods for Clinical Outcome 
Assessments ........................................................................... 50 
4.5.12.2 
Description of Clinical Outcome Assessment Instruments ....... 51 
4.5.13 
Optional Samples for Research Biosample Repository ........... 51 
4.5.13.1 
Overview of the Research Biosample Repository .................... 51 
4.5.13.2 
Approval by the Institutional Review Board or Ethics 
Committee ............................................................................... 52 
4.5.13.3 
Sample Collection .................................................................... 52 
4.5.13.4 
Confidentiality .......................................................................... 52 
4.5.13.5 
Consent to Participate in the Research Biosample 
Repository................................................................................ 53 
4.5.13.6 
Withdrawal from the Research Biosample Repository ............. 53 
4.5.13.7 
Monitoring and Oversight ......................................................... 54 
4.6 
Treatment, Patient, Study, and Site Discontinuation ................ 54 
4.6.1 
Study Treatment Discontinuation ............................................. 54 
4.6.2 
Patient Discontinuation from the Study .................................... 55 
4.6.3 
Study Discontinuation .............................................................. 55 
4.6.4 
Site Discontinuation ................................................................. 55 
5. 
ASSESSMENT OF SAFETY ......................................................... 56 
5.1 
Potential Risks Associated with PRM-151 ............................... 56 
5.1.1 
Infusion-Related Reactions ...................................................... 57 
5.1.2 
Anaphylactic and Hypersensitivity Reactions........................... 57 
5.1.3 
Post-implantation Fetal Loss ....................................................... 58 
5.1.4 
Management Guidelines for Infusion Related Reactions, 
and Anaphylactic and Hypersensitivity Reactions .................... 58 
5.2 
Management of Patients Who Experience Adverse Events ..... 60 
5.2.1 
Dose Modifications .................................................................. 60 
5.2.2 
Treatment Interruption ............................................................. 61 
5.3 
Safety Parameters and Definitions .......................................... 61 
5.3.1 
Adverse Events ........................................................................ 61 
5.3.2 
Serious Adverse Events (Immediately Reportable to the 
Sponsor) .................................................................................. 62 


PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
7/Protocol WA42294, Version 4 
5.3.3 
Adverse Events of Special Interest (Immediately 
Reportable to the Sponsor) ...................................................... 62 
5.3.4 
Collection of Survival Data (Cohort C) ..................................... 63 
5.3.5 
Lung Transplantation ............................................................... 63 
5.4 
Methods and Timing for Capturing and Assessing 
Safety Parameters ................................................................... 63 
5.4.1 
Adverse Event Reporting Period .............................................. 64 
5.4.2 
Eliciting Adverse Event Information ......................................... 64 
5.4.3 
Assessment of Severity of Adverse Events ............................. 64 
5.4.4 
Assessment of Causality of Adverse Events............................ 65 
5.4.5 
Procedures for Recording Adverse Events .............................. 66 
5.4.5.1 
Infusion-Related Reactions ...................................................... 66 
5.4.5.2 
Diagnosis versus Signs and Symptoms ................................... 66 
5.4.5.3 
Adverse Events That Are Secondary to Other Events ............. 66 
5.4.5.4 
Persistent or Recurrent Adverse Events .................................. 67 
5.4.5.5 
Abnormal Laboratory Values ................................................... 67 
5.4.5.6 
Abnormal Vital Sign Values ..................................................... 68 
5.4.5.7 
Abnormal Liver Function Tests ................................................ 68 
5.4.5.8 
Deaths ..................................................................................... 69 
5.4.5.9 
Preexisting Medical Conditions ................................................ 69 
5.4.5.10 
Lack of Efficacy or Worsening of Idiopathic Pulmonary 
Fibrosis .................................................................................... 69 
5.4.5.11 
Hospitalization or Prolonged Hospitalization ............................ 70 
5.4.5.12 
Cases of Accidental Overdose or Medication Error ................. 70 
5.5 
Immediate Reporting Requirements from Investigator to 
Sponsor ................................................................................... 71 
5.5.1 
Medical Monitors and Emergency Medical Contacts ............... 72 
5.5.2 
Reporting Requirements for Serious Adverse Events and 
Adverse Events of Special Interest .......................................... 72 
5.5.2.1 
Events That Occur prior to Study Drug Initiation ...................... 72 
5.5.2.2 
Events That Occur after Study Drug Initiation .......................... 73 
5.5.3 
Reporting Requirements for Pregnancies ................................ 73 
5.5.3.1 
Pregnancies in Female Patients .............................................. 73 
5.5.3.2 
Pregnancies in Female Partners of Male Patients ................... 73 


PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
8/Protocol WA42294, Version 4 
5.5.3.3 
Abortions.................................................................................. 74 
5.5.3.4 
Congenital Anomalies/Birth Defects ........................................ 74 
5.6 
Follow-Up of Patients after Adverse Events............................. 74 
5.6.1 
Investigator Follow-Up ............................................................. 74 
5.6.2 
All pregnancies reported during the study should be 
followed until pregnancy outcome. Sponsor Follow-Up ........... 75 
5.7 
Adverse Events That Occur after the Adverse Event 
Reporting Period ...................................................................... 75 
5.8 
Expedited Reporting to Health Authorities, Investigators, 
Institutional Review Boards, and Ethics Committees ............... 75 
6. 
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN ......... 76 
6.1 
Determination of Sample Size ................................................. 77 
6.2 
Summaries of Conduct of Study .............................................. 77 
6.3 
Safety Analyses ....................................................................... 77 
6.3.1 
Adverse Events ........................................................................ 77 
6.3.2 
Laboratory Data ....................................................................... 77 
6.4 
Efficacy Analyses ..................................................................... 77 
6.5 
Exploratory Efficacy Analysis ................................................... 78 
6.6 
Pharmacokinetic Analyses ....................................................... 79 
6.7 
Immunogenicity Analyses ........................................................ 79 
6.8 
Biomarker Analyses ................................................................. 79 
6.9 
Health Status Utility Analyses .................................................. 79 
7. 
DATA COLLECTION AND MANAGEMENT ................................. 79 
7.1 
Data Quality Assurance ........................................................... 79 
7.2 
Electronic Case Report Forms ................................................. 80 
7.3 
Electronic Patient Reported Outcome Data ............................. 80 
7.4 
Source Data Documentation .................................................... 81 
7.5 
Use of Computerized Systems ................................................ 81 
7.6 
Retention of Records ............................................................... 81 
8. 
ETHICAL CONSIDERATIONS ...................................................... 82 
8.1 
Compliance with Laws and Regulations .................................. 82 
8.2 
Informed Consent .................................................................... 82 
8.3 
Institutional Review Board or Ethics Committee ...................... 83 


PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
9/Protocol WA42294, Version 4 
8.4 
Confidentiality .......................................................................... 84 
8.5 
Financial Disclosure ................................................................. 85 
9. 
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION ....................................................................... 85 
9.1 
Study Documentation .............................................................. 85 
9.2 
Protocol Deviations .................................................................. 85 
9.3 
Management of Study Quality .................................................. 85 
9.4 
Site Inspections ....................................................................... 86 
9.5 
Administrative Structure ........................................................... 86 
9.6 
Dissemination of Data and Protection of Trade Secrets .......... 87 
9.7 
Protocol Amendments ............................................................. 88 
10. 
REFERENCES.............................................................................. 89 
 
 
LIST OF TABLES 
Table 1 
Sequence of Assessments.......................................................... 42 
Table 2 
Actions if an Infusion-Related Reactions (Grade 2) Occurs ...... 59 
Table 3 
Adverse Event Severity Grading Scale for Events Not 
Specifically Listed in NCI CTCAE ............................................... 65 
 
 
LIST OF FIGURES 
Figure 1 
Cohort Allocation ......................................................................... 28 
Figure 2 
Study Schema ............................................................................. 28 
Figure 3 
Initial Loading Doses for Cohorts A and B .................................. 29 
 
 
LIST OF APPENDICES 
Appendix 1 
Schedule of Activities for Cohorts A and B ................................. 95 
Appendix 2 
Schedule of Activities for Cohort C ........................................... 100 
Appendix 3 
Schedule of Pharmacokinetic, Immunogenicity, and 
Biomarker Samples for Cohort A .............................................. 101 
Appendix 4 
Schedule of Pharmacokinetic, Immunogenicity, and 
Biomarker Samples for Cohort B .............................................. 103 
Appendix 5 
Sampson's Criteria for Diagnosing Potential Cases of 
Anaphylaxis ............................................................................... 105 
Appendix 6 
St. George’s Respiratory Questionnaire ................................... 106 


PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
10/Protocol WA42294, Version 4 
Appendix 7 
University of California, San DiegoShortness of Breath 
Questionnaire ............................................................................ 112 
Appendix 8 
EuroQol 5-Dimension Questionnaire, 5-Level Version .............. 116 
Appendix 9 
National Cancer Institute Common Terminology Criteria for 
Adverse Events ......................................................................... 118 
Appendix 10 
 Borg Scale for Rating Dyspnea and Overall Fatigue (CR10) ... 119 
 


PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
11/Protocol WA42294, Version 4 
PROTOCOL AMENDMENT ACCEPTANCE FORM 
TITLE: 
A PHASE III OPEN-LABEL EXTENSION STUDY TO 
EVALUATE LONG-TERM SAFETY AND EFFICACY 
OF PRM-151 IN PATIENTS WITH IDIOPATHIC 
PULMONARY FIBROSIS (IPF) 
PROTOCOL NUMBER: WA42294 
VERSION NUMBER: 
4 
EUDRACT NUMBER: 
2020-001429-30 
IND NUMBER: 
110,774 
NCT NUMBER: 
NCT04594707  
TEST PRODUCT: 
Recombinant human pentraxin-2 (rhPTX-2; 
PRM-151); [Zinpentraxin Alfa] 
MEDICAL MONITOR: 
, MBBS 
SPONSOR: 
F. Hoffmann La Roche Ltd. 
 
I agree to conduct the study in accordance with the current protocol. 
 
 
 
Principal Investigator's Name  (print) 
 
 
 
 
 
Principal Investigator's Signature 
 
Date 
Please retain the signed original of this form for your study files.  Please return a copy 
of the signed form as instructed by your local study monitor. 
 


PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
12/Protocol WA42294, Version 4 
 
PROTOCOL SYNOPSIS 
TITLE: 
A PHASE III OPEN-LABEL EXTENSION STUDY TO EVALUATE 
LONG-TERM SAFETY AND EFFICACY OF PRM-151 IN PATIENTS 
WITH IDIOPATHIC PULMONARY FIBROSIS (IPF) 
PROTOCOL NUMBER: 
WA42294 
VERSION NUMBER: 
4 
EUDRACT NUMBER: 
2020-001429-30 
IND NUMBER: 
110,774 
NCT NUMBER: 
NCT04594707 
TEST PRODUCT: 
Recombinant human pentraxin-2 (rhPTX-2; PRM-151); 
Zinpentraxin Alfa 
PHASE: 
Phase III 
INDICATION: 
Idiopathic pulmonary fibrosis 
SPONSOR: 
F. Hoffmann La Roche Ltd. 
 
OBJECTIVES AND ENDPOINTS 
This study will evaluate the long-term safety, efficacy and pharmacokinetics of open-label 
PRM-151 in patients with idiopathic pulmonary fibrosis (IPF).  Specific objectives and 
corresponding endpoints for the study are outlined below. 
SAFETY OBJECTIVE 
The safety objective for this study is to confirm the long-term safety and tolerability of 10 mg/kg 
of PRM-151 administered every 4 weeks (Q4W) via intravenous (IV) infusion plus standard of 
care (SOC) treatment, on the basis of the following endpoints: 
 
Incidence and severity of all adverse events (AEs), with severity determined according to 
the 5-point severity scale (National Cancer Institute Common Terminology Criteria for 
Adverse Events, Version 5.0 [NCI CTCAE, v.5.0]) 
 
Incidence and severity of infusion related reactions (IRRs) and other AEs of special interest 
 
Proportion of patients permanently discontinuing study treatment due to AEs 
 
Change from baseline of targeted clinical laboratory test results 
EFFICACY OBJECTIVES 
The efficacy objectives are to assess the long-term efficacy of 10 mg/kg PRM-151 plus SOC 
(excluding lung transplantation) administered Q4W via IV infusion on the basis of the following 
endpoints: 
 
Annual rate of change in FVC (mL) 
 
Annual rate of change in 6-minute walk distance (6MWD) 
 
Annual rate of change in FVC% predicted 
 
Annual rate of change in DLCO 
 
Time to disease progression, defined as time to first occurrence of 10% absolute decline 
in % predicted FVC, 15% relative decline in 6MWD, or death 
 
Survival, as measured by all-cause mortality 
 
IPF-related mortality and respiratory-related mortality 


PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
13/Protocol WA42294, Version 4 
 
Exploratory Efficacy Objective 
Exploratory analyses may also be performed for additional measures and subgroups of interest 
including concurrent use of IPF treatment and geographic region on the basis of the following 
endpoints:   
 
Change from baseline in University of California, San Diego-Shortness of Breath 
Questionnaire (UCSD-SOBQ) 
 
Change from baseline in St. George Respiratory Questionnaire (SGRQ) Total Score 
 
Time to first respiratory-related hospitalizations (defined as non-elective hospitalizations 
due to any respiratory cause, including acute exacerbations of IPF, or suspected acute 
exacerbations of IPF 
 
Time to first acute exacerbation of IPF, or suspected acute exacerbation of IPF 
 
Details of all such analyses will be provided in the Statistical Analysis Plan (SAP).   
PHARMACOKINETIC OBJECTIVES 
The pharmacokinetic (PK) objective for this study is to characterize pharmacokinetics of 
PRM-151 in patients with IPF (from Cohort A, and Cohort B, who are enrolled in the WA42293 
study prior to 1 June 2022), on the basis of the following endpoint: 
 
Plasma concentrations of PRM-151 at specified timepoints 
 
The exploratory PK objectives are to evaluate the potential relationship between drug exposure 
and the efficacy and safety of PRM-151 on the basis of the following endpoints: 
 
Relationship between PK for PRM-151 and efficacy endpoints 
 
Relationship between PK for PRM-151 and safety endpoints 
 
IMMUNOGENICITY OBJECTIVES 
The immunogenicity objective for this study is to evaluate the immune response to PRM-151 in 
patients with IPF (from Cohort A and Cohort B patients who enrolled into the WA42293 prior to 
1 June 2022) on the basis of the following: 
 
Prevalence of ADAs at baseline and incidence of ADAs during the study 
 
The exploratory immunogenicity objective for this study is to evaluate potential effects of ADAs 
on the basis of the following: 
 
Relationship between ADA status and efficacy, safety, or PK endpoints 
 
BIOMARKER OBJECTIVE 
The exploratory biomarker objective for this study (from Cohort A and Cohort B) is to identify 
and/or evaluate biomarkers that can provide evidence of PRM-151 activity and the duration of 
that activity (i.e., pharmacodynamic biomarkers), are associated with acquired resistance to 
PRM-151, are associated with susceptibility to developing AEs or can lead to improved AE 
monitoring or investigation (i.e., safety biomarkers), or can increase the knowledge and 
understanding of disease biology and drug safety, on the basis of the following endpoint: 
 
Relationship between biomarkers in blood and efficacy, safety, PK, immunogenicity, or 
other biomarker endpoints. 
 
HEALTH STATUS UTILITY OBJECTIVE 
The exploratory health status utility objective for this study is to evaluate health status utility 
scores of patients treated with PRM-151 plus SOC on the basis of the following endpoint: 
Annual rate of change in EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) index-based, 
and visual analog scale (VAS) scores 
 


PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
14/Protocol WA42294, Version 4 
STUDY DESIGN 
DESCRIPTION OF STUDY 
This OLE study is being conducted to confirm the long-term safety, efficacy, and 
pharmacokinetics of PRM-151 in the treatment of eligible patients with IPF who have taken part 
in Study PRM-151-202 and received the open-label study drug (Cohort A) or completed the 
Phase III Study WA42293 (Cohort B) with PRM-151.  Additionally, patients who have 
discontinued treatment from or have completed Study WA42293 and do not want to receive 
open-label PRM-151 in this study, will be invited to enroll in survival follow-up Cohort C.  
Patients in Cohort C will not receive any treatment and will not undergo any safety or efficacy 
assessments during the study.  Patients who discontinue treatment from Cohorts A and B will 
automatically transition to Cohort C for long-term follow-up, unless they withdraw consent from 
the study. 
Patients meeting the eligibility criteria for the study will receive PRM-151 10 mg/kg Q4W.  
Throughout the study, patients will be monitored for safety by collection of AEs (both serious 
and non-serious) and by regular physical exam and safety laboratory assessments. 
Efficacy will be evaluated through assessment of functional capacity as measured by FVC, 
6MWD, other pulmonary function tests (PFTs), and assessment of patients with respiratory 
events leading to hospitalizations, progression of disease, or acute IPF exacerbations. 
Patient reported outcomes (PRO) will be assessed using the SGRQ, UCSD-SOBQ, and 
EQ-5D-5L. 
Dyspnea, fatigue, and blood oxygen saturation levels (SpO2) will be assessed based on 
measurements taken during the 6-minute walk test (6MWT).  Chest HRCT will be assessed for 
changes from Study WA42293 to Week 52 (OLE) and Week 104 (OLE), for patients in Cohort B 
who had a HRCT scan at Screening and Week 52 in Study WA42293.  Treated patients will be 
followed-up until the end of the study period, unless the patient withdraws consent for follow-up 
or death occurs. 
For all patients receiving anti-fibrotic therapy, the investigator should document the dose, 
frequency, and duration of the anti-fibrotic drug. 
During the study, patients may initiate pirfenidone or nintedanib, if determined to be clinically 
indicated by the investigator.  The Study Investigator is required to document the specific 
reason for introducing anti-fibrotic therapy in patients who started the study not on anti-fibrotic 
therapy. 
Approximately 600700 patients are expected to enroll in the study.  Patients will initially receive 
loading doses of either PRM-151 10 mg/kg IV infusion and/or placebo over 5070 minutes on 
Days 1, 3, and 5, then one infusion of PRM-151 Q4W until the end of the study.  Patients 
previously on the placebo arm of Study WA42293 will receive PRM-151 in all three loading 
doses, whereas patients previously on the active treatment arm of Study WA42293 will receive 
PRM-151 for the first dose, followed by placebo doses at the 2nd and 3rd loading dose visit.  
The loading doses will be blinded for Cohort B, to ensure that the blind in Study WA42293 is 
maintained for patients, site staff, and the Sponsor. 
Patients entering Cohort A, from Study PRM-151-202 will have an eligibility visit prior to 
commencing dosing.  The eligibility visit can occur on the same day as the dosing visit, if the 
patient is confirmed to be eligible for the study. 
Patients entering Cohort B, from Study WA42293 will have their end-of-WA42293-study visit at 
Week 52.  All assessments from the Week 52 WA42293 study visit must be completed prior to 
commencing dosing in the OLE study.  Ideally, patients will be enrolled into Cohort B on the 
same day as their Week 52 (Study WA42293) visit. 
Patients enrolling into Cohort C from Study WA42293 (e.g., those who do not wish to receive 
study treatment), or those who transition from Cohorts A and B, will be followed-up for the 
duration of this study, to collect their survival data. 
NUMBER OF PATIENTS 
Approximately 600-700 patients with IPF will be enrolled in this study. 


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TARGET POPULATION 
Inclusion Criteria 
Patients must meet the following criteria for study entry: 
 
Signed Informed Consent Form 
 
In the opinion of the Principle Investigator, participation in the study is in the best interest of 
the patient 
 
Ability to comply with the requirements of the study protocol, according to the investigator’s 
best judgment 
 
Taken part in a previous study of PRM-151, as follows:  
 
Participated in Study PRM-151-202 (completed the 28-week placebo-controlled period 
and entered the OLE), and tolerated the study drug in the opinion of the investigator 
(Cohort A) OR 
 
Completed study treatment in Study WA42293 (Cohort B) OR 
 
Participated in Study WA42293 but discontinued from study treatment (Cohort C; patients 
who completed treatment in Study WA42293, but no longer wish to take PRM-151 may also 
join Cohort C). 
 
 
For women of childbearing potential:  agreement to remain abstinent (refrain from 
heterosexual intercourse) or use contraception, as defined below: 
Women must remain abstinent or use contraceptive methods with a failure rate of 1% per 
year during the treatment period and for 8 weeks after the final dose of PRM-151. 
A woman is considered to be of childbearing potential if she is postmenarchal, has not 
reached a postmenopausal state (12 continuous months of amenorrhea with no identified 
cause other than menopause), and is not permanently infertile due to surgery (i.e., removal 
of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the 
investigator (e.g., Müllerian agenesis).  The definition of childbearing potential may be 
adapted for alignment with local guidelines or regulations. 
Examples of contraceptive methods with a failure rate of 1% per year include bilateral 
tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, 
hormone-releasing intrauterine devices, and copper intrauterine devices. 
Hormonal contraceptive methods must be supplemented by a barrier method. 
The reliability of sexual abstinence should be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the patient.  Periodic abstinence 
(e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not 
adequate methods of contraception.  If required per local guidelines or regulations, locally 
recognized adequate methods of contraception and information about the reliability of 
abstinence will be described in the local Informed Consent Form. 
 
For men:  agreement to remain abstinent (refrain from heterosexual intercourse) or use 
a condom, and agreement to refrain from donating sperm, as defined below: 
With a female partner of childbearing potential or pregnant female partner, men must 
remain abstinent or use a condom during the treatment period and for 8 weeks after the 
final dose of PRM-151 to avoid exposing the embryo.  Men must refrain from donating 
sperm during this same period. 
The reliability of sexual abstinence should be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the patient.  Periodic abstinence 
(e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not 
adequate methods of preventing drug exposure.  If required per local guidelines or 
regulations, information about the reliability of abstinence will be described in the local 
Informed Consent Form. 
 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from study entry: 


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 
Received any experimental treatment other than PRM-151 within 4 weeks or five half-lives 
of the experimental drug, whichever is longer, prior to the first dose in the OLE study 
 
Receiving strong inhibitor or inducer of CYP1A2 in patients taking pirfenidone 
 
Receiving potent inhibitor or inducer of P-gp in patients taking nintedanib 
 
Acute respiratory or systemic bacterial, viral, or fungal infection at the first visit of the OLE, 
or within 2 weeks of the first visit for patients joining Cohort A (from Study PRM-151-202) 
 
History of smoking (including cigarette, cannabis, cigar, pipe, and vaping) within 3 months 
prior to the first visit in the OLE 
 
History of alcohol or substance use disorder within 2 years prior to the first visit of OLE or 
known or suspected active alcohol or substance-use disorder 
 
History of severe allergic reaction or anaphylactic reaction to PRM-151 
 
Clinically significant abnormality on ECG during eligibility assessment that, in the opinion of 
the investigator, may pose an additional risk in administering study drug to the patient  
 
Prolonged corrected QT interval  450 ms (for men) or  470 ms (for women) based on the 
Fridericia correction formula. 
 
Clinically significant laboratory test abnormalities (hematology, serum chemistry, and 
urinalysis) that, in the opinion of the investigator, may pose an additional risk in 
administering study drug to the patient. 
 
Any of the following laboratory abnormalities known at the time of the first visit 
 
ALT and/or AST 2.5upper limit of normal (ULN)  
 
Total bilirubin 2ULN  
 
Pregnant or breastfeeding, or intending to become pregnant during the study (for Cohort A 
or B patients). 
 
END OF STUDY 
The end of this study is defined as the date when the last patient, last visit (LPLV) occurs.  The 
end of the study is expected to occur by 31-December-2028.  This date may be subject to 
change, depending on the local commercial availability of PRM-151.  Site discontinuation will 
occur upon commercial availability of PRM-151 in order for patients to transition off from this 
trial and onto commercially available PRM-151. 
INVESTIGATIONAL MEDICINAL PRODUCTS 
The investigational medicinal product (IMP) for this study is PRM-151.  Placebo is also 
considered an IMP in this study. 
TEST PRODUCT (INVESTIGATIONAL DRUG) 
Patients will receive IV infusions of 10 mg/kg PRM-151 over 5070 minutes, with dose based on 
the patient’s weight recorded at each visit (for loading or reloading doses, weight taken at the 
clinic visit for the first dose can be applied to the 2nd and 3rd doses). 
Non-Investigational Medicinal Products 
The non-investigational medicinal products (NIMP) for this study are pirfenidone and nintedanib.  
The NIMPs are considered background therapy for those patients already receiving either 
product when entering the study, and rescue therapy for any patient who commences treatment 
with either product during the study. 
STATISTICAL METHODS 
Because of the non-comparative character of the study, no statistical tests are planned.  
Demographic and baseline characteristics such as age, sex, race/ethnicity, concomitant IPF 
medication use, comorbid illnesses, and pulmonary function will be summarized by use of 
descriptive statistics. 
Cohort B collected data will not be analyzed before unblinding of the code of the treatment 
received by the patient during the parent Study WA42293.   
Additional safety update analyses may be conducted as required by Health Authorities.  The 
final analysis will take place after the LPLV.   


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Patient efficacy data will be summarized by cohort including all patients who receive at least 
one dose of PRM-151 study drug.  Efficacy in Cohorts A and B will be assessed by annual rate 
of change in FVC (mL), 6MWD, FVC% predicted, and DLCO, time to disease progression, and 
survival as measured by all-cause mortality, IPF related mortality and respiratory related 
mortality.  The annual rate of change in FVC (mL), 6MWD, FVC% predicted, and DLCO will be 
calculated using the slope from a linear mixed effect model with random intercept (subject) and 
random slope (time), using measurements collected at each time point in this study.   
Data from patients initially allocated to Cohort C will be used for survival follow-up only, without 
any safety or efficacy assessments.  Further analysis details on all cohorts will be provided in 
the SAP. 
DETERMINATION OF SAMPLE SIZE 
The number of patients enrolled in the OLE study is approximately 600-700 (i.e., eligible 
patients from Study PRM-151-202 [Cohort A] and Study WA42293 [Cohorts B and C]).  No 
formal sample size calculations were performed. 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
6MWD 
6-minute walk distance 
6MWT 
6-minute walk test 
ADA 
anti-drug antibody 
AE 
adverse event 
ALAT 
Latin American Thoracic Society 
ATS 
American Thoracic Society 
COPD 
chronic obstructive pulmonary disease 
CRO 
contract research organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
DAMP 
damage-associated molecular patterns 
DLCO 
diffusing capacity for carbon monoxide 
EC 
Ethics Committee 
ECM 
extracellular matrix 
eCRF 
electronic Case Report Form 
EDC 
electronic data capture 
EQ-5D-5L 
EuroQol 5-Dimension, 5-Level Questionnaire 
ERS 
European Respiratory Society 
FAS 
full analysis set 
FcR 
Fc gamma receptors 
FDA 
Food and Drug Administration 
FVC 
forced vital capacity 
HIPAA 
Health Insurance Portability and Accountability Act 
hPTX-2 
human pentraxin-2 
HRCT 
high-resolution computed tomography 
ICH 
International Council for Harmonization 
iDMC 
independent Data Monitoring Committee 
ILD 
interstitial lung disease 
IPF 
idiopathic pulmonary fibrosis 
IMP 
investigational medicinal product 
IND 
Investigational New Drug (Application) 
INN 
International Nonproprietary Name 
IRB 
Institutional Review Board 
IRR 
infusion-related reaction 
IV 
intravenous 
IxRS 
interactive voice or web-based response system 


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Abbreviation 
Definition 
JRS 
Japanese Respiratory Society 
LB 
lung biopsy 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI 
National Cancer Institute 
NGS 
next-generation sequencing 
NIMP 
noninvestigational- medicinal product 
NMPA 
National Medical Products Administration 
OLE 
open-label extension 
PD 
pharmacodynamics 
PFT 
pulmonary function test 
PK 
pharmacokinetic 
PRO 
patient-reported outcome 
PRR 
pattern recognition receptor 
PTX-2 
Pentraxin-2 
Q4W 
every 4 weeks 
RBR 
Research Biosample Repository 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SGRQ 
St. George Respiratory Questionnaire 
SOC 
standard of care 
SpO2 
blood oxygen saturation levels 
TEAE 
treatment emergent adverse event 
TEDE 
Total Effective Dose Equivalent  
UCSD-SOBQ 
University of California, San Diego-Shortness of Breath 
Questionnaire 
UIP 
usual interstitial pneumonia 
ULN 
upper limit of normal  
VAS 
visual analog scale 
WES 
whole exome sequencing 
WGS 
whole genome sequencing 
w/v 
weight/volume 


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1. 
BACKGROUND 
1.1 
IDIOPATHIC PULMONARY FIBROSIS 
Idiopathic pulmonary fibrosis (IPF) is a rare, specific form of chronic, fibrosing, interstitial 
pneumonia limited to the lung and leads to an irreversible loss of lung function.  It has 
the histopathologic pattern of usual interstitial pneumonia (UIP) upon analysis of 
a surgical lung biopsy (LB).  Historically, patients who received a diagnosis of IPF 
required a surgical LB; however, the current definition allows for an IPF diagnosis 
through clinical and radiological methods.  The diagnosis of IPF requires the exclusion of 
other known causes of interstitial lung disease (ILD), such as domestic and occupational 
environmental exposures, connective-tissue disease, and drug toxicity (Raghu et al. 
2011).  Patient prognosis is poor with the 5-year survival rate for IPF previously reported 
as being between 20%-40% (Olson et al. 2007).  In 2015, the incidence of IPF in 
North America and Europe was estimated at 3 to 9 cases per 100,000 person-years, 
with lower incidence in Asia and South America (Hutchinson et al. 2015).  Although rare, 
the incidence of IPF is increasing, likely due to an increasing recognition of the disease 
and the recent development of uniform diagnostic criteria (Raghu et al. 2018).  IPF 
disproportionately affects men over the age of 60 (Raghu et al. 2018). 
Pirfenidone and nintedanib are currently the only pharmacologic therapies approved for 
the treatment of IPF (Raghu et al 2015).  The rate of decline in forced vital capacity 
(FVC) is slower in patients treated with pirfenidone and nintedanib.  However, neither 
treatment halts disease progression or improves any objective measurements of disease 
status (Nathan et al. 2016).  Therefore, disease progression and respiratory decline is 
inevitable.  Thus, a need for additional novel treatment approaches remains. 
Evidence suggests that epithelial damage and abnormal wound repair contribute to the 
pathogenesis of IPF (Richeldi et al. 2017).  Fibrocytes, usually inactive fibroblast-like 
cells derived from peripheral blood monocytes, have been implicated in this process 
(De Biasi et al. 2015).  A loss of control of the mechanisms halting the normal wound 
healing process leads to persistence of inflammatory cells (particularly monocyte-derived 
cell populations such as macrophages and fibrocytes), elevated levels of cytokines, 
chemokines, growth factors, and other signaling molecules, excessive deposition of 
collagen types 1 and 3, and inhibition of enzymes that degrade extracellular matrix 
(ECM) proteins (Lupher and Gallatin 2006).  
Over time, continuing insults result in progressive lung fibrosis (pathologic accumulation 
of excessive ECM) and increasingly compromised lung function due to 
thickening/stiffening of the interstitium.  In established disease, pulmonary function tests 
identify restrictive disease (reduced total lung capacity) and abnormal gas exchange 
(reduced carbon monoxide diffusion) (Raghu et al. 2011).  Signs and symptoms that 
develop over time include exertional dyspnea and cough as well as fatigue, weight loss, 
myalgia, and clubbing of the fingers and toes (Richeldi et al. 2017). 


