Clinical trial NCT03448692
Conditions: Focal Segmental Glomerulosclerosis (FSGS)
Keywords: Proteinuria
Sponsor: Pfizer
Start date: 2018-10-15; Completion date: 2023-02-14
Enrollment: 47 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The purpose of this Phase 2 adaptive study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of PF-06730512 following multiple intravenous infusions in adult subjects with FSGS.

Detailed description:

Arms: arm 1: Subjects in cohort 1 will receive dose 1 Intravenous (IV) infusion. arm 2: Subjects in cohort 2 will receive dose 2 IV infusion. arm 3: Subjects in cohort 3 will receive dose 3 IV infusion.
Interventions: intervention 1: PF-06730512
Intervention descriptions: intervention 1: Subjects in cohort 1 will receive Dose 1 Intravenous infusion (IV). Subjects in cohort 2 will receive Dose 2 IV. Subjects in cohort 3 will receive Dose 3 IV infusion.

Protocol documents:
Prot_000.pdf: 
PF-06730512 
C0221002 
Final Protocol Amendment 5, 18 August 2021 
PFIZER CONFIDENTIAL 
Page 1 
 
 
This document and accompanying materials contain confidential information belonging to Pfizer. Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified. 
 
 
 
 
A PHASE 2, 24-WEEK, ADAPTIVE, OPEN LABEL, SEQUENTIAL COHORT 
TRIAL TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY AND 
PHARMACOKINETICS OF PF-06730512 FOLLOWING MULTIPLE DOSES IN 
ADULT SUBJECTS WITH FOCAL SEGMENTAL GLOMERULOSCLEROSIS 
(FSGS) 
 
 
Investigational Product Number: 
PF-06730512 
Investigational Product Name: 
Not Applicable (N/A) 
US IND: 
CCI  
EudraCT Number: 
2019-003607-35 
Clinical Trials.gov ID 
NCT03448692 
Protocol Number: 
C0221002 
Phase: 
2a 
 
 


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Document History 
 
Document 
Version Date 
Summary of Main Changes and Rationale 
Amendment 5 
18 Aug 2021 
The overall purpose of this amendment is to extend 
treatment duration from 12 weeks to 24 weeks, and to 
add an optional cohort to potentially explore a higher 
dose of PF-06730512. 
1. Section 1.3. Rationale, Section 3. Study Design: 
Addition of an optional cohort (Cohort 3) to allow 
evaluation of a higher dose of PF-06730512 CCI  
in subjects with FSGS, based on 
emerging data from the study. 
2. Schedule of Activities: 
The SoA has been updated to incorporate extended 
treatment duration. 
Clarifications have been made to the table and 
footnotes to improve readability, redundancies have 
been removed and sections organized. 
Rows have been added to ensure appropriate timing 
and adequate data collection related to history of 
the disease under study (FSGS) and enrollment 
timing (non-randomized). 
3. Schedule of Activities, Section 1.2.4. Nonclinical 
Safety, Section 1.3. Rationale, Section 3. Study 
Design, Section 6.3 Investigational Treatment 
Period: 
Extension of investigational treatment period from 
12 weeks to 24 weeks to evaluate longer safety and 
durability of response to PF-06730512 in subjects 
with FSGS. 
Nonclinical safety data of the 6-month toxicity 
study conducted in rats were added to support 
extension of the treatment period. 
4. Schedule of Activities, Section 6.2. Investigational 
Treatment Period: 
Additional telephone contact visits added in order 
to check on subject’s overall status, including new, 
ongoing or resolved AEs or concomitant 
medications, contraceptive use and a reminder to 


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CCI 
the subject to collect the required urine samples and 
bring to the next study visit. 
5. Schedule of Activities, Section 2. Study Objectives 
and Endpoints, Section 6.2. Investigational 
Treatment Period: 
Urine and blood sampling added to the Week 2 visit 
to enhance the understanding of pharmacokinetics 
(PK) profile and immunogenicity, as well as urine 
protein to creatinine ratio (UPCR), CCI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8. Section 1.2.5. Clinical Experience with 
PF-06730512: 
Removed TEAE tables and added reference to 
SRSD (the IB) to avoid redundancy between 
documents and streamline the protocol. 
9. Protocol Summary, Section 2. Study Objectives and 
Endpoints: 
Endpoints with time duration (ie, up to Week 13) 
have been updated to encompass the extended 
duration of treatment, as applicable. 
 


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10. Section 3.1 The Main Study to Assess 
PF-06730512, Section 6. Study Procedures: 
Delays in enrollment (up to 1 week) due to delayed 
laboratory test results will not be considered 
protocol deviations. This is to avoid requiring 
subjects to rescreen if the test results required for 
study entry are delayed due to circumstances out of 
the subject’s or site’s control, and the results are 
available within 1 week of the original screening 
window. 
11. CCI 
 
 
 
 
 
 
12. Section 4. Subject Eligibility Criteria, Section 4.1. 
Inclusion Criteria: 
Specified in summary text that repeat testing is 
allowed to verify eligibility for Screening or 
Lead-in Period. 
Inclusion criterion #2. Clarified requirement for 
FSGS diagnosis includes a renal biopsy within the 
last 5 years, evaluated locally. Specific reference to 
number of glomeruli requiring segmental sclerosis 
has been removed. 
Inclusion criteria #4, 5 and 6 have been revised to 
provide clarity on the eligibility requirements 
related to the disease under study. 
13. SoA, Section 4.1 Inclusion Criteria, Section 4.4.1 
Reproductive Criteria: 
Specific requirements related to reproductive 
criteria and contraception requirements have been 
updated in Section 4.4.1. The language has been 
updated to reflect the current required guidance 
from Pfizer template, and to streamline the 
protocol. Repetitive information was removed from 
CCI 


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multiple sections, now referenced under 
Section 4.4.1. 
14. Section 4.2 Exclusion Criteria: 
Clarifications provided; of note the context and 
content of criteria were not changed. Exclusion #11 
added potential consultation with Sponsor to assist 
with interpretation of results, if needed. 
15. Section 4.3 Criteria for Progression to Treatment on 
Day 1: 
Clarified the requirements for UPCR (from 24-hour 
urine) and eGFR results from Lead-in to confirm 
eligibility to progress to the Investigational 
Treatment Period, as not all eligibility criteria are 
required to be reconfirmed after Screening. 
16. Section 5.8. Concomitant Treatments: 
Additional revisions have been incorporated to 
allow for investigator discretion for reasonable 
duration of prior and ongoing FSGS treatments, due 
to significant variability of treatment options and 
practice in each country. 
Further, the format has been revised from table to 
text for improved readability. Clarifications were 
also incorporated to allow for appropriate and 
adequate management of FSGS supportive 
medications during study conduct. 
17. Appendix 3: 
Appendix 3 contained regional changes required by 
Health Authorities as part of Amendment 4 
(eg, require use of condom for male participants). 
These changes have been applied to the study 
population, thus Appendix 3 which contained 
country-specific requirements for Japan and the EU 
is now incorporated into the main body of the 
protocol. 
18. The administrative changes and clarifications from 
the 22 Dec 2020 Protocol Administrative Change 
Letter (PACL) have been incorporated, issued as 
PACL #1 for EU-specific regional Amendment 4 
(June 2020) and as PACL #2 for global 
Amendment 3 (Jan 2020). Of note, PACL #1 


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(12 June 2020) written under global Amendment 3 
was incorporated in regional Amendment 4. 
19. Minor corrections, clarifications to text, and 
correction of typographical errors have been made 
throughout the protocol to improve overall 
readability. 
Amendment 4 
12 June 2020 
1. A region-specific change relevant only to sites in 
the European Union (EU) member states which 
participate in the Voluntary Harmonization 
Procedure (VHP) process, as well as any additional 
countries selected for study participation in the 
future, which revises language in Section 4.4.1. 
Contraception related to male subjects using a 
condom as protection from the potential risk of 
exposure via drug in the ejaculate which would 
pose a risk to a developing embryo/fetus in a 
women of childbearing potential (WOCBP). The 
section will now read: “In this study, male subjects 
are required to use a condom as protection from the 
potential risk of exposure via drug in the ejaculate 
which would pose a risk to a developing 
embryo/fetus in a WOCBP. This is purely 
precautionary as the calculated safety margin for 
PF-06730512 is ≥100 fold between the estimated 
maternal exposure due to seminal transfer and the 
NOAEL for serious manifestations of 
developmental toxicity in nonclinical studies”. 
Rationale: This change in the form of a protocol 
amendment was requested by the VHP [grounds for 
non-acceptance (GNA) 31] and is applicable to sites 
in the EU member states which participate in the 
VHP process only and for any countries 
subsequently selected for trial participation. 
2. Section 9.6 Interim Analysis. Added summarized 
details of the planned 3 interim analyses for this 
study, including the futility stopping criteria if 
applicable. 
Rationale: Details added to align with VHP request 
for a protocol amendment (GNA 48). 


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3. Section 1.2.5.4 Benefit-Risk Assessment. Added 
text to clarify there are no important identified risks 
or important potential risks for PF-06730512, and 
based on the available safety and efficacy data for 
PF-06730512, the benefit-risk profile of the 
investigational medicinal product remains 
favorable. 
Rationale: Details added to align with VHP request 
for a Dear Investigator Letter or a protocol 
amendment (GNA 35). 
4. Section 8.1.3 Withdrawal from the Study Due to 
Adverse Events and Section 8.4.3.1 Exposure 
During Pregnancy. Instructions added to clarify 
that withdrawal from the study due to an adverse 
event related to study drug is done at the discretion 
of the principal investigator and notification to the 
sponsor of the withdrawal must be accomplished 
immediately. In addition, pregnancy in a study 
participant must result in immediate cessation of 
study drug administration and study withdrawal. 
Rationale: Details added to align with VHP request 
for a Dear Investigator Letter or a protocol 
amendment (GNA 32). 
5. Section 8.4.2 Potential Cases of Drug Induced 
Liver Injury (DILI). Instructions added to clarify 
that in case of potential DILI (Hy’s law) events, the 
investigator must decide whether to interrupt or 
discontinue further administration of study drug. 
Rationale: Details added to align with VHP request 
for a Dear Investigator Letter or a protocol 
amendment (GNA 33). 
6. Section 13.1 End of Trial in a Member State 
updated to clarify that the end of trial in all 
concerned countries is defined as last subject last 
visit (LSLV). 
Rationale: Details added to align with VHP request 
for a Dear Investigator Letter or a protocol 
amendment (GNA 34). 


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7. Section 4.2 Exclusion criterion #21 added to clarify 
subjects with a history of hypersensitivity to the 
components of the study drug are not eligible to 
participate the study. 
Rationale: Additional exclusion criterion added at 
the request of the Japanese Pharmaceuticals and 
Medical Devices Agency (PMDA). 
8. Appendix 3 Japan-Specific Requirements added to 
clarify country-specific subject selection criteria 
and highly effective contraception methods. 
Rationale: Incorporation of changes/clarifications 
made via Country (Japan) Level Protocol 
Administrative Changes and Clarifications (PACL) 
at the request of the PMDA. 
9. SCHEDULE OF ACTIVITIES footnote e and f 
updated to clarify PK samples will be collected at 
Pre-dose (within 30 minutes prior to dosing) and at 
the end of infusion (within 6 minutes after the end 
of infusion) on Days 1 and 71 (Week 11), on 
Days 15, 29, 43, 57 at Pre-dose (within 30 minutes 
prior to dosing) only, and at follow up visits; 
Cytokines are collected at Pre-dose, 1hr, 2hr and 
4hr post beginning of infusion within 
approximately ±15 minutes. 
Rationale: To provide clarification of the time 
window for PK and cytokine sample collection. 
10. Section 4.4.1 Contraception footnote c updated to 
remove template instruction text and clarify 
acceptable contraceptive methods for females are 
limited to those which inhibit ovulation as the 
primary mode of action. 
Rationale: To remove protocol template instruction 
text and provide clarification. 
11. Section 7.3.1 Serum for Analysis of PF-06730512 
updated to clarify all efforts will be made to obtain 
the PK samples at the exact nominal time relative 
to dosing and samples obtained within the time 


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windows specified in the Schedule of Activity will 
not be captured as protocol deviations. 
Rationale: To provide clarification of the time 
window for PK sample collection. 
Amendment 3 
03 January 
2020 
Amendment 3 has become necessary mainly to allow 
for further changes in Inclusion and Exclusion Criteria. 
Main changes in Amendment 3 include the following: 
1. Throughout the protocol, removed mention of 
primary FSGS and not explicitly excluding 
secondary FSGS. 
Rationale: This will allow inclusion of subjects 
with a diagnosis of secondary FSGS solely based 
on pathologic findings (percent foot process 
effacement) without evidence of a cause. 
2. Section 4.1 Inclusion Criterion #5 updated to allow 
subjects treated with at least one, but no more than 
three prior immunosuppressant drugs. 
Rationale: Sequential use of drugs (alone or 
together) is standard of practice in treating FSGS. 
This will improve the study enrollment without 
impacting subject safety and the assessment of the 
study drug. 
3. Section 4.1 Inclusion Criterion #6, Section 4.2 
Exclusion Criterion #8 and Section 5.8 
Concomitant Treatment updated to clarify that 
subjects are permitted to concomitantly take 
calcineurin inhibitors (CNIs) or mycophenolate 
mofetil (MMF) during the study provided they 
were on stable doses or serum levels prior to the 
start of the Lead-in Period. 
Rationale: This is consistent with standard of 
practice in treating FSGS. Clinicians hesitate to 
withdraw CNIs or MMF prior to entry into a FSGS 
protocol, especially when the only other drug is a 
reduced dose of corticosteroids. 


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4. Section 4.2 Exclusion Criterion #3 updated to 
delete the subject eligibility assessment based 
solely on the HbA1c. 
Rationale: Poorly controlled diabetic subject will be 
excluded per investigator judgment. 
5. Section 4.2 Exclusion Criterion #6 updated to 
increase the exclusionary Body mass index (BMI) 
from >40 kg/m2 to >45 kg/m2. 
Rationale: To include a wider range of patients with 
the rare disease FSGS. 
6. Section 4.2 Exclusion Criterion #10 updated to 
increase the exclusionary blood pressure from 
≥140/90 to ≥155/95 mmHg and allow repeat BP 
measurements on a different day. 
Rationale: This is consistent with the blood 
pressure status of patients with FSGS. 
7. Section 4.2 Exclusion Criterion #18 and Section 6 
STUDY PROCEDURES and Section 7.1.1 
Laboratory Tests updated to delete the subject 
eligibility assessment based on the screening drug 
test of tetrahydrocannabinol (THC). 
Rationale: This is consistent with the evolving 
regulatory status of the cannabidiol products. Such 
products are now legal in many States and 
Countries. 
8. Section 4.2 Exclusion Criteria updated to clarify 
that subjects with a known history of CMV disease, 
CMV mononucleosis, gammaherpesviral 
mononucleosis, parvovirus infection, or simian 
virus 40 infection, and subjects with a history of 
bilateral vesicoureteral reflux, or history of prior 
treatment with or use of interferon, lithium, 
pamidronate, mTOR inhibitors, 
testosterone/anabolic steroids, anthracycline 
(doxorubicin), heroin are not eligible to the study. 
Rationale: To exclude the majority of ineligible 
cases of secondary FSGS. 


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9. PROTOCOL SUMMARY, Section 3.1 The Main 
Study to Assess PF-06730512, and Section 6.2 
Screening and Lead-in Period Activities and 
Assessments updated to clarify that the Screening 
window is up to 39 days. 
Rationale: The protocol has inconsistent language 
regarding the screening window duration. The 
SCHEDULE OF ACTIVITIES table captures visit 
days for Screening to Lead-In Period to be up to 
39 days. 
10. Section 6 STUDY PROCEDURES and 
SCHEDULE OF ACTIVITIES updated to clarify 
that Screening procedures may be split into two 
visits if needed (however informed consent must be 
obtained prior to any study procedures taking place 
and at the beginning of the first Screening visit). 
Rationale: To improve compliance with procedures 
by increasing flexibility in screening visits. 
11. CCI 
CCI 
12. Changes addressed in Protocol Administrative 
Change and Clarification Letters (PACLs) issued 
prior to Amendment #3 have been incorporated. 
13. Additional logistical, administrative and formatting 
changes have been made, discrepancies eliminated, 
and typographical errors corrected. 
Amendment 2 
10 June 2019 
CCI 
Main changes in Amendment 2 include the following: 


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1. Inclusion and Exclusion Criteria have been 
broadened to be able to include a wider range of 
patients with the rare disease FSGS. 
Rationale: Over the past few years, there has been 
an increase of studies competing for FSGS patients. 
Without changing the eligibility criteria, it could be 
difficult to recruit 44 subjects in this competitive 
environment. 
2. CCI 
 
3. The Natural History part of the study (Part A) has 
been deleted. 
Rationale: The main study started recruiting after 
pre-planned Amendment 1 was in place; there was 
no time to perform the Natural History part. 
4. Preliminary results of study C0221001 reported in 
Amendment 1 have been updated with final results. 
Rationale: The FIH study has been completed with 
the Clinical Study Report. 
5. The content of several Protocol Administrative 
Clarification Letters (PACL A1#1 - #7) was added 
to Amendment 2. 
Rationale: PACLs became necessary over the past 
year to adjust several logistical study aspects to the 
real world. They were included to provide 


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clarifications to the investigative sites and the 
clinical research associates. 
6. Additional logistical, administrative and formatting 
changes have been made, discrepancies eliminated 
and typographical errors corrected. 
Amendment 1 
09 May 2018 
Amendment 1 has been pre-planned to allow the 
overlap of C0221001 (FIH) study completion and 
start-up activities of C0221002 in order to reduce 
overall development time. The primary reason for this 
amendment was to insert the appropriate doses, dosing 
frequency and route of administration for 
PF-06730512, based on results from the FIH study. 
Main changes made in the amendment include the 
following: 
1. Specifications for dose levels, dosing frequency 
and route of administration for PF-06730512 have 
been inserted. 
Rationale: Preliminary safety and pharmacokinetic 
data from the FIH study became available in April 
2018 and allowed final selection of dose levels, 
dosing frequency and route of administration. 
2. Section 1 has been updated with the most current 
information regarding safety and pharmacokinetics 
from the ongoing study C0221001 as well as with 
toxicology and EFD data from nonclinical studies. 
Rationale: Data from the clinical and nonclinical 
studies became available in April of 2018. 
3. Randomization of subjects to the high versus the 
low dose has been removed. Instead, a sequential 
design has been implemented allowing Cohort 1 
enrollment to complete prior to enrollment of 
Cohort 2. 
Rationale: The incorporation of an Interim 
Analysis for efficacy and safety made it necessary 
to collect data from the high dose in an adequate 
number of subjects for statistical analysis. The 


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overlap of subjects assigned to each cohort was too 
small to warrant randomization. 
4. The SOA has been revised to reflect Q2W instead 
of Q1W dosing. Any dosing frequency-related 
changes have also been corrected in Section 6 
and 7. 
Rationale: Refer to item #1 above. 
5. The requirements for contraceptive use have been 
modified for male study subjects. 
Rationale: Contraceptive (condom) use is no longer 
a requirement for male subjects in this study 
because the calculated safety margin is 100-fold 
between the estimated maternal exposure due to 
seminal transfer and the NOAEL for serious 
manifestations of developmental toxicity in 
nonclinical studies. 
6. Changes addressed in Protocol Administrative 
Change and Clarification Letters (PACLs) issued 
prior to Amendment #1 have been incorporated. 
7. CCI 
 
8. Additional logistical, administrative and formatting 
changes have been made, discrepancies eliminated 
and typographical errors corrected. 
Original 
protocol 
09 October 
2017 
Not applicable (N/A) 
This amendment incorporates all revisions to date, including amendments made at the 
request of regulatory authorities and institutional review boards (IRBs)/ethics committees 
(ECs). 