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IPF is estimated to be the primary cause of death due to respiratory failure in 60% of 
patients with IPF and acute exacerbation of the disease are associated with 
a particularly high risk of respiratory failure (Frankel and Schwarz 2009).  Other common 
causes of death include acute coronary syndromes, congestive heart failure, lung 
cancer, infection, and venous thromboembolic disease (Frankel and Schwarz 2009). 
1.2 
PRM-151 
Pentraxin-2 (PTX-2) is a highly conserved endogenous serum protein and a soluble 
pattern recognition receptor (PRR) of the innate immune system that regulates 
monocyte activation and differentiation (Steel and Whitehead 1994; Gewurz et al. 1995; 
Pepys et al. 1997; Garlanda et al. 2005; Mantovani et al. 2008). 
Recent discoveries about the biology of tissue repair and fibrosis have elucidated the 
important role that PTX-2 plays biologically in regulating processes that relate to scar 
prevention and healing.  PTX-2 is an agonist that binds to Fc gamma receptors (FcR) 
on monocytes and promotes their differentiation into regulatory macrophages, which 
function to promote epithelial healing and resolution of inflammation and scarring.  
PTX-2 also prevents the differentiation of monocytes into M2 pro-fibrotic macrophages 
and fibrocytes, preventing the formation of fibrosis.  During normal homeostasis, 
PTX-2 serves as a naturally circulating regulatory protein that specifically binds to 
apoptotic or necrotic debris in circulation and rapidly removes it through FcR-mediated 
phagocytosis by monocytes and macrophages within the spleen and liver.  This process 
suppresses a systemic innate activation response to those damage-associated 
molecular pattern (DAMP) signals (Cox et al. 2014). 
PRM-151 is a recombinant human pentraxin-2 (rhPTX-2) protein.  It is produced via 
Chinese Hamster Ovary cell culture, purified and formulated as a sterile liquid for 
intravenous infusion.  Like the native human protein, PRM-151 is expressed and purified 
as a non-covalent, homo-pentamer.  Each monomer in the pentamer exhibits the same 
204 amino acid primary sequence.  The theoretical average molecular weight of the fully 
glycosylated, bi-sialylated monomers in each pentamer is 25,462.5 Da.  The theoretical 
average molecular weight of the corresponding pentamer is 127,313 Da. 
PRM-151 mediates its activity by coupling recognition of DAMPs within injured tissue to 
specific phagocytosis through FcR on monocytes.  This process both removes the 
inflammatory and fibrotic stimulation provided by the DAMP signals, and actively 
stimulates the generation of a regulatory macrophage population identified through 
increased local expression of interleukin-10. 
Of importance, patients with IPF (in comparison to healthy subjects) have both increased 
fibrocyte numbers in circulation (Moeller et al. 2009) and decreased levels of circulating 
PTX-2 (Murray et al. 2011). 


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Supplementing endogenous PTX-2 levels through intravenous (IV) administration of 
PRM-151 should theoretically increase the regulatory capacity of PTX-2 in circulation 
and at the site of disease, thereby promoting healing and reducing fibrosis. 
Robust nonclinical and clinical data exist to support the investigation of PRM-151 in the 
treatment of fibrotic diseases, summaries of which are provided in the following sections.  
Efficacy and safety of PRM-151 is also being investigated in patients with myelofibrosis 
in a Phase II study (PRM-151G-101).  For more information on nonclinical or clinical 
investigations, refer to the PRM-151 Investigator’s Brochure.  
1.2.1 
PRM-151 Host Cell Proteins  
Mass spectroscopy analysis of PRM-151 was performed to characterize host cell protein 
(HCP) impurities, which led to the identification of Chinese hamster ovary cell galectin-1 
(CHO Gal-1) and CHO galectin-3 (CHO Gal-3).  It was found that CHO Gal-1 and CHO 
Gal-3 co-purifies with PRM-151, and has been present in Phase 2 and Phase 3 batches 
of investigational medicinal product (IMP). 
The Sponsor performed an assessment of toxicology, safety, and efficacy on the 
potential impact of the presence of CHO Gal-1/3 in the PRM-151 drug product.  
Nonclinical toxicity data suggest that the overall risk to patients of direct adverse effects 
due to CHO Gal-1/3 at levels present in the drug product is low.  There continues to be 
a favorable benefit/risk assessment based on the clinical data from the Phase 2 study to 
date (which used drug substance that has now been confirmed to have these host cell 
proteins present at the time).  Levels of HCPs in the drug product that  are equal to or 
below the levels identified in batches used to supply the Phase 2 studies, are not 
anticipated to adversely impact the known benefit/risk profile of PRM-151; there are no 
new safety risks, and there is no direct evidence of impact on efficacy.  
In order to control the CHO Gal-1/3 levels, each batch of PRM-151 will be tested for the 
two HCPs by mass spectrometry.  Only batches with levels equal or lower than the 
threshold level will be released for use in clinical studies.  An additional purification step 
will be applied to the ‘second generation’ drug product and thus it will not contain 
detectable levels of CHO galectins.  Second generation drug will be implemented in 
2022.  
1.2.2 
Galactose--1,3-galactose (α‑Gal)  
As part of the extended physicochemical characterization, the analysis of N-linked glycan 
profiles has shown the presence of galactose-α-1,3-galactose (‑Gal) at low levels in both 
1st and 2nd generation PRM‑151. The highest level of -Gal observed was 0.3% in 1st 
generation batches. For 2nd generation PRM-151, levels  3% of ‑Gal have been 
observed. 
The Sponsor conducted an assessment of safety regarding the ‑Gal glycan and 
concluded that PRM‑151 containing ‑Gal at the levels found is suitable for use in 


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clinical studies with the benefit-risk ratio remaining favorable. More information on the 
presence of α-Gal is provided in the PRM-151 Investigator’s Brochure (IB).  
1.3 
STUDY RATIONALE AND BENEFIT-RISK ASSESSMENT 
Study WA42294 is a Phase III open-label extension (OLE) study to assess the long-term 
safety, efficacy, and pharmacokinetics of PRM-151 in patients with IPF with or without 
concurrent treatment with pirfenidone or nintedanib.  Patients with IPF who have already 
completed the Phase II 28-week placebo-controlled period (PRM-151-202) and taken 
part in the OLE (Cohort A); or completed the Phase III Study WA42293 will be eligible to 
enroll in this study (Cohort B).  Additionally, patients who have discontinued treatment or 
completed the Phase III Study WA42293, and do not wish to receive open-label 
PRM-151 in this study will be followed-up for survival (Cohort C).  No safety or efficacy 
assessments will be required for these patients. 
This open-label design will allow an examination of the impact of longer treatment 
duration on safety, durability of response in lung function, exercise tolerance, and patient 
reported outcomes as well as pharmacokinetics of PRM-151. 
1.3.1 
BenefitRisk Assessment 
PRM-151, a recombinant form of an endogenous human protein, was generally well 
tolerated in nonclinical toxicity studies and in Phase I and II clinical studies.  Clinically 
and statistically significant positive effects with PRM-151 were observed in the Phase II 
IPF Study PRM-151-202, both for change in FVC (% predicted) and 6MWD through 
28 weeks of treatment.  Based on encouraging Phase I and II data in patients with IPF, 
PRM-151 has the potential to be a well-tolerated, disease modifying treatment for 
a broad spectrum of fibrotic diseases, including IPF. 
In the Phase II study (n116), PRM-151 was generally well tolerated through at least 
6 months of treatment as evidenced by the following: 
 
None of the serious adverse events (SAEs) reported during the study were 
considered related to the study treatment. 
 
Treatment-emergent adverse events (TEAE; serious and non-serious) leading to 
temporary discontinuation of study treatment were more common in the PRM-151 
group than the placebo group overall (6 patients [7.8%] and 1 patient [2.6%], 
respectively), but these events were distributed across a range of body systems with 
no single preferred term reported in more than 1 patient and did not appear to 
indicate a safety risk for PRM-151. 
 
The most common adverse event (AE) assessed as possibly or probably related to 
study treatment was fatigue (16 events in 9 patients from the PRM-151 group 
[11.7%] and 3 events in 3 patients from the placebo group [7.7%]). 
 
Adverse events of cough with possible or probable relationship to study treatment 
were reported in 7 patients from the PRM-151 group (9.1%; seven events).  No 


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patient from the placebo group was reported with possibly or probably related cough 
AEs.  
 
Four infusion-related reactions (IRRs) occurred in 3 patients: 2 patients in the 
PRM-151 group (2.6%), and 1 patient in the placebo group (2.6%).  One patient in 
the PRM-151 group experienced dizziness and another experienced a hypertensive 
crisis event; 1 patient in the placebo group experienced 2 hypertensive crisis events.  
There was no difference between treatment arms in the nature or frequency of 
IRRs.  None of the IRR events were deemed serious.  There were no IRR events 
among the 7 patients with anti-drug antibodies (ADAs [6 patients in the PRM-151 
group; 1 patient in the placebo group]) through Week 28. 
 
Risks associated with PRM-151 are inherent in it being the recombinant form of 
a naturally occurring human protein and consist of potential development of ADA and 
infusion reactions.  PRM-151 has an endogenous counterpart; therefore, ADAs could 
develop that could potentially affect the efficacy of PRM-151 treatments in addition to 
having the potential to cross-react with endogenous hPTX-2. 
PRM-151 is not a general immunosuppressant, and treatment with PRM-151 is not 
expected to increase rates of infection or adversely affect wound healing.  Individuals 
who have chronic medical issues may be at higher risk for serious illness from 
COVID-19, including those with pulmonary fibrosis.  However as stated above, it is not 
anticipated that PRM-151 will increase the risk of infection with SARS-CoV-2, nor the 
severity of infection.  Based on the mechanism of action of PRM-151, a possible 
interaction between PRM-151 treatment and COVID-19 vaccination is not expected.  For 
patients enrolling in this study and receiving PRM-151 treatment, a decision to 
administer the vaccine to a patient should be made on an individual basis by the 
investigator in consultation with the patient.  When administered, COVID-19 vaccines 
must be given in accordance with the approved or authorized vaccine label.  Receipt of 
the COVID-19 vaccine is considered a concomitant medication and should be 
documented as such (see Section 4.4.1). 
As with any protein therapeutic, the potential for reactions exists and safety procedures 
will be implemented, including careful monitoring of patients during infusions and of 
infusion sites.  Appropriate personnel, medication, and other requirements for the 
treatment of potential infusion reactions will be required by the protocol. 
PRM-151 is an investigational agent and the potential benefits of PRM-151 as a therapy 
for IPF remain to be proven in clinical efficacy studies. 
1.3.2 
Risks Associated with Radiologic Imaging 
The high-resolution computed tomography (HRCT) scans performed for this study will 
involve the delivery of small amounts of radiation to the patient.  The amount of radiation 
received has a low risk of harmful effects, and evaluation of IPF with HRCT is typical in 
clinical practice to monitor disease or response to therapy.  The protocol's radiation dose 


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is "as low as reasonably achievable" to obtain the quality of images necessary for 
imaging of lung abnormalities and quantification by image analysis software. 
The main potential risk from exposure to radiation is cancer.  The relative risk of 
developing adverse effects from radiation, such as future development of 
radiation-induced malignancy, is exceedingly small compared to the risk of mortality 
inherent to IPF.  From currently available data, the U.S. Nuclear Regulatory Commission 
has adopted a risk value for an occupational dose of one rem (0.01 Sieverts) Total 
Effective Dose Equivalent (TEDE) of approximately one chance in 2500 of fatal cancer 
per rem of TEDE received.  For this protocol, the dose will vary, depending on the 
specific HRCT scanner technology available at each site, but the volumetric HRCT dose 
index is estimated to be less than 10 milliGray with effective dose for a standard patient 
of less than 3 milliSieverts (0.003 Sieverts) per scan.  The dose will be adjusted 
appropriately to assure consistent image quality, based on patient size.  No populations 
at potentially higher risk for radiation exposure such as young children or pregnant 
women will be involved in the study.  Only patients enrolled in Cohort B, who had HRCT 
at screening and Week 52 in Study WA42293, will have further HRCT imaging at 
Week 52 and Week 104 during this extension study. 
2. 
OBJECTIVES AND ENDPOINTS 
This study will evaluate the long-term safety, efficacy, and pharmacokinetics of 
openlabel- PRM-151 in patients with IPF.  Specific objectives and corresponding 
endpoints for the study are outlined below. 
2.1 
SAFETY OBJECTIVE 
The safety objective for this study is to confirm the long-term safety and tolerability of 
10 mg/kg of PRM-151 administered every 4 weeks (Q4W) via IV infusion plus 
standard-of-care (SOC) treatment, on the basis of the following endpoints: 
 
Incidence and severity of adverse events (AE), with severity determined according 
to the 5-point severity scale (National Cancer Institute Common Terminology 
Criteria for Adverse Events, Version 5.0 [NCI CTCAE, v.5.0]) 
 
Incidence and severity of IRRs and other AEs of special interest 
 
Proportion of patients permanently discontinuing study treatment due to AEs 
 
Change from baseline in targeted clinical laboratory test results 
 
2.2 
EFFICACY OBJECTIVES 
The efficacy objectives are to assess the long-term efficacy of 10 mg/kg PRM-151 plus 
SOC (excluding lung transplantation) administered Q4W via IV infusion on the basis of 
the following endpoints: 
 
Annual rate of change in FVC (mL) 
 
Annual rate of change in 6-minute walk distance (6MWD) 


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 
Annual rate of change in FVC% predicted 
 
Annual rate of change in DLCO 
 
Time to disease progression, defined as time to first occurrence of 10% absolute 
decline in % predicted FVC, 15% relative decline in 6MWD, or death 
 
Survival, as measured by all-cause mortality 
 
IPF-related mortality and respiratory-related mortality 
 
2.3 
EXPLORATORY EFFICACY OBJECTIVE 
Exploratory analyses may also be performed for additional measures and subgroups of 
interest including concurrent use of IPF treatment and geographic region on the basis of 
the following endpoints:   
 
Change from baseline in University of California, San Diego-Shortness of Breath 
Questionnaire (UCSD-SOBQ) 
 
Change from baseline in St. George Respiratory Questionnaire (SGRQ) Total Score 
 
Time to first respiratory-related hospitalizations (defined as non-elective 
hospitalizations due to any respiratory cause, including acute exacerbations of IPF, 
or suspected acute exacerbations of IPF 
 
Time to first acute exacerbation of IPF, or suspected acute exacerbation of IPF 
 
Details of all such analyses will be provided in the Statistical Analysis Plan (SAP).   
 
2.4 
PHARMACOKINETIC OBJECTIVES 
The pharmacokinetic (PK) objective for this study is to characterize pharmacokinetics of 
PRM-151 in patients with IPF (from Cohort A, and Cohort B, who are enrolled in the 
WA42293 study prior to 1 June 2022), on the basis of the following endpoint: 
 
Plasma concentrations of PRM-151 at specified timepoints 
 
The exploratory PK objectives are to evaluate the potential relationship between drug 
exposure and the efficacy and safety of PRM-151 on the basis of the following 
endpoints: 
 
Relationship between PK for PRM-151 and efficacy endpoints 
 
Relationship between PK for PRM-151 and safety endpoints 
 
2.5 
IMMUNOGENICITY OBJECTIVES 
The immunogenicity objective for this study is to evaluate the immune response to 
PRM-151 in patients with IPF (from Cohort A and Cohort B patients who enrolled into the 
WA42293 prior to 1 June 2022) on the basis of the following: 
 
Prevalence of ADAs at baseline and incidence of ADAs during the study 
 


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The exploratory immunogenicity objective for this study is to evaluate potential effects of 
ADAs on the basis of the following: 
 
Relationship between ADA status and efficacy, safety, or PK endpoints 
 
2.6 
BIOMARKER OBJECTIVE 
The exploratory biomarker objective for this study (from Cohort A and Cohort B) is to 
identify and/or evaluate biomarkers that can provide evidence of PRM-151 activity and 
the duration of that activity (i.e., pharmacodynamic biomarkers), are associated with 
acquired resistance to PRM-151, are associated with susceptibility to developing AEs or 
can lead to improved AE monitoring or investigation (i.e., safety biomarkers), or can 
increase the knowledge and understanding of disease biology and drug safety, on the 
basis of the following endpoint: 
 
Relationship between biomarkers in blood listed in Section 4.5.10 and safety, 
efficacy, PK, immunogenicity, or other biomarker endpoints 
 
2.7 
HEALTH STATUS UTILITY OBJECTIVE 
The exploratory health status utility objective for this study is to evaluate health status 
utility scores of patients treated with PRM-151 plus SOC on the basis of the following 
endpoint: 
 
Annual rate of change in EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) 
index-based, and visual analog scale (VAS) scores 
 
3. 
STUDY DESIGN 
3.1 
DESCRIPTION OF THE STUDY 
3.1.1 
Overall Study Design and Plan 
This OLE study is being conducted to confirm the long-term safety, efficacy, and 
pharmacokinetics of PRM-151 in the treatment of eligible patients with IPF who have 
taken part in Study PRM-151-202 and received the open-label study drug (Cohort A) or 
completed the Phase III Study WA42293 (Cohort B) with PRM-151.  Additionally, 
patients who have discontinued treatment from or have completed Study WA42293 and 
do not want to receive open-label PRM-151 in this study, will be invited to enroll in 
survival follow-up Cohort C.  Patients in Cohort C will not receive any treatment and will 
not undergo any safety or efficacy assessments during the study (see Figure 1 and 
Appendix 2).  Patients who discontinue treatment from Cohorts A and B will 
automatically transition to Cohort C for long-term follow-up, unless they withdraw 
consent from the study. 


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Figure 1 Cohort Allocation 
 
a 
Only Cohorts A and B receive active treatment 
Figure 2 presents an overview of the study design.  A schedule of activities is provided in 
Appendix 1. 
Figure 2 Study Schema 
 
IVintravenous; Q4Wevery 4 weeks. 
Patients meeting the eligibility criteria for the study will receive PRM-151 10 mg/kg Q4W.  
Throughout the study, patients will be monitored for safety by collection of AEs (both 
serious and non-serious) and by regular physical exam and safety laboratory 
assessments. 
Efficacy will be evaluated through assessment of functional capacity as measured by 
FVC, 6MWD, other pulmonary function tests (PFTs), and assessment of patients with 
respiratory events leading to hospitalizations, progression of disease, or acute IPF 
exacerbations. 
Patient reported outcomes (PRO) will be assessed using the SGRQ, UCSD-SOBQ, and 
EQ-5D-5L. 


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Dyspnea, fatigue, and blood oxygen saturation levels (SpO2) will be assessed based on 
measurements taken during the 6-minute walk test (6MWT).  Chest HRCT will be 
assessed for changes from Study WA42293 to Week 52 (OLE) and Week 104 (OLE), for 
patients in Cohort B who had a HRCT scan at Screening and Week 52 in Study 
WA42293.  Treated patients will be followed-up until the end of the study period, unless 
the patient withdraws consent for follow-up or death occurs. 
For all patients receiving anti-fibrotic therapy, the investigator should document the dose, 
frequency, and duration of the anti-fibrotic drug. 
During the study, patients may initiate pirfenidone or nintedanib, if determined to be 
clinically indicated by the investigator.  The Study Investigator is required to document 
the specific reason for introducing anti-fibrotic therapy in patients who started the study 
not on anti-fibrotic therapy. 
Approximately 600700 patients are expected to enroll in the study.  Patients will initially 
receive loading doses of either PRM-151 10 mg/kg IV infusion and/or placebo over 
5070 minutes on Days 1, 3, and 5, then one infusion of PRM-151 Q4W until the end of 
the study.  Patients previously on the placebo arm of Study WA42293 will receive 
PRM-151 in all three loading doses, whereas patients previously on the active treatment 
arm of Study WA42293 will receive PRM-151 for the first dose, followed by placebo 
doses at the 2nd and 3rd loading dose visit.  The loading doses will be blinded for 
Cohort B, to ensure that the blind in Study WA42293 is maintained for patients, site staff, 
and the Sponsor (see Figure 3). 
Figure 3 Initial Loading Doses for Cohorts A and B 
Patients entering Cohort A, from Study PRM-151-202 will have an eligibility visit prior to 


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commencing dosing.  The eligibility visit can occur on the same day as the dosing visit, if 
the patient is confirmed to be eligible for the study. 
Patients entering Cohort B, from Study WA42293 will have their end-of-WA42293-study 
visit at Week 52.  All assessments from the Week 52 WA42293 study visit must be 
completed prior to commencing dosing in the OLE study.  Ideally, patients will be 
enrolled into Cohort B on the same day as their Week 52 (Study WA42293) visit. 
Patients enrolling into Cohort C from Study WA42293 (e.g., those who do not wish to 
receive study treatment), or those who transition from Cohorts A and B, will be 
followed-up for the duration of this study, to collect their survival data. 
3.2 
END OF STUDY AND LENGTH OF STUDY 
The end of this study is defined as the date when the last patient, last visit (LPLV) 
occurs.  The end of the study is expected to occur by 31 December 2028.  This date 
may be subject to change, depending on the local commercial availability of PRM-151.  
Site discontinuation will occur upon commercial availability of PRM-151 in order for 
patients to transition off from this trial and onto commercially available PRM-151. 
In addition, the Sponsor may decide to terminate the study at any time. 
3.3 
RATIONALE FOR STUDY DESIGN 
3.3.1 
Rationale for PRM-151 Dose and Schedule 
Dose selection and dosing frequency in the PRM-151 trials are based on prior 
nonclinical and clinical data demonstrating favorable safety and efficacy at doses up to 
10 mg/kg IV. 
Most recent data from 111 patients enrolled in the 128-week open-label extension of 
Study PRM-151-202 have shown durability of effect of PRM-151 at 10 mg/kg Q4W up to 
76 weeks in patients randomized to the active arm.  Furthermore, patients in the placebo 
group crossing over to receive PRM-151 in the extension phase experienced a reduction 
in the rate of decline for FVC (% predicted) and FVC (mL) and no decline in 6MWD upon 
initiation of active therapy (Raghu et al. 2019).  Every 28 weeks, patients in this study 
received PRM-151 on Days 1, 3, and 5. 
The dose for this open-label extension study of PRM-151 is a continuation of the dose 
used in the previous Phase II and III trials of PRM-151 in IPF. 
PRM-151 will be administered at 10 mg/kg on Days 1, 3, and 5 followed by Q4W 
administration thereafter. 
Loading Dose 
Patients with IPF have increased fibrocyte numbers in circulation, and decreased levels 
of circulating PTX-2.  PRM-151 mediates its activity by coupling recognition of DAMPs 


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within injured tissue to specific phagocytosis through FcγR on monocytes.  Loading 
doses were instituted in the nonclinical models to ensure that levels of PTX-2 would 
increase in the fibrotic tissue space within the lungs, to increase the likelihood that all 
local monocyte/macrophage lineage cells would be polarized to the pro-resolutive state. 
Phase-I, multiple-ascending dose, Study PRM151F-12GL showed that administration of 
510 mg/kg in humans increased circulating levels of PTX-2 by 58 fold.  This data 
suggested that a dosing regimen that includes a loading dose, may have persistent 
positive biologic effects up to 42 days after the last administration.  
Loading doses of PRM-151 on Days 1, 3, and 5, were administered in 
Study PRM-151-202, and repeat loading doses were administered in the 128-week 
open-label extension (PRM-151-202) every 28 weeks. 
Given the longer duration of this proposed study, it is expected that there may be 
occasional dose interruptions.  Repeat loading of PRM-151 will be required on the 
resumption of study treatment at Days 1, 3, and 5 if any dose of study drug is missed 
(see Section 4.3.2).  This is to ensure adequate tissue exposure of PRM-151, given the 
estimated tissue half-life of PTX-2 (2430 days, see the PRM-151 Investigator’s 
Brochure for further detail). 
3.3.2 
Rationale for the Study Design 
Enrolling patients from both Study PRM-151-202 and pivotal Study WA42293 provides 
a larger sample size of patients treated with PRM-151, in order to assess long-term 
safety and efficacy of PRM-151, as well as survival data.  This study will be open-label, 
as all patients enrolling into Cohorts A and B will receive active treatment with PRM-151.  
However, for Cohort B patients, the initial loading doses will be blinded, to maintain the 
integrity of the blind in the placebo-controlled study (Study WA42293).  Following this, 
the remainder of the study treatments will be administered in an unblinded fashion, as 
will all treatments administered to patients in Cohort A. 
FVC (mL) has been selected as a main efficacy outcome measure based on the 
common clinical use of this reproducible measure to monitor disease.  Continuous 
assessment of FVC over a longer period of time will help determine the possible 
long-term effect of PRM-151 in the preservation of lung function in these patients. 
In addition to the advantages of being easy to measure and highly reproducible, FVC is 
considered to be clinically reflective of the burden of the IPF disease process (Nathan 
and Meyer 2014; Saketkoo et al. 2014).  FVC outcomes have been associated with 
subsequent survival, as declines in FVC have been shown to correlate with increased 
risk of mortality (Collard et al. 2003; Saketkoo et al. 2014). 
The 6MWD is a valid and responsive clinical endpoint, which provides objective and 
clinically meaningful information regarding functional status and near-term prognosis 


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(Nathan et al. 2015).  A difference of 2445 meters has been reported as clinically 
important in the IPF population (du Bois et al. 2011; Verma et al. 2011; Nathan et al. 
2013).  A change of 1430.5 meters has been found to be clinically important across 
multiple patient groups (Bohannon and Crouch 2016), and the 6MWT was found to be 
associated with health-related quality of life measures in patients with IPF, representing 
a meaningful outcome for patients (Verma et al. 2011).  Furthermore, a decline of more 
than 25 meters has been independently associated with 1-year all-cause mortality in IPF 
(Swigris et al. 2010; du Bois et al. 2014; Brown and Nathan 2017). 
The data from Study PRM-151-202 (Raghu et al. 2018) have demonstrated stabilization 
of the decline in 6MWD in the group receiving PRM-151 with a placebo-corrected 
treatment effect of 31.3 meters.  A continuous assessment of this endpoint in the 
current long-term OLE study will help understand the effect of PRM-151 on exercise 
tolerance in patients with IPF. 
3.3.3 
Rationale for Collection of Survival Data in Cohort C 
Patients with IPF have a very poor prognosis despite the availability of pirfendone and 
nintedanib.  Median survival remains low, between 25 years (Jo et al. 2018).  IPF is the 
primary cause of death for 60% of patients with IPF, with death commonly occurring 
after an acute exacerbation of the disease.  When an acute exacerbation of IPF is not 
the cause of death, other common causes include acute coronary syndromes, 
congestive heart failure, lung cancer, infection, and venous thromboembolic disease 
(Frankel and Schwarz 2009). 
For patients who are unable or unwilling to continue with study treatment and/or 
assessments, the Sponsor will continue to collect their survival data unless patients 
withdraw consent to do so. 
3.3.4 
Rationale for Biomarker Assessments 
Exploratory biomarker samples will be collected from Cohort A and B during the study 
and may be used to assess PRM-151 pharmacodynamics and the relationship between 
IPF-related biomarkers, disease progression, and clinical status. 
4. 
MATERIALS AND METHODS 
4.1 
PATIENTS 
4.1.1 
Inclusion Criteria 
Approximately 600700 patients with IPF will be enrolled in this study. 
Patients must meet the following criteria for study entry: 
 
Signed Informed Consent Form 
 
In the opinion of the Principle Investigator, participation in the study is in the best 
interest of the patient 


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 
Ability to comply with the requirements of the study protocol, according to the 
investigator’s best judgment 
 
Taken part in a previous study of PRM-151, as follows: 
o Participated in Study PRM-151-202 (completed the 28-week 
placebo-controlled period and entered the OLE), and tolerated the study 
drug in the opinion of the investigator (Cohort A) OR 
o Completed study treatment in Study WA42293 (Cohort B) OR 
o Participated in Study WA42293 but have discontinued from 
study treatment (Cohort C; patients who completed treatment in 
Study WA42293, but no longer wish to take PRM-151 may also join 
Cohort C)  
 
For women of childbearing potential:  agreement to remain abstinent (refrain from 
heterosexual intercourse) or use contraception, as defined below: 
Women must remain abstinent or use contraceptive methods with a failure rate of 
1% per year during the treatment period and for 8 weeks after the final dose of 
PRM-151. 
A woman is considered to be of childbearing potential if she is postmenarchal, has 
not reached a postmenopausal state (12 continuous months of amenorrhea with 
no identified cause other than menopause), and is not permanently infertile due to 
surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as 
determined by the investigator (e.g., Müllerian agenesis).  The definition of 
childbearing potential may be adapted for alignment with local guidelines or 
regulations. 
Examples of contraceptive methods with a failure rate of 1% per year include 
bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit 
ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. 
Hormonal contraceptive methods must be supplemented by a barrier method. 
The reliability of sexual abstinence should be evaluated in relation to the duration of 
the clinical trial and the preferred and usual lifestyle of the patient.  Periodic 
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and 
withdrawal are not adequate methods of contraception.  If required per local 
guidelines or regulations, locally recognized adequate methods of contraception and 
information about the reliability of abstinence will be described in the local Informed 
Consent Form. 
 
For men:  agreement to remain abstinent (refrain from heterosexual intercourse) or 
use a condom, and agreement to refrain from donating sperm, as defined below: 
With a female partner of childbearing potential or pregnant female partner, men 
must remain abstinent or use a condom during the treatment period and for 8 weeks 
after the final dose of PRM-151 to avoid exposing the embryo.  Men must refrain 
from donating sperm during this same period. 
The reliability of sexual abstinence should be evaluated in relation to the duration of 
the clinical trial and the preferred and usual lifestyle of the patient.  Periodic 


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abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and 
withdrawal are not adequate methods of preventing drug exposure.  If required per 
local guidelines or regulations, information about the reliability of abstinence will be 
described in the local Informed Consent Form. 
 
4.1.2 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from study entry: 
 
Received any experimental treatment other than PRM-151 within 4 weeks or 
five half-lives of the experimental drug, whichever is longer, prior to the first dose in 
the OLE study. 
 
Receiving strong inhibitor or inducer of CYP1A2 in patients taking pirfenidone 
 
Receiving potent inhibitor or inducer of P-gp in patients taking nintedanib. 
 
Acute respiratory or systemic bacterial, viral, or fungal infection at the first visit of the 
OLE, or within 2 weeks of the first visit for patients joining Cohort A (from 
Study PRM-151-202). 
 
History of smoking (including cigarette, cannabis, cigar, pipe, and vaping) within 
3 months prior to the first visit in the OLE. 
 
History of alcohol or substance use disorder within 2 years prior to the first visit of 
the OLE or known or suspected active alcohol or substance-use disorder. 
 
History of severe allergic reaction or anaphylactic reaction to PRM-151. 
 
Clinically significant abnormality on ECG during eligibility assessment that, in the 
opinion of the investigator, may pose an additional risk in administering study drug 
to the patient  
 
Prolonged corrected QT  interval  450 ms (for men) or  470 ms (for women) based 
on the Fridericia correction formula. 
 
Clinically significant laboratory test abnormalities (hematology, serum chemistry, 
and urinalysis) that, in the opinion of the investigator, may pose an additional risk in 
administering study drug to the patient. 
 
Any of the following laboratory abnormalities known at the time of the first visit 
– 
ALT and/or AST 2.5upper limit of normal (ULN)  
– 
Total bilirubin 2ULN  
 
Pregnant or breastfeeding, or intending to become pregnant during the study (for 
Cohort A or B patients). 
 
4.2 
METHOD OF TREATMENT ASSIGNMENT AND BLINDING 
4.2.1 
Treatment Assignment 
In this study all patients in Cohorts A and B will receive PRM-151. 
Patients enrolling in Cohort A will receive three loading doses of open-label PRM-151 on 
Days 1, 3, and 5, followed by Q4W infusions. 


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For patients enrolling in Cohort B: 
 
Patients previously randomized to placebo in Study WA42293 will receive three 
loading doses on Days 1, 3, and 5 in a blinded fashion.  All three doses will contain 
PRM-151. 
 
Patients previously randomized to PRM-151 in Study WA42293 will receive three 
loading doses on Days 1, 3, and 5 in a blinded fashion.  First of the three doses will 
contain PRM-151, whereas the subsequent two doses will contain placebo. 
 
In order to maintain the blind to the treatment assignment of Study WA42293, all 
patients in Cohort B will be dosed in a blinded fashion on Days 1, 3, and 5 of the 
initial loading dose (see Figure 3). 
 
If the first loading dose in patients in Cohort B is delayed and occurs more than 3 weeks 
(21 days) after the Week 52 visit in Study WA42293, patients will receive all three 
loading doses with PRM-151 (in a blinded fashion). 
To minimize bias in this study, patients and the evaluating physicians will be blinded to 
treatment assignment of Study WA42293 until all patients have either completed the 
study or discontinued early from the study, the Study WA42293 database is locked, and 
the Study WA42293 analyses are final. 
4.3 
STUDY TREATMENT AND OTHER TREATMENTS RELEVANT 
TO THE STUDY DESIGN 
The investigational medicinal product (IMP) for this study is PRM-151.  Placebo is also 
considered an IMP in this study.  The non-investigational medicinal products (NIMPs) for 
this study are pirfenidone and nintedanib.  The NIMPs are considered background 
therapy for those patients already receiving either product when entering the trial and 
rescue therapy for any patient who commences treatment with either product during the 
trial. 
4.3.1 
Study Treatment Formulation and Packaging 
4.3.1.1 
PRM-151 (Zinpentraxin Alfa) 
PRM-151 Sterile Solution for Infusion is a 20 mg/mL solution of PRM-151 in 10 mM 
sodium phosphate, 5% (weight/volume [w/v]) sorbitol, and 0.01% (w/v) polysorbate 20 
with a pH of 7.5.  PRM-151 is supplied as a sterile concentrate in single-use vials in 
clear borosilicate vials.  The solution is clear to opalescent and essentially particle free.  
Refer to the pharmacy manual for detailed instructions on drug preparation, storage, and 
administration. 
CHO Gal-1 and CHO Gal-3 were identified in the first generation PRM-151 drug product.  
No new safety risks or no evidence on impact of efficacy were identified.  An additional 
purification step will be applied to the ‘second generation’ drug product and thus it will 
not contain detectable levels of CHO galectins.  All patients will transition to second 
generation PRM-151 when made available in 2022. 


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4.3.1.2 
Placebo for Initial Loading Dose 
The placebo is a solution of 10 mM sodium phosphate, 5% (w/v) sorbitol, and 
0.01% (w/v) polysorbate 20 with a pH of 7.5, matched to PRM-151 in total volume. 
Refer to the pharmacy manual for detailed instructions on drug preparation, storage, and 
administration. 
4.3.2 
Study Treatment Dosage, Administration, and Compliance 
The treatment regimens are summarized in Section 3.1. 
Refer to the pharmacy manual for detailed instructions on drug preparation, storage, and 
administration. 
On all dosing days, where applicable, dosing will occur after all efficacy and pre-dose 
safety assessments scheduled for that visit are completed.  Patients will receive 
treatment on Study Days 1, 3, and 5, followed by infusions every 4 weeks (Q4W).  If any 
scheduled Q4W infusions are missed, repeat loading doses will be required at the next 
scheduled visit (three doses, administered on alternate days). 
Details on treatment administration (e.g., dose and timing) should be noted on the 
Study Drug Administration electronic Case Report Form (eCRF).  Cases of accidental 
overdose or medication error, along with any associated adverse events, should be 
reported as described in Section 5.4.5.12. 
Guidelines for dosage modification and treatment interruption or discontinuation for 
patients who experience adverse events are provided in Section 5.2. 
Patients will receive IV infusions of 10 mg/kg PRM-151 over 5070 minutes, with dose 
based on the patient’s weight recorded at each visit (for loading or reloading doses, 
weight taken at the clinic visit for the first dose can be applied to the second and third 
doses). 
Medical personnel authorized by the investigator will be responsible for the 
administration of study drug and for observation of each patient throughout the study.  
Patients should be observed for at least 1 hour post infusion to monitor for IRRs.  The 
investigator, or designee, should assess whether any elements of the Sampson criteria 
were met after every infusion, as outlined in Appendix 5. 
In the case of occurrence of signs and symptoms consistent with IRR, follow procedures 
and medication guidelines outlined in Section 5. 


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If the patient is not able to adhere to the dosing schedule of any doses, the study 
Medical Monitor should be contacted.  The dosing schedule includes the following: 
 
To allow for flexibility around weekends, holidays, etc., the loading dose visits may 
occur over a time span of up to 8 days, with a minimum of 1 full calendar day 
between administrations of doses (patients must not be dosed on consecutive 
days). 
 
Loading doses must be completed within an 8-day window.  If any loading doses are 
missed, or cannot be completed within the 8-day window, further doses must not be 
administered outside this period.  In such instances, the patient will be required to 
repeat the loading dose regimen at the next scheduled visit. 
 
If the patient does not receive the scheduled dose within the specified visit window 
for the Week 4 visit or beyond, a protocol deviation will be documented and the 
patient should be dosed as soon as possible within 3 weeks of the original 
scheduled visit. 
 
If the dose is delayed by 3 weeks beyond the original scheduled visit (within 
1 week of the next scheduled dosing visit) the delayed dose should not be 
administered.  This will be considered a “missed dose,” and dosing should resume 
with 3 loading doses at the next scheduled visit. 
 
After a missed or delayed dose, patients should keep following the dates on the 
original dosing schedule, and visit dates should not shift, unless otherwise directed 
by the investigator or study team (e.g., additional visits to allow for reloading of three 
doses will need to be scheduled). 
 
In exceptional situations and following consultation with the Medical Monitor, if patients 
cannot attend the study site for a scheduled infusion, administration of study drug may 
be permitted in other settings (e.g., at a different investigational site).  Patient safety 
must be prioritized when utilizing off-site procedures (e.g., ensuring staff are 
appropriately qualified to deliver the infusion, and are trained to monitor for and manage 
anaphylaxis and IRRs).  In such circumstances, infusion-related safety data, safety 
laboratory assessments, and PK/pharmacodynamics (PD) samples may also be 
collected off-site. 
4.3.3 
Investigational Medicinal Product Handling and Accountability 
PRM-151 and placebo required for completion of this study will be provided by the 
Sponsor.  The study site (i.e., investigator or other authorized personnel 
[e.g., pharmacist]) is responsible for maintaining records of IMP delivery to the site, IMP 
inventory at the site, IMP use by each patient, and disposition or return of unused IMP, 
thus enabling reconciliation of all IMP received, and for ensuring that patients are 
provided with doses specified by the protocol. 
The study site should follow all instructions included with each shipment of IMP.  The 
study site will acknowledge receipt of IMPs supplied by the Sponsor, using the 
interactive voice or webbased- response system (IxRS), to confirm the shipment 


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condition and content.  Any damaged shipments will be replaced.  The investigator or 
designee must confirm that appropriate temperature conditions have been maintained 
during transit for all IMPs received and that any discrepancies have been reported and 
resolved before use of the IMPs.  All IMPs must be stored in a secure, environmentally 
controlled, and monitored (manual or automated) area in accordance with the labeled 
storage conditions, with access limited to the investigator and authorized staff. 
Only patients enrolled in the study may receive IMPs, and only authorized staff may 
supply or administer IMPs. 
IMPs will either be disposed of at the study site according to the study site's institutional 
standard operating procedure or be returned to the Sponsor with the appropriate 
documentation.  The site's method of destroying Sponsor-supplied IMPs must be agreed 
to by the Sponsor.  The site must obtain written authorization from the Sponsor before 
any Sponsor-supplied IMP is destroyed, and IMP destruction must be documented on 
the appropriate form. 
Accurate records of all IMPs received at, dispensed from, returned to, and disposed of 
by the study site should be recorded on the drug accountability log. 
Refer to the pharmacy manual and/or the PRM-151 Investigator's Brochure for 
information on IMP handling, including preparation and storage, and accountability. 
4.3.4 
Continued Access to PRM-151 
The sponsor will terminate the trial by 31 December 2028.  This date may be subject to 
change, depending on the local commercial availability of PRM-151.  Currently, the 
Sponsor does not have any plans to provide PRM-151 to patients who have completed 
the study.  The Sponsor may evaluate whether to continue providing PRM-151 in 
accordance with the Roche Global Policy on Continued Access to Investigational 
Medicinal Product is available at the following website: 
http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf 
4.4 
CONCOMITANT THERAPY 
Concomitant therapy consists of any medication (e.g., prescription drugs, 
over-the-counter drugs, vaccines, herbal or homeopathic remedies, nutritional 
supplements) used by a patient in addition to protocol-mandated treatment from the day 
of initiation of study drug to the study completion or discontinuation visit.  All such 
medications should be reported to the investigator and recorded on the Concomitant 
Medications eCRF.  Additionally, all COVID-19 vaccines received will be recorded on the 
Concomitant Medications eCRF. 
All past anti-fibrotic therapy will be recorded in the Prior and Concurrent Anti-fibrotic Use 
form of the eCRF.   


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4.4.1 
Permitted Therapy 
There are no restrictions on the use of any concomitant medication required for the 
treatment of an emerging medical condition (AE) while a patient is enrolled in the trial.  In 
such cases, all available therapies should be provided for the optimal medical 
management of the patient, including use of systemic corticosteroids in the event of 
acute exacerbation of IPF, if deemed indicated by the treating physician.  For guidance 
on the use of pirfenidone or nintedanib, see Section 4.4.3.  Additionally, use of the 
following medications as part of routine care is allowed: 
 
Chronic maintenance, low-dose oral corticosteroid use (equivalent to prednisone 
10 mg daily) is permitted. Short-term, higher doses of corticosteroid may be 
required for acute medical emergencies (for example, adrenal insufficiency, or acute 
exacerbations of IPF) and is permitted, along with subsequent corticosteroid dose 
tapering.  Reasons for corticosteroid use should be clearly documented in the 
eCRF.  
 
Inhaled bronchodilator agents, except for restricted use in the 1224 hour period 
preceding efficacy assessment measures (see Section 4.5.6). 
 
Initiation of or change in supplemental oxygen therapy as clinically indicated, except 
when performing the 6MWT, when oxygen usage should be maintained at the 
baseline oxygen flow rate established by the oxygen titration procedure (see 
Section 4.5.7) 
 
Approved vaccinations, including COVID-19 vaccinations. 
 
4.4.2 
Prohibited Therapy 
To avoid potential interactions of therapeutic agents that may interfere with either safety 
or efficacy assessments, use of the following medications are prohibited during the study 
for patients in Cohorts A and B: 
 
All investigational therapies, within 4 weeks (or 5 half-lives, whichever is longer) 
before screening and during study participation 
 
Any newly approved anti-fibrotic therapy that becomes available during the study 
 
Short-acting bronchodilator use within 4 hours before pulmonary function, DLCO, and 
6MWT assessments 
 
Once daily long-acting bronchodilators within 24 hours before pulmonary function 
testing, DLCO, and 6MWT assessments 
 
Twice daily long-acting bronchodilators within 12 hours before pulmonary function 
testing, DLCO, and 6MWT assessment 
 
Immune-suppressants (e.g., methotrexate, azathioprine, cyclophosphamide, 
cyclosporine, everolimus, or other immune-suppressants, including those used after 
organ transplant) within 4 weeks before baseline (Dosing Day 1) and during the 
study 
 
High-dose corticosteroids (equivalent to prednisone  10 mg daily) unless clinically 
indicated as per Section 4.4.1. 


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 
Strong inhibitors or inducers of CYP1A2 in patients taking pirfenidone 
 
Potent inhibitors or inducers of P-gp in patients taking nintedanib 
 
4.4.3 
Use of Pirfenidone or Nintedanib 
Standard of care anti-fibrotic therapy (pirfenidone or nintedanib) is permitted during the 
study if not contraindicated according to local prescribing information. 
For all patients receiving anti-fibrotic therapy, the investigator should document the dose 
and regimen of the anti-fibrotic drug.  For patients not receiving anti-fibrotic therapy 
during the study, the investigator should document the reason(s). 
All historic and current use, including changes in pirfenidone or nintedanib doses and 
reasons for change must be recorded in the eCRF: 
 
Patients are expected to remain on their specific dose and regimen of nintedanib or 
pirfenidone throughout the study duration, although a patient may stop, dose 
reduce, re-start, or dose increase nintedanib or pirfenidone treatment during the 
study for safety or tolerability reasons, in accordance with local prescribing 
information.  All reasons for dose changes must be documented in the eCRF. 
 
In addition, patients may switch from nintedanib to pirfenidone (or vice versa) during 
the study if clinically indicated, and if not contraindicated according to local 
prescribing information. 
 
If not on nintedanib or pirfenidone treatment for IPF at study entry, patients may 
initiate (naive users) or re-start (prior users) nintedanib or pirfenidone, as rescue, if 
determined to be clinically indicated by the investigator providing there are no 
contraindications according to local prescribing information.  The investigator may 
consider discussing changes in anti-fibrotic therapy with the Medical 
Monitor throughout the study.  Patients who start rescue therapy will be encouraged 
to remain in the study and continue study treatment. 
 
4.5 
STUDY ASSESSMENTS 
The schedule of activities to be performed during the study is provided in Appendix 1, 
Appendix 2, Appendix 3, and Appendix 4.  All activities should be performed and 
documented for each patient. 
Patients will be closely monitored for safety and tolerability throughout the study.  
Patients should be assessed for toxicity prior to each dose; dosing will occur only if the 
clinical assessment and laboratory test values from the previous visit are acceptable. 
4.5.1 
Informed Consent Forms and Eligibility Assessments 
Written informed consent for participation in the study must be obtained before 
performing any study-related procedures.  Informed Consent Forms for enrolled patients 
and for patients who are not subsequently enrolled will be maintained at the study site. 


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All eligibility criteria should be confirmed before enrollment.  Patients who are enrolling in 
the trial from Study PRM-151-202 should be assessed for eligibility against the study 
entrance criteria (Section 4.1).  For these patients, screening assessments may be 
performed during an eligibility assessment visit prior to the first dosing visit in order to 
have time to get the laboratory results back from the central lab.  Patients from 
Study WA42293 who enroll in the OLE study after a gap of 4 weeks or more should have 
their laboratory and safety assessments repeated prior to the first dose to confirm their 
eligibility. 
4.5.2 
Sequence of Assessments 
On dosing days, dosing will occur after all safety and efficacy assessments scheduled 
for that visit are complete.  When applicable, assessments should be completed as 
shown in Table 1.  For loading or reloading doses, scheduled efficacy assessments will 
only be performed on the first of the three loading dose days, if applicable. 
 
 


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Table 1 
Sequence of Assessments 
Sequence 
Assessments 
1 
 
Patient-reported outcomes (PRO) (in following order): 
– 
SGRQ 
– 
UCSD-SOBQ 
– 
EQ-5D-5L 
2 
 
Medical history, review of concomitant medications, vital signs, 
physical examination, and ECG  
3 
 
Pulmonary function tests (in following order): 
– 
Spirometry 
– 
DLCO 
3060 minute break 
– 
6MWT 
4 
 
HRCT (when completed on same day as other assessments) a 
5 
 
Laboratory samples 
6 
 
Study drug administration b 
6MWT6-minute walk test; DLCO diffusing capacity for carbon monoxide; 
eCRFelectronic Case Report Form; EQ-5D-5LEuroQol 5-Dimension, 5-Level 
Questionnaire; HRCThigh-resolution computed tomography; OLEopen-label 
extension; SGRQSt. George Respiratory Questionnaire; UCSD-SOBQUniversity of 
California, San DiegoShortness of Breath Questionnaire. 
a In order to allow flexibility in scheduling, the HRCT can be performed at an earlier 
time on a different day.   
b In exceptional circumstances, if the site is unable to perform all study procedures on 
the same day or at the same site, study drug infusion may be administered up to 
48 hours after the on-site efficacy assessments, providing that these are completed 
within the 5-day visit window.  However, the sequence of procedures must be 
maintained, and all efforts should be made to complete study assessments and 
procedures on the same date. 
 
4.5.3 
Medical History, Baseline Conditions, Concomitant Medication, 
and Demographic Data 
The following data will be collected for patients who have enrolled in the study after 
a gap following the PRM-151 Study PRM-151-202.  Data from Study WA42293 will be 
transferred to the OLE database that will include: 
 
Medical history:  number of years since IPF diagnosis, family history of IPF, clinically 
significant diseases, surgeries, cancer history (including prior cancer therapies and 
procedures), reproductive status, smoking history, and alcohol and substance use, 
that occurred prior to time of first dose of study drug should be reported as medical 
history, including: 
– 
Pulmonary hypertension 
– 
Chronic obstructive pulmonary disease (COPD)/Emphysema 


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– 
Lung cancer 
– 
Obstructive sleep apnea 
– 
Pulmonary embolism 
– 
Respiratory infections 
– 
Cardiovascular disease and risk factors, including arrhythmias, cardiac failure 
or congestive heart failure, ischemic heart disease, cerebrovascular disease 
and stroke, peripheral artery disease, systemic arterial hypertension, and 
hypercholesterolemia/hyperlipidemia, 
– 
Participation in supervised pulmonary or cardiac rehabilitation programs 
– 
Past surgical history 
 
Adverse events that are ongoing from Study WA42293. 
 
All medications (e.g., prescription drugs, over-the-counter drugs, vaccines, herbal or 
homeopathic remedies, nutritional supplements) used by the patient from the day of 
initiation of study treatment will be recorded.  For patients from Study PRM-151-202, 
medications used from 30 days prior to the initiation of study treatment will be recorded 
on the eCRF.  At the time of each follow-up physical examination, an interval medical 
history should be obtained and any changes in medications and allergies should be 
recorded.  History of anti-fibrotic therapy should also be documented since IPF was 
diagnosed (i.e., pirfenidone, nintedanib treatment; dose, duration of therapy, and 
reasons for discontinuation, if applicable).  Additionally, history of all COVID-19 
vaccinations received should be documented. 
Patient demographic information including age, sex, and self-reported race/ethnicity will 
be recorded for all patients, where allowed per local regulations. 
4.5.4 
Physical Examinations 
A complete physical examination should be performed for Cohort A patients at the 
eligibility assessment visit.  This should include an evaluation of the head, eyes, ears, 
nose, and throat, and the cardiovascular, dermatologic, musculoskeletal, respiratory, 
gastrointestinal, and neurologic systems.  Any abnormality identified at baseline should 
be recorded on the General Medical History and Baseline Conditions eCRF. 
Limited, symptom-directed physical examinations should be performed for all patients at 
specified visits and as clinically indicated.  New or worsened clinically significant 
abnormalities should be recorded as adverse events on the Adverse Event eCRF. 
Height will be recorded at eligibility assessment visit for Cohort A.  Weight will be 
recorded at each dosing visit (except for the second and third loading doses). 


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4.5.5 
Vital Signs 
Vital signs will include measurements of respiratory rate, pulse rate, systolic and 
diastolic blood pressure while the patient is in a seated position, oxygen saturation, and 
temperature.  Record abnormalities observed at baseline on the General Medical History 
and Baseline Conditions eCRF.  At subsequent visits, record new or worsened clinically 
significant abnormalities on the Adverse Event eCRF. 
At dosing visits, vital signs should be measured predose (within 60 minutes prior to 
dosing), every 15 minutes during the infusion, and 30-60 minutes postdose. 
4.5.6 
Pulmonary Function Tests 
Standardized spirometry equipment and procedure guidelines will be provided to all 
study sites.  As some PFTs are considered to be aerosol generating procedures, 
additional precautions to reduce potential spread of infection should be taken in 
accordance with local guidance.  Spirometry will be performed according to ATS/ERS 
guidelines (as referenced in the PFT manual) as per the schedule of activities.  Details 
on PFT procedures are available in the PFT manual.  PFT data will be sent for central 
review. 
DLCO will be measured according to ATS/ERS guideline (as referenced in the PFT 
manual).  DLCO will be performed using local equipment as this will not be provided by 
the Sponsor to study sites. 
On visits at which spirometry and DLCO are to be performed spirometry should be 
performed first, followed by DLCO, and then 6MWT. 
Inhaled bronchodilator use in the 1224 hour period prior to PFTs and the 6MWT is 
restricted: 
 
Short-acting bronchodilator should not be used within 4 hours before pulmonary 
function, DLCO, and 6MWT assessments. 
 
Once daily long-acting bronchodilators should not be used within 24 hours before 
pulmonary function testing, DLCO, and 6MWT assessments. 
 
Twice daily long-acting bronchodilators should not be used within 12 hours before 
pulmonary function testing, DLCO, and 6MWT assessments. 
 
4.5.7 
Six-Minute Walk Test 
Conduct of the 6MWT will be carefully defined and controlled according to the criteria 
defined and validated by du Bois et al. (2011), with additional control measures 
suggested in the ERS/ATS Guideline for field walking tests (Holland et al. 2014). 
 
The test will be performed indoors on a flat, straight corridor with a hard surface at 
least 30 meters in length. 


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 
An oxygen titration procedure will be performed for patients in cohort A who require 
supplemental oxygen during the 6MWT (up to 6 L/min of oxygen at sea level, and 
up to 8 L/min at altitude [ 5000 ft]) to establish a baseline flow rate.  The oxygen 
titration procedure should be conducted per local standard practice.  Patients in 
Cohort B should maintain the same supplemental oxygen requirements as per 
study WA42293   
 
Before each 6MWT, patients will be required to have resting oxygen saturation as 
measured by pulse oximetry of at least 89% after 10 minutes of rest breathing room 
air, or at the baseline O2 flow rate as established during the titration procedure. 
 
Patients will be instructed to walk as far as they can without jogging or running; if 
they need to slow down or stop to rest they will be permitted to do so and 
encouraged to resume walking as soon as they are able. 
 
The test will be stopped if the patient experiences chest pain, intolerable dyspnea, 
leg cramps, diaphoresis, or desaturation below 83% for at least 10 seconds.  
 
The pre-test conditions for oxygen use will be maintained throughout the study as 
much as possible, as noted at the Day 1 visit prior to first dose. 
 
As previously described, the 6MWT assessment should be performed after PFTs, 
allowing for a short recovery period.  In the rare instance that it is not possible to 
complete the 6MWT last, allow a 3060 minute recovery time before continuing with the 
next efficacy assessment. 
A procedure manual and training video (video instructions) detailing the testing method 
recommended by the ATS and the European Respiratory Society (ATS 2002; Holland et 
al. 2014) for the 6MWT will be provided separately.  These materials will include detailed 
instructions for standardized execution of the 6MWT, and describe the equipment and 
personnel required to conduct the assessment as well as the testing methods. 
The Borg Scale of Perceived Exertion (Appendix 9) will be assessed just prior to and 
immediately following the completion of the 6MWT. 
4.5.8 
High-Resolution Computed Tomography 
Patients in Cohort B who had high-resolution computed tomography (HRCT) at 
screening and Week 52 in Study WA42293, will have further HRCT imaging at Week 52 
and Week 104 during this extension study. 
Patients in Cohort A and C, and patients in Cohort B who did not have any HRCT scans 
in Study WA42293, will not be required to have any imaging during this study. 
4.5.9 
Assessment of Acute Exacerbations of IPF, Hospitalizations 
for Respiratory Causes, and Deaths (Adjudication Events)  
An independent, blinded Clinical Adjudication Committee will be convened to review all 
available data for all potential cases of acute exacerbations of IPF, hospitalizations for 
respiratory causes, and all deaths (applicable for Cohorts A and B only).  This Clinical 


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Adjudication Committee will be comprised of pulmonary disease physicians familiar with 
IPF exacerbations.  A charter for the Clinical Adjudication Committee will provide further 
details.  The Clinical Adjudication Committee will determine if the reported events meet 
the criteria of acute exacerbation of IPF, hospitalization for respiratory causes, and 
deaths (including deaths related specifically to respiratory causes) as defined in the 
charter.  
4.5.9.1 
Acute Exacerbations of IPF and Suspected Acute 
Exacerbations of IPF 
Acute exacerbation of IPF is defined as an acute, clinically significant respiratory 
deterioration characterized by evidence of new widespread alveolar abnormality, marked 
by the following diagnostic criteria (Collard et al. 2016): 
 
Previous or concurrent diagnosis of IPF 
 
Acute worsening or development of dyspnea typically 30 days in duration 
 
Computed tomography with new bilateral ground-glass opacity and/or consolidation 
superimposed on a background pattern consistent with usual interstitial pneumonia 
pattern 
 
Deterioration not fully explained by cardiac failure or fluid overload 
 
Acute exacerbations of IPF are further categorized as triggered acute exacerbation or 
idiopathic acute exacerbation, depending on whether an underlying trigger for acute 
exacerbation is found (e.g., infection, post-procedural/postoperative, drug toxicity, 
aspiration). 
Events that are clinically considered to meet the definition of acute exacerbation of IPF 
but fail to meet all four diagnostic criteria owing to missing computed tomography data 
are termed “suspected acute exacerbations of IPF”. 
At each study visit, the investigator will ask directed questions and review the patient file 
to assess the possibility that the patient experienced an acute IPF exacerbation since 
the preceding study visit.  An acute IPF exacerbation should be reported as an AE of 
special interest (see Section 5.3.3) (or SAE as applicable). 
All relevant AE data (summary on clinical course, signs and symptoms; laboratory, lung 
function and imaging results; and treatment provided, including hospitalizations) relating 
to the exacerbation must be collected and entered onto the adverse event form.  
A charter for the Clinical Adjudication Committee describes the process for the data to 
be reviewed and criteria for defining an IPF exacerbation. 
4.5.9.2 
Hospitalizations for Respiratory Causes 
Hospitalizations for respiratory causes are defined as non-elective hospitalizations due 
to any respiratory cause, including acute exacerbations of IPF, or suspected acute 
exacerbations of IPF.  All investigator reported hospitalizations for respiratory causes will 


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be assessed by an independent Clinical Adjudication Committee, as described in the 
charter. 
4.5.9.3 
Deaths Due to Respiratory Causes 
All deaths occurring during the study must be recorded.  The event or condition that 
caused or contributed to the fatal outcome should be recorded as a single medical 
concept on the Adverse Event eCRF. 
All investigator-reported deaths that occur in Cohort A or B will be assessed by an 
independent Clinical Adjudication Committee to determine whether each death was 
related to IPF, another respiratory cause or an alternative (non-respiratory and non-IPF) 
cause.  Deaths occurring in Cohort C will not be adjudicated. 
4.5.9.4 
Health Care Utilization for Respiratory Events 
The following events will be recorded as health care utilization for respiratory events: 
 
Unscheduled visits to a healthcare professional/clinic for any respiratory event 
 
Urgent care or emergency room visits for respiratory events  
 
Hospitalization days for a respiratory cause, including for exacerbation of respiratory 
symptoms 
 
During hospitalization, any stay in ICU, including ICU days 
 
4.5.10 
Laboratory, Biomarker, and Other Biological Samples 
Samples for the following laboratory tests will be sent to one or several central 
laboratories for analysis: 
 
Hematology:  WBC count, RBC count, hemoglobin, hematocrit, platelet count, and 
differential count (lymphocytes, eosinophils, neutrophils, monocytes, basophils) 
 
Serum chemistries and liver function tests:  chloride, potassium, BUN, creatinine, 
albumin, AST, total bilirubin, sodium, bicarbonate (CO2), calcium, glucose, ALK, 
ALT, total protein, C-reactive protein, estimated glomerular filtration rate. 
 
Coagulation tests:  PT, PTT, INR 
 
Pregnancy test 
All women of childbearing potential will have a serum pregnancy test at eligibility 
assessment visit.  Urine pregnancy tests will be performed at specified 
subsequent visits.  If a urine pregnancy test is positive, it must be confirmed by 
a serum pregnancy test. 
 
Urinalysis, including dipstick (pH, specific gravity, glucose, protein, ketones, blood) 
and microscopic examination (sediment, RBCs, WBCs, casts, crystals, epithelial 
cells, bacteria) 
 
SARS-CoV-2 serology testing (IgM, IgG) 
 


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In exceptional situations, upon Sponsor approval, laboratory samples may be collected 
off-site.  The following samples will be sent to one or several central laboratories or to 
the Sponsor or a designee for analysis: 
 
Serum sample for ADA analysis 
 
Serum sample for tryptase and complement C3 in case of  Grade 2 IRRs or 
suspected anaphylaxis or hypersensitivity reactions 
 
PRM-151 plasma sample for PK analysis 
Blood samples for determination of PRM-151 concentration will be collected from 
all IPF patients enrolled in Cohort A (see Appendix 3) and Cohort B patients who 
enrolled into the WA42293 prior to 1 June 2022 (see Appendix 4) for PK 
measurements 
 
Plasma concentration (including but not limited to predose PK samples) to measure 
the endogenous level of human pentraxin-2 [hPTX-2] will be analyzed from IPF 
patients enrolled in Cohort A and Cohort B patients who enrolled into the WA42293 
prior to 1 June 2022. 
 
Serum and plasma samples for biomarker analysis will be collected from all IPF 
patients enrolled in both Cohort A (see Appendix 3) and Cohort B (see Appendix 4) 
for PD measurements.  
 
Blood PAXgene for RNA biomarker analysis will be collected from all patients with 
IPF enrolled in both Cohort A (see Appendix 3) and Cohort B (see Appendix 4) for 
PD measurements. 
 
Circulating blood biomarkers that may provide information on PRM-151 
pharmacodynamic activity or the course of fibrosis will be measured.  IPF-related 
biomarkers that will be investigated may include, but are not limited to, CCL18, 
osteopontin, CXCL13, periostin, and COMP.  Longitudinal samples will be used to 
assess biomarker changes over time.  If novel PTX-2 or IPF-related biomarkers are 
identified, they may be measured from stored blood, serum, or plasma. 
Eligibility blood samples, from patients in Study PRM-151-202 Cohort A who do not 
enroll in the study, may be used for future research and/or development of 
disease-related tests or tools. 
For sampling procedures, storage conditions, and shipment instructions, see the 
laboratory manual. 
Unless the patient gives specific consent for his or her leftover samples to be stored for 
optional exploratory research (see Section 4.5.13), biological samples will be destroyed 


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no later than the time of completion of the final Clinical Study Report, with the following 
exceptions: 
 
PK or immunogenicity analysis may be needed for additional immunogenicity 
characterization and for PK or immunogenicity assay development and validation.  
PK and ADA samples collected for study-related analyses will be stored for up to 
5 years after the final study results have been reported. 
 
Blood samples collected for biomarker research and biomarker assay development 
will be destroyed no later than 5 years after the final Clinical Study Report has been 
completed, unless the patient consents optionally to have leftover samples retained 
as part of the Roche Biosample Repository (see Section 4.5.13).  However, the 
storage period will be in accordance with the Institutional Review Board/Ethics 
Committee (IRB/EC)-approved Informed Consent Form and applicable laws 
(e.g., health authority requirements. 
 
When a patient withdraws from the study, samples collected prior to the date of 
withdrawal may still be analyzed, unless the patient specifically requests that the 
samples be destroyed or local laws require destruction of the samples.  However, if 
samples have been tested prior to withdrawal, results from those tests will remain as 
part of the overall research data. 
Data arising from sample analysis will be subject to the confidentiality standards 
described in Section 8.4. 
Given the complexity and exploratory nature of exploratory biomarker analyses, data 
derived from these analyses will generally not be provided to study investigators or 
patients unless required by law.  The aggregate results of any conducted research will 
be available in accordance with the effective Sponsor policy on study data publication. 
4.5.11 
Electrocardiograms 
ECG will be collected prior to study drug dosing at selected visits (see Appendix 1).  
Apart from the scheduled assessment, ECG may also be collected in the event of an 
IRR as soon as possible after stabilization of the patient. 
All ECG recordings must be performed using a standard high-quality, high-fidelity digital 
electrocardiograph machine equipped with computer-based interval measurements.  
ECGs for each patient should be obtained from the same machine whenever possible to 
minimize variability. Lead placement should be as consistent as possible.  ECG 
recordings must be performed after the patient has been resting in a supine position for 
at least 10 minutes.  Scheduled ECGs are to be obtained prior to other procedures 
scheduled at that same time (e.g., vital sign measurements, blood draws).  
Circumstances that may induce changes in heart rate, including environmental 
distractions (e.g., television, radio, conversation) should be avoided during the pre-ECG 
resting period and during ECG recording. For safety monitoring purposes, the 
investigator must review, sign, and date all ECG tracings. 