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TABLE OF CONTENTS 
LIST OF TABLES ................................................................................................................... 19 
LIST OF FIGURES .................................................................................................................. 19 
PROTOCOL SUMMARY ....................................................................................................... 20 
SCHEDULE OF ACTIVITIES ................................................................................................ 24 
1. INTRODUCTION ................................................................................................................ 28 
1.1. Mechanism of Action/Indication ............................................................................. 28 
1.2. Background and Rationale ....................................................................................... 28 
1.2.1. Rationale for Development of PF-06730512 .............................................. 28 
1.2.2. Nonclinical Pharmacology .......................................................................... 28 
1.2.2.1. In Vitro Assays .......................................................................... 28 
1.2.2.2. In Vivo Studies .......................................................................... 29 
1.2.3. Nonclinical Pharmacokinetics ..................................................................... 29 
1.2.4. Nonclinical Safety ....................................................................................... 29 
1.2.5. Clinical Experience with PF-06730512 ...................................................... 30 
1.2.5.1. Safety in Phase 1 C0221001 Study ............................................ 31 
1.2.5.2. Pharmacokinetics ....................................................................... 31 
1.2.5.3. Immunogenicity ......................................................................... 32 
1.2.5.4. Safety in Phase 2 C0221002 Study ............................................ 32 
1.2.5.5. Benefit-Risk Assessment ........................................................... 32 
1.3. Rationale .................................................................................................................. 33 
1.3.1. Study Rationale ........................................................................................... 33 
1.3.2. Dose Rationale ............................................................................................ 34 
2. STUDY OBJECTIVES AND ENDPOINTS ....................................................................... 36 
3. STUDY DESIGN ................................................................................................................. 37 
3.1. The Main Study to Assess PF-06730512 ................................................................. 37 
4. SUBJECT ELIGIBILITY CRITERIA ................................................................................. 39 
4.1. Inclusion Criteria ..................................................................................................... 40 
4.2. Exclusion Criteria .................................................................................................... 41 
4.3. Criteria for Progression to Treatment on Day 1 ...................................................... 43 
CCI 


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4.4. Lifestyle Requirements ............................................................................................ 44 
4.4.1. Woman of Childbearing Potential (WOCBP) ............................................. 44 
4.4.2. Contraception .............................................................................................. 45 
4.5. Sponsor’s Qualified Medical Personnel ................................................................... 46 
5. STUDY TREATMENTS ..................................................................................................... 47 
5.1. Allocation to Treatment ........................................................................................... 47 
5.2. Subject Compliance ................................................................................................. 48 
5.3. Investigational Product Supplies ............................................................................. 48 
5.3.1. Dosage Form(s) and Packaging .................................................................. 48 
5.3.2. Preparation and Dispensing ......................................................................... 48 
5.4. Administration ......................................................................................................... 48 
5.5. Infusion Discontinuation .......................................................................................... 49 
5.6. Investigational Product Storage ............................................................................... 49 
5.7. Investigational Product Accountability.................................................................... 50 
5.7.1. Destruction of Investigational Product Supplies ......................................... 50 
5.8. Concomitant Treatment(s) ....................................................................................... 50 
5.8.1. Permitted FSGS Medications ...................................................................... 51 
5.8.2. Prohibited Medications ............................................................................... 51 
6. STUDY PROCEDURES ...................................................................................................... 52 
6.1. Screening and Lead-in Period Activities and Assessments...................................... 52 
6.2. Investigational Treatment Period (Study Weeks 1 to 24) ........................................ 57 
6.3. Follow-up Period Activities and Assessments (Study Weeks 25 to 33) .................. 72 
6.4. Subject Withdrawal/Early Termination ................................................................... 76 
7. ASSESSMENTS .................................................................................................................. 78 
7.1. Safety ....................................................................................................................... 78 
7.1.1. Laboratory Tests ......................................................................................... 78 
7.1.2. Pregnancy Testing ....................................................................................... 80 
7.1.3. Physical Examinations ................................................................................ 80 
7.1.4. Vital Signs (Blood Pressure, Pulse Rate and Body Temperature) .............. 80 
7.1.5. Electrocardiogram ....................................................................................... 81 
CCI 
 
7.1.7. Infusion Site Reaction ................................................................................. 82 


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7.2. Efficacy .................................................................................................................... 82 
7.2.1. Urine Protein:Creatinine/:CCI 
(UPCR/CCI 
82 
CCI 
83 
7.3. Pharmacokinetics .................................................................................................... 84 
7.3.1. Serum for Analysis of PF-06730512 .......................................................... 84 
7.3.2. Urine for Analysis of PF-06730512 ........................................................... 84 
CCI 
 
7.4. Immunogenicity ...................................................................................................... 85 
7.4.1. Immunogenicity Analyses .......................................................................... 85 
CCI 
 
7.7. Blood Volume .......................................................................................................... 87 
8. ADVERSE EVENT REPORTING ...................................................................................... 87 
8.1. Requirements ........................................................................................................... 87 
8.1.1. Additional Details on Recording Adverse Events on the CRF ................... 88 
8.1.2. Eliciting Adverse Event Information .......................................................... 88 
8.1.3. Withdrawal from the Study Due to Adverse Events ................................... 89 
8.1.4. Time Period for Collecting AE/SAE Information ...................................... 89 
8.1.4.1. Reporting SAEs to Pfizer Safety ............................................... 89 
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF .................. 89 
8.1.5. Causality Assessment .................................................................................. 90 
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities ................... 90 
8.2. Definitions ............................................................................................................... 90 
8.2.1. Adverse Events ........................................................................................... 90 
8.2.2. Abnormal Test Findings .............................................................................. 91 
8.2.3. Serious Adverse Events .............................................................................. 91 
8.2.4. Hospitalization ............................................................................................ 92 
8.3. Severity Assessment ................................................................................................ 93 
8.4. Special Situations .................................................................................................... 93 
8.4.1. Protocol-Specified Serious Adverse Events ............................................... 93 
8.4.2. Potential Cases of Drug-Induced Liver Injury ............................................ 94 
8.4.3. Exposure to the Investigational Product During Pregnancy or 


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Breastfeeding, and Occupational Exposure .................................................... 95 
8.4.3.1. Exposure During Pregnancy ..................................................... 95 
8.4.3.2. Exposure During Breastfeeding ................................................ 97 
8.4.3.3. Occupational Exposure ............................................................. 97 
8.4.4. Medication Errors ....................................................................................... 97 
8.4.4.1. Medication Errors ..................................................................... 97 
9. DATA ANALYSIS/STATISTICAL METHODS .............................................................. 98 
9.1. Sample Size Determination .................................................................................... 98 
9.2. Efficacy Analysis .................................................................................................... 99 
9.2.1. Analysis of the Primary Endpoint .............................................................. 99 
9.2.2. Analysis of Secondary Endpoints ............................................................ 100 
CCI 
 
9.3. Pharmacokinetic Analysis .................................................................................... 100 
9.3.1. Analysis Population ................................................................................. 100 
CCI 
 
9.5. Safety Analysis ..................................................................................................... 101 
9.5.1. Electrocardiogram (ECG) Analysis .......................................................... 101 
9.6. Interim Analysis ................................................................................................... 102 
9.7. Data Monitoring Committee ................................................................................. 102 
10. QUALITY CONTROL AND QUALITY ASSURANCE .............................................. 103 
11. DATA HANDLING AND RECORD KEEPING ........................................................... 103 
11.1. Case Report Forms/Electronic Data Record ....................................................... 103 
11.2. Record Retention ................................................................................................ 104 
12. ETHICS ........................................................................................................................... 104 
12.1. Institutional Review Board/Ethics Committee ................................................... 104 
12.2. Ethical Conduct of the Study .............................................................................. 104 
12.3. Subject Information and Consent ....................................................................... 105 
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ......................................................................................................................... 105 
13. DEFINITION OF END OF TRIAL ................................................................................ 106 
13.1. End of Trial in a Member State .......................................................................... 106 
13.2. End of Trial in All Other Participating Countries ............................................... 106 
14. SPONSOR DISCONTINUATION CRITERIA ............................................................... 106 


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15. PUBLICATION OF STUDY RESULTS ........................................................................ 106 
15.1. Communication of Results by Pfizer ................................................................... 106 
15.2. Publications by Investigators ............................................................................... 107 
16. REFERENCES ................................................................................................................. 109 
17. APPENDICES .................................................................................................................. 110 
17.1. Appendix 1: Abbreviations ................................................................................. 110 
 
 
LIST OF TABLES 
Table 1. 
Safety Laboratory Tests ........................................................................... 79 
Table 2. 
Safety QTcF Assessment ....................................................................... 101 
 
 
LIST OF FIGURES 
Figure 1. 
Schematic of the Study Design ................................................................ 38 


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PROTOCOL SUMMARY 
Background and Rationale 
PF-06730512, a recombinant human Roundabout Guidance Receptor 2 (ROBO2) human 
immunoglobulin (Ig) G1 crystallized fragment (Fc) fusion protein that acts as a Slit Guidance 
Ligand (SLIT) neutralizing ligand trap, is currently being developed for the treatment of 
Focal Segmental Glomerulosclerosis (FSGS). 
Proteinuria is a hallmark of podocyte injury in kidney disease, including FSGS, which is the 
most common glomerular disease leading to end stage renal disease in the United States. 
Features of FSGS include progressive scarring of glomeruli and diffuse podocyte effacement. 
Initially, scarring is focused on portions of specific glomeruli, and as the disease progresses, 
scarring worsens within glomeruli and the number of affected glomeruli increases. Podocyte 
injury leads to effacement of the podocyte foot processes and a breakdown of the glomerular 
filtration barrier.1,2 Directly targeting podocyte effacement could slow disease progression of 
FSGS patients. 
Roundabout Guidance Receptor 2 (ROBO2) is a receptor for Slit Guidance Ligand (SLIT) 
protein ligands.3 ROBO2 is expressed at the basal surface of glomerular podocytes in the 
kidney and Slit Guidance Ligand 2 (SLIT2) is present in kidney glomeruli. Upon SLIT2 
binding, ROBO2 forms a complex with nephrin in the glomerular filtration barrier and acts 
as a negative regulator to inhibit nephrin-induced actin polymerization. The loss of ROBO2 
increases the actin polymerization in the podocyte and alleviates the abnormal podocyte 
structural phenotype found in nephrin-null mice.4 Loss of ROBO2 also increases adhesion of 
podocytes to the glomerular basement membrane in mice.5 PF-06730512 is a SLIT 
neutralizing ligand trap currently under development for the treatment of FSGS. 
PF-06730512 consists of the first two immunoglobulin (Ig) domains of ROBO2 fused to a 
human immunoglobulin G1 crystallized fragment (IgG1 Fc) through a glycine serine linker. 
PF-06730512 contains three mutations in the Fc region to reduce effector function of the 
molecule. The mechanism of PF-06730512 is to bind SLIT and prevent its interaction with 
the ROBO2 receptor on podocytes, thereby improving the structural integrity of podocytes, 
and reducing proteinuria. 
Study Rationale 
An “Early Signal of Efficacy” (ESoE) design was chosen to enable the sponsor to relatively 
quickly identify if PF-06730512 is efficacious in the FSGS patient population prior to 
expanding the sample size and population to fully demonstrate efficacy and safety that is 
required for registration. Thus, although the purpose of this Phase 2 adaptive study is to 
evaluate the efficacy, safety, tolerability and pharmacokinetics of PF-06730512 following 
multiple intravenous administrations in adult subjects with FSGS, the primary intention is to 
obtain an early indication of efficacy. Up to 3 doses of PF-06730512 may be assessed in up 
to 3 separate cohorts. 


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All subjects will be required to complete an approximate 8-week Lead-in Period prior to 
receiving treatment with PF-06730512 in the Investigational Treatment Period. The 
Investigational Treatment Period will be 24 weeks in duration. Given the rarity of the 
disease and small sample size of the study, a placebo control is not being used. Adequate 
safety assessment will be feasible based on data obtained in the study’s Lead-in Period in 
comparison to the Investigational Treatment Period and to historical data from previous 
clinical studies conducted in FSGS patients. 
STUDY OBJECTIVES AND ENDPOINTS 
 
Primary Objective(s): 
• To evaluate the efficacy of PF-06730512 
compared to baseline in the reduction of 
proteinuria following 12 weeks of 
treatment in patients with FSGS. 
Secondary Objective(s): 
• To evaluate the safety and tolerability of 
PF-06730512 following up to 24 weeks 
of treatment in subjects with FSGS. 
• To evaluate the effects of PF-06730512 
on proteinuria time course. 
• To evaluate the effect of PF-06730512 
on renal function. 
• To evaluate the serum exposure of 
PF-06730512 in FSGS patients. 
• To evaluate the immunogenicity profile 
of PF-06730512. 
 
 
 
 
 
 
CCI 
Primary Endpoint(s): 
• Percentage change from baseline to 
Week 13 in Urinary Protein to 
Creatinine Ratio (UPCR), calculated 
from the 24-hour urine collection. 
Secondary Endpoint(s): 
• Adverse Events, Laboratory Safety 
Tests (Hematology, Clinical 
Chemistry, Urinalysis), Body Weight, 
Blood Pressure, Pulse Rate, Body 
Temperature and Electrocardiogram 
(ECG). 
• Percentage change from baseline to 
Weeks 2, 5, 9, and beyond Week 13, as 
applicable in UPCR. 
• Percentage change from baseline to 
Weeks 3, 5, 9, 13 and beyond, as 
applicable, in estimated glomerular 
filtration rate (eGFR). 
• Serum concentration of PF-06730512. 
• Incidence of the development of 
anti-drug antibody (ADA) and 
neutralizing antibody (NAb). 


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STUDY DESIGN 
The adaptive study consists of a Screening Period of up to 43 days, an approximately 8-week 
Lead-in Period, an Investigational Treatment Period of up to 24 weeks during which subjects 
will receive PF-06730512 once every 2 weeks (Q2W), followed by a 9-week Follow-up 
Period. 
Subjects in the Lead-in Period will be eligible for transition to active treatment if at Week -1 
the UPCR and eGFR meet eligibility criteria, as described in Section 4.3. 
Upon commencement of active treatment with PF-06730512, subjects will be dosed 
intravenously Q2W for up to 24 weeks, but the primary endpoint result will be based on 
UPCR from a 24-hour urine collection at Week 13. There will be a maximum of 
12 infusions of PF-06730512 within the 24-week Investigational Treatment Period. 
Telephone contact visits will be conducted the weeks in between dosing visits to check the 
subject’s overall status, including new or worsening adverse events, changes to concomitant 
medications, compliance with appropriate contraceptive use, and reminders about upcoming 
urine collections, when applicable. 
The study will investigate up to 3 doses of PF-06730512 in up to 3 cohorts, each consisting 
of up to approximately 22 subjects. CCI 
 
 
 
All cohorts will collect the same procedures at the same 
timepoints, according to the Schedule of Activities. Interim analyses may be conducted 
• CCI 


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whilst the study is ongoing to determine futility of any evaluated dose, and to inform 
selection of next dose level to be evaluated (Section 9.6). 


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SCHEDULE OF ACTIVITIES 
The schedule of activities table provides an overview of the protocol visits and procedures. Refer to the STUDY PROCEDURES and 
ASSESSMENTS sections of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed on the schedule of activities table, in order to 
conduct evaluations or assessments required to protect the well-being of the subject. 
Visit days and Visit weeks are relative to first dosing day, Week 1 Day 1; listed days are the first days of the upcoming week. 
 