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Paper copies of ECG tracings will be kept as part of the patient's permanent study file at 
the site. De-identified copies of all ECGs will be electronically transmitted or mailed for 
storage centrally at a designated contract research organization (CRO). 
Clinically significant ECG abnormalities should be reported as adverse events. If 
considered appropriate by the Sponsor, ECGs may be analyzed retrospectively at 
a central laboratory. 
4.5.12 
Clinical Outcome Assessments 
PRO instruments will be completed to assess the treatment benefit and patient 
experience of PRM-151.  PRO data will be collected through use of the following 
instruments:  SGRQ, UCSD-SOBQ, and EQ-5D-5L (assessed in that order). 
4.5.12.1 
Data Collection Methods for Clinical Outcome Assessments 
PRO instruments will be self-administered at the clinic at specified timepoints during the 
study (see schedule of activities in Appendix 1).  At the clinic, instruments will be 
administered before the patient receives any information on disease status, prior to the 
performance of non‑PRO assessments, and prior to the administration of study 
treatment, unless otherwise specified. 
PRO instruments, translated into the local language as appropriate, will be completed 
through use of an electronic device provided by the Sponsor.  The device will be 
pre-programmed to enable the appropriate instruments to be administered in the correct 
order at each specified timepoint.  The electronic device and instructions for completing 
the instruments electronically will be provided by the site staff.  The data will be 
transmitted to a centralized database maintained by the electronic device vendor.  The 
data will be available for access by appropriate study personnel. 
During clinic visits, instruments should be administered as outlined below: 
 
Patients' health status should not be discussed prior to administration of the 
instruments. 
 
Sites must administer the official version of each instrument, as provided by the 
Sponsor.  Instruments must not be copied from the protocol. 
 
Sites should allow sufficient time for patients to complete the instruments. 
 
Sites should administer the instruments in a quiet area with minimal distractions and 
disruptions. 
 
Patients should be instructed to answer questions to the best of their ability; there 
are no right or wrong answers. 
 
Site staff should not interpret or explain questions, but may read questions verbatim 
upon request. 
 
Patients should not obtain advice or help from others (e.g., family members or 
friends) when completing the instruments. 
 


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4.5.12.2 
Description of Clinical Outcome Assessment Instruments 
St. George’s Respiratory Questionnaire 
The SGRQ is a 50-item respiratory-specific quality-of-life questionnaire initially 
developed and validated for use in COPD (Jones et al. 1992; see Appendix 6).  It 
includes questions that assess the impact of disease on symptoms, activity, and 
functionality.  The symptom scale assesses the severity of respiratory symptoms, the 
activity scale examines impairment in patient activity as a result of respiratory symptoms, 
and the impact scale evaluates effects of respiratory symptoms on overall function and 
well-being.  Each scale is scored from 0 to 100, and a total score represents the 
weighted average of these three subscores.  Items are assessed on various response 
scales, including a 5-point Likert scale and a true/false scale.  The SGRQ has a recall 
period of the past 4 weeks. 
University of California, San DiegoShortness of Breath Questionnaire 
The UCSD-SOBQ is a 24-item questionnaire used to assess dyspnea severity during 
specific activities (21 items) and limitations caused by dyspnea in daily life (4 items) (see 
Appendix 7). Items are assessed using a 6-point Likert scale and summed to produce 
a total score ranging from 0120, with higher scores reflecting greater dyspnea severity.  
Respondents are asked to provide their answers based on an average day during the 
past week. 
EuroQol 5-Dimension Questionnaire, 5-Level Version 
The EQ-5D-5L is a validated self-report health status questionnaire that is used to 
calculate a health status utility score for use in health economic analyses (EuroQol 
Group 1990; Brooks 1996; Herdman et al. 2011; Janssen et al. 2013) (see Appendix 8).  
There are two components to the EQ-5D-5L:  a five-item health state profile that 
assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as 
well as a VAS that measures health state.  The EQ-5D-5L is designed to capture the 
patient's current health status.  Published weighting systems allow for creation of 
a single composite score of the patient's health status. 
4.5.13 
Optional Samples for Research Biosample Repository 
4.5.13.1 
Overview of the Research Biosample Repository 
The Research Biosample Repository (RBR) is a centrally administered group of facilities 
used for the long-term storage of human biological specimens, including body fluids, 
solid tissues, and derivatives thereof (e.g., DNA, RNA, proteins, peptides).  The 
collection, storage, and analysis of RBR samples will facilitate the rational design of new 
pharmaceutical agents and the development of diagnostic tests, which may allow for 
individualized drug therapy for patients in the future. 
Samples for the RBR will be collected from patients who give specific consent to 
participate in this optional research.  RBR samples will be analyzed to achieve one or 
more of the following objectives: 
 
To study the association of biomarkers with efficacy or disease progression 


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 
To identify safety biomarkers that are associated with susceptibility to developing 
adverse events or can lead to improved adverse event monitoring or investigation 
 
To increase knowledge and understanding of disease biology and drug safety 
 
To study drug response, including drug effects and the processes of drug absorption 
and disposition 
 
To develop biomarker or diagnostic assays and establish the performance 
characteristics of these assays 
 
4.5.13.2 
Approval by the Institutional Review Board or Ethics 
Committee 
Collection, storage, and analysis of RBR samples is contingent upon the review and 
approval of the exploratory research and the RBR portion of the Informed Consent Form 
by each site's IRB/EC and, if applicable, an appropriate regulatory body.  If a site has not 
been granted approval for RBR sampling, this section of the protocol (Section 4.5.13) 
will not be applicable at that site. 
4.5.13.3 
Sample Collection 
The following samples will be stored in the RBR and used for research purposes, 
including, but not limited to, research on biomarkers related to PTX-2 or PRM-151, 
diseases, or drug safety: 
 
Urine samples collected as per Appendix 4. 
 
Leftover blood, serum, plasma and urine samples and any derivatives thereof 
(e.g., RNA, proteins, peptides) 
Data generated from RBR samples will be analyzed in the context of this study but may 
also be explored in aggregate with data from other studies.  The availability of a larger 
dataset will assist in identification and characterization of important biomarkers and 
pathways to support future drug development. 
For sampling procedures, storage conditions, and shipment instructions, see the 
laboratory manual. 
RBR samples are to be stored until they are no longer needed or until they are 
exhausted.  However, the RBR storage period will be in accordance with the 
IRB/EC-approved Informed Consent Form and applicable laws (e.g., health authority 
requirements). 
4.5.13.4 
Confidentiality 
RBR samples and associated data will be labeled with a unique patient identification 
number. 
Patient medical information associated with RBR samples is confidential and may be 
disclosed to third parties only as permitted by the Informed Consent Form (or separate 


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authorization for use and disclosure of personal health information) signed by the 
patient, unless permitted or required by law. 
Given the complexity and exploratory nature of the analyses of RBR samples, data 
derived from these analyses will generally not be provided to study investigators or 
patients unless required by law.  The aggregate results of any conducted research will 
be available in accordance with the effective Sponsor policy on study data publication. 
Data generated from RBR samples must be available for inspection upon request by 
representatives of national and local health authorities, and Sponsor monitors, 
representatives, and collaborators, as appropriate. 
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of the RBR data will become and remain the exclusive and unburdened property 
of the Sponsor, except where agreed otherwise. 
4.5.13.5 
Consent to Participate in the Research Biosample Repository 
The Informed Consent Form will contain a separate section that addresses participation 
in the RBR.  The investigator or authorized designee will explain to each patient the 
objectives, methods, and potential hazards of participation in the RBR.  Patients will be 
told that they are free to refuse to participate and may withdraw their consent at any time 
and for any reason during the storage period.  A separate, specific signature will be 
required to document a patient's agreement to provide optional RBR samples.  Patients 
who decline to participate will not provide a separate signature. 
The investigator should document whether or not the patient has given consent to 
participate and (if applicable) the date(s) of consent, by completing the RBR Research 
Sample Informed Consent eCRF. 
In the event of an RBR participant's death or loss of competence, the participant's 
samples and data will continue to be used as part of the RBR research. 
4.5.13.6 
Withdrawal from the Research Biosample Repository 
Patients who give consent to provide RBR samples have the right to withdraw their 
consent at any time for any reason.  After withdrawal of consent, any remaining samples 
will be destroyed.  However, if RBR samples have been tested prior to withdrawal of 
consent, results from those tests will remain as part of the overall research data.  If 
a patient wishes to withdraw consent to the testing of his or her RBR samples during the 
study, the investigator must inform the Medical Monitor in writing of the patient's wishes 
through use of the appropriate RBR Subject Withdrawal Form and must enter the date of 
withdrawal on the RBR Research Sample Withdrawal of Informed Consent eCRF.  If 
a patient wishes to withdraw consent to the testing of his or her RBR samples after 


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closure of the site, the investigator must inform the Sponsor by emailing the study 
number and patient number to the following email address: 
global_rcr-withdrawal@roche.com 
 
A patient's withdrawal from this study does not, by itself, constitute withdrawal of consent 
for testing of RBR samples.  Likewise, a patient's withdrawal of consent for testing of 
RBR samples does not constitute withdrawal from this study. 
4.5.13.7 
Monitoring and Oversight 
RBR samples will be tracked in a manner consistent with Good Clinical Practice by 
a quality-controlled, auditable, and appropriately validated laboratory information 
management system, to ensure compliance with data confidentiality as well as 
adherence to authorized use of samples as specified in this protocol and in the Informed 
Consent Form.  Sponsor monitors and auditors will have direct access to appropriate 
parts of records relating to patient participation in the RBR for the purposes of verifying 
the data provided to the Sponsor.  The site will permit monitoring, audits, IRB/EC review, 
and health authority inspections by providing direct access to source data and 
documents related to the RBR samples. 
4.6 
TREATMENT, PATIENT, STUDY, AND SITE DISCONTINUATION 
4.6.1 
Study Treatment Discontinuation 
Patients must permanently discontinue study treatment if they experience any of the 
following: 
 
Any medical condition that the investigator or Sponsor determines may jeopardize 
the patient's safety if he or she continues to receive study treatment 
 
Investigator or Sponsor determination that treatment discontinuation is in the best 
interest of the patient 
 
Pregnancy 
 
Anaphylaxis or serious hypersensitivity reaction 
 
Grade 4 IRR or two Grade 3 IRRs (the first occurrence of the Grade 3 IRR can be 
either in the Phase II Study PRM-151-202, Phase III Study WA42293, or in this 
Study WA42294) 
 
Lung Transplant 
 
The primary reason for study treatment discontinuation should be documented on the 
appropriate eCRF.  Patients who discontinue study treatment prematurely will not be 
replaced. 
If a patient discontinues study drug treatment prematurely for any reason, patients will 
return to the clinic for a treatment discontinuation visit 4 weeks after the final dose of 
study drug (see Appendix 1 for additional details).  Every effort should be made to collect 


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safety data at time of the treatment discontinuation visit.  Survival data will continue to be 
collected unless the patient declines to be included in Cohort C. 
4.6.2 
Patient Discontinuation from the Study 
Patients will return to the clinic for a treatment discontinuation visit (4 weeks after the 
final dose), followed by a study discontinuation visit (4 weeks after the treatment 
discontinuation visit). 
Patients have the right to voluntarily withdraw from the study at any time for any reason.  
In addition, the investigator has the right to withdraw a patient from the study at any time. 
Reasons for patient discontinuation from the study may include, but are not limited to, 
the following: 
 
Patient withdrawal of consent 
 
Study termination or site closure 
 
Adverse event 
 
Loss to follow-up 
 
Every effort should be made to obtain a reason for patient discontinuation from the 
study.  The primary reason for discontinuation from the study should be documented on 
the appropriate eCRF.  If a patient requests to be withdrawn from the study, this request 
must be documented in the source documents and signed by the investigator.  Patients 
who withdraw from the study will not be replaced. 
For patients who withdraw from the study, survival status may be ascertained through 
the use of Death Registries, where approved and available, unless patients withdraw 
consent for such data collection. 
4.6.3 
Study Discontinuation 
The Sponsor has the right to terminate this study at any time.  Reasons for terminating 
the study may include, but are not limited to, the following: 
 
The incidence or severity of adverse events in this or other studies indicates 
a potential health hazard to patients 
 
Patient enrollment is unsatisfactory 
 
The Sponsor will notify the investigator if the Sponsor decides to discontinue the study. 
4.6.4 
Site Discontinuation 
The Sponsor has the right to close a site at any time.  Reasons for closing a site may 
include, but are not limited to, the following: 
 
Excessively slow recruitment 
 
Poor protocol adherence 


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 
Inaccurate or incomplete data recording 
 
Non-compliance with the International Council for Harmonization (ICH) guideline for 
Good Clinical Practice 
 
No study activity (i.e., all patients have completed the study and all obligations have 
been fulfilled) 
 
Commercial availability of PRM-151 
 
5. 
ASSESSMENT OF SAFETY 
PRM-151 is not approved and clinical development is ongoing.  The safety plan for 
patients in this study is based on clinical experience with PRM-151 in completed and 
ongoing studies.  The anticipated important safety risks for PRM-151 are outlined below.  
Refer to the PRM-151 Investigator's Brochure for detailed safety information.  
Several measures will be taken to ensure the safety of patients participating in this 
study.  Eligibility criteria have been designed to exclude patients at higher risk for 
toxicities.  Patients will undergo safety monitoring during the study, including 
assessment of the nature, frequency, and severity of adverse events.  In addition, 
guidelines for managing adverse events, including criteria treatment interruption or 
discontinuation, are provided below. 
If patients have been prescribed pirfenidone or nintedanib, this should comply with local 
prescribing information.  Patients should adhere to the instructions and 
recommendations stated in the respective local labels.  Investigators should consult local 
prescribing information for management of AEs, including guidance on dose reductions 
and discontinuation of these treatments.    
In exceptional circumstances, if patients cannot attend a study site for a scheduled visit, 
patients should be followed up ideally by telephone around the time of the scheduled 
visit, to collect information on any AEs and changes to concomitant medications. 
Pandemic Preparedness 
Patients with active infection are excluded from study participation.  In the setting of 
a pandemic or epidemic, screening for infections prior to and during study participation 
should be considered according to local or institutional guidelines or those of applicable 
professional societies. 
5.1 
POTENTIAL RISKS ASSOCIATED WITH PRM-151 
Potential risks for PRM-151 include infusion-related reactions (IRRs), anaphylactic and 
hypersensitivity reactions, post-implantation fetal loss, and immunogenicity.  Outlined 
below is the safety plan for managing the potential risks of IRRs, anaphylactic and 
hypersensitivity reactions, and post-implantation fetal loss.  Please refer to the latest IB 
for further information.  


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Infusion-related reaction (see Section 5.4.5.1) is a temporal and causality-based event.  
This is not a clinical syndrome or medical concept and cannot be characterized by 
clinical criterion.  Whereas, hypersensitivity reaction is considered as an immune related 
reaction which can be immediate or delayed.  There is a great degree of overlap in signs 
and symptoms between IRR and hypersensitivity reaction.  Investigators should use 
their medical judgement to assess if an event is immune mediated. 
5.1.1 
Infusion-Related Reactions 
Infusion-related reaction risks associated with PRM-151 are inherent in it being the 
recombinant form of a naturally-occurring human protein.  PRM-151 has an endogenous 
counterpart and ADAs could potentially affect the efficacy of PRM-151 treatments in 
addition to having the potential to cross-react with endogenous hPTX-2.  Patients should 
be monitored for IRRs, which may occur within 24 hours of administration of PRM-151. 
Signs and symptoms of an infusion reaction may include the following:  headache, fever, 
facial flushing, pruritus, myalgia, nausea, chest tightness, dyspnea, vomiting, erythema, 
abdominal discomfort, diaphoresis, shivers, hypertension, hypotension, lightheadedness, 
palpitations, urticaria, and somnolence.  Although unlikely, serious allergic reactions 
(e.g., anaphylaxis) may occur at any time during the infusion. 
In Study PRM-151-202 (n116), 2 patients treated with PRM-151 (2.6%) experienced 
IRRs during the randomized period (in Weeks 1 and 8), and 10 patients treated with 
PRM-151 (9.0%) during the OLE period (occurring from Study Weeks 28 to 108).  All 
IRRs were either Grade 1 or 2, except for one Grade 3 IRR. 
5.1.2 
Anaphylactic and Hypersensitivity Reactions 
Anaphylactic and hypersensitivity reactions are considered a potential risk with all 
biologic medications, including PRM-151.  Appropriate precautions should be taken to 
ensure appropriate measures to manage anaphylaxis are available.  PRM-151 was 
found to contain small amounts of the sugar -Gal (Section 1.2.2).  The -Gal epitope 
is present in red meat, the gastrointestinal tract of ticks with long shells, and also i n 
some drugs of animal origin (e.g., porcine or bovine gelatin) and therapeutic chimeric 
monoclonal antibodies (e.g., cetuximab).  In patients presenting immunoglobulin E 
(IgE) sensitization to -Gal (e.g., red meat allergy or a history of tick bites), clinical 
allergic reactions having immediate onset may be induced by the first parenteral 
exposure to drugs containing -Gal (Popescu et al. 2019).  As a result, the risk of 
anaphylactic or hypersensitivity reactions may be increased in patients with a history 
of tick bites, red meat allergy, or patients with IgE antibodies directed against -Gal. 
More information on the presence of -Gal in PRM-151 is provided in the PRM‑151 
IB. 
In Phase I/II clinical trials of PRM-151 to date, one event was reported as an 
anaphylactic reaction in a patient taking part in the Phase II Study PRM-151G-101 in 


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patients with myelofibrosis.  The event occurred 17 days following the fifth dose of 
PRM-151 (for additional details see Investigator’s Brochure). 
Investigators and health care professionals administering study treatment should be 
trained to recognize and manage the signs and symptoms of a potential anaphylactic, or 
hypersensitivity reaction and should be familiar with Sampson’s criteria for defining 
anaphylaxis (Sampson et al. 2006; Appendix 5).  Investigators and health care 
professionals should also be trained to accurately and appropriately report these events 
immediately to the Sponsor as adverse events of special interest and as SAEs if 
appropriate (see Section 5.5).  Health care professionals should also instruct patients on 
how to recognize the symptoms of any anaphylactic, or hypersensitivity reaction and to 
contact a health care provider or seek emergency care in case of any such symptoms.  
Patients will need to be clinically stable prior to each dose of study drug as assessed by 
clinical evaluations, including vital signs and spirometry measurements. 
If a patient experiences a suspected and/or non-serious hypersensitivity reaction, the 
case should be discussed with the Medical Monitor prior to continuing dosing.  If 
a patient has signs or symptoms of an anaphylactic or serious hypersensitivity reaction, 
administration of the study drug must be discontinued permanently. 
The patient should be treated according to the SOC for management of anaphylaxis or 
hypersensitivity reaction. 
5.1.3 
Post-implantation Fetal Loss 
In a rabbit dose range finding embryo fetal development study, PRM-151-‑related 
adverse effects at 60 mg/kg/day included a high number of embryo-fetal deaths, 
post‑implantation loss rate, high placental remnant rate, and lower fetal viability rate.  
At 200 mg/kg/day, PRM-151 treatment resulted in complete post-implantation fetal 
loss.   
No pregnancies have been reported across any of the completed Phase 1 and 2 studies 
with PRM-151. 
In this study, women of childbearing potential (WOCBP) must remain abstinent or use 
contraceptive methods with a failure rate of   1% per year during the treatment period 
and for 8 weeks after the final dose of PRM-151.  Male subjects with a female partner of 
childbearing potential or pregnant female partner must remain abstinent or use 
a condom during the treatment period and for 8 weeks after the final dose of PRM-151. 
5.1.4 
Management Guidelines for Infusion Related Reactions, and 
Anaphylactic and Hypersensitivity Reactions 
If an IRR Grade ≥2 event occurs the steps outlined in Table 2 should be followed.  For 
Grade 1 IRRs, investigators should treat as per medical judgement or local procedures. 


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Table 2 
Actions if an Infusion-Related Reactions (Grade 2) Occurs 
Event 
Actions 
IRR Event Occurs 
If NCI CTCAE Grade 2 (Section 5.4.3) signs and symptoms 
are present: 
 
Treat per local guidelines 
 
Reduce rate of study drug infusion (to 120 minutes) 
 
Collect ECG and after patient stabilizes, collect labs 
(serum tryptase c, ADA, PK sample, complement C3) 
 
Capture signs and symptoms per Sampson criteria 
If NCI CTCAE Grade 3 signs and symptoms are present: 
 
Treat per local guidelines 
 
Stop study drug infusion 
 
Collect ECG and after patient stabilizes, collect labs 
(serum tryptase c, ADA, PK sample, complement C3).   
 
Capture signs and symptoms per Sampson criteria 
If NCI CTCAE Grade 4 signs and symptoms are present or 
a patient experiences a second occurrence of a Grade 3 
IRR, in addition to the above guidance for a Grade 3 IRR 
event: b 
 
Permanently discontinue study drug treatment. 
IRR (Grade 2 and Grade 3 
[1 occurrence]) resolved after 
treatment and/or reduced infusion 
rate 
 
Complete study drug infusion at reduced rate 
(120 minutes) 
 
Closely monitor patient 
IRR not resolved after treatment 
and/or reduced infusion rate 
 
Stop study drug infusion.  
 
Treat and closely monitor patient 
IRR (Grade 2 and Grade 3 
[1 occurrence]) resolved after 
continued treatment 
 
Restart study drug infusion at reduced rate 
(120 minutes). 
 
Next study drug infusion should be at reduced rate and 
pre-medication should be used. a 
 
Subsequent study drug infusions may be at reduced 
rate with premedication. 
 
Please note, if a patient experiences a second 
occurrence of a Grade 3 IRR or a Grade 4 IRR event, 
study drug treatment must be permanently 
discontinued. 
ADAanti-drug antibody; IRRinfusion-related reaction; PK  pharmacokinetics; NCI 
CTCAENational Cancer Institute Common Terminology Criteria for Adverse Events. 
a Diphenhydramine or clemastine and dexamethasone are recommended (see details in text 
below). 
b The first occurrence of the Grade 3 IRR can be either in the Phase II Study PRM-151-202, 
Phase III Study WA42293, or in this Study WA42294. 
c Serum tryptase should be collected between 1 and 6 hours after the event 
  


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The next study drug infusion after a Grade  2 IRR or non-serious hypersensitivity 
reactions should be infused over 120 minutes and the following premedications are 
recommended for all subsequent study drug administrations after these events: 
 
Diphenhydramine 50 mg IV or clemastine 2 mg IV (or an equivalent dose of an 
antihistaminic drug) 
 
Dexamethasone 10 mg IV (or an equivalent dose of a long acting corticosteroid) 
 
If subsequent infusion(s) are uneventful, the investigator may resume 5070 minute 
infusions of study treatment and may discontinue premedication. 
Suspected IRRs (Grade 2), anaphylactic, and hypersensitivity (all grades) reactions 
must be reported as an Adverse Event of Special Interest as described in Section 5.3.3.  
See reporting of IRRs discussed in Section 5.1.1.  
Assessment of potential anaphylaxis will be conducted at every infusion per the clinical 
criterion for diagnosing anaphylaxis as described by Sampson et al. 2006 NIAID/FAAN 
(Appendix 5).  Patients experiencing suspected anaphylaxis or hypersensitivity reaction 
should be managed as per local guidelines. If a patient experiences a suspected 
anaphylaxis and/or hypersensitivity reaction regardless of seriousness or severity, an 
ECG should be collected after the patient stabilizes.  Blood samples for ADA, serum 
tryptase, complement C3, and PK analysis should be obtained at the time of the event 
whenever possible (serum tryptase should be collected between 1 and 6 hours after the 
event), and a blood sample for ADA, serum tryptase, and complement C3 should be 
obtained at the first follow-up visit after the event. 
All potential anaphylaxis cases reported by investigators to the Sponsor will be 
subsequently submitted for adjudication to an Anaphylaxis Adjudication Committee 
composed of external experts in allergic diseases.  The Committee will assess whether 
the reported event is a true anaphylaxis event (based on Sampson's criteria) and 
whether the reported anaphylaxis event is causally related to PRM-151. 
If a patient has signs or symptoms of an anaphylactic or serious hypersensitivity reaction 
(including events deemed to have met the criteria as described by Sampson according 
to the blinded Anaphylaxis Adjudication Committee), administration of the study drug 
must be discontinued permanently. 
Anaphylaxis adjudication process has been outlined in the Anaphylaxis Adjudication 
Committee Charter.  
5.2 
MANAGEMENT OF PATIENTS WHO EXPERIENCE ADVERSE 
EVENTS 
5.2.1 
Dose Modifications 
Dose modifications of PRM-151 or matching placebo are not permitted in the study. 


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5.2.2 
Treatment Interruption 
Study treatment may be temporarily suspended in patients who experience toxicity 
considered to be related to study drug.  Resumption of study treatment should be 
discussed with the Medical Monitor. 
In the event that one or more doses of study treatment is missed, the patient will be 
required to reload with three doses of study treatment at the next scheduled visit, 
allowing alternate days between infusions.  Reasons for any such dose interruptions 
should be recorded in the eCRF.  The investigator should discuss with the 
Medical Monitor prior to reloading after a dose is missed due to an adverse event. 
5.3 
SAFETY PARAMETERS AND DEFINITIONS 
Safety assessments will consist of monitoring and recording AEs, including SAEs and 
adverse events of special interest, performing protocol-specified safety laboratory 
assessments, measuring protocol-specified vital signs, and conducting other 
protocol-specified tests that are deemed critical to the safety evaluation of the study. 
Certain types of events require immediate reporting to the Sponsor, as outlined in 
Section 5.5. 
5.3.1 
Adverse Events 
According to the ICH guideline for Good Clinical Practice, an AE is any untoward 
medical occurrence in a clinical investigation subject administered a pharmaceutical 
product, regardless of causal attribution.  An AE can therefore be any of the following: 
 
Any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product 
 
Any new disease or exacerbation of an existing disease (a worsening in the 
character, frequency, or severity of a known condition) (see Sections 5.4.5.9 
and 5.4.5.10 for more information) 
 
Recurrence of an intermittent medical condition (e.g., headache) not present at 
baseline 
 
Any deterioration in a laboratory value or other clinical test (e.g., ECG, X-ray) that is 
associated with symptoms or leads to a change in study treatment or concomitant 
treatment or discontinuation from study drug 
 
AEs that are related to a protocol-mandated intervention, including those that occur 
prior to assignment of study treatment (e.g., screening invasive procedures such as 
biopsies) 
 


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5.3.2 
Serious Adverse Events (Immediately Reportable to the 
Sponsor) 
An SAE is any AE that meets any of the following criteria: 
 
Is fatal (i.e., the AE actually causes or leads to death) 
 
Is life threatening (i.e., the AE, in the view of the investigator, places the patient at 
immediate risk of death) 
 
This does not include any AE that, had it occurred in a more severe form or was 
allowed to continue, might have caused death. 
 
Requires or prolongs inpatient hospitalization (see Section 5.4.5.11) 
 
Results in persistent or significant disability/incapacity (i.e., the AE results in 
substantial disruption of the patient's ability to conduct normal life functions) 
 
Is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to 
study drug 
 
Is a significant medical event in the investigator's judgment (e.g., may jeopardize the 
patient or may require medical/surgical intervention to prevent one of the outcomes 
listed above) 
 
The terms "severe" and "serious" are not synonymous.  Severity refers to the intensity of 
an AE (e.g., rated as mild, moderate, or severe, or according to NCI CTCAE; see 
Section 5.4.3); the event itself may be of relatively minor medical significance (such as 
severe headache without any further findings). 
Severity and seriousness need to be independently assessed for each adverse event 
recorded on the eCRF. 
Serious adverse events are required to be reported by the investigator to the Sponsor 
immediately (i.e., no more than 24 hours after learning of the event; see Section 5.5.2 for 
reporting instructions). 
5.3.3 
Adverse Events of Special Interest (Immediately Reportable to 
the Sponsor) 
Adverse events of special interest are required to be reported by the investigator to the 
Sponsor immediately (i.e., no more than 24 hours after learning of the event; see 
Section 5.5.2 for reporting instructions).  Adverse events of special interest for this study 
are as follows. 
Adverse Events of Special Interest Related to Drug Development in General: 
 
Cases of potential drug-induced liver injury that include an elevated ALT or AST in 
combination with either an elevated bilirubin or clinical jaundice, as defined by 
Hy's Law (see Section 5.4.5.7) 


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 
Suspected transmission of an infectious agent by the study drug, as defined below: 
Any organism, virus, or infectious particle (e.g., prion protein transmitting 
transmissible spongiform encephalopathy), pathogenic or non-pathogenic, is 
considered an infectious agent.  A transmission of an infectious agent may be 
suspected from clinical symptoms or laboratory findings that indicate an infection 
in a patient exposed to a medicinal product.  This term applies only when 
a contamination of the study drug is suspected. 
 
Adverse Events of Special Interest Relevant to PRM-151: 
 
Suspected IRR with NCI CTCAE Grade 2 
 
Suspected anaphylactic and hypersensitivity reactions (all grades) 
 
Acute or suspected exacerbation of IPF (all grades) 
 
5.3.4 
Collection of Survival Data (Cohort C) 
All efforts will be made to collect survival data for patients in Cohort C.  Survival data 
collection will be accomplished remotely (i.e., via telephone or electronically), provided 
these communications are well documented.  
Information on survival may be collected in multiple ways, including telephone calls or 
patient medical records, approximately every 6 months until death, or study termination 
by the Sponsor. 
Women who become pregnant during the WA42293 study or in Cohort A or B of the 
WA42294 study can join Cohort C of WA42294 study. 
If a patient is lost to follow-up or withdraws consent from the study, survival status will be 
ascertained through the use of Death Registries, where approved and available. 
5.3.5 
Lung Transplantation 
Qualification for lung transplant will be assessed by the investigator.  In general, 
qualification for lung transplant may be regarded as the point in time when a patient 
would be referred for evaluation for lung transplantation using local guidelines or 
practice, under ideal circumstances (e.g., no obvious contraindication for lung 
transplant).  When applicable, date of qualification as assessed by investigator will be 
collected.  Date of actual lung transplantation will be collected, when applicable. 
5.4 
METHODS AND TIMING FOR CAPTURING AND ASSESSING 
SAFETY PARAMETERS 
The investigator is responsible for ensuring that all adverse events (see Section 5.3.1 for 
definition) are recorded on the Adverse Event eCRF and reported to the Sponsor in 
accordance with instructions provided in this section and in Sections 5.55.7. 


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For each AE recorded on the Adverse Event eCRF, the investigator will make an 
assessment of seriousness (see Section 5.3.2 for seriousness criteria), severity (see 
Section 5.4.3), and causality (see Section 5.4.4). 
5.4.1 
Adverse Event Reporting Period 
Investigators will seek information on adverse events at each patient contact.  All AEs, 
whether reported by the patient or noted by study personnel, will be recorded in the 
patient's medical record and on the Adverse Event eCRF. 
After informed consent has been obtained but prior to initiation of study drug, only SAEs 
caused by a protocol-mandated intervention (e.g., invasive procedures such as biopsies, 
discontinuation of medications) should be reported (see Section 5.5.2 for instructions for 
reporting serious adverse events).  For patients in Cohort A and B, all other medical 
occurrences that begin before the start of study treatment but after obtaining informed 
consent will be recorded on the General Medical History and Baseline Conditions eCRF, 
and not on the Adverse Event eCRF.  Adverse events that are ongoing from study 
WA42293 for Cohort B patients will be transferred over from the WA42293 database in 
in the WA42294 Adverse Event eCRF. 
After initiation of study drug, all AEs will be reported until 8 weeks after the final dose of 
study drug. 
Instructions for reporting AEs that occur after the adverse event reporting period are 
provided in Section 5.7. 
5.4.2 
Eliciting Adverse Event Information 
A consistent methodology of non-directive questioning should be adopted for eliciting 
adverse event information at all patient evaluation timepoints.  Examples of non-directive 
questions include the following: 
"How have you felt since your last clinic visit?" 
"Have you had any new or changed health problems since you were last here?" 
 
5.4.3 
Assessment of Severity of Adverse Events 
The adverse event severity grading scale for the NCI CTCAE (v5.0) will be used for 
assessing adverse event severity (see Appendix 9).  Table 3 will be used for assessing 
severity for AEs that are not specifically listed in the NCI CTCAE. 


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Table 3 
Adverse Event Severity Grading Scale for Events Not Specifically 
Listed in NCI CTCAE 
Grade 
Severity 
1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; or intervention not indicated 
2 
Moderate; minimal, local, or non-invasive intervention indicated; or limiting 
age-appropriate instrumental activities of daily living a 
3 
Severe or medically significant, but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; or 
limiting self-care activities of daily living b, c 
4 
Life-threatening consequences or urgent intervention indicated d 
5 
Death related to adverse event d 
 
NCI CTCAENational Cancer Institute Common Terminology Criteria for Adverse Events. 
Note:  Based on the most recent version of NCI CTCAE (v5.0), which can be found at:  
http://ctep.cancer.gov/protocolDevelopment/electronic applications/ctc.htm 
a Instrumental activities of daily living refer to preparing meals, shopping for groceries or 
clothes, using the telephone, managing money, etc. 
b Examples of self-care activities of daily living include bathing, dressing and undressing, 
feeding oneself, using the toilet, and taking medications, as performed by patients who are 
not bedridden. 
c If an event is assessed as a "significant medical event," it must be reported as a serious 
adverse event (see Section 5.5.2 for reporting instructions), per the definition of serious 
adverse event in Section 5.3.2. 
d Grade 4 and 5 events must be reported as serious adverse events (see Section 5.5.2 for 
reporting instructions), per the definition of serious adverse event in Section 5.3.2. 
 
5.4.4 
Assessment of Causality of Adverse Events 
Investigators should use their knowledge of the patient, the circumstances surrounding 
the event, and an evaluation of any potential alternative causes to determine whether an 
adverse event is considered to be related to the study drug, indicating "yes" or "no" 
accordingly.  The following guidance should be taken into consideration: 
 
Temporal relationship of event onset to the initiation of study drug 
 
Course of the event, with special consideration of the effects of discontinuation of 
study drug, or reintroduction of study drug (as applicable) 
 
Known association of the event with the study drug or with similar treatments 
 
Known association of the event with the disease under study 
 
Presence of risk factors in the patient or use of concomitant medications known to 
increase the occurrence of the event 
 
Presence of non-treatment-related factors that are known to be associated with the 
occurrence of the event 
 


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5.4.5 
Procedures for Recording Adverse Events 
Investigators should use correct medical terminology/concepts when recording adverse 
events on the Adverse Event eCRF.  Avoid colloquialisms and abbreviations. 
Only one adverse event term should be recorded in the event field on the Adverse Event 
eCRF. 
5.4.5.1 
Infusion-Related Reactions 
Adverse events that occur during or within 24 hours after study drug administration and 
are judged to be related to study drug infusion should be captured as a diagnosis 
(e.g., "infusion-related reaction", or "anaphylactic reaction") on the Adverse Event eCRF.  
If possible, avoid ambiguous terms such as "systemic reaction".  Associated signs and 
symptoms should be recorded on the dedicated Infusion-Related Reaction eCRF.  If 
a patient experiences both a local and systemic reaction to the same dose of study drug, 
each reaction should be recorded separately on the Adverse Event eCRF, with signs 
and symptoms also recorded separately on the dedicated Infusion-Related Reaction 
eCRF. 
5.4.5.2 
Diagnosis versus Signs and Symptoms 
A diagnosis (if known) should be recorded on the Adverse Event eCRF rather than 
individual signs and symptoms (e.g., record only liver failure or hepatitis rather than 
jaundice, asterixis, and elevated transaminases).  However, if a constellation of signs 
and/or symptoms cannot be medically characterized as a single diagnosis or syndrome 
at the time of reporting, each individual event should be recorded on the Adverse Event 
eCRF.  If a diagnosis is subsequently established, all previously reported adverse events 
based on signs and symptoms should be nullified and replaced by one adverse event 
report based on the single diagnosis, with a starting date that corresponds to the starting 
date of the first symptom of the eventual diagnosis. 
5.4.5.3 
Adverse Events That Are Secondary to Other Events 
In general, adverse events that are secondary to other events (e.g., cascade events or 
clinical sequelae) should be identified by their primary cause, with the exception of 
severe or serious secondary events.  A medically significant secondary adverse event 
that is separated in time from the initiating event should be recorded as an independent 
event on the Adverse Event eCRF.  For example: 
 
If vomiting results in mild dehydration with no additional treatment in a healthy adult, 
only vomiting should be reported on the eCRF. 
 
If vomiting results in severe dehydration, both events should be reported separately 
on the eCRF. 
 
If a severe gastrointestinal hemorrhage leads to renal failure, both events should be 
reported separately on the eCRF. 
 
If dizziness leads to a fall and consequent fracture, all three events should be 
reported separately on the eCRF. 


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 
If neutropenia is accompanied by an infection, both events should be reported 
separately on the eCRF. 
 
All adverse events should be recorded separately on the Adverse Event eCRF if it is 
unclear as to whether the events are associated. 
5.4.5.4 
Persistent or Recurrent Adverse Events 
A persistent adverse event is one that extends continuously, without resolution, between 
patient evaluation timepoints.  Such events should only be recorded once on the 
Adverse Event eCRF.  The initial severity (intensity or grade) of the event will be 
recorded at the time the event is first reported.  If a persistent adverse event becomes 
more severe, the most extreme severity should also be recorded on the Adverse Event 
eCRF.  If the event becomes serious, it should be reported to the Sponsor immediately 
(i.e., no more than 24 hours after learning that the event became serious; see 
Section 5.5.2 for reporting instructions).  The Adverse Event eCRF should be updated 
by changing the event from "non-serious" to "serious," providing the date that the event 
became serious, and completing all data fields related to serious adverse events. 
A recurrent adverse event is one that resolves between patient evaluation timepoints 
and subsequently recurs.  Each recurrence of an adverse event should be recorded as 
a separate event on the Adverse Event eCRF. 
5.4.5.5 
Abnormal Laboratory Values 
Not every laboratory abnormality qualifies as an adverse event.  A laboratory test result 
must be reported as an adverse event if it meets any of the following criteria: 
 
Is accompanied by clinical symptoms 
 
Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation) 
 
Results in a medical intervention (e.g., potassium supplementation for hypokalemia) 
or a change in concomitant therapy 
 
Is clinically significant in the investigator's judgment 
 
It is the investigator's responsibility to review all laboratory findings.  Medical and 
scientific judgment should be exercised in deciding whether an isolated laboratory 
abnormality should be classified as an adverse event. 
If a clinically significant laboratory abnormality is a sign of a disease or syndrome 
(e.g., alkaline phosphatase and bilirubin 5ULN associated with cholestasis), only the 
diagnosis (i.e., cholestasis) should be recorded on the Adverse Event eCRF. 
If a clinically significant laboratory abnormality is not a sign of a disease or syndrome, 
the abnormality itself should be recorded on the Adverse Event eCRF, along with 
a descriptor indicating whether the test result is above or below the normal range 
(e.g., "elevated potassium," as opposed to "abnormal potassium").  If the laboratory 


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abnormality can be characterized by a precise clinical term per standard definitions, the 
clinical term should be recorded as the adverse event.  For example, an elevated serum 
potassium level of 7.0 mEq/L should be recorded as "hyperkalemia." 
Observations of the same clinically significant laboratory abnormality from visit to visit 
should only be recorded once on the Adverse Event eCRF (see Section 5.4.5.4 for 
details on recording persistent adverse events). 
5.4.5.6 
Abnormal Vital Sign Values 
Not every vital sign abnormality qualifies as an adverse event.  A vital sign result must 
be reported as an adverse event if it meets any of the following criteria: 
 
Is accompanied by clinical symptoms 
 
Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation) 
 
Results in a medical intervention or a change in concomitant therapy 
 
Is clinically significant in the investigator's judgment 
 
It is the investigator's responsibility to review all vital sign findings.  Medical and scientific 
judgment should be exercised in deciding whether an isolated vital sign abnormality 
should be classified as an AE. 
If a clinically significant vital sign abnormality is a sign of a disease or syndrome 
(e.g., high blood pressure), only the diagnosis (i.e., hypertension) should be recorded on 
the Adverse Event eCRF. 
Observations of the same clinically significant vital sign abnormality from visit to visit 
should only be recorded once on the Adverse Event eCRF (see Section 5.4.5.4 for 
details on recording persistent adverse events). 
5.4.5.7 
Abnormal Liver Function Tests 
The finding of an elevated ALT or AST ( 3  ULN) in combination with either an elevated 
total bilirubin ( 2  ULN) or clinical jaundice in the absence of cholestasis or other 
causes of hyperbilirubinemia is considered to be an indicator of severe liver injury (as 
defined by Hy’s Law).  Therefore, investigators must report as an adverse event the 
occurrence of either of the following: 
 
Treatment-emergent ALT or AST  3  ULN in combination with total bilirubin 
 2  ULN 
 
Treatment-emergent ALT or AST  3  ULN in combination with clinical jaundice  
 
The most appropriate diagnosis or (if a diagnosis cannot be established) the abnormal 
laboratory values should be recorded on the Adverse Event eCRF (see Section 5.4.5.2) 
and reported to the Sponsor immediately (i.e., no more than 24 hours after learning of 
the event), either as a serious adverse event or an adverse event of special interest (see 


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Section 5.5.2).  Any such events should be managed according to local practices and 
guidelines.  No drug-specific management guideline is available, as abnormal liver 
function tests are not a known adverse drug reaction or risk for PRM-151. 
5.4.5.8 
Deaths 
All deaths that occur during the protocol-specified adverse event reporting period (see 
Section 5.4.1), regardless of relationship to study drug, must be recorded on the 
Adverse Event eCRF and immediately reported to the Sponsor (see Section 5.5.2).  This 
includes death attributed to progression of IPF. 
Death should be considered an outcome and not a distinct event.  The event or condition 
that caused or contributed to the fatal outcome should be recorded as the single medical 
concept on the Adverse Event eCRF.  Generally, only one such event should be 
reported.  If the cause of death is unknown and cannot be ascertained at the time of 
reporting, "unexplained death" should be recorded on the Adverse Event eCRF.  If the 
cause of death later becomes available (e.g., after autopsy), "unexplained death" should 
be replaced by the established cause of death.  The term "sudden death" should not be 
used unless combined with the presumed cause of death (e.g., "sudden cardiac death"). 
If the death is attributed solely to progression of IPF, "Idiopathic pulmonary fibrosis 
progression" should be recorded on the Adverse Event eCRF.  
Deaths that occur after the AE reporting period should be reported as described in 
Section 5.7. 
5.4.5.9 
Preexisting Medical Conditions 
A preexisting medical condition is one that is present prior the first dosing visit for this 
study.  Such conditions should be recorded on the General Medical History and Baseline 
Conditions eCRF. 
A preexisting medical condition should be recorded as an adverse event only if the 
frequency, severity, or character of the condition worsens during the study.  When 
recording such events on the Adverse Event eCRF, it is important to convey the concept 
that the preexisting condition has changed by including applicable descriptors 
(e.g., "more frequent headaches"). 
5.4.5.10 
Lack of Efficacy or Worsening of Idiopathic Pulmonary 
Fibrosis 
Medical occurrences or symptoms of deterioration that are anticipated as part of 
idiopathic pulmonary fibrosis should be recorded as an adverse event if judged by the 
investigator to have unexpectedly worsened in severity or frequency or changed in 
nature at any time during the study.  When recording an unanticipated worsening of 
idiopathic pulmonary fibrosis on the Adverse Event eCRF, it is important to convey the 
concept that the condition has changed by including applicable descriptors 
(e.g., "accelerated worsening of idiopathic pulmonary fibrosis”). 


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5.4.5.11 
Hospitalization or Prolonged Hospitalization 
Any adverse event that results in hospitalization (i.e., inpatient admission to a hospital) 
or prolonged hospitalization should be documented and reported as a serious adverse 
event (per the definition of serious adverse event in Section 5.3.2), except as outlined 
below. 
An event that leads to hospitalization under the following circumstances should not be 
reported as an AE or a SAE: 
 
Hospitalization for a preexisting condition, provided that all of the following criteria 
are met: 
The hospitalization was planned prior to the study or was scheduled during the 
study when elective surgery became necessary because of the expected normal 
progression of the disease. 
The patient has not experienced an adverse event. 
 
An event that leads to hospitalization under the following circumstances is not 
considered to be a SAE, but should be reported as an AE instead: 
 
Hospitalization that was necessary because of patient requirement for outpatient 
care outside of normal outpatient clinic operating hours 
 
5.4.5.12 
Cases of Accidental Overdose or Medication Error 
Accidental overdose and medication error (hereafter collectively referred to as "special 
situations"), are defined as follows: 
 
Accidental overdose:  accidental administration of a drug in a quantity that is higher 
than the assigned dose 
 
Medication error:  accidental deviation in the administration of a drug 
In some cases, a medication error may be intercepted prior to administration of 
the drug. 
 
Special situations are not in themselves AEs, but may result in AEs.  Each AE 
associated with a special situation should be recorded separately on the Adverse Event 
eCRF.  If the associated AE fulfills seriousness criteria, the event should be reported to 
the Sponsor immediately (i.e., no more than 24 hours after learning of the event; see 
Section 5.5.2).  For PRM-151, AEs associated with special situations should be recorded 
as described below for each situation: 
 
Accidental overdose:  Enter the adverse event term.  Check the "Accidental 
overdose" and "Medication error" boxes. 
 
Medication error that does not qualify as an overdose:  Enter the adverse event 
term.  Check the "Medication error" box. 
 
Medication error that qualifies as an overdose:  Enter the adverse event term.  
Check the "Accidental overdose" and "Medication error" boxes. 
 


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In addition, all special situations associated with PRM-151, regardless of whether they 
result in an AE, should be recorded on the Adverse Event eCRF as described below: 
 
Accidental overdose:  Enter the drug name and "accidental overdose" as the event 
term.  Check the "Accidental overdose" and "Medication error" boxes. 
 
Medication error that does not qualify as an overdose:  Enter the name of the drug 
administered and a description of the error (e.g., wrong dose administered, wrong 
dosing schedule, incorrect route of administration, wrong drug, expired drug 
administered) as the event term.  Check the "Medication error" box. 
 
Medication error that qualifies as an overdose:  Enter the drug name and "accidental 
overdose" as the event term.  Check the "Accidental overdose" and "Medication 
error" boxes.  Enter a description of the error in the additional case details. 
 
Intercepted medication error:  Enter the drug name and "intercepted medication 
error" as the event term.  Check the "Medication error" box.  Enter a description of 
the error in the additional case details. 
 
As an example, an accidental overdose that resulted in a headache would require two 
entries on the Adverse Event eCRF, one entry to report the accidental overdose and one 
entry to report the headache.  The "Accidental overdose" and "Medication error" boxes 
would need to be checked for both entries. 
5.5 
IMMEDIATE REPORTING REQUIREMENTS FROM 
INVESTIGATOR TO SPONSOR 
Certain events require immediate reporting to allow the Sponsor to take appropriate 
measures to address potential new risks in a clinical trial.  The investigator must report 
such events to the Sponsor immediately; under no circumstances should reporting take 
place more than 24 hours after the investigator learns of the event.  The following is a list 
of events that the investigator must report to the Sponsor within 24 hours after learning 
of the event, regardless of relationship to study drug: 
 
SAEs (defined in Section 5.3.2; see Section 5.5.2 for details on reporting 
requirements) 
 
AEs of special interest (defined in Section 5.3.3; see Section 5.5.2 for details on 
reporting requirements) 
 
Pregnancies (see Section 5.5.3 for details on reporting requirements) 
 
For SAEs and AEs of special interest, the investigator must report new significant 
follow-up information to the Sponsor immediately (i.e., no more than 24 hours after 
becoming aware of the information).  New significant information includes the following: 
 
New signs or symptoms or a change in the diagnosis 
 
Significant new diagnostic test results 
 
Change in causality based on new information 
 
Change in the event's outcome, including recovery 


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 
Additional narrative information on the clinical course of the event 
 
Investigators must also comply with local requirements for reporting serious adverse 
events to the local health authority and IRB/EC. 
5.5.1 
Medical Monitors and Emergency Medical Contacts 
In the event of an emergency, the investigator or other physician should use their 
medical judgment and do what is best for the patient, regardless of protocol 
requirements.  The investigator or other physician in attendance in such an emergency 
must contact the Medical Monitor as soon as possible to discuss the circumstances of 
the emergency. 
The Medical Monitor, in conjunction with the investigator, will decide whether the patient 
should continue to participate in the study.  All protocol deviations and reasons for such 
deviations must be documented. 
Contact Information  
Medical Monitor {/Emergency Medical Contact}: To be provided by Sponsor 
Telephone No.: 
To be provided by Sponsor 
Mobile Telephone No.: 
To be provided by Sponsor 
Medical Monitor {/Emergency Medical Contact}: To be provided by Sponsor (Secondary) 
Telephone No.: 
To be provided by Sponsor  
 
Mobile Telephone No.: 
To be provided by Sponsor  
 
To ensure the safety of study patients, an Emergency Medical Call Center will be 
available 24 hours per day, 7 days per week, in case the above-listed contacts cannot 
be reached.  The Emergency Medical Call Center will connect the investigator with an 
Emergency Medical Contact, provide medical translation service if necessary, and track 
all calls.  Contact information, including toll-free numbers for the Emergency Medical Call 
Center, will be distributed to investigators. 
5.5.2 
Reporting Requirements for Serious Adverse Events and 
Adverse Events of Special Interest 
5.5.2.1 
Events That Occur prior to Study Drug Initiation 
After informed consent has been obtained but prior to initiation of study drug, only 
serious adverse events caused by a protocol-mandated intervention should be reported.  
The paper Clinical Trial Serious Adverse Event/Adverse Event of Special Interest 
Reporting Form provided to investigators should be completed and submitted to the 
Sponsor or its designee immediately (i.e., no more than 24 hours after learning of the 
event), either by faxing or by scanning and emailing the form using the fax number or 
email address provided to investigators. 


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5.5.2.2 
Events That Occur after Study Drug Initiation 
After initiation of study drug, SAEs and AEs of special interest will be reported until 
8 weeks after the final dose of study drug.  Investigators should record all case details 
that can be gathered immediately (i.e., within 24 hours after learning of the event) on the 
Adverse Event eCRF and submit the report via the electronic data capture (EDC) 
system.  A report will be generated and sent to Roche Safety Risk Management by the 
EDC system. 
In the event that the EDC system is unavailable, the paper Clinical Trial Serious Adverse 
Event/Adverse Event of Special Interest Reporting Form provided to investigators should 
be completed and submitted to the Sponsor or its designee immediately (i.e., no more 
than 24 hours after learning of the event), either by faxing or by scanning and emailing 
the form using the fax number or email address provided to investigators.  Once the 
EDC system is available, all information will need to be entered and submitted via the 
EDC system. 
Instructions for reporting serious adverse events that occur 8 weeks after the final dose 
of study treatment are provided in Section 5.7. 
5.5.3 
Reporting Requirements for Pregnancies 
5.5.3.1 
Pregnancies in Female Patients 
Female patients of childbearing potential will be instructed to immediately inform the 
investigator if they become pregnant during the study or within 8 weeks after the final 
dose of study drug.  A paper Clinical Trial Pregnancy Reporting Form should be 
completed and submitted to the Sponsor or its designee immediately (i.e., no more than 
24 hours after learning of the pregnancy), either by faxing or by scanning and emailing 
the form using the fax number or email address provided to investigators.  Pregnancy 
should not be recorded on the Adverse Event eCRF.  The investigator should 
discontinue study drug and counsel the patient, discussing the risks of the pregnancy 
and the possible effects on the fetus.  Monitoring of the patient should continue until 
conclusion of the pregnancy.  Any serious adverse events associated with the 
pregnancy (e.g., an event in the fetus, an event in the mother during or after the 
pregnancy, or a congenital anomaly/birth defect in the child) should be reported on the 
Adverse Event eCRF.  In addition, the investigator will submit a Clinical Trial Pregnancy 
Reporting Form when updated information on the course and outcome of the pregnancy 
becomes available. 
5.5.3.2 
Pregnancies in Female Partners of Male Patients 
Male patients will be instructed through the Informed Consent Form to immediately 
inform the investigator if their partner becomes pregnant during the study or within 
8 weeks after the final dose of study drug.  A paper Clinical Trial Pregnancy Reporting 
Form should be completed and submitted to the Sponsor or its designee immediately 
(i.e., no more than 24 hours after learning of the pregnancy), either by faxing or by 
scanning and emailing the form using the fax number or email address provided to 


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investigators.  Attempts should be made to collect and report details of the course and 
outcome of any pregnancy in the partner of a male patient exposed to study drug.  When 
permitted by the site, the pregnant partner would need to sign an Authorization for Use 
and Disclosure of Pregnancy Health Information to allow for follow-up on her pregnancy.  
If the authorization has been signed, the investigator should submit a Clinical Trial 
Pregnancy Reporting Form when updated information on the course and outcome of the 
pregnancy becomes available.  An investigator who is contacted by the male patient or 
his pregnant partner may provide information on the risks of the pregnancy and the 
possible effects on the fetus, to support an informed decision in cooperation with the 
treating physician and/or obstetrician. 
5.5.3.3 
Abortions 
A spontaneous abortion should be classified as a SAE (as the Sponsor considers 
abortions to be medically significant), recorded on the Adverse Event eCRF, and 
reported to the Sponsor immediately (i.e., no more than 24 hours after learning of the 
event; see Section 5.5.2). 
If a therapeutic or elective abortion was performed because of an underlying maternal or 
embryofetal toxicity, the toxicity should be classified as a serious adverse event, 
recorded on the Adverse Event eCRF, and reported to the Sponsor immediately (i.e., no 
more than 24 hours after learning of the event; see Section 5.5.2).  A therapeutic or 
elective abortion performed for reasons other than an underlying maternal or 
embryofetal toxicity is not considered an adverse event. 
All abortions should be reported as pregnancy outcomes on the paper Clinical Trial 
Pregnancy Reporting Form.  
5.5.3.4 
Congenital Anomalies/Birth Defects 
Any congenital anomaly/birth defect in a child born to a female patient exposed to study 
drug or the female partner of a male patient exposed to study drug should be classified 
as a SAE, recorded on the Adverse Event eCRF, and reported to the Sponsor 
immediately (i.e., no more than 24 hours after learning of the event; see Section 5.5.2). 
5.6 
FOLLOW-UP OF PATIENTS AFTER ADVERSE EVENTS 
5.6.1 
Investigator Follow-Up 
The investigator should follow each AE until the event has resolved to baseline grade or 
better, the event is assessed as stable by the investigator, the patient is lost to follow-up, 
or the patient withdraws consent.  Every effort should be made to follow all SAEs 
considered to be related to study drug or trial-related procedures until a final outcome 
can be reported. 
During the study period, resolution of adverse events (with dates) should be documented 
on the Adverse Event eCRF and in the patient's medical record to facilitate source data 
verification. 


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5.6.2 
All pregnancies reported during the study should be followed 
until pregnancy outcome. Sponsor Follow-Up 
For SAEs, AEs of special interest, and pregnancies, the Sponsor or a designee may 
follow up by telephone, fax, email, and/or a monitoring visit to obtain additional case 
details and outcome information (e.g., from hospital discharge summaries, consultant 
reports, autopsy reports) in order to perform an independent medical assessment of the 
reported case. 
5.7 
ADVERSE EVENTS THAT OCCUR AFTER THE ADVERSE 
EVENT REPORTING PERIOD 
After the end of the adverse event reporting period (defined as 8 weeks after the final 
dose of study drug), all deaths, regardless of cause, should be reported through use of 
the Long-Term Survival Follow-Up eCRF. 
In addition, if the investigator becomes aware of a serious adverse event that is believed 
to be related to prior exposure to study drug, the event should be reported through use 
of the Adverse Event eCRF.  However, if the EDC system is not available, the 
investigator should report these events directly to the Sponsor or its designee, either by 
faxing or by scanning and emailing the paper Clinical Trial Serious Adverse 
Event/Adverse Event of Special Interest Reporting Form using the fax number or email 
address provided to investigators. 
5.8 
EXPEDITED REPORTING TO HEALTH AUTHORITIES, 
INVESTIGATORS, INSTITUTIONAL REVIEW BOARDS, 
AND ETHICS COMMITTEES 
The Sponsor will promptly evaluate all serious adverse events and adverse events of 
special interest against cumulative product experience to identify and expeditiously 
communicate possible new safety findings to investigators, IRBs, ECs, and applicable 
health authorities based on applicable legislation. 
To determine reporting requirements for single adverse event cases, the Sponsor will 
assess the expectedness of these events through use of the reference safety 
information in the document listed below: 
 
PRM-151 Investigator's Brochure 
 
The Sponsor will compare the severity of each event and the cumulative event 
frequency reported for the study with the severity and frequency reported in the 
applicable reference document. 
Reporting requirements will also be based on the investigator's assessment of causality 
and seriousness, with allowance for upgrading by the Sponsor as needed. 


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The suspected unexpected serious adverse reaction (SUSAR) reporting will be as per 
the national regulatory requirements in participating countries in accordance with the 
Sponsor’s internal standard operating procedures. 
An independent Data Monitoring Committee (iDMC) will be established to review safety 
data from this study only up until the time the database for primary analysis for Study 
WA42293 is locked, and Study WA42293 is unblinded to the Sponsor (i.e., for the 
duration of Study WA42293), thereby better ensuring the safety of study participants.  
Consistent with U.S. Food and Drug Administration (FDA) recommendations (FDA 
Guidance for Industry, Establishment and Operation of Clinical Trial Data Monitoring 
Committees, 2006), the iDMC will be constituted of independent clinicians expert in the 
field of IPF and clinical research and a statistician.  A formal charter will be established 
for the conduct of the iDMC.  The Committee is planned to review the safety data in an 
unblinded manner. 
6. 
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN 
All analyses will be reported separated by cohort.  Not all analyses are applicable to all 
cohorts.  
The safety analyses will be performed on the safety evaluable population, unless 
otherwise specified.  Safety will be assessed through descriptive summaries of exposure 
to PRM-151 study drug, AEs, and laboratory test results.   
All efficacy analyses will be performed on the full analysis set (FAS) population, unless 
otherwise specified.  Participants in Cohort B will be analyzed by treatment as assigned 
at randomization in the parent study and for all patients overall. 
Because of the non-comparative character of the study, no statistical tests are planned.  
Demographic and baseline characteristics such as age, sex, race/ethnicity, concomitant 
IPF medication use, comorbid illnesses, and pulmonary function will be summarized by 
use of descriptive statistics. 
Cohort B collected data will not be analyzed before unblinding of the code of the 
treatment received by the patient during the parent Study WA42293.   
Additional safety update analyses may be conducted as required by Health Authorities.  
The final analysis will take place after the LPLV.   
The following sections are applicable to Cohorts A and B of the study.  Data from 
patients initially allocated to Cohort C will be used for survival follow-up only, without any 
safety or efficacy assessments.  Further analysis details on all cohorts will be provided in 
the SAP. 


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6.1 
DETERMINATION OF SAMPLE SIZE 
The number of patients enrolled in the OLE study is approximately 600700 (i.e., eligible 
patients from Study PRM-151-202 [Cohort A] and Study WA42293 [Cohorts B and C]).  
No formal sample size calculations were performed. 
6.2 
SUMMARIES OF CONDUCT OF STUDY 
The number of patients who enroll, discontinue, or complete the study will be 
summarized.  Reasons for premature study withdrawal will be listed and summarized.  
Enrollment and major protocol deviations will be listed and evaluated for their potential 
effects on the interpretation of study results. 
6.3 
SAFETY ANALYSES 
The safety analyses will include all patients who receive at least one administration (full 
or partial dose) of PRM-151 study drug. 
Safety will be assessed through descriptive summaries of exposure to PRM-151 study 
drug, adverse events, SAEs, AESIs, and laboratory test results.  Data will be reported by 
cohort.  
6.3.1 
Adverse Events 
Verbatim descriptions of TEAE will be coded using the most current version of the 
Medical Dictionary for Regulatory Activities (MedDRA) and adverse event severity will be 
graded according to NCI CTCAE v5.0 scale.  A TEAE is defined as any new adverse 
event reported or any worsening of an existing condition on or after the first dose of 
study drug. 
The incidence and observation time-adjusted rate will be summarized, as appropriate.  
In addition, separate summaries will be generated for serious adverse events, deaths, 
adverse events of special interest, and adverse events leading to discontinuation of 
PRM-151.  Adverse events will be summarized by mapped term, appropriate thesaurus 
level, and toxicity grade. 
6.3.2 
Laboratory Data 
Relevant laboratory data will be displayed by time, with grades identified where 
appropriate.  Additionally, a shift table of selected laboratory tests will be used to 
summarize the baseline and maximum post baseline severity grade. 
6.4 
EFFICACY ANALYSES 
Patient efficacy data will be summarized by cohort including all patients who receive at 
least one administration (full or partial dose) of PRM-151 study drug.  Efficacy will be 
assessed by annual rate of change in FVC (mL), 6MWD, FVC% predicted, and DLCO, 
time to disease progression , and survival as measured by all-cause mortality, 
IPF-related mortality and respiratory-related mortality.  The annual rate of change in FVC 


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(mL), 6MWD, FVC% predicted, and DLCO will be calculated using the slope from a linear 
mixed effect model with random intercept (subject) and random slope (time), using 
measurements collected at each time point in this study.  Additionally, change from 
baseline to Weeks 52 and 104 in quantitative imaging analysis parameters of HRCT 
scan of the thorax will be summarized.  All efficacy parameters will be summarized 
descriptively, and as all patients will be receiving PRM-151, there will be no hypothesis 
testing between treatment groups. 
As is planned for the WA42293 study, in the assessment of spirometry data (FVC [mL], 
FVC% predicted, and DLCO), all measurements that meet the minimal level of quality will 
be used.  With respect to handling of missing data, for the purpose of determining the 
annual rate of change estimates, appropriate strategy will be adopted in this study for 
the data impacted by intercurrent events.  For lung transplantation, a hypothetical 
strategy will be utilized where measurements collected after transplantation will not be 
used in the analysis, and values will be implicitly imputed from the model.  For death, 
a composite strategy will be utilized where assessments following death will be assigned 
with values to designate treatment failure.  Further details will be specified in the 
Statistical Analysis Plan.  In addition, summaries using all observed data will be 
performed. 
Kaplan-Meier estimates for the median and quartiles will be computed for time to 
disease progression (defined as time to first occurrence of  10% absolute decline 
in % predicted FVC,  15% relative decline in 6MWD, or death) and time to death; 
estimates will be presented together with their 95% confidence intervals. 
6.5 
EXPLORATORY EFFICACY ANALYSIS  
Exploratory analyses will be performed on the following endpoints and may also be 
performed for additional endpoints and subgroups of interest including concurrent use of 
IPF treatment and geographic region: 
 
Change from baseline in University of California, San Diego Shortness of Breath 
Questionnaire (UCSD SOBQ) 
 
Change from baseline in St. George Respiratory Questionnaire (SGRQ) Total Score 
 
Time to first respiratory-related hospitalizations (defined as non-elective 
hospitalizations due to any respiratory cause, including acute exacerbations of IPF, 
or suspected acute exacerbations of IPF 
 
Time to first acute exacerbation of IPF, or suspected acute exacerbation of IPF 
 
All efficacy exploratory parameters will be summarized descriptively.  For time to event 
endpoints, Kaplan-Meier estimates for the median and quartiles will be computed and 
estimates will be presented together with their 95% confidence intervals. 
Further details for the exploratory analyses will be provided in the Statistical Analysis 
Plan. 