Study Procedures 
Abbreviations in this Table 
may be found in Appendix 1: 
Abbreviations 
Screening 
Period 
Lead-in 
Period 
Investigational Treatment Period 
Follow-up Period 
Early 
Termi 
Visit Weeka 
-12 to -9 
-8 
-4 
-1 
1 
2 
3 
5 
7 
9 
11 
13 
15 
17 
19 
21 
23 
25 
27 
29 
33 
Visit Daysa 
-90 to -57 -56 -28 
-7 
1 
8 
15 
29 
43 
57 
71 
85 
99 
113 
127 
141 
155 
169 
183 
197 225 
Visit Window (days) 
-5 
±5 
±5 
±5 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±5 
±5 
±5 
±7 
Informed Consent 
Xb 
Demography (smoking, 
alcohol) 
Xb 
X 
Eligibility criteria 
X 
Xr 
Xr 
Medical history 
X 
X 
FSGS history; prior and 
ongoing FSGS treatment 
Xt 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Prior and Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examinationd 
X 
X 
X 
X 
Xc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CCI 
Contraception Check 
Xb 
X 
X 
X 
Xc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE Monitoring 
Xb 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
X 
X 
12-lead ECG supine 
X 
X 
X 
Xc 
X 
X 
X 
X 
Xl 
Xl 
X 
X 
X 
Vital Signs (BP, PR, 
temperature) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CCI 
 
 
 
 
 
 
 
 
 
 
 
 
 
Telephone Visitk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Study Procedures 
Abbreviations in this Table 
may be found in Appendix 1: 
Abbreviations 
Screening 
Period 
Lead-in 
Period 
Investigational Treatment Period 
Follow-up Period 
Early 
Termi 
Visit Weeka 
-12 to -9 
-8 
-4 
-1 
1 
2 
3 
5 
7 
9 
11 
13 
15 
17 
19 
21 
23 
25 
27 
29 
33 
Visit Daysa 
-90 to -57 -56 -28 
-7 
1 
8 
15 
29 
43 
57 
71 
85 
99 
113 
127 
141 
155 
169 
183 
197 225 
Visit Window (days) 
-5 
±5 
±5 
±5 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±5 
±5 
±5 
±7 
Study Treatment 
Cohort Enrollment 
(non-randomized) 
Xs 
PF-06730512 
Administratione 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Infusion Site Reaction 
Assessmente 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory Assessments 
Clinical Laboratory Tests 
(Section 7.1) 
X 
X 
X 
X 
Xc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum β-HCG (females of 
childbearing potential) 
X 
X 
X 
Xc,n 
Xn 
Xn 
Xn 
Xn 
Xn 
Xn 
Xn 
Xn 
Xn 
Xn 
Xn 
X 
X 
X 
X 
FSH (postmenopausal 
females), HBsAg, HBsAb, 
HBcAb, HCVAb, HIV 
X 
Lipid profile(post 8-hour 
fast) 
X 
X 
X 
Xc 
X 
X 
X 
X 
X 
X 
X 
X 
eGFR 
X 
X 
X 
Xs 
Xc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PF-06730512 PK 
Xc,f 
X 
Xg 
Xg 
Xg 
Xg 
Xf 
Xg 
Xg 
Xg 
Xg 
Xg 
Xf 
X 
X 
X 
X 
X 
Cytokinesh 
X 
X 
X 
CCI 
 
 
 
 
 
 
 
 
 
Immunogenicity (ADA, 
NAb) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CCI 
 
Urine Collection 
First Morning Void (FMV) 
(Subject to bring) 
Xb,j 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
24-Hour Urine (Subject to 
bring) 
Xj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine for PK (20 mL from 
24-hour urine collection) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Study Procedures 
Abbreviations in this Table 
may be found in Appendix 1: 
Abbreviations 
Screening 
Period 
Lead-in 
Period 
Investigational Treatment Period 
Follow-up Period 
Early 
Termi 
Visit Weeka 
-12 to -9 
-8 
-4 
-1 
1 
2 
3 
5 
7 
9 
11 
13 
15 
17 
19 
21 
23 
25 
27 
29 
33 
Visit Daysa 
-90 to -57 -56 -28 
-7 
1 
8 
15 
29 
43 
57 
71 
85 
99 
113 
127 
141 
155 
169 
183 
197 225 
Visit Window (days) 
-5 
±5 
±5 
±5 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±5 
±5 
±5 
±7 
CCI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine reserve aliquot (10 mL 
from 24-hour collection)p 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine drug test 
Xm 
Urinalysis, including 
microscopy 
X 
X 
X 
X 
Xc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine Containers Distribution 
Xb,j 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine Collection Diary 
Distribution 
X 
Check Completion of Urine 
Collection Diary 
Xo 
X 
Xo 
Xo 
Xo 
Xo 
Xo 
Xo 
Xo 
Xo 
Xo 
a. 
Visit day in study is relative to Day 1. 
b. Subject written informed consent must be obtained prior to any study procedures taking place. The Screening process will require at least 2 site visits to 
accommodate at-home urine collection required to confirm eligibility (refer to footnote j). The subject must be provided with containers for urine collection 
and comprehensive instructions for the urine collection process at Screening Visit 1. For detailed collection procedures see Section 7.2.1. 
c. 
All procedures and assessments should be done before dosing of PF-06730512, except for infusion site assessment, post-infusion electrocardiogram (ECG), 
and post-infusion PK and cytokine blood sampling (see footnotes f and h). 
d. All physical examinations (full and brief examinations) must include edema assessment and weight. Full physical examination must be completed either at 
Screening or Week -8 Visit (first day of Lead-in Period); otherwise, brief examinations are performed if findings during previous examination or new/open 
AEs, at investigator discretion. Height is only measured once at Screening. 
e. 
Investigational product (IP) administration will last approximately 60 minutes including the flush for the intravenous (IV) infusion. Post-infusion safety 
observation period of at least 3 hours is required after the first 3 doses of IP (Weeks 1, 3, and 5). The post-infusion observation period for all remaining IP 
administrations will be 1 hour (Weeks 7 – 23), provided no safety issues are observed. 


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f. 
Two PK samples will be collected: 1 sample at pre-dose (within 30 minutes prior to dosing), and 1 sample at the end of infusion (within 6 minutes after the 
end of infusion) on Days 1 and 71 (Week 11) and 155 (Week 23). 
g. Only pre-dose PK samples will be collected on Weeks 3, 5, 7, 9, 13, 15, 17, 19, and 21 (within 30 minutes prior to dosing) 
h. Cytokines are collected at pre-dose (within 30 minutes prior to dosing), and 1, 2 and 4 hours post beginning of infusion ±15 minutes. Extra blood samples 
for cytokine measurements should be taken immediately if a subject develops symptoms typical for an infusion reaction during the IP administration. 
i. 
Subject who prematurely withdraws during Investigational Treatment Period (Week 1 through Week 24) should return for an Early Withdrawal/Termination 
visit and then enter into the Follow-up Period. 
j. 
The 24-Hour and FMV urine collections are to be obtained from subject at follow-up Screening Visit (Screening Visit 2). 
k. Telephone contact: Approximately 7 days after IP administration (±3 days at Weeks 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24) the subject will be contacted 
by telephone to discuss concomitant medications, contraceptive use and any new or changing adverse events. Subjects should also be reminded to collect 
urine samples as required and to bring the full containers back to site at the next visit (see footnote o below). 
l. 
On IP administration days, 12-lead ECGs are done pre-dose and at the end of infusion, within an approximately 45-minute window. 
m. The urine drug test at Screening is performed by the central lab. 
n. Blood sample for serum β-HCG are collected for central lab testing (in females of child-bearing potential, Screening Visit 2, Weeks -8, -1, 25, 29 and 33). 
On all IP administration days, serum for pregnancy tests via test strip as a stat procedure performed locally at the site, with the negative result being available 
prior to the administration of IP (Weeks 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21 and 23). 
o. Site personnel to call subject prior to the upcoming visit to remind the subject to perform FMV and a 24-hour urine collection, explain how to correctly 
collect and to bring the full FMV and 24-hour urine containers to the site at their scheduled study visit. This call is critical before Week -1, Week 13 and 
Week 25 and Week 33 Visits, or any Early Termination visits. This call may be part of the Telephone contact calls, when applicable. 
p. Prepare reserve 10-mL urine aliquot from the 24-hour collection (for UPCR measurement) which is to be sent to the central lab with a shipment separate 
from main urine shipment, but on the same day. Any residual of this sample may also be used for exploratory purposes. 
q. 
r. 
 
 
 
 
s. 
Prior to enrollment and first dose on Day 1, subjects must meet the eGFR and UPCR criteria outlined in Section 4.3. 
t. 
A complete history of the subject’s FSGS will be collected at screening, including initial diagnosis date, recurrence date if applicable, and prior and ongoing 
FSGS medications/treatments. Subjects will also be asked to provide their most recent diagnostic biopsy report. This request is optional and not required for 
enrollment. 
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1. INTRODUCTION 
1.1. Mechanism of Action/Indication 
PF-06730512, a recombinant human Roundabout Guidance Receptor 2 (ROBO2)-human 
immunoglobulin (Ig) G1 crystallized fragment (Fc) fusion protein that acts as a SLIT 
neutralizing ligand trap, is currently being developed for the treatment of Focal Segmental 
Glomerulosclerosis (FSGS). 
1.2. Background and Rationale 
1.2.1. Rationale for Development of PF-06730512 
Proteinuria is a hallmark of podocyte injury in kidney disease, FSGS, which is the most 
common glomerular disease leading to end stage renal disease. Features of FSGS include 
progressive scarring of glomeruli and segmental or diffuse podocyte effacement. Initially, 
scarring is focused to portions of specific glomeruli, and as the disease progresses, scarring 
worsens within glomeruli and the number of affected glomeruli increases. Podocyte injury 
leads to effacement of the podocyte foot processes and a breakdown of the glomerular 
filtration barrier.1,2 Directly targeting podocyte effacement could slow disease progression of 
FSGS patients. 
Roundabout Guidance Receptor 2 (ROBO2) is a receptor for Slit Guidance Ligand (SLIT) 
protein ligands.3 ROBO2 is expressed at the basal surface of glomerular podocytes in the 
kidney and Slit Guidance Ligand 2 (SLIT2) is present in kidney glomeruli. Upon SLIT2 
binding, ROBO2 forms a complex with nephrin in the glomerular filtration barrier and acts 
as a negative regulator to inhibit nephrin-induced actin polymerization. The loss of ROBO2 
increases the actin polymerization in the podocyte and alleviates the abnormal podocyte 
structural phenotype found in nephrin-null mice.4 Loss of ROBO2 also increases adhesion of 
podocytes to the glomerular basement membrane in mice.5 PF-06730512 is a SLIT 
neutralizing ligand trap currently under development for the treatment of FSGS. 
PF-06730512 consists of the first two immunoglobulin (Ig) domains of ROBO2 fused to a 
human immunoglobulin G1 crystallized fragment (IgG1 Fc) through a glycine serine linker. 
PF-06730512 contains three mutations in the Fc region to reduce effector function of the 
molecule. The mechanism of PF-06730512 is to bind SLIT and prevent its interaction with 
the ROBO2 receptor on podocytes, thereby improving the structural integrity of podocytes, 
and reducing proteinuria. 
CCI 
 
 


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1.2.5. Clinical Experience with PF-06730512 
PF-06730512 was evaluated in a First-in-Human (FIH) study (C0221001) that has been 
completed and is being assessed in an ongoing Phase 2 study (C0221002). 


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1.2.5.1. Safety in Phase 1 C0221001 Study 
In the FIH Study, C0221001, the safety of PF-06730512 was assessed in 79 (59 active and 
20 placebo) healthy adult subjects. This study was a combined single ascending dose plus 
multiple ascending dose (SAD/MAD) study which was completed on 10 December 2018 
with the Clinical Study Report. The study was a randomized, investigator- and 
subject-blinded (sponsor-open), placebo-controlled investigation of the safety, tolerability 
and PK of PF-06730512, following IV or SC administration (Cohorts 1-10). Additionally, an 
open label investigation of the safety, tolerability and PK of a single dose administration of 
PF-06730512 was conducted in healthy Japanese male subjects (Cohort 11). A total of 
79 subjects were enrolled, with 6 subjects per cohort for Cohorts 1-3, 8 subjects per cohort 
for Cohorts 4-10 and 5 Japanese subjects in Cohort 11. 
 
There were no deaths, treatment-related Serious Adverse Events (SAEs), severe 
Treatment-Emergent Adverse Events (TEAEs) or infusion reactions. The majority of TEAEs 
were mild in severity and there was no clear dose-dependent increase in the frequency of 
TEAEs with increase in doses. 
There were no clinically significant adverse safety laboratory changes or apparent adverse 
trends in the safety laboratory data. There were no dose-response relationships in fasting 
lipids identified in the study. No abnormalities in laboratory tests, vital signs, or ECGs were 
considered to be clinically significant or reported as AEs by the investigator. 
 
Complete safety information for this study can be found in the SRSD for PF-06730512, 
which for this study is the current Investigator Brochure. 
1.2.5.2. Pharmacokinetics 
In healthy non-Japanese subjects, Cmax was observed shortly after the end of the infusion 
(median time for Cmax [Tmax] range of approximately 2.1 to 3.0 hours after the start of 
a 2-hour infusion) following single IV administration of PF-06730512 CCI 
 
Serum concentrations post Cmax exhibited a biphasic decline over time. 
Mean terminal halflife- (t½) ranged from 5.3 to 13 days with a shorter t½ observed at the 
lower doses, probably due to sensitivity limitation of the bioanalytical assay, ie, lack of 
quantifiable concentrations at later time points at lower doses. The geometric mean 
clearance (CL) values ranged between 0.034 to 0.054 L/hr across the doses and geometric 
mean volume of distribution at steady state (Vss) values ranged from 9.3 to 14 L. CCI  


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CCI 
 
 
 
 
1.2.5.3. Immunogenicity 
In the SAD part of Study C0221001, none of the 35 subjects who received PF-06730512 was 
confirmed positive for anti-drug antibodies (ADA). In the MAD part of Study C0221001, 
2 of the 24 subjects CCI 
 who 
received PF-06730512 were confirmed positive for ADA, with 1 out of 24 subjects having 
positive neutralizing antibody (Nab). As the overall immunogenicity incidence was low, 
there was insufficient data to fully evaluate the effect of ADA/NAb on PK and safety. 
Evaluating the 2 subjects with positive ADA (and 1 of the 2 with NAb), no AEs, clinically 
significant findings or differences in PK were observed in relation to ADA/NAb. 
There were no changes in cytokines considered to be clinically significant or reported as AEs 
by the investigator. 
1.2.5.4. Safety in Phase 2 C0221002 Study 
 
To date no adverse drug reactions have been 
identified from data collected. 
1.2.5.5. Benefit-Risk Assessment 
There are no adverse drug reactions identified from the nonclinical and clinical data 
collected. As such, there are no important risks or important potential risks for 
PF-06730512. Based on the available safety and efficacy data for PF-06730512, the 
benefit-risk profile of the medicinal product remains favorable. 
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1.3. Rationale 
1.3.1. Study Rationale 
An “Early Signal of Efficacy” (ESoE) design was chosen to enable the sponsor to relatively 
quickly identify if PF-06730512 is efficacious in the FSGS patient population prior to 
expanding the sample size and population to fully demonstrate efficacy and safety that is 
required for registration. Thus, although the purpose of this phase 2 adaptive study is to 
evaluate the efficacy, safety, tolerability and pharmacokinetics of PF-06730512 following 
multiple IV administrations in adult subjects with FSGS, the primary intention is to obtain an 
early indication of efficacy. Up to 3 doses of PF-06730512 may be assessed in up to 3 
separate cohorts. 
All subjects will be required to complete an approximately 8-week Lead-in Period prior to 
receiving treatment with PF-06730512 in the Investigational Treatment Period. The Lead-in 
Period is designed to: 
1. Provide stable baseline data for proteinuria, as measured by urine protein to creatinine 
ratio (UPCR) and other laboratory and clinical markers of kidney function before 
subjects receive active treatment, thus enabling potential sensitivity analyses to the 
primary analysis using internal comparisons. 
2. Assist in the interpretation of safety assessments by improving the differentiation of 
adverse events related to the course of FSGS under standard of care versus adverse 
events potentially related to investigational product during the Treatment Period. 
The Investigational Treatment Period will be 24 weeks in duration. 
Given the rarity of the disease and small sample size of the study, a placebo control is not 
being used. Adequate safety assessment will be feasible based on data obtained in the 
study’s Lead-in Period in comparison to the Investigational Treatment Period and to 
historical data from previous clinical studies conducted in FSGS patients. 
Safety monitoring will commence once the subject has provided informed consent. In the 
Lead-in Period, the focus will be on possible symptoms and complications of nephrotic 
syndrome including edema in peripheral (facial, extremity) and central (pleural effusion, 
ascites) locations, weight gain due to edema, ulcerations and infections in edema-dependent 
regions and worsening of hypertension. In addition, adverse events may occur due to 
thromboembolic complications related to FSGS which may manifest as renal venous 
thrombosis potentially extending to the inferior vena cava, deep venous thrombosis of the 
lower extremities and subsequent pulmonary embolism.7 Adverse events may be related to 
side effects of previous or current FSGS therapy including cataracts, osteoporotic bone 
disease or avascular necrosis of the femoral head. A prolonged course of corticosteroids is 
associated with significant side effects, including diabetes, increased infection rates, 
osteoporosis, and weight gain. Nephrotoxicity is of great concern in the usage of calcineurin 
inhibitors in treatment of steroid-resistant FSGS with chronically impaired renal function. 


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1.3.2. Dose Rationale 
 
 


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As there is currently no mechanistic biomarker that can provide the link to pathway 
modulation, PK/pharmacodynamic (PD) modeling approach was employed for projections of 
ROBO2-SLIT2 % reduction using a kidney site-of-action model. This incorporates 
preliminary PK modeling from study C0221001, ROBO2 and SLIT2 biomeasure from FSGS 
kidney samples, and in vitro binding data. The premise is translation of reduction in 
ROBO2-SLIT2 binding, and hence signaling, to efficacy ie, proteinuria reduction. CCI 
 
 
 
 
Planned infusion duration in this study is approximately 1 hour, and the monitoring 
requirements post-infusion are detailed in Section 7.1.7. 