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6.6 
PHARMACOKINETIC ANALYSES 
The PK analysis population will consist of patients with sufficient data to determine 
plasma concentrations of PRM-151 at specified timepoints, unless major protocol 
deviations or unavailability of information (e.g., exact blood sampling time) occurred 
which may interfere with PK evaluation, with patients grouped according to treatment 
received. 
Individual and mean plasma PRM-151 concentration versus time data will be tabulated 
and summarized descriptively.  The pharmacokinetics of PRM-151 will be summarized 
by one or more key PK parameters (as appropriate for data collected).  Estimates for 
these parameters will be tabulated and summarized (mean, standard deviation, 
coefficient of variation, median, minimum, and maximum). 
Additional exploratory PK analyses will be conducted as appropriate. 
6.7 
IMMUNOGENICITY ANALYSES 
The immunogenicity analysis population will consist of all patients with at least one ADA 
assessment. 
The number and percentage of ADA positive patients at baseline and during the study 
will be tabulated by cohort.  The relationship between ADA status and safety, efficacy, 
and PK, may be analyzed and reported via descriptive statistics. 
6.8 
BIOMARKER ANALYSES 
Biomarkers will be assessed at baseline and subsequent timepoints following 
administration of PRM-151.  Biomarkers will be presented as absolute value over time 
and/or percent change relative to baseline over time.  Biomarker levels at baseline or 
over time may be compared with efficacy or safety measurements to assess prognostic 
or predictive properties.   
Descriptive or summary statistics will be used to describe biomarker assessments.  
6.9 
HEALTH STATUS UTILITY ANALYSES 
Annual rate of change in EQ-5D-5L health utility index-based and VAS scores will be 
summarized descriptively. 
7. 
DATA COLLECTION AND MANAGEMENT 
7.1 
DATA QUALITY ASSURANCE 
The Sponsor will be responsible for data management of this study, including quality 
checking of the data.  Data entered manually will be collected via EDC through use of 
eCRFs.  Sites will be responsible for data entry into the EDC system.  In the event of 
discrepant data, the Sponsor will request data clarification from the sites, which the sites 
will resolve electronically in the EDC system. 


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The Sponsor will produce an EDC Study Specification document that describes the 
quality checking to be performed on the data.  Central laboratory data, spirometry, 
HRCT, DLCO and other non-eCRF data will be sent directly to the Sponsor, using the 
Sponsor's standard procedures to handle and process the electronic transfer of these 
data. 
eCRFs and correction documentation will be maintained in the EDC system's audit trail.  
System backups for data stored by the Sponsor and records retention for the study data 
will be consistent with the Sponsor's standard procedures. 
PRO data will be collected through the use of an electronic device provided by a vendor 
(see Section 7.3 for details). 
7.2 
ELECTRONIC CASE REPORT FORMS 
eCRFs are to be completed through use of a Sponsor-designated EDC system.  Sites 
will receive training and have access to a manual for appropriate eCRF completion.  
eCRFs will be submitted electronically to the Sponsor and should be handled in 
accordance with instructions from the Sponsor. 
All eCRFs should be completed by designated, trained site staff.  eCRFs should be 
reviewed and electronically signed and dated by the investigator or a designee. 
At the end of the study, the investigator will receive patient data for his or her site in 
a readable format that must be kept with the study records.  Acknowledgement of receipt 
of the data is required. 
7.3 
ELECTRONIC PATIENT REPORTED OUTCOME DATA 
An electronic device will be used to capture PRO data.  The device is designed for entry 
of data in a way that is attributable, secure, and accurate, in compliance with FDA 
regulations for electronic records (21 CFR Part 11).  The data will be transmitted to 
a centralized database maintained by the electronic device vendor. 
The electronic data will be available for view access only, via a secure web server.  Only 
identified and trained users may view the data, and their actions will become part of the 
audit trail.  The Sponsor will have view access only.  System backups for data stored by 
the Sponsor and records retention for the study data will be consistent with the 
Sponsor's standard procedures. 
Once the study is complete, the data, audit trail, and trial and system documentation will 
be archived.  The investigator will receive patient data for the site in both human and 
machine-readable formats that must be kept with the study records as source data.  
Acknowledgement of receipt of the data is required.  In addition, the Sponsor will receive 
all data in a machine-readable format. 


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7.4 
SOURCE DATA DOCUMENTATION 
Study monitors will perform ongoing source data verification and review to confirm that 
critical protocol data (i.e., source data) entered into the eCRFs by authorized site 
personnel are accurate, complete, and verifiable from source documents.  
Source documents (paper or electronic) are those in which patient data are recorded 
and documented for the first time.  They include, but are not limited to, hospital records, 
clinical and office charts, laboratory notes, memoranda, patient-reported outcomes, 
evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, copies of transcriptions that are certified after verification as being accurate 
and complete, microfiche, photographic negatives, microfilm or magnetic media, X-rays, 
patient files, and records kept at pharmacies, laboratories, and medico-technical 
departments involved in a clinical trial. 
Before study initiation, the types of source documents that are to be generated will be 
clearly defined in the Trial Monitoring Plan.  This includes any protocol data to be 
entered directly into the eCRFs (i.e., no prior written or electronic record of the data) and 
considered source data. 
Source documents that are required to verify the validity and completeness of data 
entered into the eCRFs must not be obliterated or destroyed and must be retained per 
the policy for retention of records described in Section 7.6. 
To facilitate source data verification and review, the investigators and institutions must 
provide the Sponsor/ or delegate CRO direct access to applicable source documents 
and reports for trial-related monitoring, Sponsor audits, and IRB/EC review.  The study 
site must also allow inspection by applicable health authorities. 
7.5 
USE OF COMPUTERIZED SYSTEMS 
When clinical observations are entered directly into a study site's computerized medical 
record system (i.e., in lieu of original hardcopy records), the electronic record can serve 
as the source document if the system has been validated in accordance with health 
authority requirements pertaining to computerized systems used in clinical research.  An 
acceptable computerized data collection system allows preservation of the original entry 
of data.  If original data are modified, the system should maintain a viewable audit trail 
that shows the original data as well as the reason for the change, name of the person 
making the change, and date of the change. 
7.6 
RETENTION OF RECORDS 
Records and documents pertaining to the conduct of this study and the distribution of 
IMP, including eCRFs, electronic PRO and clinician-reported outcome data 
(if applicable), Informed Consent Forms, laboratory test results, and medication 
inventory records, must be retained by the Principal Investigator for 15 years after 


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completion or discontinuation of the study or for the length of time required by relevant 
national or local health authorities, whichever is longer.  After that period of time, the 
documents may be destroyed, subject to local regulations.   
No records may be disposed of without the written approval of the Sponsor.  Written 
notification should be provided to the Sponsor prior to transferring any records to 
another party or moving them to another location. 
Roche will retain study data for 25 years after the final study results have been reported 
or for the length of time required by relevant national or local health authorities, 
whichever is longer. 
8. 
ETHICAL CONSIDERATIONS 
8.1 
COMPLIANCE WITH LAWS AND REGULATIONS 
This study will be conducted in full conformance with the ICH E6 guideline for Good 
Clinical Practice and the principles of the Declaration of Helsinki, or the applicable laws 
and regulations of the country in which the research is conducted, whichever affords the 
greater protection to the individual.  The study will comply with the requirements of the 
ICH E2A guideline (Clinical Safety Data Management:  Definitions and Standards for 
Expedited Reporting).  Studies conducted in the United States or under a U.S. 
Investigational New Drug (IND) Application will comply with U.S. FDA regulations and 
applicable local, state, and federal laws.  Studies conducted in the European Union or 
European Economic Area will comply with the E.U. Clinical Trial Directive (2001/20/EC) 
and applicable local, regional, and national laws. 
8.2 
INFORMED CONSENT 
The Sponsor's sample Informed Consent Form (and ancillary sample Informed Consent 
Forms such as an Assent Form or Mobile Nursing Informed Consent Form, if applicable) 
will be provided to each site.  If applicable, it will be provided in a certified translation of 
the local language.  The Sponsor or its designee must review and approve any proposed 
deviations from the Sponsor's sample Informed Consent Forms or any alternate consent 
forms proposed by the site (collectively, the "Consent Forms") before IRB/EC 
submission.  The final IRB/EC-approved Consent Forms must be provided to the 
Sponsor for health authority submission purposes according to local requirements. 
If applicable, the Informed Consent Form will contain separate sections for any optional 
procedures.  The investigator or authorized designee will explain to each patient the 
objectives, methods, and potential risks associated with each optional procedure.  
Patients will be told that they are free to refuse to participate and may withdraw their 
consent at any time for any reason.  A separate, specific signature will be required to 
document a patient's agreement to participate in optional procedures.  Patients who 
decline to participate will not provide a separate signature. 


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The Consent Forms must be signed and dated by the patient or the patient's legally 
authorized representative before his or her participation in the study.  The case history or 
clinical records for each patient shall document the informed consent process and that 
written informed consent was obtained prior to participation in the study. 
The Consent Forms should be revised whenever there are changes to study procedures 
or when new information becomes available that may affect the willingness of the patient 
to participate.  The final revised IRB/EC-approved Consent Forms must be provided to 
the Sponsor for health authority submission purposes. 
If the Consent Forms are revised (through an amendment or an addendum) while 
a patient is participating in the study, the patient or a legally authorized representative 
must re-consent by signing the most current version of the Consent Forms or the 
addendum, in accordance with applicable laws and IRB/EC policy.  For any updated or 
revised Consent Forms, the case history or clinical records for each patient shall 
document the informed consent process and that written informed consent was obtained 
using the updated/revised Consent Forms for continued participation in the study. 
A copy of each signed Consent Form must be provided to the patient or the patient's 
legally authorized representative.  All signed and dated Consent Forms must remain in 
each patient's study file or in the site file and must be available for verification by study 
monitors at any time. 
For sites in the United States, each Consent Form may also include patient authorization 
to allow use and disclosure of personal health information in compliance with the U.S. 
Health Insurance Portability and Accountability Act (HIPAA) of 1996.  If the site utilizes 
a separate Authorization Form for patient authorization for use and disclosure of 
personal health information under the HIPAA regulations, the review, approval, 
and other processes outlined above apply except that IRB review and approval may not 
be required per study site policies. 
Upon treatment discontinuation, patients in Cohort A or B will automatically transition 
into Cohort C.  Subjects who have discontinued treatment from or have completed study 
WA42293 and do not wish to receive open label PRM-151, and want to participate in the 
study, will be required to sign a Cohort C informed consent form.  
8.3 
INSTITUTIONAL REVIEW BOARD OR ETHICS COMMITTEE 
This protocol, the Informed Consent Forms, any information to be given to the patient, 
and relevant supporting information must be submitted to the IRB/EC by the 
Principal Investigator and reviewed and approved by the IRB/EC before the study is 
initiated.  In addition, any patient recruitment materials must be approved by the IRB/EC.  
The Principal Investigator is responsible for providing written summaries of the status of 
the study to the IRB/EC annually or more frequently in accordance with the 


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requirements, policies, and procedures established by the IRB/EC.  Investigators are 
also responsible for promptly informing the IRB/EC of any protocol amendments (see 
Section 9.6). 
In addition to the requirements for reporting all adverse events to the Sponsor, 
investigators must comply with requirements for reporting serious adverse events to the 
local health authority and IRB/EC.  Investigators may receive written IND safety reports 
or other safety-related communications from the Sponsor.  Investigators are responsible 
for ensuring that such reports are reviewed and processed in accordance with health 
authority requirements and the policies and procedures established by their IRB/EC, and 
archived in the site's study file.  
8.4 
CONFIDENTIALITY 
The Sponsor maintains confidentiality standards by coding each patient enrolled in the 
study through assignment of a unique patient identification number.  This means that 
patient names are not included in data sets that are transmitted to any Sponsor location. 
Patient medical information obtained by this study is confidential and may be disclosed 
to third parties only as permitted by the Informed Consent Form (or separate 
authorization for use and disclosure of personal health information) signed by the 
patient, unless permitted or required by law. 
Medical information may be given to a patient's personal physician or other appropriate 
medical personnel responsible for the patient's welfare, for treatment purposes. 
Given the complexity and exploratory nature of exploratory biomarker analyses, data 
derived from these analyses will generally not be provided to study investigators or 
patients unless required by law.  The aggregate results of any conducted research will 
be available in accordance with the effective Sponsor policy on study data publication 
(see Section 9.5). 
Data generated by this study must be available for inspection upon request by 
representatives of national and local health authorities, Sponsor monitors, 
representatives, and collaborators, and the IRB/EC for each study site, as appropriate. 
Study data, which may include data on genomic variants, may be submitted to 
government or other health research databases or shared with researchers, government 
agencies, companies, or other groups that are not participating in this study.  These data 
may be combined with or linked to other data and used for research purposes, to 
advance science and public health, or for analysis, development, and commercialization 
of products to treat and diagnose disease.  In addition, redacted Clinical Study Reports 
and other summary reports will be provided upon request (see Section 9.5). 


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8.5 
FINANCIAL DISCLOSURE 
Investigators will provide the Sponsor with sufficient, accurate financial information in 
accordance with local regulations to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate health authorities.  
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study (see definition of end of 
study in Section 3.2). 
9. 
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION 
9.1 
STUDY DOCUMENTATION 
The investigator must maintain adequate and accurate records to enable the conduct of 
the study to be fully documented, including, but not limited to, the protocol, protocol 
amendments, Informed Consent Forms, and documentation of IRB/EC and 
governmental approval.  In addition, at the end of the study, the investigator will receive 
the patient data, including an audit trail containing a complete record of all changes to 
data. 
9.2 
PROTOCOL DEVIATIONS 
The investigator should document and explain any protocol deviations.  The investigator 
should promptly report any deviations that might have an impact on patient safety and 
data integrity to the Sponsor and to the IRB/EC in accordance with established IRB/EC 
policies and procedures.  The Sponsor will review all protocol deviations and assess 
whether any represent a serious breach of Good Clinical Practice guidelines and require 
reporting to health authorities.  As per the Sponsor's standard operating procedures, 
prospective requests to deviate from the protocol, including requests to waive protocol 
eligibility criteria, are not allowed. 
9.3 
MANAGEMENT OF STUDY QUALITY 
The Sponsor or delegate CRO will implement a system to manage the quality of the 
study, focusing on processes and data that are essential to ensuring patient safety and 
data integrity.  Prior to study initiation, the Sponsor or CRO will identify potential risks 
associated with critical trial processes and data and will implement plans for evaluating 
and controlling these risks.  Risk evaluation and control will include the selection of 
risk-based parameters (e.g., adverse event rate, protocol deviation rate) and the 
establishment of quality tolerance limits for these parameters prior to study initiation.  
Detection of deviations from quality tolerance limits will trigger an evaluation to 
determine if action is needed.  Details on the establishment and monitoring of quality 
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9.4 
SITE INSPECTIONS 
Site visits will be conducted by the Sponsor or an authorized representative for 
inspection of study data, patients' medical records, and eCRFs.  The investigator will 
permit national and local health authorities; Sponsor monitors, representatives, and 
collaborators; and the IRBs/ECs to inspect facilities and records relevant to this study. 
9.5 
ADMINISTRATIVE STRUCTURE 
This study is sponsored and managed by F. Hoffmann-La Roche Ltd.  A CRO will 
manage clinical site operations and medical monitoring. 
Approximately 400 sites globally will participate to enroll approximately 600700 
patients.  An IxRS will be used for study drug inventory management and to enroll 
patients onto this study. 
Central facilities will be used for certain study assessments throughout the study 
(e.g., specified laboratory tests, biomarker and PK analyses, PFTs), as specified in 
Section 4.5. 
Samples for urine pregnancy tests will be analyzed at site locally. 
Samples for PD, PK, biomarker and antibody tests will be sent to the Sponsor or 
a designee for storage and analysis. 
PRO data will be recorded electronically via devices supplied by a PRO vendor. 
HRCT imaging will be read centrally and managed by a central reading vendor(s). 
An iDMC will be employed to monitor and evaluate patient safety in Study WA42294 
only up until the time the database for primary analysis for Study WA42293 is locked, 
and Study WA42293 is unblinded to the Sponsor (i.e., for the duration of Study 
WA42293). 
A Clinical Adjudication Committee, an independent and blinded expert clinician panel, 
will adjudicate potential cases of acute exacerbations of IPF, hospitalizations for 
respiratory causes, and all deaths (for patients in Cohorts A and B only).  The definition 
of events for independent assessment, criteria for adjudication of events and details of 
the adjudication process will be provided in a charter.  The clinical expert panel's 
composition and a description of its responsibilities will also be provided in the charter. 
An Anaphylaxis Adjudication Committee, an independent and blinded committee 
composed of external experts in allergic diseases, will adjudicate all potential 
anaphylaxis cases reported by investigators to the Sponsor.  The committee will assess 
whether the reported event is a true anaphylaxis event (based on Sampson's criteria) 


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and whether the reported anaphylaxis event is causally related to study treatment.  
Further details will be provided in the Anaphylaxis Adjudication Charter. 
An external global Steering Committee, comprised of recognized experts in IPF, will 
provide oversight of Study WA42293 and Study WA42294.  Their roles and 
responsibilities will be outlined in the Steering Committee Charter. 
9.6 
DISSEMINATION OF DATA AND PROTECTION OF TRADE 
SECRETS 
Regardless of the outcome of a trial, the Sponsor is dedicated to openly providing 
information on the trial to healthcare professionals and to the public, at scientific 
congresses, in clinical trial registries, and in peer-reviewed journals.  The Sponsor will 
comply with all requirements for publication of study results.  Study data may be shared 
with others who are not participating in this study (see Section 8.4 for details), and 
redacted Clinical Study Reports and other summary reports will be made available upon 
request.  For more information, refer to the Roche Global Policy on Sharing of Clinical 
Trials Data at the following website: 
www.roche.com/roche_global_policy_on_sharing_of_clinical_study_information.pdf 
The results of this study may be published or presented at scientific congresses.  For all 
clinical trials in patients involving an IMP for which a marketing authorization application 
has been filed or approved in any country, the Sponsor aims to submit a journal 
manuscript reporting primary clinical trial results within 6 months after the availability of 
the respective Clinical Study Report.  In addition, for all clinical trials in patients involving 
an IMP for which a marketing authorization application has been filed or approved in any 
country, the Sponsor aims to publish results from analyses of additional endpoints and 
exploratory data that are clinically meaningful and statistically sound. 
The investigator must agree to submit all manuscripts or abstracts to the Sponsor prior 
to submission for publication or presentation.  This allows the Sponsor to protect 
proprietary information and to provide comments based on information from other 
studies that may not yet be available to the investigator. 
In accordance with standard editorial and ethical practice, the Sponsor will generally 
support publication of multicenter trials only in their entirety and not as individual center 
data.  In this case, a coordinating investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements.  Any formal publication 
of the study in which contribution of Sponsor personnel exceeded that of conventional 
monitoring will be considered as a joint publication by the investigator and the 
appropriate Sponsor personnel. 


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Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of data from this study will become and remain the exclusive and unburdened 
property of the Sponsor, except where agreed otherwise. 
9.7 
PROTOCOL AMENDMENTS 
Any protocol amendments will be prepared by the Sponsor.  Protocol amendments will 
be submitted to the IRB/EC and to regulatory authorities in accordance with local 
regulatory requirements. 
Approval must be obtained from the IRB/EC and regulatory authorities (as locally 
required) before implementation of any changes, except for changes necessary to 
eliminate an immediate hazard to patients or changes that involve logistical or 
administrative aspects only (e.g., change in Medical Monitor or contact information). 


PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
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10. 
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Ji Z, Ke ZJ, and Geng JG. SAP suppresses the development of experimental 
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Jo HE, Glaspole I, Moodley Y, et al. Disease progression in idiopathic pulmonary fibrosis 
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King TE Jr, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in 
patients with idiopathic pulmonary fibrosis. N Engl J Med 2014;370:208392. 
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Lettieri CJ, Nathan SD, Barnett SD, et al. Prevalence and outcomes of pulmonary 
arterial hypertension in advanced idiopathic pulmonary fibrosis. Chest 
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Lupher ML Jr, Gallatin WM. Regulation of fibrosis by the immune system. Adv Immunol 
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Mallinckrodt C, Lin Q, Lipkovich I, et al. A structured approach to choosing estimands 
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Mantovani A, Garlanda C, Doni A, et al. Pentraxins in innate immunity: From C-reactive 
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Moreira AP, Cavassani KA, Hullinger R, et al. Serum amyloid P attenuates M2 
macrophage activation and protects against fungal spore-induced allergic airway 
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Naik-Mathuria B, Pilling D, Crawford JR, et al. Serum amyloid P inhibits dermal wound 
healing. Wound Repair Regen 2008;16:26673. 
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following clinically meaningful declines in forced vital capacity: Analysis of data 
from three phase 3 trials in patients with idiopathic pulmonary fibrosis. Thorax 
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Nathan SD, Du Bois RM, Albera C, et al. 6-Minute walk test (6MWT) in patients with 
idiopathic pulmonary fibrosis (IPF): Confirmation of test performance 
characteristics [abstract]. Am Thorac Soc 2013; abstract 2360. 
Nathan SD, Du Bois RM, Albera C, et al. Validation of test performance characteristics 
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idiopathic pulmonary fibrosis. Respir Med. 2015;109:91422. 
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2014;20:46371. 
Neighbors M, Cabanski CR, Ramalingam TR, et al. Prognostic and predictive 
biomarkers for patients with idiopathic pulmonary fibrosis treated with pirfenidone: 
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Nintedanib [package insert]. Boeringher-Ingerlheim; 2019. 
Olson AL, Swigris JJ, Lezotte DC, et al. Mortality from pulmonary fibrosis increased in 
the United States from 1992 to 2003. Am J Respir Crit Care Med 
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Pepys MB, Booth DR, Hutchinson WL, et al. Amyloid P component. A critical review. 
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Pirfenidone [package insert]. Genentech; 2019. 
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Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: 
idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and 
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Raghu G, van den Blink B, Hamblin MJ, et al. Long-Term Safety and Efficacy of 
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definition and management of anaphylaxis: summary report: Second National 
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European Respiratory Society/American Thoracic Society: Measurement 
properties of field walking tests in chronic respiratory disease. Eur Respir J 
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Saketkoo LA, Mittoo S, Huscher D, et al. Connective tissue disease related interstitial 
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Swigris JJ, Wamboldt FS, Behr J, et al. The six-minute walk in idiopathic pulmonary 
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Wolters PJ, Blackwell TS, Eickelberg O, et al. Time for a change: Is idiopathic pulmonary 
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the disease. PLoS One 2011;6:e22659. 








 
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Appendix 1 Schedule of Activities for Cohorts A and B (cont.) 
 
ADAanti-drug antibody; AEadverse event; Discon.discontinued; DLCOdiffusing capacity for carbon monoxide; EOSend of study; 
EQ-5D-5LEuroQol 5-Dimension, 5-Level Questionnaire; HRCThigh-resolution computed tomography; IPFidiopathic pulmonary fibrosis; 
IRRinfusion-related reaction; OLEopen-label extension; PCRpolymerase chain reaction; PDpharmacodynamic; PKpharmacokinetic; 
SGRQSt. George Respiratory Questionnaire; SAEserious adverse event; SARS-CoV-2severe acute respiratory syndrome coronavirus 2; 
UCSD-SOBQUniversity of California, San DiegoShortness of Breath Questionniare; W52Week 52; WOCBwomen of childbearing potential. 
a Eligibility visit can occur on the same day as dosing as long as eligibility criteria have been confirmed prior to dosing. 
b Patients who are rolling-over from Study WA42293 will not be required to repeat safety and efficacy assessment at Day 1 if the visit occurs within 
4 weeks of Week 52. 
c Patients from the active treatment arm in Study WA42293 will be given placebo doses at Day 3 and Day 5. 
d Treatment discontinuation visit should occur 4 weeks after the last dose of study drug.  Study discontinuation visit should occur, 4 weeks after 
the treatment discontinuation visit (8 weeks after the last dose of study drug). 
e To allow for flexibility around weekends, holidays, etc., the loading dose visits may occur over a time span of up to 8 days, with a minimum of 
1 full calendar day between administration of doses (patients must not be dosed on consecutive days). In case one or more loading doses have 
been missed or delayed beyond the 8-day loading phase window, loading doses should be administered again at the next scheduled visit.  No 
loading doses should be administered outside of the 8-day loading phase window. 
f On dosing days, vital signs should be completed predose (within 60 minutes prior to dosing), every 15 minutes during infusion, and 60 minutes 
postdose. 
g Full physical exam at eligibility visit and an abbreviated physical exam, thereafter. 
h Clinical laboratories will be assessed every 4 weeks for the first 12 weeks and every 12 weeks thereafter.   
i Patients will have a baseline assessment for SARS-CoV-2 serology at baseline, then every 3 months for exploratory efficacy objectives.  In the 
event of an acute respiratory exacerbation or infection during the study, additional SARS-CoV-2 serology or PCR testing may be performed as 
needed, according to local guidelines. 
j Blood samples for ADA, serum tryptase, and complement C3 analyses should be obtained at the time of the events of  Grade 2 infusion-related 
reactions, or suspected anaphylaxis, or hypersensitivity reactions whenever possible.  Serum tryptase should be collected between 1 and 6 
hours after the event.  Blood samples for ADA, serum tryptase, and complement C3 analyses should be obtained at the first follow-up visit after 
the events of suspected anaphylaxis, or hypersensitivity reactions. 
k SGRQ, UCSD-SOBQ, and EQ-5D-5L are to be completed in this order and prior to any other trial related procedures. 
l HRCT will be performed at Week 52 and Week 104 only for patients who had HRCTs performed during Study WA42293.  


 
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m Repeat loading doses will be required if patients miss any 4-weekly infusions of study treatment.  Following a missed infusion, the patient should 
receive three doses on alternate days, at the next scheduled visit; scheduled efficacy assessments will only be performed on the first of the three 
loading dose days, if applicable.  In exceptional circumstances, if the site is unable to perform all study procedures on the same day or at the 
same site, study drug infusion may be administered up to 48 hours after the on-site efficacy assessments, providing that these are completed 
within the 5-day visit window.  However, the sequence of procedures must be maintained, and all efforts should be made to complete study 
assessments and procedures on the same date. 
 






Appendix 3 
Schedule of Pharmacokinetic, Immunogenicity, and Biomarker Samples for 
Cohort A  
 
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Visit 
Timepoint 
Window
Sample Type a 
Week 12 
Prior to the start of IV infusion 
2 to 
0 hours
PRM-151 PK b 
PRM-151 PD biomarker (serum, 
plasma, and Paxgene for RNA) 
PRM-151 ADA b 
2 hours after the start of 
IV infusion 
 
15 min 
PRM-151 PK b 
 
PRM-151 PD biomarker (serum, 
plasma, and Paxgene for RNA) 
Week 24 
Prior to the start of IV infusion 
2 to 
0 hours 
PRM-151 PK b 
PRM-151 PD biomarker (serum, 
plasma, and Paxgene for RNA) 
PRM-151 ADA b 
2 hours after the start of 
IV infusion 
15 min 
PRM-151 PK b 
 
 
PRM-151 PD biomarker (serum, 
plasma, and Paxgene for RNA) 
Unscheduled 
visit c 
NA 
NA 
PRM-151 PK b 
PRM-151 PD biomarker (serum, 
plasma, and Paxgene for RNA) 
PRM-151 ADA b 
ADAanti-drug antibody; IPFidiopathic pulmonary fibrosis; IVintravenous; 
PDpharmacodynamic; PKpharmacokinetic. 
a Blood draws for PK/ADA/PD biomarker samples must be taken from the opposite arm from 
study drug administration. 
b PK samples will be collected as plasma, and ADA samples will be collected as serum.  
c Up to 24 weeks of treatment, in circumstances when drug reloading is required, if the first day of 
the start of reloading does not coincide with the planned sample collection dates, PK, ADA, and 
biomarker samples should be taken prior to the start of the first loading dose. 
 




Appendix 4 
Schedule of Pharmacokinetic, Immunogenicity, and Biomarker Samples for 
Cohort B 
 
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Week 24 
Prior to the start 
of IV infusion 
−2 to 
0 hours 
PRM-151 PK b 
Urine d 
PRM151 PD biomarker (serum, 
plasma, and Paxgene- for RNA) 
PRM-151 ADA b 
2 hours after the 
start of 
IV infusion 
15 min 
PRM-151 PK b 
PRM151 PD biomarker (serum, 
plasma, and Paxgene for RNA) 
Unscheduled 
visit c 
NA 
NA 
PRM-151 PK b 
 
PRM-151 PD biomarker (serum, 
plasma, and Paxgene for RNA) 
PRM-151 ADA b 
Every 12 
weeks up to 2 
years 
Prior to the start 
of IV infusion 
−2 to 
0 hours 
Urine d 
ADAanti-drug antibody; IPFidiopathic pulmonary fibrosis; IVintravenous; PDpharmacodynamic; 
PKpharmacokinetic. 
a Blood draws for PK/ADA/PD biomarker samples must be taken from the opposite arm from study 
drug administration. 
b PK samples will be collected as plasma, and ADA samples will be collected as serum.  PK/ADA 
samples will ONLY be collected from patients who enrolled into the WA42293 prior to 1 June 
2022.  
c Up to 24 weeks of treatment, in circumstances when drug reloading is required, if the first day of 
the start of reloading does not coincide with the planned sample collection dates, PK, ADA, and 
biomarker samples should be taken prior to the start of the first loading dose. 
d The urine samples are optional and should be obtained from any individual from cohort B who 
signs the separate RBR Informed Consent Form to collect residual samples at assigned clinical 
visits, and only for up to 2 years. 
 


PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
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Appendix 5 Sampson's Criteria for Diagnosing Potential Cases 
of Anaphylaxis 
Anaphylaxis is highly likely when any one of the following three criteria is fulfilled: 
1. 
Acute onset of an illness (minutes to several hours) with involvement of the skin, 
mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen 
lips-tongue-uvula) 
AND AT LEAST ONE OF THE FOLLOWING: 
a) Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced 
peak expiratory flow [PEF], hypoxemia) 
b) Reduced blood pressure (BP) or associated symptoms of end-organ dysfunction 
(e.g., hypotonia [collapse], syncope, incontinence) 
 
2. 
Two or more of the following that occur rapidly after exposure to a likely allergen for 
that patient (minutes to several hours): 
a) Involvement of the skinmucosal tissue (e.g., generalized hives, itchflush, 
swollen lipstongueuvula) 
b) Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced 
PEF, hypoxemia) 
c) 
Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, 
incontinence) 
d) Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting) 
 
3. 
Reduced BP after exposure to known allergen for that patient (minutes to several 
hours): 
a) Adults:  systolic BP of less than 90 mm Hg or greater than 30% decrease from 
that person's baseline 
 
REFERENCE 
Sampson HA, Munoz-Furlong A, Campbell RL, et al: Second symposium on the 
definition and management of anaphylaxis: summary report: Second National 
Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network 
Symposium. J Allergy Clin Immunol 2006;117: 3917. 
 
 


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Appendix 6 St. George’s Respiratory Questionnaire 
Do not reproduce or distribute.  The Sponsor will provide 
sites with all instruments to be completed in this study. 
 