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2. STUDY OBJECTIVES AND ENDPOINTS 
Primary Objective(s): 
• 
To evaluate the efficacy of PF-06730512 
compared to baseline in the reduction of 
proteinuria following 12 weeks of treatment in 
patients with FSGS. 
Secondary Objective(s): 
• 
To evaluate the safety and tolerability of 
PF-06730512 following up to 24 weeks of 
treatment in subjects with FSGS. 
• 
To evaluate the effects of PF-06730512 on 
proteinuria time course. 
• 
To evaluate the effect of PF-06730512 on renal 
function. 
• 
To evaluate the serum exposure of PF-06730512 
in FSGS patients. 
• 
To evaluate the immunogenicity profile of 
PF-06730512. 
 
 
Primary Endpoint(s): 
• 
Percentage change from baseline to Week 13 
in Urinary Protein to Creatinine Ratio (UPCR), 
calculated from the 24-hour urine collection. 
 
Secondary Endpoint(s): 
• 
Adverse Events, Laboratory Safety Tests 
(Hematology, Clinical Chemistry, Urinalysis), 
Body Weight, Blood Pressure, Pulse Rate, 
Body temperature and Electrocardiogram 
(ECG). 
• 
Percentage change from baseline to 
Weeks 2, 5, 9, and beyond Week 13, as 
applicable, in UPCR. 
• 
Percentage change from baseline to Weeks 3, 
5, 9, 13 and beyond, as applicable, in estimated 
glomerular filtration rate (eGFR). 
• 
Serum concentration of PF-06730512. 
• 
Incidence of the development of anti-drug 
antibody (ADA) and neutralizing antibody 
(NAb). 
 
 
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Interim analyses may be conducted 
3. STUDY DESIGN 
3.1. The Main Study to Assess PF-06730512 
The adaptive study consists of a Screening Period of up to 43 days, an approximately 8-week 
Lead-in Period, an Investigational Treatment Period of up to 24 weeks during which subjects 
will receive PF-06730512 once every 2 weeks (Q2W), followed by an approximately 9-week 
Follow-up Period. Delays to the beginning of Lead-in or Investigational Treatment Period 
(up to 1 week from visit window specified) due to pending primary or repeat laboratory 
results that are submitted for analysis within the protocol specified window, will not be 
considered protocol deviations. Any such delays should be documented and brought to the 
Sponsor’s attention immediately. 
 
whilst the study is ongoing to determine futility of any evaluated dose, as well as determine 
which dose level will be evaluated next (see Section 9.6). Cohorts will be enrolled in 
sequence, but depending on the timing and the results of the pre-specified formal interim 
analyses, as well as the status of enrollment, the optional Cohort 3 may be initiated prior to 
(or instead of) the start and/or completion of Cohort 2. Any change from one cohort to 
another will be communicated formally to all investigators, along with the specific dose of 
PF-06730512 for that given cohort. 


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+ 
+/- 
Follow-up 
Period 
(9 weeks) 
Treatment 
Period 
PF-06730512 
12 doses 
(24 weeks) 
Lead-in 
Period 
(8 weeks) 
3
rd dose level CCI 
Optional Cohort 3 (n= up to 22) 
Follow-up 
Period 
(9 weeks) 
Treatment 
Lead-in 
 
Period 
Period 
PF-06730512 
(8 weeks) 
12 doses 
(24 weeks) 
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Cohort 2 (n=22, ~18 Completers) 
Follow-up 
Period 
(9 weeks) 
Treatment 
Period 
PF-06730512 
12 doses 
(24 weeks) 
Lead-in 
Period 
(8 weeks) 
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Cohort 1 (n=22, ~18 Completers) 
Figure 1. 
Schematic of the Study Design 
 
 
 
Subjects will be seen at Screening (2 Screening Visits) and at Weeks -8, -4 and -1 during the 
Lead-in Period prior to Day 1 (start of PF-06730512 treatment). Subjects in the Lead-in 
Period will be eligible for transition to active treatment if at Week -1 the UPCR and eGFR 
meet eligibility criteria, as described in Section 4.3. 
Upon commencement of active treatment with PF-06730512, subjects will be dosed 
intravenously Q2W for up to 24 weeks, but the primary endpoint result will be based on 
UPCR from a 24-hour urine collection at Week 13. There will be a maximum of 
12 infusions of PF-06730512 within the 24-week Investigational Treatment Period (starting 
at Day 1/Week 1 and at Weeks 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, and 23 respectively). 
Telephone contact visits will be conducted the weeks in between dosing visits to check the 
subject’s overall status, including new or worsening adverse events, changes to concomitant 
medications, compliance with appropriate contraceptive use, and reminders about upcoming 
urine collections, when applicable. 


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. 
For this study, subjects with FSGS should have undergone a diagnostic biopsy within the 
past 5 years (see Section 4.1; Inclusion Criterion #2). For all sites, if possible and upon 
obtaining subject’s written informed consent, the central renal histopathologist, will obtain a 
redacted copy of the subject’s original, locally-read and anonymized FSGS diagnostic report 
for exploratory purposes only. Subjects who do not provide this optional diagnostic report 
are still eligible to participate in the study. 
Finally, if emergent safety or PK data dictate, further dosing could be halted pending 
additional data evaluation. Safety assessments, including physical examination, vital signs, 
electrocardiogram (ECG) and laboratory parameters will be performed throughout the study. 
The duration of study participation will be up to approximately 11 months from Screening to 
the last post-treatment Follow-up Period visit. The durations of the study periods are listed 
below: 
• Screening Period up to 43 days; 
• Lead-in Period: approximately 8 weeks; 
• Investigational Treatment Period: up to 24 weeks (primary endpoint assessment at 
Week 13); 
• Follow-up Period: approximately 9 weeks (after last dose given at visit Week 23). 
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4. SUBJECT ELIGIBILITY CRITERIA 
This study can fulfill its objectives only if appropriate subjects are enrolled. The following 
eligibility criteria are designed to select subjects for whom participation in the study is 
considered appropriate. All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular subject is suitable for this protocol. 
Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study. 
NOTE: Screening and Lead-in laboratory results considered by the investigator to be 
transient and inconsistent with the subject’s clinical condition may be repeated once during 
the respective period for confirmation of eligibility. The reason for repeating the assessment 
should be documented. 
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4.1. Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study: 
1. Evidence of a personally signed and dated informed consent document indicating that 
the subject has been informed of all pertinent aspects of the study. 
2. Male or female subject age ≥18 years must have a confirmed biopsy diagnosis of 
FSGS within 5 years prior (+3-month window) to Screening. 
• If a subject did not undergo a biopsy confirming the diagnosis of FSGS within the 
specified timeframe, a new renal biopsy would be required and read locally to 
assess this criterion. 
3. Estimated glomerular filtration rate (eGFR) ≥45 ml/min/1.73 m2 based on the Chronic 
Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. 
• If eGFR is 30-45 ml/min/1.73 m2, a recent biopsy (within 12 months prior to 
Screening) must demonstrate <50% tubulo-interstitial fibrosis. If a biopsy has not 
been performed within 12 months prior to Screening, a new renal biopsy would be 
required and read locally to assess this criterion. 
4. UPCR >1.5 g protein/g creatinine at Screening. 
5. Based on all previous treatment received for FSGS, subject is eligible if: 
a. Subject has been treated with an adequate course per investigator judgement of at 
least 1, and up to 3 classes of Immunosuppressants* either alone or in 
combination; 
OR 
b. Subject has a contraindication to any class of Immunosuppressant (may include 
steroids) or is considered to be intolerant to any class of Immunosuppressant (may 
include steroids) per investigator judgment. 
*Class of Immunosuppressants (one or more representatives of that same class). Single class 
examples: corticosteroids, CNIs, inosine monophosphate dehydrogenase (IMPDH) inhibitors (eg, 
mycophenolate mofetil [MMF], mizoribine), cytotoxic agents, rituximab. 
 
6. Subjects on ongoing corticosteroid treatment must have received an adequate course 
and be on a stable dose for at least 4 weeks prior to the Lead-in Period and expected 
to remain stable throughout the study. The same requirements apply to ongoing 
treatment with CNIs and/or MMF so long as subjects have been receiving either or 
both of these treatments for at least 3 months prior to the Lead-in Period. Refer to 
Section 5.8.1 for additional information. 


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7. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and 
other study procedures including completion of daily diaries to record symptoms and 
urine collections. 
8. Female subjects of non-childbearing potential will meet at least 1 of the reproductive 
criteria in Section 4.4.1. Females of childbearing potential and male subjects must 
agree to Contraception Methods in Section 4.4.2. 
4.2. Exclusion Criteria 
Subjects with any of the following characteristics/conditions will not be included in the 
study: 
1. Diagnosis of collapsing FSGS. 
2. Advanced chronic changes on renal biopsy as evidenced by >50% tubulo-interstitial 
fibrosis. 
3. Evidence or history of clinically significant hematological, endocrine (including 
Type 1 diabetes mellitus), pulmonary, gastrointestinal, cardiovascular, hepatic, 
psychiatric, neurological, or hepatic disease, like cirrhosis or chronic active liver 
disease. 
Note the following: 
• Steroid-induced diabetes is not excluded. 
• Type 2 diabetes mellitus is not excluded if well-controlled and if a recent biopsy 
(within 12 months prior to Screening) shows no histological changes indicating 
diabetic nephropathy. If a biopsy has not been performed within 12 months prior 
to Screening, a new renal biopsy would be required and read locally to assess this 
criterion. 
4. Organ transplantation. 
5. History of any malignancy except for subjects who had a basal or squamous cell skin 
cancer which has been treated and fully resolved for a minimum of 5 years. 
6. Body mass index (BMI) >45 kg/m2 (based on an estimated dry weight as per 
judgment of the investigator, if applicable). 
7. Treatment with rituximab within 6 months prior to start of the Lead-in Period. 
• If Rituximab treatment is longer than 6 months (prior to start of the Lead-in 
Period), subject is still excluded if no peripheral CD19+ B-cells are identified in 
the local laboratory prior to first study drug dosing. 


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8. The following immunosuppressant medications within the past 28 days prior to start 
of the Lead-in Period: azathioprine (Imuran), cytotoxic agents, acthar. 
9. Excessive alcohol consumption that may impair the subject’s ability to participate in 
the study per investigator judgment in accordance with national guidelines, if 
available. 
10. Screening sitting blood pressure (BP) ≥155 mm Hg (systolic) or ≥95 mm Hg 
(diastolic), following at least 5 minutes of sitting rest. If BP is ≥155 mm Hg 
(systolic) or ≥95 mm Hg (diastolic), the BP should be repeated 2 more times and the 
average of the 3 BP values should be used to determine the subject’s eligibility. 
Repeat BP measurements on a different day are allowed to meet this eligibility 
criterion. Note: Repeat BP measurement should be done within designated screening 
window and may be considered as unplanned visit. 
11. Active/serious infection including, but not limited to, Hepatitis B or C, human 
immunodeficiency virus (HIV). This includes subjects with a known history of 
cytomegalovirus (CMV), CMV mononucleosis, gammaherpesviral mononucleosis, 
parvovirus infection, or simian virus 40 infection. Note: Laboratory test results for 
these types of infections may require medical interpretation by the investigator and 
consultation with the Sponsor or designee. 
12. Subjects with a history of bilateral vesicoureteral reflux. 
13. Subjects with a history of prior treatment with or use of interferon, lithium, 
pamidronate, mTOR inhibitors (eg, sirolimus), testosterone/anabolic steroids, 
anthracycline (eg, doxorubicin), heroin. 
14. Subjects with ANY of the following abnormalities in clinical laboratory tests at 
Screening, as assessed by the study-specific laboratory and confirmed by a repeat test, 
if deemed necessary: 
a. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level 
1.5× upper limit of normal (ULN); 
b. Total bilirubin level 1.5× ULN; subjects with a history of Gilbert's syndrome may 
have direct bilirubin measured and would be eligible for this study provided the 
direct bilirubin level is ≤ ULN. 
15. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or 
subjects who are Pfizer employees, including their family members, directly involved 
in the conduct of the study. 
16. Previous known participation in a study investigating PF-06730512. 


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17. Participation in other studies involving investigational drug(s) within 30 days (or as 
determined by the local requirement) or 5 half-lives prior to study entry and/or during 
study participation. 
18. A positive urine drug test at Screening (except positive for tetrahydrocannabinol 
[THC]). 
19. Pregnant female subjects; breastfeeding female subjects; lactating female subjects; 
male subjects and female subjects of childbearing potential who are unwilling or 
unable to use 1 highly effective method of contraception as outlined in this protocol 
for the duration of the study and for at least 9 weeks (63 days) after the last dose of 
investigational product. 
20. Other acute or chronic medical or psychiatric condition including recent (within the 
past year) or active suicidal ideation or behavior or laboratory abnormality that may 
increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the subject inappropriate for entry into this 
study. 
21. Subjects with a history of hypersensitivity to the components of the study drug. 
4.3. Criteria for Progression to Treatment on Day 1 
Subjects will be progressed to treatment on Day 1 of Week 1 of the Investigational Treatment 
Period if the following criteria are satisfied: 
1. UPCR >1.5 g protein/g creatinine at Week -8 and Week -1 during the Lead-in Period 
based on 24-hour urine collections. 
• Subjects with substantial change in proteinuria during the Lead-in Period, defined 
as Week 1 UPCR value < 30% or >200% of the UPCR value at Week -8 (based 
on 24-hour urine collections), will not be permitted to progress into the 
Investigational Treatment Period. 
2. eGFR must be maintained per the eligibility criteria: 
• eGFR ≥45 ml/min/1.73 m2 based on the CKD-EPI formula at Week -8 and 
Week -1. 
• If eGFR at Week -1 is between 30-44 ml/min/1.73 m2, subjects will only be 
eligible for the Investigational Treatment Period if a biopsy demonstrating 
<50% tubulo-interstitial fibrosis has been performed within 12 months prior to 
Screening. 


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• Clinical laboratory tests may be repeated to assess eligibility when appropriate in the 
medical judgment of the investigator. Any therapies or interventions to treat FSGS 
that are introduced or discontinued in the Lead-in or Investigational Treatment 
Periods should be discussed with the Sponsor to confirm that the subject may 
continue in the study (Section 5.8.1). 
4.4. Lifestyle Requirements 
It is important that subjects continue their typical dietary habits and physical activity 
throughout the study, ie, from Screening until the on-site follow-up visits. Subjects will be 
asked not to change their diet and macronutrient composition and/or their exercise routine. 
4.4.1. Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered. 
Women in the following categories are not considered WOCBP: 
1. Premenopausal female with 1 of the following: 
• Documented hysterectomy; 
• Documented bilateral salpingectomy; 
• Documented bilateral oophorectomy. 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry. 
Note: Documentation for any of the above categories can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history 
interview. The method of documentation should be recorded in the participant’s medical 
record for the study. 
2. Postmenopausal female: 
• A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. In addition: 
• A high FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years of age and not using hormonal 
contraception or HRT. 


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• A female on HRT and whose menopausal status is in doubt will be required to 
use one of the nonestrogen hormonal highly effective contraception methods 
if she plans to continue HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment. 
4.4.2. Contraception 
In this study, male subjects and female subjects who are of childbearing potential as 
applicable to the study will receive PF-06730512, which has been associated with suspected 
teratogenicity/fetotoxicity. 
Female subjects who are, in the opinion of the investigator, sexually active and at risk for 
pregnancy with their partner(s) must agree to use 1 method of highly effective contraception 
throughout the study and for at least 63 days after the last dose of PF-06730512. Highly 
effective methods of contraception are those that result in a failure rate of <1% per year when 
used consistently and correctly. The investigator or his/her designee, in consultation with the 
subject, will confirm that the female subject has selected 1 method of highly effective 
contraception for the individual subject and her partner(s) from the list below, and will 
confirm that the subject has been instructed in their consistent and correct use. Contraceptive 
use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
Male subjects are required to use a condom as protection from the potential risk of exposure 
via PF-06730512 in the ejaculate which would pose a risk to a developing embryo/fetus in 
WOCBP. This is purely precautionary as the calculated safety margin for PF-06730512 is 
≥100-fold between the estimated maternal exposure due to seminal transfer and the NOAEL 
for serious manifestations of developmental toxicity in nonclinical studies. 
At time points indicated in the Schedule of Activities, the investigator or designee will 
inform the subject of the need to use 1 highly effective method of contraception consistently 
and correctly and document the conversation, and the subject’s affirmation, in the subject’s 
chart. In addition, the investigator or designee will instruct the subject to call immediately if 
the use of the selected contraception method is discontinued or if pregnancy is known or 
suspected in the subject or partner. 
Highly Effective Methods That Are User Dependent 
Items marked with an asterisk (*) denote contraceptives that are not approved for use in 
Japan. 
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.* 
2. Intrauterine device. 
3. Intrauterine hormone-releasing system. 


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4. Bilateral tubal occlusion (eg, bilateral tubal ligation). 
5. Vasectomized partner: 
• A vasectomized partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the WOCBP and the absence of sperm has 
been confirmed. If not, an additional highly effective method of contraception 
should be used. The spermatogenesis cycle is approximately 90 days. 
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation: 
• Oral 
• Intravaginal* 
• Transdermal* 
7. Progestogen-only hormone contraception associated with inhibition of ovulation: 
• Oral* 
• Injectable* 
8. Sexual abstinence: 
• Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant. 
9. Progestogen-only oral hormonal contraception where inhibition of ovulation is not the 
primary mode of action. 
10. Male or female condom with or without spermicide. 
11. Cervical cap, diaphragm, or sponge with spermicide. 
12. A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods). 
4.5. Sponsor’s Qualified Medical Personnel 
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the Investigator Site Master File. 


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To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card. The contact card contains, 
at a minimum, protocol and investigational product identifiers, subject study numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
subject’s participation in the study. The contact number can also be used by investigator 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available. It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study. The contact 
number is not intended for use by the subject directly, and if a subject calls that number, he 
or she will be directed back to the investigator site. 
5. STUDY TREATMENTS 
For the purposes of this study, and per International Conference on Harmonisation (ICH) 
guidelines, investigational product is defined as a pharmaceutical form of an active 
ingredient or placebo being tested or used as a reference/comparator in a clinical trial, 
including a product with a marketing authorization when used or assembled (formulated or 
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use (ICH E6 1.33). 
For this study, the investigational product is PF-06730512, a lyophilized powder for injection 
that requires reconstitution with sterile Water for Injection (WFI). This study does not 
include the use of placebo. 
5.1. Allocation to Treatment 
Subjects will be enrolled into Cohort 2 or Cohort 3 after approximately 22 subjects have been 
enrolled into Cohort 1. The sponsor will issue a formal communication to all sites upon 
transition from one cohort to the next. Allocation of subjects to the respective cohort (1, 2, 
or 3) will be conducted through the use of an interactive response technology (IRT) system 
(interactive Web-based response [IWR]). The site personnel (study coordinator or specified 
designee) will be required to enter or select information including but not limited to the 
user’s identification (ID) and password, the protocol number, and the subject number. The 
site personnel will then be provided with a cohort assignment, randomization number 
(enrollment), and dispensable unit (DU) or container number when investigational product is 
being supplied via the IRT system. The IRT system will provide a confirmation report 
containing the subject number, randomization (enrollment) number, and DU or container 
number assigned. The confirmation report must be stored in the site’s files. 
The study-specific IRT reference manual will provide the contact information and further 
details on the use of the IRT system. 


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The reconstituted drug 
5.2. Subject Compliance 
Investigational Product, PF-06730512, will be administered once every two weeks by 
qualified investigator site personnel at visits indicated in the Schedule of Activities. 
5.3. Investigational Product Supplies 
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product is intended for intravenous administration. Details of the preparation and 
administration of the investigational product are outlined in the Investigational Product (IP) 
Manual. 
5.3.2. Preparation and Dispensing 
Within this protocol, preparation refers to the investigator site activities performed to make 
the investigational product ready for administration or dispensing to the subject/caregiver by 
qualified staff. Dispensing is defined as the provision of investigational product, 
concomitant treatments, and accompanying information by qualified staff member(s) to a 
healthcare provider, subject, or caregiver in accordance with this protocol. Local health 
authority regulations or investigator site guidelines may use alternative terms for these 
activities. 
PF-06730512 lyophilized powder will be reconstituted using sterile WFI. The investigational 
product will be prepared at the investigational site or at a site-contracted qualified pharmacy 
by two operators; one of whom should be a licensed healthcare professional, preferably a 
qualified pharmacist. The operators must be fully trained and experienced in the 
reconstitution and preparation of sterile product solutions for intravenous administration. 
Dose preparation will be performed with locally accepted sterile handling technique. 
5.4. Administration 
PF-06730512 will be administered by qualified study site staff as an IV infusion over 
approximately 60 minutes using a calibrated infusion pump according to the IP Manual. The 
infusion line is flushed using a sufficient volume of Normal Saline (0.9% sodium chloride) 
that is greater than or equal to the hold-up volume of the infusion line/set. The flush solution 
should be administered at the same rate to ensure complete delivery of the dosing solution. 
The start and stop time of the infusion will be recorded on the case report form (CRF). The 
infusion stop time should be recorded as the time when the end of the saline flush is 
complete. The post-infusion observation period for each subject shall be 3 hours for the first 
3 doses. The observation period can be decreased to 1 hour after the end of infusion for the 
subsequent doses, provided that no infusion reactions are noted. 


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If an arm is used for IV infusion, the opposite arm should be used for the 
pharmacokinetic/pharmacodynamic (PK/PD) blood sample collections, if possible. 
Premedication with an antihistamine and acetaminophen is optional and might be provided 
per investigator judgment. See the IP Manual for detailed instructions on how to administer 
the investigational product. 
5.5. Infusion Discontinuation 
If a subject experiences symptoms typical of anaphylaxis, the IP administration should be 
discontinued immediately and permanently. 
If a subject experiences symptoms typical of infusion reactions (eg, lightheadedness, nausea, 
chills, fever), the study drug infusion should be stopped. At the discretion of the 
Investigator, the infusion can be restarted at a slower rate if symptoms are resolved within 
1 hour after the stop of infusion. If symptoms return, then the IP administration should be 
discontinued immediately and permanently. 
In the event that there is an infusion interruption, the entire duration of the infusion, from the 
initial start of infusion to the completion of infusion, should not exceed 3 hours. Subjects 
will receive appropriate treatment at the discretion of the investigator. 
5.6. Investigational Product Storage 
Drug product vials of PF-06730512 shall be stored at 2 to 8°C. Refer to the IP Manual for 
the in-use stability of the prepared dosing solutions. The investigator or an approved 
representative, eg, pharmacist, will ensure that all investigational products are stored in a 
secured area with controlled access under required storage conditions and in accordance with 
applicable regulatory requirements. 
Investigational products should be stored in their original containers and in accordance with 
the labels. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the product label. 
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated, and/or room-temperature products). This should 
be captured from the time of investigational product receipt throughout the study. Even for 
continuous-monitoring systems, a log or site procedure that ensures active evaluation for 
excursions should be available. The intent is to ensure that the minimum and maximum 
temperature is checked each business day to confirm that no excursion occurred since the last 
evaluation and to provide the site with the capability to store or view the minimum/maximum 
temperature for all non-working days upon return to normal operations. The operation of the 
temperature-monitoring device and storage unit (for example, refrigerator), as applicable, 
should be regularly inspected to ensure they are maintained in working order. 


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Any excursions from the product-label storage conditions should be reported to Pfizer upon 
discovery. The site should actively pursue options for returning the product to the storage 
conditions described in the labeling, as soon as possible. Deviations from the storage 
requirements, including any actions taken, must be documented and reported to Pfizer. 
Once an excursion is identified, the investigational product must be quarantined and not used 
until Pfizer provides permission to use the investigational product. It will not be considered a 
protocol deviation if Pfizer approves the use of the investigational product after the 
temperature excursion. Use of the investigational product prior to Pfizer approval will be 
considered a protocol deviation. Specific details regarding information the site should report 
for each excursion will be provided to the site. 
5.7. Investigational Product Accountability 
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies. All investigational products will be 
accounted for using a drug accountability form/record. 
5.7.1. Destruction of Investigational Product Supplies 
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site). If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by 
Pfizer, and all destruction must be adequately documented. 
5.8. Concomitant Treatment(s) 
Subjects will abstain from all prohibited medications that are listed in the Exclusion Criteria 
section and outlined in Section 5.8.2. 
For blood pressure control, a systolic value below 155 mm Hg is recommended. If it is 
necessary, in the opinion of the investigator, to add an antihypertensive medication, this will 
be listed as concomitant treatment. While the doses of the renin–angiotensin–aldosterone 
system (RAAS) blockers are required to be stable during the entire Investigational Treatment 
Phase and Follow-up Period, blood pressure control can be further optimized by titrating 
diuretics and/or other anti-hypertensive medications, in addition to the stable doses of RAAS 
blockers. 
Note: treatment with RAAS blockers is not mandatory. 
All concomitant medications taken during the study must be recorded with indication, daily 
dose, and start and stop dates of administration. All subjects will be questioned about 
concomitant medication at each visit. 
Medications taken from Screening up to the first dose of study medication will be 
documented as ‘prior medication’. Medications taken after the first dose of study medication 
will be documented as ‘concomitant medication’. 


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5.8.1. Permitted FSGS Medications 
All FSGS therapies administered prior to study should be captured on the CRF. FSGS 
therapies administered during the study period should adhere to the following guidelines 
below. 
Dose adjustments and discontinuations are discouraged during the study (Lead-in, 
Investigational Treatment and Follow-up Periods), however doses may be adjusted or 
discontinued if a safety issue arises. Dose changes to therapies listed below during Lead-in 
or Investigational Treatment Period must be discussed with the Sponsor to evaluate study 
continuation for the subject. Dose changes and discontinuations during the Follow-up Period 
will be at the investigator’s discretion but are discouraged for reasons other than subject 
safety concerns. 
1. RAAS blockers, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and 
glucagon-like peptide 1 (GLP1) agonists: Subjects receiving any of these therapies 
must be on stable dose approximately 4 weeks prior to beginning of the Lead-in 
Period and expected to remain on stable dose throughout the study. 
2. Corticosteroids: Prior treatment with an adequate course of corticosteroid, per 
investigator judgment. Subjects on ongoing corticosteroid treatment must be on a 
stable dose 4 weeks prior to the initiation of the Lead-in Period. 
3. CNIs and/or IMPDH inhibitors (eg, MMF, mizoribine [MZB]): 
• Ongoing treatment is permitted, so long as initiated at least 3 months prior to 
Lead-in Period, and subject is on a stable dose for at least 4 weeks prior to start of 
the Lead-in Period. 
• CNIs and IMPDH inhibitors may be given standalone or in combination. CNIs 
can be monitored with whole blood levels, per investigative site standard of care. 
Any such dose adjustments should be discussed with the Sponsor to confirm that 
the subject may safely continue in the study. 
Of note, discontinuation from any of the above listed therapies should occur no later than 
4 weeks prior to the start of the Lead-in Period. 
5.8.2. Prohibited Medications 
• Prior or concurrent treatment with interferon, lithium, pamidronate, mTOR inhibitors 
(eg, sirolimus), testosterone/anabolic steroids, anthracycline (eg, doxorubicin), 
heroin. 
• More than 3 prior regimens of immunosuppressive therapies. 


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• The following immunosuppressives must have been discontinued at least 4 weeks 
prior to the Lead-in Period and are not permitted during study participation, 
including: 
• azathioprine (Imuran) 
• cytotoxic agents 
• acthar 
• Rituximab must have been discontinued at least 6 months prior to Lead-in Period and 
is not permitted during study participation. 
• Any other investigational therapy within 4 weeks of Lead-in Period or during study 
participation. 
6. STUDY PROCEDURES 
6.1. Screening and Lead-in Period Activities and Assessments 
Subjects will have up to 43 days for Screening procedures to be initiated before the Week -8 
Lead-in Period Visit (refer to Schedule of Activities for details and visit windows). In 
addition, to prepare for participation into the study, subjects will be instructed on the 
Lifestyle Requirements, including Contraception Methods (Section 4.4.2) and Concomitant 
Treatments (Section 5.8). In particular, it is important that all prior FSGS treatments are 
stabilized or discontinued as described in the Concomitant Treatment(s) section of the 
protocol. 
Please also refer to the Schedule of Activities and Section 7 for details of the study 
procedures. 
A subject may be re-screened, after an agreement has been reached between the investigator 
and sponsor. If eligibility criteria are not met or evaluable within the Screening or Lead-in 
window, the subject will be Screen Failed. For subjects who consent to re-screen a new 
8-digit study specific subject identification (SSID) number will be assigned and all screening 
procedures must be repeated. If eligibility confirmation for the Screening or Lead-in Period 
is delayed due to delayed primary or repeat laboratory results, the subject may enroll once 
eligibility is confirmed by test results provided the results are received within one week of 
the specified window. 
Screening procedures may be split into 2 or more visits as recommended below. 
Alternatively, all procedures may be accomplished at one visit, with the exception of FMV 
and 24-hour urine collection. Subject written informed consent must be obtained prior to any 
study-specific procedures taking place. 
Screening Visit 1 
• Obtain informed consent from potential subject; 


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CCI 
CCI 
CCI 
• Obtain potential subject’s medical history, prior and ongoing medication details, 
demographic information and history of smoking and alcohol consumption); 
• A complete history of the subject’s FSGS will be collected at screening, including 
initial diagnosis date, recurrence date if applicable, and prior FSGS treatments 
administered, as well as capturing any contraindications or intolerance to these 
medications. 
• 
 
 
 
 
• Review inclusion and exclusion criteria with subject to determine eligibility; 
• Review contraceptive use with potential subject; 
• Provide subject with container for urine collection and explain the urine collection 
process; 
• Instruct subject to collect urine samples for 24-hour urine collection and first morning 
void (FMV) before next visit (Screening Visit 2); 
• Renal biopsy if required for eligibility: a renal biopsy should be obtained and 
assessed locally to confirm the subject is eligible for study participation. May be 
collected at this visit or the next visit (Screening Visit 2), so long as there is sufficient 
time to confirm eligibility prior to the Lead-in Period. 
• 
a renal biopsy may be obtained during Screening or 
Lead-in Phase, but must be collected prior to first dose of IP. 
 
 
 
 
Screening Visit 2 
• Verify potential subject’s medical and medication history, including demographic 
information and history of smoking and alcohol consumption; 
• Review inclusion and exclusion criteria with subject to verify eligibility; 
CCI 
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• All full PE and Brief PEs must include edema assessment and weight measurement. 
Full physical exam must be completed either at Screening or Week -8 (first day of the 
Lead-in Period); otherwise, brief exams are performed, if no findings during previous 
exam or new or ongoing AEs, and if appropriate as per investigator’s discretion; 
• Height measurement is only performed once at Screening; 
• Review contraceptive use with potential subject; 
• Perform serious and non-serious adverse event monitoring; 
• Perform single 12 lead ECG; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• Collect blood sample for clinical laboratory test, eGFR and fasting lipid profile 
(subjects must be fasting at least 8 hours prior to blood draw with no food or drink 
except water); 
• Collect blood sample for HCG (female of child bearing potential); 
• Collect blood sample for FSH (postmenopausal female); 
• Collect blood sample for HBsAg, HBcAb, HCVAb, and HIV; 
• Subject to bring container with FMV for CCI  and UPCR; 
• Subject to bring container with 24-hour urine collection for CCI  and UPCR; 
• Collect urine samples for urinalysis and drug test at the central lab; 
• Provide subject with container for urine collection and explain the urine collection 
process. 
• Instruct subject to collect FMV and 24-hour urine before the next visit; 
• 
 
Study Week -8 Visit 
• Review criteria for continuation to the Treatment Phase, as described in Section 4.3; 
• Review concomitant medications; 
• Review demographic information and history of smoking use and alcohol 
consumption; 
CCI 


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• All full PE and Brief PEs must include edema assessment. Full physical exam must 
be completed either at Screening or Week -8; otherwise, brief exam is performed, if 
no findings during previous exam or new or ongoing AEs, if appropriate as per 
investigator’s discretion. Height measurement is only performed once at Screening; 
• Review contraceptive use as applicable; 
• Perform serious and non-serious adverse event monitoring; 
• Perform single 12-lead ECG; 
• Obtain vital signs (single PR, BP and body temperature); 
• CCI 
 
 
• Collect blood sample for clinical laboratory test, eGFR and fasting lipid profile 
(subjects must be fasting at least 8 hours prior to blood draw - no food or drink except 
water); 
• Collect blood sample for HCG (female of child-bearing potential); 
• CCI 
 
• Subject to bring container with FMV; 
• Subject to bring container with 24-hour urine collection; 
• Prepare urine for PK (20 mL from 24-hour urine collection); 
• 
 
 
• CCI 
 
• Prepare reserve 10 mL urine aliquot from the 24-hour collection (for UPCR 
measurement) which is to be sent to the central lab with a shipment separate from the 
main urine shipment, but on the same day; 
• Provide subject with the Urine Collection Instruction and Diary; 
• Provide subject with container for urine collection and explain the urine collection 
process; request that subject perform FMV for CCI  and UPCR before next study 
visit. 
CCI 


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Study Week -4 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• Review contraceptive use with subject; 
• Perform serious and non-serious adverse event monitoring; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• CCI 
; 
• Collect blood sample for clinical laboratory test and eGFR; 
• Subject to bring container with FMV for CCI  and UPCR; 
• Collect urine samples for urinalysis; 
• Provide subject with containers for urine collection and explain the urine collection 
process; request that subject perform 24-hr urine collection and FMV before next 
visit; 
• Site personnel to call subject within 3 days before Visit Week -1 to remind him/her to 
perform FMV and a 24-hour urine collection, explain how to correctly collect and to 
bring the urine containers for FMV and 24-hour urine collection to clinic site at 
Week -1. 
Study Week -1 
• Review criteria for continuation to the Investigational Treatment Phase, as described 
in Section 4.3; 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• Review contraceptive use with subject; 
• Perform serious and non-serious adverse event monitoring; 
• Perform single 12-lead ECG; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• CCI 
 


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• Collect blood sample for clinical laboratory test, eGFR and fasting lipid profile 
(subjects must be fasting at least 8 hours prior to blood draw with no food or drink 
except water); 
• Collect blood sample for HCG (female of child-bearing potential); 
• CCI 
 
• Verify subject’s return/completion of Urine Collection Diary; 
• Subject to bring container with FMV for CCI 
 UPCR; 
• Subject to bring container with 24-hour urine collection for CCI 
 UPCR; 
• Prepare urine for PK (20 mL from 24-hour urine collection); 
• 
 
 
• Prepare reserve 10 mL urine aliquot from the 24-hour collection (for UPCR 
measurement) which is to be sent to the central lab with a shipment separate from the 
main urine shipment, but on the same day; 
• CCI 
 