 


Appendix 6: St. George’s Respiratory Questionnaire 
 
PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
107/Protocol WA42294, Version 4 
 


Appendix 6: St. George’s Respiratory Questionnaire 
 
PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
108/Protocol WA42294, Version 4 


Appendix 6: St. George’s Respiratory Questionnaire 
PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
109/Protocol WA42294, Version 4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Appendix 6: St. George’s Respiratory Questionnaire 
PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
110/Protocol WA42294, Version 4 
 
 
 


Appendix 6: St. George’s Respiratory Questionnaire 
PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
111/Protocol WA42294, Version 4 
 
 


 
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112/Protocol WA42294, Version 4 
Appendix 7 University of California, San DiegoShortness of 
Breath Questionnaire 
Do not reproduce or distribute.  The Sponsor will provide 
sites with all instruments to be completed in this study. 
 
 


Appendix 7:  University of California, San DiegoShortness- of Breath Questionnaire 
PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
113/Protocol WA42294, Version 4 
 
 


Appendix 7:  University of California, San DiegoShortness- of Breath Questionnaire 
PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
114/Protocol WA42294, Version 4 
 
 


Appendix 7:  University of California, San DiegoShortness- of Breath Questionnaire 
PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
115/Protocol WA42294, Version 4 
 
 


PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
116/Protocol WA42294, Version 4 
Appendix 8 EuroQol 5-Dimension Questionnaire, 5-Level 
Version 
Do not reproduce or distribute.  The Sponsor will provide 
sites with all instruments to be completed in this study. 
 
 


Appendix 8:  EuroQol 5-Dimension Questionnaire, 5-Level Version 
 
PRM-151(Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd. 
117/Protocol WA42294, Version 4 


 
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Appendix 9 National Cancer Institute Common Terminology 
Criteria for Adverse Events 
The United States of America (USA) National Cancer Institute Common Terminology 
Criteria for Adverse Events, version 5.0 (NCI CTCAE, v.5.0) can be found on the 
following website. 
https://ctep.cancer.gov/protocolDevelopment/electronic applications/ctc.htm#ctc 50 
[Accessed: 21 September 2019] 
This version of CTCAE is compatible at the AE (Adverse Event) term level where each 
CTCAE term is a Medical Dictionary for Regulatory Activities Terminology (MedDRA) 
LLT (Lowest Level Term).  CTCAE v5.0 includes 811 AE terms and 26 'Other, specify' 
options for reporting text terms not listed in CTCAE.  Each AE term is associated with a 
5-point severity scale. 
 
 


 
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Appendix 10  
Borg Scale for Rating Dyspnea and Overall 
Fatigue (CR10) 
 
 
 
 
 
 
 


Signature Page for: System identifier:RIM-CLIN-438682
Protocol - WA42294 - ZINPENTRAXIN ALFA - v4 - Global/Core- Published
Approval Task
Company Signatory
28-Apr-2022 09:00:20 GMT+0000

SAP_001.pdf: 
 
Official Title: A Phase III Open-Label Extension Study to Evaluate Long-Term 
Safety and Efficacy of PRM-151 in Patients With Idiopathic Pulmonary 
Fibrosis (IPF) 
NCT Number: NCT04594707 
Document Dates: SAP Version 1: 24-August-2022 
 
 
 


STATISTICAL ANALYSIS PLAN APPROVAL 
 
 
SPONSOR: 
LEGAL REGISTERED 
ADDRESS: 
F. Hoffmann-La Roche Ltd 
Grenzacherstrasse 124 
4070 Basel, Switzerland 
DATE FINAL: 
See electronic signature on the last page of this 
document. 
CONFIDENTIAL 
 
This is an F. Hoffmann-La Roche Ltd document that contains confidential information.  Nothing 
herein is to be disclosed without written consent from F. Hoffmann-La Roche Ltd. 
 
PRM-151 (Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd 
Statistical Analysis Plan WA42294 
 
STATISTICAL ANALYSIS PLAN 
STUDY TITLE: A PHASE III OPEN-LABEL EXTENSION STUDY TO EVALUATE 
LONG-TERM SAFETY AND EFFICACY OF PRM-151 IN PATIENTS 
WITH IDIOPATHIC PULMONARY FIBROSIS (IPF) 
 
STUDY NUMBER: 
WA42294 
 
STUDY NAME:  
STARSCAPE OLE 
 
VERSION NUMBER: 
1 
 
ROCHE COMPOUND: 
Recombinant human pentraxin-2 (rhPTX-2; PRM-151; 
RO7490677) [Zinpentraxin Alfa] 
 
EUDRACT NUMBER: 
2020-001429-30 
 
IND NUMBER: 
110,774 
 
NCT NUMBER: 
NCT04594707 
 
PLAN PREPARED BY: 
, Ph.D. 
 


 
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STATISTICAL ANALYSIS PLAN VERSION HISTORY 
This Statistical Analysis Plan (SAP) was developed based on Roche SAP model 
document Version 2, 26 October 2020. 
SAP Version 
Approval Date 
Based on Protocol  
(Version, Approval Date) 
1 
See electronic signature on 
the last page of this 
document 
Version 4, 28 April 2022 
 


 
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TABLE OF CONTENTS 
1. 
INTRODUCTION ............................................................................. 7 
1.1 
Objectives and Endpoints .......................................................... 7 
1.2 
Study Design ........................................................................... 10 
1.2.1 
Treatment Assignment ............................................................. 13 
1.2.2 
Independent Review Facility .................................................... 14 
1.2.2.1 
Assessment for Suspected Anaphylaxis .................................. 14 
1.2.2.2 
Acute Exacerbations of IPF and Suspected Acute 
Exacerbations of IPF ............................................................... 15 
1.2.2.3 
Hospitalizations for Respiratory Causes .................................. 16 
1.2.2.4 
Deaths due to Respiratory Causes .......................................... 16 
1.2.2.5 
Health Care Utilization for Respiratory Events ......................... 16 
1.2.3 
Data Monitoring ....................................................................... 16 
2. 
STATISTICAL HYPOTHESES ...................................................... 16 
3. 
SAMPLE SIZE DETERMINATION ................................................ 17 
4. 
ANALYSIS SETS .......................................................................... 17 
5. 
STATISTICAL ANALYSES ........................................................... 18 
5.1 
General Considerations ........................................................... 19 
5.1.1 
Treatment/Patient Group Terminology by Cohort .................... 19 
5.2 
Patient Disposition ................................................................... 20 
5.3 
Safety Analysis ........................................................................ 20 
5.3.1 
Extent of Exposure .................................................................. 21 
5.3.2 
Adverse Events ........................................................................ 21 
5.3.3 
Adjudicated Anaphylactic and Hypersensitivity Reactions ....... 23 
5.3.4 
Laboratory Data ....................................................................... 23 
5.3.5 
Vital Signs ................................................................................ 24 
5.3.6 
ECGs ....................................................................................... 24 
5.3.7 
Other Safety Endpoints ............................................................ 24 
5.4 
Efficacy Analysis ...................................................................... 24 
5.4.1 
Time-to-Event Endpoints ......................................................... 26 
5.5 
Exploratory Efficacy Analysis ................................................... 27 


 
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5.5.1 
Time-to-Event Exploratory Endpoints ...................................... 28 
5.5.2 
Additional Exploratory Efficacy Endpoints ............................... 29 
5.6 
Other Analyses ........................................................................ 30 
5.6.1 
Summaries of Conduct of Study .............................................. 30 
5.6.2 
Summaries of Demographics and Baseline Characteristics .... 30 
5.6.3 
Pharmacokinetic Analyses ....................................................... 30 
5.6.4 
Biomarker Analyses ................................................................. 31 
5.6.5 
Immunogenicity Analyses ........................................................ 32 
5.6.6 
Analyses of Subgroups of Interest ........................................... 32 
5.6.7 
Analyses of China Subpopulation ............................................ 33 
5.6.8 
Other Analyses ........................................................................ 33 
6. 
SUPPORTING DOCUMENTATION .............................................. 33 
7. 
REFERENCES.............................................................................. 34 
 
LIST OF TABLES 
Table 1 
Objectives and Corresponding Endpoints ..................................... 7 
Table 2 
Analysis Populations ................................................................... 17 
Table 3 
Analysis Strategy for Intercurrent Events for FVC, 6MWD, 
FVC% Predicted, and DLCO ........................................................ 25 
Table 4 
Strategy for Addressing Intercurrent Events: Time-to-Event 
Endpoints .................................................................................... 27 
Table 5 
Strategy for Addressing Intercurrent Events: Time-to-Event 
Exploratory Endpoints ................................................................. 29 
Table 6 
Subgroup Definitions ................................................................... 33 
 
 
LIST OF FIGURES 
Figure 1 
Cohort Allocation ......................................................................... 11 
Figure 2 
Study Schema ............................................................................. 11 
Figure 3 
Initial Loading Doses for Cohorts A and B .................................. 13 


 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
6MWD 
6-minute walk distance 
6MWT 
6-minute walk test 
ADA 
anti-drug antibody 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
CI 
confidence interval 
COVID-19 
Coronavirus Disease 2019 
DLCO 
carbon monoxide diffusing capacity 
eCRF 
electronic Case Report Form 
EQ-5D-5L 
EuroQol 5-Dimension, 5-Level Questionnaire 
EuroQol 
European Quality of Life Scale 
FAS 
full analysis set 
FDA 
U.S. Food and Drug Administration 
FVC 
forced vital capacity 
HRCT 
high-resolution computed tomography 
iDMC 
independent Data Monitoring Committee 
IPF 
idiopathic pulmonary fibrosis 
IRR 
infusion-related reaction 
IV 
intravenous 
IxRS 
interactive voice/web-based response system 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse 
Events 
OLE 
open-label extension 
PD 
pharmacodynamic 
PFTs 
pulmonary function tests 
PK 
pharmacokinetic 
PRO 
patient-reported outcomes 
PT 
Preferred Term 
Q4W 
every 4 weeks 
zinpentraxin alfa 
recombinant human pentraxin 2, PRM-151 
SAE 
serious adverse events 
SAP 
Statistical Analysis Plan 


 
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SGRQ 
St. George Respiratory Questionnaire 
SOC 
standard of care 
SpO2 
oxygen saturation levels 
TEAE 
treatment-emergent adverse event 
UCSD-SOBQ 
University of California, San Diego Shortness of Breath 
Questionnaire 
ULN 
upper limit of normal 
 
 


 
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1. 
INTRODUCTION 
This Statistical Analysis Plan (SAP) provides details on the study design, outcome 
measures, and statistical analysis plan for Study WA42294 (STARSCAPE OLE).  The 
International Nonproprietary Name (INN) zinpentraxin alfa is now the preferred name of 
the study drug under investigation (rather than PRM-151 or rhPTX-2); it will be used 
throughout this SAP wherever possible.  The analyses and endpoints specified in this 
document supersede the analysis plan described in the study protocol. 
1.1 
OBJECTIVES AND ENDPOINTS 
This study will evaluate the long-term safety, efficacy, and pharmacokinetics of 
open-label zinpentraxin alfa in patients with idiopathic pulmonary fibrosis (IPF).  Specific 
objectives and corresponding endpoints for the study are outlined in Table 1. 
Table 1 
Objectives and Corresponding Endpoints 
Safety Objective 
Corresponding Endpoints 
 
To confirm the long-term safety 
and tolerability of 10 mg/kg of 
zinpentraxin alfa administered 
every 4 weeks (Q4W) via IV 
infusion plus standard of care 
(SOC) treatment 
 
Incidence and severity of adverse events (AE), with 
severity determined according to the 5-point 
severity scale (National Cancer Institute Common 
Terminology Criteria for Adverse Events, Version 
5.0 [NCI CTCAE, v.5.0]) 
 
Incidence and severity of infusion-related reactions 
(IRRs) and other AEs of special interest 
 
Proportion of patients permanently discontinuing 
study treatment due to AEs 
 
Change from baseline in targeted clinical 
laboratory test results 
Efficacy Objective 
Corresponding Endpoints 
 
To assess the long-term efficacy 
of 10 mg/kg zinpentraxin alfa 
plus SOC (excluding lung 
transplantation) administered 
Q4W via IV infusion 
 
Annual rate of change in FVC (mL) 
 
Annual rate of change in 6-minute walk distance 
(6MWD) 
 
Annual rate of change in FVC% predicted 
 
Annual rate of change from baseline in carbon 
monoxide diffusing capacity (DLCO) 
 
Time to disease progression, defined as time to 
first occurrence of 10% absolute decline in % 
predicted FVC,   5% relative decline in 6MWD, or 
death 
 
Survival, as measured by all-cause mortality  
 
IPF-related mortality and respiratory-related 
mortality 


 
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Table 1 
Objectives and Corresponding Endpoints (cont.)  
Exploratory Efficacy 
Objective(s) 
Corresponding Endpoints 
 
To assess the long-term efficacy 
of 10 mg/kg zinpentraxin alfa 
plus SOC (excluding lung 
transplantation) administered 
Q4W via IV infusion 
 
Change from baseline in University of California, 
San Diego Shortness of Breath Questionnaire 
(UCSD SOBQ) 
 
Change from baseline in St. George Respiratory 
Questionnaire (SGRQ) Total Score 
 
Time to first respiratory-related hospitalizations 
(defined as non-elective hospitalizations due to any 
respiratory cause, including acute exacerbations of 
IPF, or suspected acute exacerbations of IPF, as 
determined by Adjudication Committee) 
 
Time to first acute exacerbation of IPF 
 
See Section 5.5 
 
To explore additional measures 
and subgroups of interest 
including concurrent use of IPF 
treatment and geographic region 
 
See Section 5.6.6  
 
To assess the long-term impact 
of 10 mg/kg zinpentraxin alfa 
plus SOC on healthcare 
utilization for respiratory events. 
 
Length of hospital stay in days for respiratory-
related hospitalizations 
 
Total time in intensive care units in days due to 
respiratory causes 
 
Unscheduled outpatient clinic/urgent 
care/emergency room utilization related to 
respiratory events 
 
 
 


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Table 1 
Objectives and Corresponding Endpoints (cont.) 
Pharmacokinetic Objective 
Corresponding Endpoint 

To characterize
pharmacokinetics of zinpentraxin
alfa in patients with IPF (from
Cohort A, and Cohort B, who are
enrolled in the WA42293 study
prior to 1 June 2022)

Plasma concentrations of zinpentraxin alfa at
specified timepoints
Exploratory Pharmacokinetic 
Objective 
Corresponding Endpoint 

To evaluate the potential
relationship between drug
exposure and the efficacy and
safety of zinpentraxin alfa (from
Cohort A, and Cohort B, who are
enrolled in the WA42293 study
prior to 1 June 2022)

Relationship between PK for zinpentraxin alfa and
efficacy endpoints

Relationship between PK for zinpentraxin alfa and
safety endpoints
Immunogenicity Objective 
Corresponding Endpoint 

To evaluate the immune
response to zinpentraxin alfa in
patients with IPF (from Cohort A,
and Cohort B, who are enrolled
in the WA42293 study prior to
1 June 2022)

Prevalence of ADAs at baseline and incidence of
ADAs during the study
Exploratory Immunogenicity 
Objective 
Corresponding Endpoint 

To evaluate the immune
response to zinpentraxin alfa in
patients with IPF (from Cohort A,
and Cohort B, who are enrolled
in the WA42293 study prior to
1 June 2022)

Relationship between ADA status and efficacy,
safety, or PK endpoints


 
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Table 1 
Objectives and Corresponding Endpoints (cont.)  
Exploratory Biomarker 
Objective 
Corresponding Endpoint 
 
To identify and/or evaluate 
biomarkers that can provide 
evidence of zinpentraxin alfa 
activity and the duration of that 
activity (i.e., pharmacodynamic 
biomarkers), are associated with 
acquired resistance to 
zinpentraxin alfa, are associated 
with susceptibility to developing 
AEs or can lead to improved AE 
monitoring or investigation 
(i.e., safety biomarkers), or can 
increase the knowledge and 
understanding of disease biology 
and drug safety (Cohort A and 
Cohort B) 
 
Relationship between biomarkers in blood listed in 
Protocol Section 4.5.10 (Laboratory, Biomarker, 
and Other Biological Samples) and safety, efficacy, 
PK, immunogenicity, or other biomarker endpoints 
Exploratory Health Status 
Utility Objective 
Corresponding Endpoint 
 
To evaluate health status utility 
scores of patients treated with 
zinpentraxin alfa plus SOC 
 
Annual rate of change in EuroQol 5 Dimension, 5 
Level Questionnaire (EQ 5D 5L) index based, and 
visual analog scale (VAS) scores 
ADAanti-drug antibody; AE  adverse event; DLCOcarbon monoxide diffusing capacity; 
EuroQol  European Quality of Life Scale; FVCforced vital capacity; IRRinfusion-related 
reaction; PK  pharamcokinetic; zinpentraxin alfa  Recombinant human pentraxin-2 (PRM-151, 
RO7490677). 
  
1.2 
STUDY DESIGN 
This open-label extension (OLE) study is being conducted to confirm the long-term 
safety, efficacy, and pharmacokinetics of zinpentraxin alfa in the treatment of eligible 
patients with IPF.  Eligible patients from the Phase II Study PRM-151-202 who have 
received the open-label zinpentraxin alfa will be enrolled into Cohort A and patients who  
have completed the Phase III Study WA42293 will be enrolled into Cohort B.  
Additionally, patients who have discontinued treatment from or have completed 
Study WA42293 and do not want to receive open-label zinpentraxin alfa in this study, will 
be invited to enroll in survival follow-up Cohort C.  Patients in Cohort C will not receive 
any treatment and will not undergo any safety or efficacy assessments during the study 
(see Figure 1).  Patients who discontinue treatment from Cohorts A and B will 
automatically transition to Cohort C for long-term follow-up, unless they withdraw 
consent from the study. 
The study schema is shown in Figure 2. 


 
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Figure 1 Cohort Allocation  
 
a 
Only Cohorts A and B receive active treatment. 
OLE  open-label extension. 
 
Figure 2 Study Schema 
 
IVintravenous; Q4Wevery 4 weeks.  
PRM-151 to be read as zinpentraxin alfa or rhPTX-2. 
  
Patients meeting the eligibility criteria for the study will receive zinpentraxin alfa 
10 mg/kg every 4 weeks (Q4W).  Throughout the study, patients will be monitored for 
safety by collection of adverse events (AEs; both serious and non-serious) and by 
regular physical exam and safety laboratory assessments. 
Efficacy will be evaluated through assessment of functional capacity as measured by 
forced vital capacity (FVC), 6-minute walk distance (6MWD), other pulmonary function 
tests (PFTs), and assessment of patients with respiratory events leading to 
hospitalizations, progression of disease, or acute IPF exacerbations. 


 
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Patient reported outcomes (PRO) will be assessed using the St. George Respiratory 
Questionnaire (SGRQ), University of California, San Diego Shortness of Breath 
Questionnaire (UCSD-SOBQ), and European Quality of Life Scale (EuroQol) 
5‑Dimension, 5-Level Questionnaire (EQ-5D-5L). 
Dyspnea, fatigue, and blood oxygen saturation levels (SpO2) will be assessed based on 
measurements taken during the 6-minute walk test (6MWT).  High-resolution computed 
tomography (HRCT) of the chest will be assessed for changes between Week 52 from 
Study WA42293 to Week 52 (OLE) and Week 104 (OLE).  Treated patients will be 
followed-up until the end of the study period, unless the patient withdraws consent for 
follow-up or death occurs. 
For all patients receiving anti-fibrotic therapy, the investigator should document the dose, 
frequency, and duration of the anti-fibrotic drug. 
During the study, patients may initiate background therapy of pirfenidone or nintedanib, if 
determined to be clinically indicated by the investigator.  The study investigator is 
required to document the specific reason for introducing anti-fibrotic therapy in patients 
who started the study not on anti-fibrotic therapy. 
Approximately 600700 patients are expected to enroll in the study.  Patients will initially 
receive loading doses of either zinpentraxin alfa 10 mg/kg intravenous (IV) infusion 
and/or placebo over 5070 minutes on Days 1, 3, and 5, then one infusion of 
zinpentraxin alfa Q4W until the end of the study.  Patients previously on the placebo arm 
of Study WA42293 will receive zinpentraxin alfa in all three loading doses, whereas 
patients previously on the active treatment arm of Study WA42293 will receive 
zinpentraxin alfa for the first dose, followed by placebo doses at the second and third 
loading dose visit.  The loading doses will be blinded for Cohort B, to ensure that the 
blind in Study WA42293 is maintained for patients, site staff, and the Sponsor (see 
Figure 3). 


 
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Figure 3 Initial Loading Doses for Cohorts A and B 
 
PRM-151 to be read as zinpentraxin alfa. 
  
Patients entering Cohort A, from Study PRM-151-202, will have an eligibility visit prior to 
commencing dosing.  The eligibility visit can occur on the same day as the dosing visit, if 
the patient is confirmed to be eligible for the study. 
Patients entering Cohort B, from Study WA42293, will have their end-of-WA42293-study 
visit at Week 52.  All assessments from the Week 52 Study WA42293 visit must be 
completed prior to commencing dosing in the OLE study.  Ideally, patients will be 
enrolled into Cohort B on the same day as their Week 52 (Study WA42293) visit. 
Patients enrolling into Cohort C from Study WA42293 (e.g., those who do not wish to 
receive study treatment), or those who transition from Cohorts A and B, will be 
followed-up for the duration of this study, to collect their survival data. 
1.2.1 
Treatment Assignment 
In this study all patients in Cohorts A and B will receive zinpentraxin alfa. 
Patients enrolling in Cohort A will receive three loading doses of open-label zinpentraxin 
alfa on Days 1, 3, and 5, followed by Q4W infusions. 
For patients enrolling in Cohort B: 
 
Patients previously randomized to placebo in Study WA42293 will receive three 
loading doses on Days 1, 3, and 5 in a blinded fashion.  All three doses will contain 
zinpentraxin alfa. 


 
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 
Patients previously randomized to zinpentraxin alfa in Study WA42293 will receive 
three loading doses on Days 1, 3, and 5 in a blinded fashion.  First of the three 
doses will contain zinpentraxin alfa, whereas the subsequent two doses will contain 
placebo. 
 
In order to maintain the blind to the treatment assignment of Study WA42293, all 
patients in Cohort B will be dosed in a blinded fashion on Days 1, 3, and 5 of the 
initial loading dose (see Figure 3). 
 
If the first loading dose in patients in Cohort B is delayed and occurs more than 3 weeks 
(21 days) after the Week 52 visit in Study WA42293, patients will receive all three 
loading doses with zinpentraxin alfa (in a blinded fashion). 
To minimize bias in this study, patients and the evaluating physicians will be blinded to 
treatment assignment of Study WA42293 until all patients have either completed the 
study or discontinued early from the study, the Study WA42293 database is locked, and 
the Study WA42293 analyses are final. 
1.2.2 
Independent Review Facility 
An Anaphylaxis Adjudication Committee, an independent and blinded committee 
composed of external experts in allergic diseases, will adjudicate all potential 
anaphylaxis cases reported by investigators to the Sponsor.  The committee will assess 
whether the reported event is a true anaphylaxis event (based on Sampson's criteria) 
and whether the reported anaphylaxis event is causally related to study treatment.  
Further details will be provided in the Anaphylaxis Adjudication Charter. 
An independent, blinded Adjudication Committee will be convened to review all available 
data for all potential cases of acute exacerbations of IPF, hospitalizations for respiratory 
causes, and all deaths (applicable for Cohorts A and B only).  This Adjudication 
Committee will be comprised of pulmonary disease physicians familiar with IPF 
exacerbations.  A charter for the Adjudication Committee will provide further details.  
The Adjudication Committee will determine if the reported events meet the criteria of 
acute exacerbation of IPF, hospitalization for respiratory causes, and deaths (including 
deaths related specifically to respiratory causes) as defined in the charter.  
1.2.2.1 
Assessment for Suspected Anaphylaxis 
Assessment of potential anaphylaxis will be conducted at every infusion per the clinical 
criterion for diagnosing anaphylaxis as described in Appendix 4 of Protocol  Sampson's 
Criteria for Diagnosing Potential Cases of Anaphylaxis.  Patients experiencing suspected 
anaphylaxis should be managed as per local guidelines.  Laboratory samples (serum 
tryptase, anti-drug antibody [ADA], complement C3) should be collected similarly to 
infusion-related reactions (IRRs). 
All potential anaphylaxis cases reported by investigators to the Sponsor will be 
subsequently submitted for adjudication to an Anaphylaxis Adjudication Committee 


 
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composed of external experts in allergic diseases.  The committee will assess whether 
the reported event is a true anaphylaxis event (based on Sampson's criteria) and 
whether the reported anaphylaxis event is causally related to zinpentraxin alfa. 
If a patient has signs or symptoms of an anaphylactic or serious hypersensitivity reaction 
(including events deemed to have met the criteria as described by Sampson according 
to the blinded Anaphylaxis Adjudication Committee), administration of the study drug 
must be discontinued permanently. 
Further details are outlined in the Anaphylaxis Adjudication Charter.  
1.2.2.2 
Acute Exacerbations of IPF and Suspected Acute 
Exacerbations of IPF 
Acute exacerbation of IPF is defined as an acute, clinically significant respiratory 
deterioration characterized by evidence of new widespread alveolar abnormality, marked 
by the following diagnostic criteria (Collard et al. 2016): 
 
Previous or concurrent diagnosis of IPF 
 
Acute worsening or development of dyspnea typically 30 days in duration 
 
Computed tomography with new bilateral ground-glass opacity and/or consolidation 
superimposed on a background pattern consistent with usual interstitial pneumonia 
pattern 
 
Deterioration not fully explained by cardiac failure or fluid overload 
 
Acute exacerbations of IPF are further categorized as triggered acute exacerbation or 
idiopathic acute exacerbation, depending on whether an underlying trigger for acute 
exacerbation is found (e.g., infection, post-procedural/postoperative, drug toxicity, 
aspiration). 
Events that are clinically considered to meet the definition of acute exacerbation of IPF 
but fail to meet all four diagnostic criteria owing to missing computed tomography data 
are termed “suspected acute exacerbations of IPF”. 
At each study visit, the investigator will ask directed questions and review the patient file 
to assess the possibility that the patient experienced an acute IPF exacerbation since 
the preceding study visit.  An acute IPF exacerbation should be reported as an AE of 
special interest (see Section of the Protocol “Adverse Events of Special Interest 
[Immediately Reportable to the Sponsor]”) or serious adverse event (SAE) as applicable. 
All relevant AE data (summary on clinical course, signs and symptoms; laboratory, lung 
function and imaging results; and treatment provided, including hospitalizations) relating 
to the exacerbation must be collected and entered onto the adverse event form.  A 
charter for the Committee describes the process for the data to be reviewed and criteria 
for defining an IPF exacerbation. 


 
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1.2.2.3 
Hospitalizations for Respiratory Causes 
Hospitalizations for respiratory causes are defined as non-elective hospitalizations due 
to any respiratory cause, including acute exacerbations of IPF, or suspected acute 
exacerbations of IPF.  All investigatorreported hospitalizations for respiratory causes 
will be assessed by an independent Adjudication Committee, as described in the charter. 
1.2.2.4 
Deaths due to Respiratory Causes 
All deaths occurring during the study must be recorded.  The event or condition that 
caused or contributed to the fatal outcome should be recorded as a single medical 
concept on the Adverse Event electronic Case Report Form (eCRF). 
All investigator-reported deaths that occur in Cohorts A or B will be assessed by an 
independent Adjudication Committee to determine whether each death was related to 
IPF, another respiratory cause or an alternative (non-respiratory and non-IPF) cause.  
Deaths occurring in Cohort C will not be adjudicated. 
1.2.2.5 
Health Care Utilization for Respiratory Events 
The following events will be recorded as health care utilization for respiratory events: 
 
Unscheduled visits to a healthcare professional/clinic for any respiratory event 
 
Urgent care or emergency room visits for respiratory events  
 
Hospitalization days for a respiratory cause, including for exacerbation of respiratory 
symptoms 
 
During hospitalization, any stay in ICU, including ICU days 
 
1.2.3 
Data Monitoring 
An independent Data Monitoring Committee (iDMC) will be employed to monitor and 
evaluate patient safety in Study WA42294 only up until the time the database for primary 
analysis for Study WA42293 is locked and Study WA42293 is unblinded to the Sponsor 
(i.e., for the duration of Study WA42293), thereby better ensuring the safety of study 
patients.  Consistent with U.S. Food and Drug Administration (FDA) recommendations 
(FDA Guidance for Industry 2006), the iDMC will be constituted of independent clinician 
experts in the field of IPF and clinical research and a statistician.  A formal charter will be 
established for the conduct of the iDMC.  The committee is planned to review the safety 
data in an unblinded manner. 
2. 
STATISTICAL HYPOTHESES 
Because of the non-comparative character of the study, no statistical tests are planned.  
All efficacy parameters will be summarized descriptively.   


 
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3. 
SAMPLE SIZE DETERMINATION 
The number of patients enrolled in the OLE study is approximately 600-700 (i.e., eligible 
patients from Study PRM-151-202 [Cohort A] and Study WA42293 [Cohorts B and C]).  
No formal sample size calculations were performed. 
4. 
ANALYSIS SETS 
The analysis populations presented in this section are based on patients enrolled during 
the global enrollment phase of the study and will not include the China extension 
patients, unless otherwise specified. 
The analysis populations are defined in Table 2. 
Table 2 
Analysis Populations 
Cohort  
Population 
Definition 
Cohort A 
Full analysis set (FAS)  
All enrolled patients who received at least 
one administration (full or partial dose) of 
study drug. 
Safety-evaluable  
All enrolled patients who received at least 
one administration (full or partial dose) of 
study drug. 
PRO-evaluable  
All enrolled patients who received at least 
one administration (full or partial dose) of 
study drug and have a baseline and at 
least 1 post-baseline assessment. 
PK-evaluable  
All enrolled patients who received at least 
one administration (full or partial dose) of 
study drug and have at least one evaluable 
post-dose PK sample that is above the 
lower limit of quantification and with 
sufficient data to determine plasma 
concentrations of zinpentraxin alfa at 
specified timepoints, unless major protocol 
deviations or unavailability of information 
(e.g., exact blood sampling time) occurred 
which may interfere with PK evaluation. 
Immunogenicity-
evaluable  
All enrolled patients who received at least 
one administration (full or partial dose) of 
study drug and have at least one ADA 
assessment. 
Biomarker-evaluable  
All enrolled patients who received at least 
one administration (full or partial dose) of 
study drug and have genetic data to 
enable assessment of MUC5B status. 


 
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Table 2  
Analysis Populations (cont.) 
Cohort  
Population 
Definition 
Cohort B 
FAS  
All enrolled patients who received at least 
one administration (full or partial dose) of 
study drug. Patients will be grouped 
according to the treatment assignment as 
described in Section 5.1.1 
Treatment/Patient Group Terminology by 
Cohort. 
Safety-evaluable  
All patients enrolled in the OLE study who 
received at least one administration (full or 
partial dose) of zinpentraxin alfa. Patients 
will be grouped according to the treatment 
assignment as described in Section 5.1.1 
Treatment/Patient Group Terminology by 
Cohort. 
PRO-evaluable  
All enrolled patients who received at least 
one administration (full or partial dose) of 
study drug and have an OLE baseline and 
at least 1 post-baseline assessment. 
HRCT-evaluable  
All enrolled patients who received at least 
one administration (full or partial dose) of 
study drug and have an OLE baseline and 
at least 1 post-baseline assessment. 
PK-evaluable  
All enrolled patients who received at least 
one administration (full or partial dose) of 
study drug and have at least one evaluable 
post-dose PK sample that is above the 
lower limit of quantification and with 
sufficient data to determine plasma 
concentrations of zinpentraxin alfa at 
specified timepoints, unless major protocol 
deviations or unavailability of information 
(e.g., exact blood sampling time) occurred 
which may interfere with PK evaluation. 
Cohort A, B, C 
Survival population 
All patients that entered the study 
FAS  full analysis set; HRCT  high-resolution computed tomography; PRO  patient-reported 
outcomes; PKpharmacokinetic. 
  