• Provide subject with container for urine collection and explain the urine collection 
process; request that subject perform FMV before next visit. 
6.2. Investigational Treatment Period (Study Weeks 1 to 24) 
Refer to the Schedule of Activities and Section 7 Assessments for the study procedures to be 
completed during the Investigational Treatment Period. The 24-week Investigational 
Treatment Period begins in Study Week 1 and continues through Study Week 24, and 
subjects will receive intravenous treatment with PF-06730512 every other week. In addition, 
subjects will be reminded on the use of the Lifestyle Requirements (Section 4.4) and 
Concomitant Treatment(s) of the protocol, in particular, protocol restrictions regarding other 
FSGS treatments as described in the Concomitant Treatment(s) section of the protocol. 
The activities and assessments listed below are to be completed during the Investigational 
Treatment Period. Please refer to the Schedule of Activities for visit windows and Section 7 
Assessments for the study procedures to be completed during this period. 
CCI 


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If an intravenous catheter is placed for serial blood sample collections, ECGs and vital signs 
(PR, BP) assessments should be either collected prior to the insertion of the catheter or 
following a sufficient rest period after catheter insertion introduced to minimize impact of 
catheter placement on these assessments. 
Study Week 1 - Day 1 
• Review criteria for continuation to the Investigational Treatment Phase, as described 
in Section 4.3, to confirm eligibility; 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• CCI 
 
• Review contraceptive use with subject; 
• Perform serious and non-serious adverse event monitoring; 
• Perform single 12-lead ECG pre-dose and at the end of infusion within an 
approximately 45-minute window; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• Collect blood sample for clinical laboratory test, eGFR and fasting lipid profile 
(subjects must be fasting at least 8 hours prior to blood draw with no food or drink 
except water); 
• Use serum for pregnancy test via test strip as a stat procedure performed locally at the 
site, in females of child-bearing potential, with the negative result confirmed prior to 
the administration of investigational product; 
• Collect blood sample for pre-dose PK, ADA and NAb, and cytokines (within 
30 minutes prior to dosing); 
• Enroll the subject via IRT to allocate treatment as described in Section 5.1. 
• Intravenously administer PF-06730512 per IP Manual; 
• Collect blood sample for PK within 6 minutes after the end of infusion; 
• Collect blood samples for cytokines at 1, 2 and 4 hours post beginning of infusion, 
within approximately ±15 minutes; 
• Monitor subject for AEs and infusion site reaction for approximately 3 hours post end 
of infusion; 


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• CCI 
 
• Subject to bring container with FMV for CCI 
 UPCR; 
• Collect urine samples for urinalysis. 
• Provide subject with containers for urine collection and explain the urine collection 
process; request that subject perform 24-hr urine collection and FMV before next 
visit. 
Study Week 2 - Day 8 
• Perform a physical exam including body weight and edema assessment; 
• Review concomitant medications; 
• Review contraceptive use with subject; 
• Perform serious and non-serious adverse event monitoring; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• Collect blood sample for pre-dose PK, ADA and NAb; 
• Verify subject’s return/completion of Urine Collection Diary; 
• Subject to bring container with FMV for CCI 
 UPCR; 
• Subject to bring container with 24-hour urine collection for CCI 
UPCR; 
• Prepare urine for PK (20 mL from 24-hour urine collection); 
• 
 
 
• Prepare reserve 10 mL urine aliquot from the 24-hour collection (for UPCR 
measurement) which is to be sent to the central lab with a shipment separate from the 
main urine shipment, but on the same day; 
• CCI 
 
• Collect urine samples for urinalysis; 
• Provide subject with container for urine collection and explain the urine collection 
process; request that subject perform FMV before next visit. 
CCI 


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Study Week 3 - Day 15 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• Review contraceptive use with subject; 
• Perform serious and non-serious adverse event monitoring; 
• Perform single 12-lead ECG pre-dose and at the end of infusion within an 
approximately 45-minute window; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• Use serum for pregnancy test via test strip as a stat procedure performed locally at the 
site, in females of child-bearing potential, with the negative result being available 
prior to the administration of investigational product; 
• CCI 
 
• Collect blood sample for clinical laboratory test and eGFR; 
• Collect blood sample for pre-dose PK, ADA and NAb, and cytokines; 
• Intravenously administer PF-06730512 per IP Manual; 
• Collect blood samples for cytokines at 1, 2 and 4 hours post beginning of infusion, 
within approximately ±15 minutes; 
• Monitor subject for AEs and infusion site reaction for approximately 3 hours post end 
of infusion; 
• Collect urine samples for urinalysis; 
• Subject to bring container with FMV for CCI 
 UPCR; 
• Provide subject with containers for urine collection and explain the urine collection 
process; request that subject perform 24-hr urine collection and FMV urine collection 
for CCI 
 UPCR before next visit at Week 5. 
Study Week 4 - Day 22 (Telephone Visit) 
• Phone call to conduct inquiry about any spontaneously reported AEs by asking the 
subject to respond to a non-leading question such as “how do you feel?” 
• Review concomitant medications; 


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• Review contraceptive use; 
• Remind subject of FMV and 24-hour urine collections prior to next visit. 
Study Week 5 - Day 29 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• Review contraceptive use; 
• Perform serious and non-serious adverse event monitoring; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• CCI 
 
• Collect blood sample for pre-dose PK, ADA and NAb, and cytokines; 
• Collect blood sample for clinical laboratory test, eGFR and fasting lipid profile 
(subjects must be fasting at least 8 hours prior to blood draw with no food or drink 
except water); 
• Use serum for pregnancy test via test strip as a stat procedure performed locally at the 
site, in females of child-bearing potential, with the negative result being available 
prior to the administration of investigational product; 
• Intravenously administer IP per IP Manual; 
• Collect blood samples for cytokines at 1, 2 and 4 hours post beginning of infusion, 
within approximately ±15 minutes; 
• Monitor subject for AEs and infusion site reaction for approximately 3 hours post end 
of infusion; 
• Verify subject’s return/completion of Urine Collection Diary; 
• Subject to bring container with FMV for CCI 
 UPCR; 
• Subject to bring container with 24-hour urine collection for CCI 
 UPCR; 
• Prepare urine for PK (20 mL from 24-hour urine collection); 
• CCI 


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• CCI 
 
• Prepare reserve 10 mL urine aliquot from the 24-hour collection (for UPCR 
measurement) which is to be sent to the central lab with a shipment separate from 
main urine shipment, but on the same day; 
• CCI 
 
Study Week 6 - Day 36 (Telephone Visit) 
• Phone call to conduct inquiry about any spontaneously reported AEs by asking the 
subject to respond to a non-leading question such as “how do you feel?” 
• Review concomitant medications; 
• Review contraceptive use. 
Study Week 7 - Day 43 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• Review contraceptive use; 
• Perform serious and non-serious adverse event monitoring; 
• Perform single 12-lead ECG Pre-dose and at the end of infusion within an 
approximately 45--minute window; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• Collect blood sample for pre-dose PK, ADA and NAb; 
• Collect blood sample for clinical laboratory test and eGFR; 
• Use serum for pregnancy test via test strip as a stat procedure performed locally at the 
site, in females of child-bearing potential, with the negative result being available 
prior to the administration of investigational product; 
• Intravenously administer of IP per IP Manual; 
• Monitor subject for AEs and infusion site reaction for approximately 1 hour post end 
of infusion; 
• Collect urine samples for urinalysis; 


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•  Provide subject with containers for urine collection and explain the urine collection 
process; request that subject perform 24-hour urine collection and FMV for CCI  
CCI UPCR before next visit. 
Study Week 8 - Day 50 (Telephone Visit) 
• Phone call to conduct inquiry about any spontaneously reported AEs by asking the 
subject to respond to a non-leading question such as “how do you feel?” 
• Review concomitant medications; 
• Review contraceptive use; 
• Remind subject of FMV and 24-hour urine collections prior to next visit. 
Study Week 9 - Day 57 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• Review contraceptive use; 
• Perform serious and non-serious adverse event monitoring; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• Collect blood sample for clinical laboratory test, eGFR and fasting lipid profile 
(subjects must be fasting at least 8 hours prior to blood draw with no food or drink 
except water); 
• Use serum for pregnancy test via test strip as a stat procedure performed locally at the 
site, in females of child-bearing potential, with the negative result being available 
prior to the administration of investigational product; 
• Collect blood sample for pre-dose PK, ADA and NAb; 
• CCI 
 
 
• Monitor subject for AEs and infusion site reaction for approximately 1 hour post end 
of infusion; 
• Verify subject’s return/completion of Urine Collection Diary; 
• Subject to bring container with FMV for CCI 
 UPCR; 


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• Subject to bring container with 24-hour urine collection for CCI 
 UPCR; 
• Prepare urine for PK (20 mL from 24-hour urine collection); 
• 
 
• Prepare reserve 10 mL urine aliquot from the 24-hour collection (for UPCR 
measurement) which is to be sent to the central lab with a shipment separate from the 
main urine shipment, but on the same day; 
• CCI 
 
 
• Provide subject with container for urine collection and explain the urine collection 
process; request that subject perform FMV for CCI 
 UPCR before next visit. 
Study Week 10 - Day 64 (Telephone Visit) 
• Review concomitant medications; 
• Review contraceptive use; 
• Perform serious and non-serious adverse event monitoring; 
• Remind subject of FMV urine collection prior to next visit. 
Study Week 11 - Day 71 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• Review contraceptive use; 
• Perform serious and non-serious adverse event monitoring; 
• Perform single 12-lead ECG Pre-dose and at the end of infusion within an 
approximately 45-minute window; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• CCI 
 
• Collect blood sample for clinical laboratory test and eGFR; 
CCI 


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• Use serum for pregnancy test via test strip as a stat procedure performed locally at the 
site, in females of child-bearing potential, with the negative result being available 
prior to the administration of investigational product; 
• Collect blood sample for pre-dose PK, ADA and NAb; 
• Intravenously administer IP per IP Manual; 
• Collect blood sample for PK at the end of infusion, within 6 minutes after the end of 
infusion; 
• Monitor subject for AEs and infusion site reaction for approximately 1 hour post end 
of infusion; 
• Collect urine samples for urinalysis; 
• Subject to bring container with FMV for CCI 
 UPCR; 
•  Provide subject with containers for urine collection and explain the urine collection 
process; request that subject perform 24-hour urine collection and FMV for CCI  
 UPCR before next visit. 
Study Week 12 - Day 78 (Telephone Visit) 
• Phone call to conduct inquiry about any spontaneously reported AEs by asking the 
subject to respond to a non-leading question such as “how do you feel?” 
• Review concomitant medications; 
• Review contraceptive use; 
• Remind subject of FMV and 24-hour urine collections prior to Week 13 Visit. 
Study Week 13 - Day 85 
• Site personnel to call subject 3 days before Visit Week 13 to remind him/her to 
perform FMV and a 24-hour urine collection, explain how to correctly collect and to 
bring the urine containers for FMV and 24-hour urine collection to clinic site. 
Reminder: Primary Endpoint (UPCR) and all other endpoints are collected and 
compared to baseline at Week 13 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• Review contraceptive use; 


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• Perform serious and non-serious adverse event monitoring; 
• Perform single 12-lead ECG Pre-dose and at the end of infusion within an 
approximately 45-minute window; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• CCI 
 
• Collect blood sample for clinical laboratory test, eGFR and fasting lipid profile 
(subjects must be fasting at least 8 hours prior to blood draw with no food or drink 
except water); 
• Use serum for pregnancy test via test strip as a stat procedure performed locally at the 
site, in females of child-bearing potential, with the negative result being available 
prior to the administration of investigational product; 
• CCI 
 
• Collect blood sample for pre-dose PK, ADA, NAb; 
• Intravenously administer IP per IP Manual; 
• Monitor subject for AEs and infusion site reaction for approximately 1-hour post end 
of infusion; 
• Verify subject’s return/completion of Urine Collection Diary; 
• Subject to bring container with FMV for CCI 
 UPCR; 
• Subject to bring container with 24-hour urine collection for CCI 
 UPCR; 
• Prepare urine for PK (20 mL from 24-hour urine collection); 
• 
 
• CCI 
 
• Prepare reserve 10 mL urine aliquot from the 24-hour collection (for UPCR 
measurement) which is to be sent to the central lab with a shipment separate from the 
main urine shipment, but on the same day; 
• CCI 
 
• Provide subject with container for urine collection and explain the urine collection 
process; request that subject perform FMV for CCI 
 UPCR before next visit. 
CCI 


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Study Week 14 - Day 92 (Telephone Visit) 
• Phone call to conduct inquiry about any spontaneously reported AEs by asking the 
subject to respond to a non-leading question such as “how do you feel?” 
• Review concomitant medications; 
• Review contraceptive use; 
• Remind subject of FMV urine collections prior to next visit. 
Study Week 15 - Day 99 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• Review contraceptive use; 
• Perform serious and non-serious adverse event monitoring; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• Collect blood sample for clinical laboratory test and eGFR; 
• Use serum for pregnancy test via test strip as a stat procedure performed locally at the 
site, in females of child-bearing potential, with the negative result being available 
prior to the administration of investigational product; 
• Collect blood sample for pre-dose PK, ADA, NAb; 
• Intravenously administer IP per IP Manual; 
• Monitor subject for AEs and infusion site reaction for approximately 1 hour post end 
of infusion; 
• Collect urine samples for urinalysis; 
• Subject to bring container with FMV for CCI 
 UPCR; 
• Provide subject with containers for urine collection and explain the urine collection 
process; request that subject perform 24-hour urine collection and FMV for CCI  
UPCR before next visit. 


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Study Week 16 - Day 106 (Telephone Visit) 
• Phone call to conduct inquiry about any spontaneously reported AEs by asking the 
subject to respond to a non-leading question such as “how do you feel?” 
• Review concomitant medications; 
• Review contraceptive use; 
• Remind subject of FMV and 24-hour urine collections prior to next visit. 
Study Week 17 - Day 113 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• Review contraceptive use; 
• Perform serious and non-serious adverse event monitoring; 
• Perform single 12-lead ECG Pre-dose and at the end of infusion within an 
approximately 45-minute window; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• Collect blood sample for clinical laboratory test, eGFR and fasting lipid profile 
(subjects must be fasting at least 8 hours prior to blood draw with no food or drink 
except water); 
• Use serum for pregnancy test via test strip as a stat procedure performed locally at the 
site, in females of child-bearing potential, with the negative result being available 
prior to the administration of investigational product; 
• Collect blood samples for pre-dose PK, ADA, NAb; 
• Intravenously administer IP per IP Manual; 
• Monitor subject for AEs and infusion site reaction for approximately 1 hour post end 
of infusion; 
• Verify subject’s return/completion of Urine Collection Diary; 
• Subject to bring container with FMV for CCI 
 UPCR; 
• Subject to bring container with 24-hour urine collection for CCI 
 UPCR; 


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• Prepare urine for PK (20 mL from 24-hour urine collection); 
• 
 
• Prepare reserve 10 mL urine aliquot from the 24-hour collection (for UPCR 
measurement) which is to be sent to the central lab with a shipment separate from the 
main urine shipment, but on the same day; 
• CCI 
 
• CCI 
 
Study Week 18 - Day 120 (Telephone Visit) 
• Phone call to conduct inquiry about any spontaneously reported AEs by asking the 
subject to respond to a non-leading question such as “how do you feel?” 
• Review concomitant medications; 
• Review contraceptive use. 
Study Week 19 - Day 127 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• Review contraceptive use; 
• Perform serious and non-serious adverse event monitoring; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• Collect blood sample for clinical laboratory test and eGFR; 
• Use serum for pregnancy test via test strip as a stat procedure performed locally at the 
site, in females of childbearing potential, with the negative result being available prior 
to the administration of investigational product; 
• Collect blood sample for pre-dose PK, ADA and NAb; 
• Intravenously administer IP per IP Manual; 
• Monitor subject for AEs and infusion site reaction for approximately 1 hour post end 
of infusion; 
CCI 


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• Collect urine samples for urinalysis; 
•  Provide subject with containers for urine collection and explain the urine collection 
process; request that subject perform 24-hour urine collection and FMV for CCI  
UPCR before next visit. 
Study Week 20 - Day 134 (Telephone Visit) 
• Phone call to conduct inquiry about any spontaneously reported AEs by asking the 
subject to respond to a non-leading question such as “how do you feel?” 
• Review concomitant medications; 
• Review contraceptive use; 
• Remind subject of FMV and 24-hour urine collections prior to next visit. 
Study Week 21 - Day 141 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• Review contraceptive use; 
• Perform serious and non-serious adverse event monitoring; 
• Perform single 12-lead ECG Pre-dose and at the end of infusion within an 
approximately 45-minute window; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• Collect blood sample for clinical laboratory test, eGFR and fasting lipid profile 
(subjects must be fasting at least 8 hours prior to blood draw with no food or drink 
except water); 
• Use serum for pregnancy test via test strip as a stat procedure performed locally at the 
site, in females of child-bearing potential, with the negative result being available 
prior to the administration of investigational product; 
• Collect blood samples for pre-dose PK, ADA, NAb; 
• CCI 
 
• Intravenously administer IP per IP Manual; 


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• Monitor subject for AEs and infusion site reaction for approximately 1 hour post end 
of infusion; 
• Verify subject’s return/completion of Urine Collection Diary; 
• Subject to bring container with FMV for CCI 
 UPCR; 
• Subject to bring container with 24-hour urine collection for CCI 
 UPCR; 
• Prepare urine for PK (20 mL from 24-hour urine collection); 
• 
 
• Prepare reserve 10 mL urine aliquot from the 24-hour collection (for UPCR 
measurement) which is to be sent to the central lab with a shipment separate from the 
main urine shipment, but on the same day; 
• CCI 
 
• CCI 
 
• Provide subject with container for urine collection and explain the urine collection 
process; request that subject perform FMV for CCI 
 UPCR before next visit. 
Study Week 22 - Day 148 (Telephone Visit) 
• Phone call to conduct inquiry about any spontaneously reported AEs by asking the 
subject to respond to a non-leading question such as “how do you feel?” 
• Review concomitant medications; 
• Review contraceptive use; 
• Remind subject of FMV urine collections prior to next visit. 
Study Week 23 - Day 155 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• Review contraceptive use; 
• Perform serious and non-serious adverse event monitoring; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
CCI 


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• CCI 
 
• Collect blood sample for clinical laboratory test and eGFR; 
• Use serum for pregnancy test via test strip as a stat procedure performed locally at the 
site, in females of child-bearing potential, with the negative result being available 
prior to the administration of investigational product; 
• Collect blood sample for pre-dose PK, ADA and NAb; 
• Intravenously administer IP per IP Manual; 
• Collect blood sample for PK at the end of infusion, within 6 minutes after the end of 
infusion; 
• Monitor subject for AEs and infusion site reaction for approximately 1 hour post end 
of infusion; 
• Collect urine samples for urinalysis; 
• Subject to bring container with FMV for CCI 
 UPCR; 
•  Provide subject with containers for urine collection and explain the urine collection 
process; request that subject perform 24-hour urine collection and FMV for CCI  
UPCR before next visit. 
Study Week 24 - Day 162 (Telephone Visit) 
• Phone call to conduct inquiry about any spontaneously reported AEs by asking the 
subject to respond to a non-leading question such as “how do you feel?” 
• Review concomitant medications; 
• Review contraceptive use; 
• Remind subject of FMV and 24-hour urine collections prior to next visit. 
6.3. Follow-up Period Activities and Assessments (Study Weeks 25 to 33) 
Following the conclusion of the Investigational Treatment Period, all subjects will enter the 
Follow-up Period for approximately 9 weeks from last dose of IP (Study Weeks 25-33). 
The activities and assessments listed below are to be completed during the Follow-Up Period. 
Please also refer to the Schedule of Activities for the study procedures to be completed 
during this period and the associated visit windows. 


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Study Week 25 - Day 169 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• CCI 
 
• Review contraceptive use; 
• Perform serious and non-serious adverse event monitoring; 
• Perform single 12-lead ECG; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• CCI 
 
• Collect blood sample for clinical laboratory test, eGFR and fasting lipid profile 
(subjects must be fasting at least 8 hours prior to blood draw with no food or drink 
except water); 
• Collect blood sample for HCG (for women of child-bearing potential); 
• CCI 
 
• Collect blood sample for PK, ADA, NAb; 
• Verify subject’s return/completion of Urine Collection Diary; 
• Subject to bring container with FMV for CCI 
 UPCR; 
• Subject to bring container with 24-hour urine collection for CCI 
 UPCR; 
• Prepare urine for PK (20 mL from 24-hour urine collection); 
• 
 
 
• Prepare reserve 10 mL urine aliquot from the 24-hour collection (for UPCR 
measurement) which is to be sent to the central lab with a shipment separate from the 
main urine shipment, but on the same day; 
• CCI 
 
CCI 


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• Provide subject with container for urine collection and explain the urine collection 
process; request that subject perform FMV and 24-hour collection for CCI 
 
UPCR before next visit; 
• 
 
 
 
Study Week 27 - Day 183 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• Review contraceptive use; 
• Perform serious and non-serious adverse event monitoring; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• Collect blood sample for PK, ADA, NAb; 
• Verify subject’s return/completion of Urine Collection Diary; 
• Subject to bring container with FMV for CCI 
 UPCR; 
• Subject to bring container with 24-hour urine collection for CCI 
 UPCR; 
• Prepare urine for PK (20 mL from 24-hour urine collection); 
• 
 
 
• Prepare reserve 10 mL urine aliquot from the 24-hour collection (for UPCR 
measurement) which is to be sent to the central lab with a shipment separate from the 
main urine shipment, but on the same day; 
• CCI 
 
Study Week 29 - Day 197 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
CCI 
CCI 


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• Review contraceptive use; 
• Perform serious and non-serious adverse event monitoring; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• CCI 
 
• Collect blood sample for clinical laboratory test and eGFR; 
• Collect blood sample for HCG (for women of child-bearing potential); 
• Collect blood sample for PK, ADA, NAb; 
• Collect urine samples for urinalysis; 
• Provide subject with container for urine collection and explain the urine collection 
process; request that subject perform FMV and 24-hour collection for CCI 
 
UPCR before next visit. 
Study Week 33 – Day 225 
• Site personnel to call subject 3 days before Visit Week 33 to remind him/her to 
perform FMV and a 24-hour urine collection, explain how to correctly collect and to 
bring the urine containers for FMV and 24-hour urine collection to clinic site. 
• Review concomitant medications; 
• Perform a physical exam including body weight and edema assessment; 
• CCI 
 
• Review contraceptive use; 
• Perform serious and non-serious adverse event monitoring; 
• Perform single 12-lead ECG; 
• Obtain vital signs (sitting single PR, BP and body temperature); 
• CCI 
 
• Collect blood sample for clinical laboratory test, eGFR and fasting lipid profile 
(subjects must be fasting at least 8 hours prior to blood draw with no food or drink 
except water); 
• Collect blood sample for HCG (for women of child-bearing potential); 


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• CCI 
 
• Collect blood sample for PK, ADA, NAb; 
• Verify subject’s return/completion of Urine Collection Diary; 
• Subject to bring container with FMV for CCI 
 UPCR; 
• Subject to bring container with 24-hour urine collection for CCI 
 UPCR; 
• Prepare urine for PK (20 mL from 24-hour urine collection); 
• 
 
 
• Prepare reserve 10 mL urine aliquot from the 24-hour collection (for UPCR 
measurement) which is to be sent to the central lab with a shipment separate from the 
main urine shipment, but on the same day; 
• CCI 
 
6.4. Subject Withdrawal/Early Termination 
Please refer to the Schedule of Activities for additional guidance on the procedures. 
Withdrawal of consent: 
Subjects who request to discontinue receipt of study treatment will remain in the study and 
must continue to be followed for protocol specified follow-up procedures. The only 
exception to this is when a subject specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the subject to provide this information. 
Subjects should notify the investigator in writing of the decision to withdraw consent from 
future follow-up, whenever possible. The withdrawal of consent should be explained in 
detail in the medical records by the investigator, as to whether the withdrawal is only from 
further receipt of investigational product or also from study procedures and/or post-treatment 
study follow-up and entered on the appropriate CRF page. In the event that vital status 
(whether the subject is alive or dead) is being measured, publicly available information 
should be used to determine vital status only as appropriately directed in accordance with 
local law. 
CCI 


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Lost to follow-up: 
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status. This includes follow-up with persons authorized by the subject as noted above. Lost 
to follow-up is defined by the inability to reach the subject after a minimum of 2 documented 
phone calls, faxes, or e-mails as well as lack of response by the subject to 1 registered mail 
letter. All attempts should be documented in the subject’s medical records. If it is 
determined that the subject has died, the site will use locally permissible methods to obtain 
the date and cause of death. If the investigator’s use of a third-party representative to assist 
in the follow-up portion of the study has been included in the subject’s informed consent, 
then the investigator may use a sponsor-retained third-party representative to assist site staff 
with obtaining the subject’s contact information or other public vital status data necessary to 
complete the follow-up portion of the study. The site staff and representative will consult 
publicly available sources, such as public health registries and databases, in order to obtain 
updated contact information. If, after all attempts, the subject remains lost to follow-up, then 
the last-known-alive date as determined by the investigator should be reported and 
documented in the subject’s medical records. 
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety (see also the 
Withdrawal From the Study Due to Adverse Events section) or behavioral reasons, or the 
inability of the subject to comply with the protocol-required schedule of study visits or 
procedures at a given study site. 
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject. All attempts to contact the subject and information received during contact attempts 
must be documented in the subject’s medical record)]. In any circumstance, every effort 
should be made to document subject outcome, if possible. The investigator should inquire 
about the reason for withdrawal, request that the subject return all unused investigational 
product(s), request that the subject return for a final visit, if applicable, and follow up with 
the subject regarding any unresolved adverse events (AEs). 
If the subject withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected. The sponsor may retain and continue to use any data collected before such 
withdrawal of consent. 
Subjects who withdraw from the study may be replaced at the discretion of the investigator 
upon consultation with the sponsor. 


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7. ASSESSMENTS 
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside of the control of the investigator that may make it unfeasible to 
perform the test. In these cases, the investigator will take all steps necessary to ensure the 
safety and well-being of the subject. When a protocol-required test cannot be performed, the 
investigator will document the reason for this and any corrective and preventive actions that 
he or she has taken to ensure that normal processes are adhered to as soon as possible. The 
study team will be informed of these incidents in a timely manner. 
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study. 
7.1. Safety 
7.1.1. Laboratory Tests 
The following safety laboratory tests as noted in Table 1 are performed at times defined in 
the Schedule of Activities section of this protocol. Additional laboratory results may be 
reported on these samples as a result of the method of analysis or the type of analyzer used 
by the clinical laboratory; or as derived from calculated values. These additional tests would 
not require additional collection of blood. Unscheduled clinical laboratory measurements 
may be obtained at any time during the study to assess any perceived safety concerns and/or 
to confirm eligibility to participate in the study. 
If an intravenous catheter is placed for serial blood sample collections, ECGs and vital signs 
(PR, BP) assessments should be either collected prior to the insertion of the catheter or 
following a sufficient rest period after catheter insertion introduced to minimize impact of 
catheter placement on these assessments. 


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Table 1. 
Safety Laboratory Tests 
 
Hematology 
Chemistry 
Urinalysis 
Other 
Hemoglobin 
Hematocrit 
RBC count 
MCV 
MCH 
MCHC 
Platelet count 
WBC count 
Total neutrophils 
(Absolute and %) 
Eosinophils (Absolute 
and %) 
Monocytes (Absolute 
and %) 
Basophils (Absolute 
and %) 
Lymphocytes 
(Absolute and %) 
BUN/urea and creatinine 
Glucose 
Calcium 
Sodium 
Potassium 
Chloride 
Total CO2 (bicarbonate) 
AST, ALT 
Total bilirubin 
Alkaline phosphatase 
Uric acid 
Albumin 
Total protein 
Prothrombin time - INR 
pH 
Glucose (qualitative) 
Protein (qualitative) 
Blood (qualitative) 
Ketones 
Nitrites 
Leukocyte esterase 
Urobilinogen 
Urine bilirubin 
Specific Gravity 
Microscopya 
CCI  
UPCR 
FSH;b 
Serum pregnancy test 
Urine drug screeningc 
Hepatitis B surface 
antigend 
Hepatitis B surface 
antibodyd 
Hepatitis B core 
antibodyd 
Hepatitis C core 
antibodyd 
Human 
immunodeficiency virusd 
Lipid profile (post 8 h 
fast) 
Cytokines:e TNF-α, IL-6 
and IFN-γ 
Additional Tests 
(Needed for Hy’s Law) 
AST, ALT (repeat) 
Total bilirubin (repeat) 
Albumin (repeat) 
Alkaline phosphatase 
(repeat) 
Direct bilirubin 
Indirect bilirubin 
Creatine kinase 
GGT 
Total bile acids 
Acetaminophen drug 
and/or protein adduct 
levels 
a. 
Only if urine dipstick is positive for blood, protein, nitrites or leukocyte esterase. 
b. At Screening only once in females amenorrheic ≥12-months. 
c. 
The urine drug test at Screening is performed by the central lab. If the Screening drug test is positive 
for drugs other than THC, subjects are excluded. The minimum requirement for drug screening 
includes cocaine, opiates/opioids, benzodiazepines, and amphetamines. Subjects may undergo 
random urine drug testing at the discretion of the investigator. 
d. At Screening only once. 
e. 
Extra blood samples for cytokine measurement should be taken immediately if a subject develops 
symptoms typical for infusion reaction during the IP administration. CCI 


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7.1.2. Pregnancy Testing 
One form of appropriate contraception must be used from Screening onward and continued 
throughout the Investigational Treatment and Follow-Up Phases. Serum pregnancy tests 
(HCG) are performed throughout the study as indicated in the Schedule of Activities. 
Pregnancy tests will also be done whenever one (1) menstrual cycle is missed, if applicable; 
during the Investigational Treatment and Follow-up Phases and when potential pregnancy is 
otherwise suspected and may be repeated if requested by institutional review boards 
(IRBs)/ethics committees (ECs) or if required by local regulations. In the case of a positive 
confirmed pregnancy, the subject will be withdrawn from administration of investigational 
product and from the study. 
All serum pregnancy tests used in this study must have a sensitivity of at least 25 mIU/mL. 
Serum pregnancy tests will be done locally by the site on all dosing days during the 
Investigational Treatment Period, as indicated in the Schedule of Activities, with a negative 
result required prior to the administration of investigational product. All other serum 
pregnancy tests, which are required at the Screening, Lead-in and Follow-up Periods (or 
Early Termination visit) will be submitted to the certified central laboratory. 
7.1.3. Physical Examinations 
The physical examinations will be administered at times specified in the Schedule of 
Activities. Physical examinations may be conducted by a physician, trained physician's 
assistant, or nurse practitioner as acceptable according to local regulation. 
• A full physical examination will include head, ears, eyes, nose, mouth, skin, heart and 
lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological 
systems. 
• The brief physical examination will be focused on general appearance, the respiratory 
and cardiovascular systems, as well as toward subject reported symptoms. 
Both, the full and brief physical examination should include presence/absence of edema and 
any changes in edema from one visit to the next. Leg edema, for example of the ankle or in 
the pretibial area, should be graded according to a scale from ‘Trace’ to 1+, 2+ or 3+ pitting 
edema. 
For measuring weight, a scale with appropriate range and resolution is used and must be 
placed on a stable, flat surface. Subjects must remove shoes, bulky layers of clothing, and 
jackets so that only light clothing remains. They must also remove the contents of their 
pockets and remain still during measurement of weight. 
7.1.4. Vital Signs (Blood Pressure, Pulse Rate and Body Temperature) 
Vital sign measurements (sitting BP, PR, and body temperature) will be performed at all time 
points as indicated in the Schedule of Activities. Additional collection times, or changes to 
collection times of BP and PR will be permitted, as necessary, to ensure appropriate 
collection of safety data. 


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Qualified staff members will perform the BP measurement with the subject’s arm supported 
at the level of the heart and recorded to the nearest mm Hg, while the subject is sitting. The 
same arm (preferably the dominant arm) will be used throughout the trial. If possible, blood 
pressure measurements will be taken from the same arm (opposite the arm that is used for 
blood sample collection). If there is a clinically important change in blood pressure from the 
previous recording, measurements will be repeated immediately to confirm the change. 
All scheduled BP and PR measurements should be performed after the subject has rested 
quietly for at least 5 minutes. The same size blood pressure cuff, which has been properly 
sized, will be used to measure blood pressure each time. The use of automatic devices for 
measuring BP, PR, and respiratory rate are acceptable, although, when done manually, PR 
will be measured in the brachial/radial artery for at least 30 seconds. When the timing of 
these measurements coincides with a blood collection, BP and PR should be obtained prior to 
the nominal time of the blood collection. 
Based on his or her judgment, the investigator makes the decision whether collecting 
orthostatic data is clinically meaningful. If deemed necessary, the procedure for collecting 
orthostatic data will be as follows: 
• Assess BP after subject is in supine position for a minimum of 5 minutes; 
• Stand subject up for 2 minutes; 
• Assess BP after subject is in the standing position for 2 minutes. 
Orthostatic hypotension is defined as a decrease of ≥20 mmHg for systolic blood pressure or 
≥10 mmHg for diastolic blood pressure 2 minutes after standing from a supine position. 
Body temperature should be measured per the instructions provided with the thermometer. 
The temperature will be reported in degrees Celsius. 
7.1.5. Electrocardiogram 
Electrocardiograms (ECGs) should be collected at times specified in the section of this 
protocol; additionally, please note that ECG is performed Pre-dose and at the End of Infusion 
(approximately 45 minute window from end of infusion) during the visits in the 
Investigational Treatment Period, as indicated in the Schedule of Activities. 
All scheduled ECGs should be performed after the subject has rested quietly for at least 
10 minutes in a supine position. A single standard 12-lead ECG will be performed at the 
Baseline (Day 1 pre-dose). A single standard 12-lead ECG will be performed at time points 
as indicated in the Schedule of Activities. 
Interpretation of ECGs will be performed locally by the site, and ECG data as well as any 
clinically important findings (eg, suspected QTc prolongation) will be recorded on the 
appropriate CRF. The results will include heart rate, PR interval, QRS interval, QT interval, 
and QTc interval, and assessment of rhythm and morphology. 


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CCI 
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality. It is important that leads are placed in the 
same positions each time in order to achieve precise ECG recordings. If a machine read 
states QTc value is prolonged, as defined above, repeat measurements may not be necessary 
if a qualified physician’s interpretation determines that the QTc values are in the acceptable 
range. 
 
 
 
7.1.7. Infusion Site Reaction 
Infusion site reactions will be assessed according to the Schedule of Activities. Infusion site 
reactions may include but are not limited to: erythema, induration, ecchymosis, pain and 
pruritus. The size and severity of infusion site reactions will be assessed and documented. 
7.2. Efficacy 
7.2.1. Urine Protein:Creatinine/:CCI 
 (UPCR/CCI ) 
UPCR represents the primary endpoint of the study and therefore, it is very important to 
generate reliable and accurate data for UPCR. The collection procedures by the subject, the 
handling of the FMV and the 24-hour collections by the site and the shipping as well as the 
receiving and analytical processes by the central lab have to be extremely carefully 
performed to avoid any errors or mishaps along the way. 
Depending on the visit, subjects will be instructed to bring a FMV for a “spot” urine 
assessment or a full 24-hour urine collection or both collections to the scheduled clinic visit. 
A detailed explanation will be provided to the subject on the method of collection, together 
with receptacles, and storage containers for urine collections. Subjects are advised to 
complete collection of their FMV and 24-hour samples within 24 to 48 hours prior to 
attending their scheduled clinic visit. 
At home, subjects are advised to collect the FMV in the morning within 24-48 hours before 
their visit at the clinic; the FMV should be collected into a small container, separate from the 
24-hour urine collection container. Immediately after obtaining the FMV, the 24-hour 
collection starts with the next urine void and includes all subsequent voids, up to and 
including the first morning urine void on the following day. All of these urine voids must be 
collected to obtain the full 24-hour urine collection, and must be placed into the large split 
urine container. The small FMV and the large containers have to be brought to the clinic. 