5. 
STATISTICAL ANALYSES 
Because of the non-comparative character of the study, no statistical tests are planned.  
All efficacy parameters will be summarized descriptively.  Demographic and baseline 
characteristics such as age, sex, race/ethnicity, concomitant IPF medication use, 
comorbid illnesses, and pulmonary function will be summarized by use of descriptive 
statistics. 


 
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The following sections are applicable to Cohorts A and B of the study.  Patients initially 
allocated to Cohort C will be used for survival follow-up only without any safety or 
efficacy assessments. 
5.1 
GENERAL CONSIDERATIONS 
All analyses will be reported separated by cohort.  
Patients who are rolling-over from Study WA42293 will not be required to repeat safety 
and efficacy assessment at Day 1 if the visit occurs within 4 weeks of Week 52: in these 
cases, assessments from Week 52 of Study WA42293 will be used as Day 1 
assessments. 
The safety analyses will be performed on the safety-evaluable population, unless 
otherwise specified.  Safety will be assessed through descriptive summaries of exposure 
to zinpentraxin alfa study drug, AEs, and laboratory test results.   
All efficacy analyses will be performed on the full analysis set (FAS) population, unless 
otherwise specified.  Patients in Cohort B will be analyzed according to the treatment 
assigned at randomization by interactive voice/Web-based response system (IxRS) in 
the parent study. 
Cohort B collected data will not be analyzed before unblinding of the code of the 
treatment received by the patient during the parent Study WA42293.  The main analysis 
will take place at the time of unblinding and main analysis of the parent Study WA42293.  
If unblinding of the Study WA42293 will occur earlier than the 52-week visit of the last 
patient enrolled in Cohort B, additional efficacy analysis will be implemented at the time 
when all patients in Cohort B had their 52-week visit or withdrew from the study, 
whichever is earlier. 
Additional safety update analyses maybe conducted as required by Health Authorities.  
The final analysis will take place after the last patient last visit (LPLV).  
All outputs relevant to Cohort C will have a footnote specifying that most part of the 
patients has contributed also to Cohort A and Cohort B. 
5.1.1 
Treatment/Patient Group Terminology by Cohort 
The terminology of treatment/patient groups for each cohort under each analysis 
population is defined below: 
Cohort A 
 
zinpentraxin alfa: all data for all patients 
 
Cohort B 
 
Placebo: all data for patients as assigned to placebo during analysis in the parent 
study (actual or planned, depending on the type of the analysis) 


 
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 
Zinpentraxin alfa: all data for patients as assigned to zinpentraxin alfa during 
analysis in the parent study (actual or planned, depending on the type of the 
analysis) 
 
All patients 
 
Survival population for Cohort C 
 
From Cohort A:  survival data from patients that discontinued or died from Cohort A  
 
From Cohort B:  survival data from patients that discontinued or died from Cohort B 
for the following treatments 
– 
Placebo: survival data for patients as assigned to placebo during analysis in the 
parent study (planned treatment) 
– 
Zinpentraxin alfa: survival data for patients as assigned to zinpentraxin alfa 
during analysis in the parent study (planned treatment) 
– 
All patients 
 
 
Directly from Study WA42293:  survival data from patients that have discontinued 
from study treatment or have completed Study WA42293 and have not wanted to 
receive open‑label zinpentraxin alfa. 
– 
Placebo: survival data for patients as assigned to placebo during analysis in the 
parent study (planned treatment) 
– 
Zinpentraxin alfa: survival data for patients as assigned to inpentraxin alfa 
during analysis in the parent study (planned treatment) 
– 
All patients 
 
5.2 
PATIENT DISPOSITION 
The number of patients recruited in OLE study will be tabulated for each cohort (A, B, 
and C) by region, country, study site, and treatment arm.  The FAS, safety-evaluable, 
HRCT-evaluable, pharmacokinetic (PK)-evaluable, pharmacodynamics (PD)-evaluable, 
PRO-evaluable populations, and survival population, including numbers of patients in 
each population will be summarized by cohort as applicable.  Patient disposition (the 
number of patients treated and are ongoing at the end of study reporting period) will be 
tabulated by Cohorts A and B and the treatment arm.  Premature treatment 
discontinuation and study discontinuation, as well as reasons for discontinuations, will be 
summarized for Cohorts A and B. 
5.3 
SAFETY ANALYSIS 
The safety objective for this study is to confirm the long-term safety and tolerability of 
10 mg/kg of zinpentraxin alfa administered Q4W via IV infusion plus standard of care 
(SOC) treatment, on the basis of the following endpoints: 
 
Incidence and severity of AEs, with severity determined according to the 5-point 
severity scale (National Cancer Institute Common Terminology Criteria for Adverse 
Events, Version 5.0 [NCI CTCAE, v.5.0]) 


 
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 
Incidence and severity of IRRs and other AEs of special interest (AESIs) 
 
Proportion of patients permanently discontinuing study treatment due to AEs 
 
Change from baseline in targeted clinical laboratory test results 
 
Safety analyses will be based on patients from safety populations and grouped 
according to cohorts and the treatment groups described in Section 5.1.1. 
Safety will be assessed through descriptive summary of exposure to study drug, 
seriousness and severity of AEs, and AESIs, changes in laboratory test results, death, 
discontinuation from study treatment, ECG and vital signs.  These summaries will be 
produced for the entire study period, from the start of OLE period till the time of the 
snapshot or end of the study. 
5.3.1 
Extent of Exposure 
Extent of exposure to study drug during OLE, will be summarized descriptively (mean, 
standard deviation, median, range, and proportions where appropriate) for the following 
measures: 
 
Number of patients exposed  
 
Treatment duration (weeks), measured from date of first administration at Baseline 
Day 1 of OLE phase till the date of the last treatment administration + 4 weeks or 
the date of the snapshot, whichever occurs first 
 
Study Duration (Weeks), measured from date of first administration at Baseline Day 
1 of OLE phase till the date of the last safety assessment or the date of the 
snapshot, whichever occurs first 
 
Cumulative number of infusions  total number of non-zero infusions 
 
Cumulative volume of infusion received  total volume of non-zero infusions 
 
Number of missed infusions 
 
Number of patients receiving reloading infusions 
 
Number of infusion cycles, defined as either up to 3 loading or reloading infusion or 
1 regular infusion 
 
Exposure to concurrent use of pirfenidone and/or nintedanib will also be summarized 
descriptively by cohort and treatment group as defined in Section 5.1.1. 
5.3.2 
Adverse Events 
All verbatim (“investigator-reported”) AE terms will be assigned a standardized term (the 
“Preferred Term [PT]”) and a superclass term using the most current version of the 
Medical Dictionary for Regulatory Activities (MedDRA) thesaurus terms, and adverse 
event severity will be graded according to NCI CTCAE v5.0 scale.  A by-patient AE data 
listing including onset study day, duration, PT, treatment, severity, relationship to 
treatment, treatment for AE, action taken, and outcome will be provided.  


 
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All AEs, SAEs, AEs leading to death, AESIs, and AEs leading to study treatment 
discontinuation that occur during or after the first dose of study treatment (i.e., treatment 
emergent adverse events [TEAEs]) will be summarized by PT and severity grade as 
appropriate.  An exacerbation or worsening of a pre-existing condition will be considered 
treatment-emergent only if the most extreme intensity is greater than the intensity at 
baseline (i.e., the intensity for a given AE increases and its end date is on or after the 
date of the first dose in the OLE study).  For events of varying severity, the highest grade 
will be used in the summaries.  Listings of AEs, SAEs, and AESIs will also be produced.  
Any non-treatment emergent SAEs, will also be listed separately (SAE occurring in 
Cohorts A, B, and C before or after the AE reporting period, as described in Protocol 
Section 5.4 and Protocol Section 5.7). 
Number of patients with AE, number of AEs, cumulative incidence of AE as well as the 
AE rate per 100 patient-years exposure (defined as the number of events/total duration 
in the study multiplied by 100) will be calculated, along with the corresponding 95% 
confidence intervals (CIs) for the patient-years’ rates of the SOC (exact based on the 
Chi-square distribution [Ulm 1990]).  
Summary tables of the following will be provided for each cohort and the treatment 
groups as described in Section 5.1.1, including, but not limited to: 
 
AEs and SAEs of any grade 
 
AEs by highest NCI CTCAE grade 
 
Severe AEs (NCI CTCAE Grade 3 or above) 
 
AEs leading to death  
 
AEs leading to study treatment discontinuation 
 
AEs leading to drug interruption 
 
AEs leading to withdrawal from study 
 
Treatment related AEs and SAEs 
 
AESIs defined as follows: 
– 
Cases of potential drug-induced liver injury that include an elevated alanine 
aminotransferase (ALT) or aspartate aminotransferase (AST) in combination 
with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law (see 
Protocol Section 5.4.) 
– 
Suspected transmission of an infectious agent by the study drug, as defined in 
Protocol Section 5.3.  
– 
Suspected IRR with NCI CTCAE Grade  2 
– 
Suspected anaphylactic or hypersensitivity reactions (all grades)  
– 
Acute or suspected exacerbation of IPF (all grades) 
 


 
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 
Common AEs, i.e., those occurring in at least 5% of patients  
 
Suspected IRR (all grades) 
 
Summaries of safety data by baseline concurrent anti-fibrotic therapy will be provided as 
appropriate. 
Deaths and causes of death will be summarized and a listing of patients who died during 
the study will be provided. 
Summaries of confirmed or suspected Coronavirus Disease 2019 (COVID-19) AEs and 
AEs associated with COVID-19 will also be provided. 
A listing of all pregnancies will be presented. 
5.3.3 
Adjudicated Anaphylactic and Hypersensitivity Reactions 
Anaphylaxis and hypersensitivity events as adjudicated positively by the anaphylaxis 
adjudication committee will be summarized descriptively.  Listing of TEAEs of 
anaphylaxis and hypersensitivity and their assessment by an Independent Anaphylaxis 
Adjudication Committee as per the Anaphylaxis Adjudication Committee Charter will be 
produced by cohort.  
5.3.4 
Laboratory Data 
Descriptive summaries of laboratory values at baseline (defined as the last assessment 
before or on Day 1 of OLE study), by visit, and change from baseline throughout the 
study will be tabulated by cohort and each treatment arm as defined in Section 5.1.1.  
Highest NCI CTCAE grade post-baseline will also be reported and shift tables from 
baseline to worst value during the study post-baseline will be presented by cohort and 
treatment arm as defined in Section 5.1.1. 
Summaries will be analyzed for the following parameters:  hematology (hemoglobin, 
hematocrit, platelet count, RBC count, WBC count, and differential counts [lymphocytes, 
eosinophils, neutrophils, monocytes, and basophils]), serum chemistries and liver 
function tests (sodium, potassium, chloride, bicarbonate, glucose, blood urea nitrogen, 
creatinine, calcium, total and direct bilirubin, total protein, albumin, alanine 
aminotransferase, aspartate aminotransferase, alkaline phosphatase, C-reactive protein 
[CRP], estimated glomerular filtration rate) and urinalysis (pH, specific gravity, glucose, 
protein, ketones, blood, sediment, RBCs, WBCs, casts, crystals, epithelial cells, 
bacteria). 
Proportion of patients experiencing clinically significant changes relative to baseline will 
be summarized by cohort and treatment arm as appropriate for the parameters listed 
above. 


 
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A Hy’s law analysis will be provided.  The potential Hy’s law quadrant is defined as ALT 
or AST increases above 3-fold the upper limit of normal (ULN) with concomitant total 
bilirubin increases above 2-fold the ULN or clinical jaundice in the absence of 
cholestasis or other causes of hyperbilirubinemia is considered as an indicator of severe 
liver injury (as defined by Hy’s Law).  
Visual plots (box plots or line plots) will be used to display selected laboratory 
parameters over time/by visit where appropriate.  
5.3.5 
Vital Signs 
Values, along with change from baseline, will be summarized using descriptive statistics 
for each vital sign parameter. 
Summary statistics on absolute values and their change from baseline for all observed 
vital signs (respiratory rate, pulse rate, systolic and diastolic blood pressure while the 
patient is in a seated position, oxygen saturations, and temperature) will be presented 
over time by cohort and treatment group as defined in Section 5.1.1.  Baseline is defined 
as the last assessment prior to treatment on Day 1 of OLE study.  
5.3.6 
ECGs 
A shift table for patients with ECGs clinically significant abnormalities (from baseline to 
worst condition after baseline) will be produced.  
5.3.7 
Other Safety Endpoints 
Summaries of safety data by ADA status will be provided as appropriate.  See 
Section 5.6.5 for more details on ADA status. 
5.4 
EFFICACY ANALYSIS 
All efficacy analyses will be performed on the FAS population for cohort A and B, unless 
otherwise specified. Efficacy analysis will be presented over time by cohort and 
treatment group as defined in Section 5.1.1. 
Efficacy will be assessed by annual rate of change in FVC (mL), 6MWD, FVC% 
predicted, and carbon monoxide diffusing capacity (DLCO), time to disease progression, 
and survival as measured by all-cause mortality, IPF-related mortality and 
respiratory‑related mortality. 
All efficacy parameters will be summarized descriptively, and as all patients will be 
receiving zinpentraxin alfa, there will be no hypothesis testing between treatment groups 
defined for cohort B. Wherever possible 95% confidence intervals will be reported for 
estimates. 
The annual rate of change in FVC (mL), 6MWD, FVC% predicted, and DLCO will be 
calculated using the slope from a linear mixed effect model with random intercept 


 
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(subject) and random slope (time), using measurements collected at each time point in 
this study.  The model will include patient gender, age, and height at baseline, study day 
of the visit and strata (region and concurrent use of IPF treatment).  When analyzing 
data from Cohort B, treatment group and treatment by time interaction will be added to 
the model as covariates. 
With respect to handling of missing data in the assessment of spirometry data 
(FVC [mL], FVC% predicted, and DLCO), all measurements that meet the minimal level of 
quality (except those recorded after lung transplantation) will be used.  For the purpose 
of determining the annual rate of change estimates, a hypothetical strategy will be 
utilized where values will be implicitly imputed from the model for the majority of data 
impacted by intercurrent events with the exception of death due to IPF.  
For death, a hypothetical strategy will be utilized where after death assessments will be 
implicitly imputed using linear mixed-effect model.  See Table 3 for details. 
Table 3 
Analysis Strategy for Intercurrent Events for FVC, 6MWD, FVC% 
Predicted, and DLCO 
Intercurrent Event (ICE) 
Analysis Strategy 
Any change to treatment 
Permanent study drug 
discontinuation 
 
Hypothetical strategy 
 
Implicit imputation using linear 
mixed-effect model  
Any change in standard of care 
(SOC), with pirfenidone or 
nintedanib therapy 
SOC started during study 
Treatment policy 
 
All measurements post ICE 
analyzed  
Change in dose of SOC 
SOC discontinued 
SOC switch (from pirfenidone 
to nintedanib or vice-versa) 
Other concomitant treatment 
Use of prohibited concurrent 
medication (Protocol Section 
4.4.2 ) 
Treatment Policy  
 
All measurements post ICE 
analyzed  
Terminal events 
Death  
 
 
Hypothetical strategy 
 
Assessments following death will be 
implicitly imputed using linear 
mixed-effect model 
 
Lung transplantation 
Hypothetical strategy 
 
Measurements collected after lung 
transplantation excluded from the 
analysis  
 
Implicit imputation using linear 
mixed-effect model 
 
Hospitalization for COVID-19 
Treatment Policy strategy 
 
All measurements post ICE 
analyzed 
COVID-19Coronavirus Disease 2019; ICE = intercurrent event; SOC = standard of care. 


 
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In the hypothetical strategy, the model implicitly imputes missing data based on an 
individual’s estimated rate of worsening of lung function prior to study discontinuation 
(i.e., assuming missing at random). 
In addition, summaries using all observed data will be performed.  
Summary statistics (number of patients, mean, standard deviation, median, minimum, 
maximum) on absolute values and their change from baseline for several observed 
efficacy evaluations (FVC [mL], 6MWD, FVC% predicted, and DLCO) will be presented 
over time by cohort and treatment group as defined in Section 5.1.1.  Baseline is defined 
as any last assessment prior to treatment on Day 1 of OLE study. 
5.4.1 
Time-to-Event Endpoints 
The time-to-event secondary endpoints are listed below: 
 
Time to disease progression, defined as time to first occurrence of ≥10% absolute 
decline in % predicted FVC, 15% relative decline in 6MWD, or death 
 
Survival, as measured by all-cause mortality, IPF-related mortality and respiratory-
related mortality  
 
Descriptive statistics for the frequency of each type of event will be provided.  The 
Kaplan-Meier plot, median time to event, and their 95% CIs.  
Time-to-event will be measured in reference to Baseline Day 1 of OLE study through the 
end of study or the time of the data-cut, whichever occurs first.  For time to disease 
progression and survival (as measured by all-cause mortality, IPF-related mortality and 
respiratory-related mortality), patients without an event will be censored at the last clinic 
assessment. 
The strategy for the time-to-event endpoints is summarized below in Table 4.  


 
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Table 4 
Strategy for Addressing Intercurrent Events: Time-to-Event 
Endpoints 
Endpoint 
Intercurrent Events and Strategy 
Time to disease progression, defined as 
time to first occurrence of 10% absolute 
decline in % predicted FVC, 15% relative 
decline in 6MWD, or death 
Any patients who undergo lung transplantation will 
be censored at the date of the transplant 
(hypothetical strategy) 
Any patients who withdraw from treatment will be 
censored at the date of last disease progression 
assessment, i.e., % predicted FVC and 6MWD 
(hypothetical strategy)  
Survival, as measured by all-cause 
mortality, IPF-related mortality and 
respiratory-related mortality 
Any patients who undergo lung transplantation will 
be censored at the date of the transplantation 
(hypothetical strategy)  
Any patients who withdraw from treatment will be 
censored at the date of withdrawal (hypothetical 
strategy)  
6MWD   6-minute walk distance; FVC  forced vital capacity; IPF  idiopathic pulmonary fibrosis. 
  
5.5 
EXPLORATORY EFFICACY ANALYSIS 
Some exploratory efficacy analyses will be performed on the FAS population, if not 
otherwise specified.  Patients in Cohort B will be analyzed according to the treatment as 
it was assigned during efficacy analysis of the parent study.  Analysis will be presented 
over time by cohort and treatment group as defined in Section 5.1.1.  Baseline is defined 
as the last assessment prior to treatment on Day 1 of OLE study. 
No intercurrent event will be considered in the exploratory endpoint analysis (with the 
exception of the time to event exploratory endpoints) and no imputation of the missing 
data is forecasted. 
Patient-Reported Outcomes (PRO)  
Summary statistics (number of patients, mean, standard deviation, median, minimum, 
maximum) on observed values and their change from baseline for patient-reported 
outcomes (PRO) efficacy endpoints (UCSD-SOBQ, SGRQ [individual domains and total 
score], and EuroQol 5-Dimension, 5-Level Questionnaire [EQ-5D-5L] index-based, and 
visual analog scale scores) will be presented for the PRO analysis population over time 
by cohort and treatment group as defined in Section 5.1.1.  


 
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Change-from-Baseline Exploratory Endpoints: HRCT 
In Cohort B patients, summary statistics (number of patients, mean, standard deviation, 
median, minimum, maximum) on the raw values at each visit and the change from 
baseline to each visit through Week 52 and Week 104 will be computed for the 
quantitative HRCT imaging analysis parameters by treatment group as defined in 
Section 5.1.1 for Cohort B.  
Acute Exacerbation of IPF Endpoints 
Summary statistics for continuous variables will be prepared by cohort and treatment 
group (as defined in Section 5.1.1) for the total number and rate (per year) of acute or 
suspected exacerbations during the OLE period. 
The number and proportion of patients with at least one acute or suspected exacerbation 
during the OLE period, as determined by Adjudication Committee, will be tabulated by 
cohort and treatment group as defined in Section 5.1.1. 
Healthcare Utilization Exploratory Endpoints 
Summary statistics (number of patients, mean, standard deviation, median, minimum, 
maximum) on absolute values will be prepared for: 
 
Length of hospital stay in days for respiratory-related hospitalizations; 
 
Total time in intensive care units in days due to respiratory causes; 
 
Unscheduled outpatient clinic/urgent care/emergency room utilization related to 
respiratory events. 
 
Statistics will be presented over time by cohort and treatment group as defined in 
Section 5.1.1. 
5.5.1 
Time-to-Event Exploratory Endpoints 
The time-to-event exploratory endpoints are listed below: 
 
Time to first respiratory-related hospitalizations (defined as non-elective 
hospitalizations due to any respiratory cause, including acute exacerbations of IPF, 
or suspected acute exacerbations of IPF, as determined by Adjudication Committee) 
 
Time to first acute exacerbation of IPF, or suspected acute exacerbation of IPF, as 
determined by Adjudication Committee 
 
Time-to-event will be measured in reference to baseline Day 1 of OLE study through the 
end of study or the time of the data-cut, whichever occurs first.  For time to first 
respiratory-related hospitalizations and time to first acute exacerbation of IPF, patients 
not experiencing an event will be censored at the earliest of the last known alive day.  
The strategy for the time-to-event endpoints is summarized below in Table 5. 


 
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Table 5 
Strategy for Addressing Intercurrent Events: Time-to-Event 
Exploratory Endpoints 
Endpoint 
Intercurrent Events and Strategy 
Time to first respiratory-related 
hospitalizations (defined as non-elective 
hospitalizations due to any respiratory 
cause, including acute exacerbations of 
IPF, or suspected acute exacerbations of 
IPF, as determined by Adjudication 
Committee) 
Deaths due to IPF or other respiratory causes will be 
treated as disease progression and counted as event 
of interest (composite strategy)  
Deaths due to other causes will be censored 
Any patients who undergo lung transplantation will 
be censored at the date of the transplantation 
(hypothetical strategy) 
Any patients who withdraw from treatment will be 
censored at the date of withdrawal (hypothetical 
strategy)  
Time to first acute exacerbation of IPF, or 
suspected acute exacerbation of IPF, as 
determined by Adjudication Committee 
Deaths due to IPF will be treated as disease 
progression and counted as event of interest 
(composite strategy)  
Deaths due to non-IPF causes will be censored 
Any patients who undergo lung transplantation will 
be censored at the date of the transplantation 
(hypothetical strategy) 
Any patient who withdraws from treatment will be 
censored at the date of withdrawal (hypothetical 
strategy)  
IPF  idiopathic pulmonary fibrosis. 
 
5.5.2 
Additional Exploratory Efficacy Endpoints 
Exploratory analyses may also be performed for additional measures (see below the list 
of additional exploratory efficacy endpoints) and subgroups of interest including 
concurrent use of IPF treatment and geographic region (see Section 5.6.6 for the 
complete list).  
The additional exploratory efficacy endpoints are: 
 
Change from baseline in FVC% predicted, FVC (mL), by concurrent therapy stratum 
(i.e., with nintedanib treatment vs. with pirfenidone treatment vs. without pirfenidone 
or nintedanib treatment)  
 
Change from baseline in FVC% predicted, FVC (mL), by MUC5B status 
 
Change from baseline in 6MWD (m), by concurrent therapy stratum (i.e., with 
nintedanib treatment vs. with pirfenidone treatment vs. without pirfenidone or 
nintedanib treatment) 
 
Summary statistics (number of patients, mean, standard deviation, median, minimum, 
maximum) on absolute values and their change from baseline. 


 
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5.6 
OTHER ANALYSES 
5.6.1 
Summaries of Conduct of Study 
Eligibility criteria deviations and other major protocol deviations will be summarized.  
The impact of COVID-19 will be assessed by including major protocol deviations related 
to COVID-19 and by summarizing COVID-19-related intercurrent events by treatment 
arm. 
Compliance analysis will be performed for the overall UCSD-SOBQ and SGRQ 
questionnaires.  Compliance rates will be summarized by number and proportion of 
patients among those expected to complete the UCSD-SOBQ or SGRQ at each time 
point. 
5.6.2 
Summaries of Demographics and Baseline Characteristics 
Unless otherwise specified, the baseline value for each variable will be considered for 
the assessment collected on baseline Day 1, prior to administration of first study drug 
during OLE period.  For subjects in Cohort C directly recruited from Study WA42293, 
baseline will be Day 1, prior to administration of first study drug during double-blind 
period. 
Demographic and baseline characteristics (including, but not limited to, age, sex, 
race/ethnicity, concomitant IPF medication use, comorbid illnesses, and pulmonary 
function) will be summarized overall for the FAS population and by cohort and treatment 
group (as defined in Section 5.1.1) using descriptive statistics as appropriate.  
Compliance with study drug will be computed for each patient as the proportion of 
prescribed study drug actually taken for the safety population. 
Proportions of patients taking each concomitant medication will be provided for the 
safety population. 
Medical history will be summarized using summary statistics, reporting the proportion of 
patients with at least one medical condition and the total number of medical conditions 
based on the safety population. 
5.6.3 
Pharmacokinetic Analyses 
The pharmacokinetic (PK)-evaluable population will consist of patients from Cohort A 
and Cohort B with sufficient data to determine plasma concentrations of zinpentraxin alfa 
at specified timepoints, unless major protocol deviations or unavailability of information 
(e.g., exact blood sampling time) occurred which may interfere with PK evaluation, with 
patients grouped according to treatment received. 
Individual and mean plasma zinpentraxin alfa concentration versus time data will be 
listed and summarized (mean, standard deviation, coefficient of variation mean, 


 
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geometric mean, coefficient of variation geometric mean, median, minimum, and 
maximum).  
The PK parameters for zinpentraxin alfa in plasma will be estimated as appropriate for 
each subject profile by non-compartmental analysis methods using Phoenix WinNonlin 
software (v8.3 or later, Certara USA, Inc.).  Plasma PK parameters definitions are as 
below: 
 
Cmax:  maximum observed concentration 
 
Tmax:  time to maximum observed concentration 
 
AUC0-t:  area under the concentration-time curve from hour 0 to the last measurable 
concentration, calculated using the linear trapezoidal rule for increasing 
concentrations and the logarithmic rule for decreasing concentrations 
 
AUC0-∞:  area under the concentration-time curve extrapolated to infinity, calculated 
using the formula: 
AUC0-∞    AUC0-t +Ct/z 
where Ct is the last measurable concentration and z is the terminal elimination rate 
constant 
 
%AUCextrap:  percentage of area under the concentration-time curve that is due to 
extrapolation from the last measurable concentration to infinity 
 
z:  terminal elimination rate constant, where z is the magnitude of the slope of the 
linear regression of the log concentration versus time profile during the terminal 
phase 
 
t1/2:  terminal elimination half-life (whenever possible), where t1/2    (ln 2)/z 
 
CL:  systemic clearance 
 
V:  volume of distribution 
 
Other parameters may be added as appropriate.  PK parameters analysis will use actual 
times as recorded on the eCRF. 
Estimates for PK parameters will be listed and summarized (mean, standard deviation, 
coefficient of variation mean, geometric mean, coefficient of variation geometric mean, 
median, minimum, and maximum). 
Additional exploratory PK analyses will be conducted as appropriate.  Exploratory PK 
analyses to evaluate potential relationships between drug exposure and the efficacy and 
safety of zinpentraxin alfa might be described in a separate document and presented in 
a separate report. 
5.6.4 
Biomarker Analyses 
Biomarkers will be assessed at baseline and subsequent timepoints following 
administration of zinpentraxin alfa (both Cohort A and Cohort B).  Biomarkers will be 


 
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presented as absolute value over time and/or percent change relative to baseline over 
time.  Biomarker levels at baseline or over time may be compared with efficacy or safety 
measurements to assess prognostic or predictive properties. 
Descriptive or summary statistics will be used to describe biomarker assessments. 
Exploratory biomarker analyses will be performed to identify and/or evaluate biomarkers 
in the context of drug activity, efficacy, PK, safety, and/or immunogenicity endpoints. 
5.6.5 
Immunogenicity Analyses 
The following summaries will be provided for both Cohort A and Cohort B (only for 
patients who enrolled into the Study WA42293 prior to 1 June 2022) by the treatment 
group as defined in Section 5.1.1: 
 
Numbers and proportions of ADA-positive patients and ADA-negative patients at 
baseline (baseline prevalence) and after drug administration (post-baseline 
incidence)  
 
Number and percent of patients with at least one treatment-induced ADA 
 
Drug concentration at ADA collection timepoints 
 
A by-patient listing of ADA status will be provided.  
When determining post-baseline incidence, patients are considered to be ADA positive; 
if they are ADA negative or have missing data at baseline but develop an ADA response 
following study drug exposure (treatment-induced ADA response), or if they are ADA 
positive at baseline and the titer of one or more post-baseline samples is at least 
0.60 titer unit greater than the titer of the baseline sample (treatment-enhanced ADA 
response).  Patients are considered to be ADA negative if they are ADA negative or 
have missing data at baseline and all post-baseline samples are negative, or if they are 
ADA positive at baseline but do not have any post-baseline samples with a titer that is at 
least 0.60 titer unit greater than the titer of the baseline sample (treatment unaffected). 
The relationship between ADA status and safety, efficacy, and pharmacokinetics may be 
analyzed and reported via descriptive statistics. 
5.6.6 
Analyses of Subgroups of Interest 
The generalizability of efficacy endpoint results will be investigated by estimating the 
longitudinal treatment effect in subgroups based on stratification factors used in the 
parent study and key baseline demographics, disease characteristics, etc., as listed 
in Table 6.  
Descriptive summaries including number and proportion of patients in each category will 
be provided overall and by cohort and treatment group as defined in Section 5.1.1.  
Summaries of some selected endpoints by these subgroups will be provided in forest 
plots. 


 
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Safety and immunogenicity analyses will be performed separately for first and second 
generation of zinpentraxin alfa. 
Table 6 
Subgroup Definitions 
Patient Characteristics 
Categories 
Baseline concomitant 
medications 
Concurrent use of either nintedanib or pirfenidone 
treatment 
Concurrent use of nintedanib treatment 
Concurrent use of pirfenidone treatment 
No concurrent treatment 
Geographic region 
China 
North America  
Europe 
Latin America 
Rest of World 
Age 
  65 years 
65 to   75 years 
  75 years 
Sex 
Female 
Male 
Generation drug product 
First generation of zinpentraxin alfa 
Second generation of zinpentraxin alfa 
  
5.6.7 
Analyses of China Subpopulation 
If applicable, a separate analysis will be performed for the China subpopulation.  
The analysis population for the China subpopulation analyses includes all patients 
enrolled during WA42293 study at sites in mainland China, Hong Kong, and Taiwan.  
Data for the China subpopulation will be analyzed using the same statistical methods as 
described in Sections 5.15.5 when data allow. 
5.6.8 
Other Analyses 
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology will be 
summarized descriptively by time point and treatment group. 
6. 
SUPPORTING DOCUMENTATION 
Refer to Appendix 1 below for details. 


 
PRM-151 (Zinpentraxin Alfa)—F. Hoffmann-La Roche Ltd 
Statistical Analysis Plan WA42294 
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Appendix 1 Changes to Protocol-Planned Analyses 
The objective “To assess the long-term impact of 10 mg/kg zinpentraxin alfa plus SOC 
on healthcare utilization for respiratory events” with the respective endpoints are added 
in Table 1 even if not reported in the objective section of the protocol.  Analysis are 
described in Section 5.5 at the “Healthcare Utilization Exploratory Endpoints” subsection. 
 
7. 
REFERENCES 
Collard HR, Ryerson CJ, Corte TJ, et al. Acute exacerbation of idiopathic pulmonary 
fibrosis. An international working group report. Am J Respir Crit Care Med 
2016;194:26575. 
FDA Guidance for Industry 2006.  US Food and Drug Administration. Guidance for 
clinical trial sponsors: establishment and operation of clinical trial data monitoring 
[resource on the internet]. 2006 [cited: 12 March 2020]. 
Ulm K. A simple method to calculate the confidence interval of a standardized mortality 
ratio (SMR). Am J Epidemiol 1990;131:373−5. 


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