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Both the FMV and the 24-hour collection urine will be used to measure urine protein to 
creatinine ratio (UPCR) and CCI 
 At the subject’s 
home while collecting the urine and in the clinic, all urine containers must be stored in the 
refrigerator or in an insulated cooler or cooler bag with frozen refrigeration packs provided 
by the central lab to maximize stability of the samples. 
Subjects will receive Urine Collection Instructions and a Urine Collection Diary in which 
they will fill in the dates of their urine collection, the time they collected the FMV and the 
time they began and ended the 24-hour period of collecting. Subjects will enter the time of 
each urine void during the 24 hours. 
Site personnel will call the subject approximately 3 days before each visit that urine 
containers are collected from the subject, to remind the subject to perform the FMV and the 
24-hour urine collections according to the Schedule of Activities, explain again how to 
correctly collect and to bring the urine containers for FMV and 24-hour urine collections to 
the clinic site. In addition, when the performing the telephone visits the site personnel 
reminds the subject of the urine collections for the upcoming visits. 
A repeat of 24-hour urine collection is allowed, for example in case the subject forgot to fill 
one or more of the voids into the container. 
It is of great importance that the site completes the Requisition Form for shipment to the 
central laboratory in accordance to the central laboratory manual, including the following 
data: 
• Total volume of the 24-hour urine collection 
• Date of urine collection 
• Time of start and end of urine collection 
A 10 mL reserve urine aliquot is prepared from the 24-hour collection urine which is to be 
sent to the central lab with a shipment separate from the main urine shipment, but on the 
same day. Any urine aliquots not used for the purposes described above will be considered 
exploratory biomarker urine samples in accordance with Section 7.3.3. 
A 20 mL aliquot of the 24-hour urine samples collected from the Investigational Treatment 
and Follow-up Periods may also be used for exploratory PK analysis (Section 7.3.2). 
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7.3. Pharmacokinetics 
7.3.1. Serum for Analysis of PF-06730512 
Blood samples (approximately 3 mL whole blood) to provide a minimum of 1 mL of serum 
for pharmacokinetic (PK) analysis will be collected into appropriately labeled tubes at times 
specified in the Schedule of Activities section of the protocol. 
The actual sampling times may change, but the number of samples will remain the same. All 
efforts will be made to obtain the PK samples at the exact nominal time relative to dosing. 
However, samples obtained within the time windows specified in the Schedule of Activity 
will not be captured as protocol deviations. 
In addition to samples collected at the scheduled times, an additional blood sample for 
determination of PF-06730512 PK may be collected from subjects experiencing unexpected 
and/or serious AEs. The date and time of the blood sample collection and of the last dosing 
prior to PK collection will be documented in the CRF. 
Samples will be analyzed using a validated analytical method in compliance with Pfizer 
standard operating procedures (SOPs). 
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the sponsor. 
On a case-by-case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised. Any deviation from the specified sample handling 
procedure resulting in compromised sample integrity will be considered a protocol deviation. 
 
7.3.2. Urine for Analysis of PF-06730512 
A 20 mL aliquot of the 24-hour urine samples from the Investigational Treatment and 
Follow-up Periods will be collected. As part of understanding the PK of the investigational 
product, the samples may be used for evaluation of the bioanalytical method, 
 
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7.4. Immunogenicity 
7.4.1. Immunogenicity Analyses 
Blood samples (approximately 5 mL) to provide at least 2 mL of serum to detect ADA and 
NAb against PF-06730512 (~1 mL each for ADA and NAb) will be collected from subjects 
enrolled at the times specified in the Schedule of Activities. Samples will be analyzed using 
a validated analytical method in compliance with Pfizer/vendor standard operating 
procedures (SOPs). Samples determined to be positive for ADA may be further 
characterized for NAb. 
Subjects with positive results at the conclusion of the study may be requested to return for 
additional follow-up for up to approximately 3 months after the last scheduled follow-up 
visit. An additional immunogenicity sample will be collected and the information recorded 
as an unscheduled visit. 
The immunogenicity samples must be processed and shipped as indicated in the instructions 
provided to the investigator site to maintain sample integrity. Any deviations from the 
immunogenicity sample handling procedure (eg, sample collection and processing steps, 
interim storage or shipping conditions), including any actions taken, must be documented and 
reported to the sponsor. On a case-by-case basis, the sponsor may make a determination as 
to whether sample integrity has been compromised. Any deviation from the specified sample 
handling procedure resulting in compromised sample integrity will be considered a protocol 
deviation. 
 
 
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biospecimens will be stored for many years (no time limit) to allow for research in the future, 
 
 
 
• 
 
 
 
 
 
 
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7.7. Blood Volume 
The total blood sampling volume for individual subjects is approximately 560 mL for 
participating in the study. The blood volumes increase by approximately 72 mL in WOCBP 
due to serum pregnancy tests; the blood volumes increase by 5 mL in women of 
non-child-bearing potential due to FSH measurement. 
The actual collection times of blood sampling may change, but the total blood volume 
collected will not increase. Additional blood samples may be taken for safety assessments at 
times specified by the Sponsor, provided the total volume taken during the study does not 
exceed 550 mL during any period of 56 consecutive days. 
8. ADVERSE EVENT REPORTING 
8.1. Requirements 
The table below summarizes the requirements for recording safety events on the CRF and for 
reporting safety events on the Clinical Trial (CT) Serious Adverse Event (SAE) Report Form 
to Pfizer Safety. These requirements are delineated for 3 types of events: (1) SAEs; 
(2) non-serious adverse events (AEs); and (3) exposure to the investigational product under 
study during pregnancy or breastfeeding, and occupational exposure. 
 
Safety Event 
Recorded on the CRF 
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness 
SAE 
All 
All 
Non-serious AE 
All 
None 
Exposure to the 
All (regardless of whether 
Exposure during pregnancy, 
investigational product 
associated with an AE), 
exposure via breastfeeding, 
under study during 
except occupational 
occupational exposure 
pregnancy or 
exposure 
(regardless of whether 
breastfeeding, and 
associated with an AE) 
occupational exposure 
All observed or volunteered events regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
paragraphs. 
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Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report 
Form within 24 hours of awareness of the event by the investigator are to be reported 
regardless of whether the event is determined by the investigator to be related to an 
investigational product under study. In particular, if the SAE is fatal or life-threatening, 
notification to Pfizer Safety must be made immediately, irrespective of the extent of available 
event information. This time frame also applies to additional new (follow-up) information on 
previously forwarded reports. In the rare situation that the investigator does not become 
immediately aware of the occurrence of an event, the investigator must report the event 
within 24 hours after learning of it and document the time of his/her first awareness of the 
event. 
For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see the Serious Adverse Events section below). In addition, the investigator may be 
requested by Pfizer Safety to obtain specific follow-up information in an expedited fashion. 
This information is more detailed than that recorded on the CRF. In general, this will include 
a description of the event in sufficient detail to allow for a complete medical assessment of 
the case and independent determination of possible causality. Any information relevant to 
the event, such as concomitant medications and illnesses, must be provided. In the case of a 
subject death, a summary of available autopsy findings must be submitted as soon as possible 
to Pfizer Safety. Any pertinent additional information must be reported on the CT SAE 
Report Form; additional source documents (eg, medical records, CRF, laboratory data) are to 
be sent to Pfizer Safety ONLY upon request. 
As part of ongoing safety reviews conducted by the sponsor, any non-serious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE. To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study. 
8.1.1. Additional Details on Recording Adverse Events on the CRF 
All events detailed in the table above will be recorded on the AE page(s) of the CRF. It 
should be noted that the CT SAE Report Form for reporting of SAE information is not the 
same as the AE page of the CRF. When the same data are collected, the forms must be 
completed in a consistent manner. AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE Report 
Form for reporting of SAE information. 
8.1.2. Eliciting Adverse Event Information 
The investigator is to record on the CRF all directly observed AEs and all AEs spontaneously 
reported by the study subject. In addition, each study subject will be questioned about the 
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8.1.3. Withdrawal from the Study Due to Adverse Events 
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted below, and recorded on the CRF. Withdrawal from 
the study due to an adverse event that is related to study drug is done at the discretion of the 
principal investigator. Notification to the sponsor of the withdrawal must be accomplished 
immediately. Pregnancy in a study participant must result in immediate cessation of study 
drug administration. 
When a subject withdraws from or is withdrawn from the study because of an SAE, the SAE 
must be recorded on the CRF and reported, as appropriate, on the CT SAE Report Form, in 
accordance with the Requirements section above. 
8.1.4. Time Period for Collecting AE/SAE Information 
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each subject begins from the time the subject provides informed consent, which 
is obtained before the subject’s participation in the study (ie, before undergoing any 
study-related procedure and/or receiving investigational product), through and including a 
minimum of 70 ±7 calendar days after the last administration of the investigational product. 
For subjects who are screen failures, the active collection period ends when screen failure 
status is determined. 
8.1.4.1. Reporting SAEs to Pfizer Safety 
All SAEs occurring in a subject during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form. 
SAEs occurring in a subject after the active collection period has ended are reported to Pfizer 
Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety. 
Follow up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment. 
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF 
During the active collection period, both non-serious AEs and SAEs are recorded on the 
CRF. 
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment. 


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8.1.5. Causality Assessment 
The investigator’s assessment of causality must be provided for all AEs (serious and 
non-serious); the investigator must record the causal relationship on the CRF, and report such 
an assessment in accordance with the SAE reporting requirements, if applicable. An 
investigator’s causality assessment is the determination of whether there exists a reasonable 
possibility that the investigational product caused or contributed to an AE; generally, the 
facts (evidence) or arguments to suggest a causal relationship should be provided. If the 
investigator does not know whether or not the investigational product caused the event, then 
the event will be handled as “related to investigational product” for reporting purposes, as 
defined by the sponsor. If the investigator's causality assessment is “unknown but not 
related” to investigational product, this should be clearly documented on study records. 
In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, and 
report such an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements. 
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities 
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations. 
8.2. Definitions 
8.2.1. Adverse Events 
An AE is any untoward medical occurrence in a study subject administered a product or 
medical device; the event need not necessarily have a causal relationship with the treatment 
or usage. Examples of AEs include, but are not limited to: 
• Abnormal test findings; 
• Clinically significant signs and symptoms; 
• Changes in physical examination findings; 
• Hypersensitivity; 
• Progression/worsening of underlying disease; 
• Drug abuse; 
• Drug dependency. 
Additionally, AEs may include signs and symptoms resulting from: 
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• Drug withdrawal; 
• Drug misuse; 
• Drug interactions; 
• Extravasation; 
• Exposure during pregnancy (EDP); 
• Exposure via breastfeeding; 
• Medication error; 
• Occupational exposure. 
8.2.2. Abnormal Test Findings 
Abnormal objective test findings should be recorded as AEs when any of the following 
conditions are met: 
• Test result is associated with accompanying symptoms; and/or 
• Test result requires additional diagnostic testing or medical/surgical intervention; 
and/or 
• Test result leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional concomitant 
drug treatment, or other therapy; and/or 
• Test result is considered to be an AE by the investigator or sponsor. 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE. Any abnormal test result that is determined to be an error does not require 
recording as an AE. 
8.2.3. Serious Adverse Events 
A serious adverse event is any untoward medical occurrence at any dose that: 
• Results in death; 
• Is life-threatening (immediate risk of death); 
• Requires inpatient hospitalization or prolongation of existing hospitalization; 
• Results in persistent or significant disability/incapacity (substantial disruption of the 
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• Results in congenital anomaly/birth defect. 
Or that is considered to be: 
• An important medical event. 
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event. An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization. However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious. 
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse. 
8.2.4. Hospitalization 
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility, or any prolongation of an existing admission. Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit). An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit is assessed for medical importance. 
Hospitalization does not include the following: 
• Rehabilitation facilities; 
• Hospice facilities; 
• Respite care (eg, caregiver relief); 
• Skilled nursing facilities; 
• Nursing homes; 
• Same-day surgeries (as outpatient/same-day/ambulatory procedures). 
Hospitalization or prolongation of hospitalization in the absence of a precipitating clinical 
AE is not in itself an SAE. Examples include: 
• Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for 
workup of a persistent pretreatment laboratory abnormality); 
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• Administrative admission (eg, for yearly physical examination); 
• Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol); 
• Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery); 
• Hospitalization for observation without a medical AE; 
• Preplanned treatments or surgical procedures. These should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject. 
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as SAEs. However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an SAE. For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the 
AE. 
8.3. Severity Assessment 
 
If required on the AE page of the CRF, the investigator will use the adjectives MILD, 
MODERATE, or SEVERE to describe the maximum intensity of the AE. For purposes 
of consistency, these intensity grades are defined as follows: 
MILD 
Does not interfere with subject's usual function. 
MODERATE 
Interferes to some extent with subject's usual function. 
SEVERE 
Interferes significantly with subject's usual function. 
Note the distinction between the severity and the seriousness of an AE. A severe event is not 
necessarily an SAE. For example, a headache may be severe (interferes significantly with 
the subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above. 
8.4. Special Situations 
8.4.1. Protocol-Specified Serious Adverse Events 
There are no protocol-specified SAEs in this study. All SAEs will be reported to Pfizer 
Safety by the investigator as described in previous sections, and will be handled as SAEs in 
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8.4.2. Potential Cases of Drug-Induced Liver Injury 
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.” In some subjects, transaminase elevations are a harbinger of a more 
serious potential outcome. These subjects fail to adapt and therefore are "susceptible" to 
progressive and serious liver injury, commonly referred to as drug-induced liver injury 
(DILI). Subjects who experience a transaminase elevation above 3 times the upper limit of 
normal (× ULN) should be monitored more frequently to determine if they are an “adaptor” 
or are “susceptible.” 
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks. The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same lab sample). 
In rare instances, by the time TBili elevations are detected, AST/ALT values might have 
decreased. This occurrence is still regarded as a potential DILI. Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded. 
The threshold of laboratory abnormalities for a potential DILI case depends on the subject’s 
individual baseline values and underlying conditions. Subjects who present with the 
following laboratory abnormalities should be evaluated further as potential DILI (Hy’s law) 
cases to definitively determine the etiology of the abnormal laboratory values: 
• Subjects with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available; 
• For subjects with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline: 
• Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller). 
• Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller). 
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor. 


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The subject should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history, and physical assessment. 
In addition to repeating measurements of AST and ALT and TBili, laboratory tests should 
include albumin, creatine kinase (CK), direct and indirect bilirubin, gamma-glutamyl 
transferase (GGT), prothrombin time (PT)/international normalized ratio (INR), total bile 
acids, alkaline phosphatase and acetaminophen drug and/or protein adduct levels. 
Consideration should also be given to drawing a separate tube of clotted blood and an 
anticoagulated tube of blood for further testing, as needed, for further contemporaneous 
analyses at the time of the recognized initial abnormalities to determine etiology. A detailed 
history, including relevant information, such as review of ethanol, acetaminophen (either by 
itself or as a co-formulated product in prescription or over-the-counter medications), 
recreational drug, supplement (herbal) use and consumption, family history, sexual history, 
travel history, history of contact with a jaundiced person, surgery, blood transfusion, history 
of liver or allergic disease, and potential occupational exposure to chemicals, should be 
collected. Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging 
(eg, biliary tract) may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the liver function test (LFT) abnormalities has yet been found. Such 
potential DILI (Hy’s law) cases are to be reported as SAEs, irrespective of availability 
of all the results of the investigations performed to determine etiology of the LFT 
abnormalities. The investigator then must decide whether to interrupt or discontinue further 
administration of study drug because of the potential DILI. 
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology. 
8.4.3. Exposure to the Investigational Product During Pregnancy or Breastfeeding, and 
Occupational Exposure 
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness. 
8.4.3.1. Exposure During Pregnancy 
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy (EDP) occurs if: 
• A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
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• An example of environmental exposure would be a case involving direct contact with 
a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant and has 
been exposed to chemotherapeutic products); 
• A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy; 
• If a subject or subject’s partner becomes or is found to be pregnant during the 
subject’s treatment with the investigational product, the investigator must report this 
information to Pfizer Safety on the CT SAE Report Form and an EDP supplemental 
form, regardless of whether an SAE has occurred. In addition, the investigator must 
submit information regarding environmental exposure to a Pfizer product in a 
pregnant woman (eg, a subject reports that she is pregnant and has been exposed to a 
cytotoxic product by inhalation or spillage) to Pfizer Safety using the EDP 
supplemental form. This must be done irrespective of whether an AE has occurred 
and within 24 hours of awareness of the exposure. The information submitted should 
include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 
If a subject becomes pregnant during treatment with the investigational product, 
administration of the product must immediately cease and the patient must be withdrawn 
from further treatment. Follow-up is conducted to obtain general information on the 
pregnancy and its outcome for all EDP reports with an unknown outcome. The investigator 
will follow the pregnancy until completion (or until pregnancy termination) and notify Pfizer 
Safety of the outcome as a follow-up to the initial EDP supplemental form. In the case of a 
live birth, the structural integrity of the neonate can be assessed at the time of birth. In the 
event of a termination, the reason(s) for termination should be specified and, if clinically 
possible, the structural integrity of the terminated fetus should be assessed by gross visual 
inspection (unless pre-procedure test findings are conclusive for a congenital anomaly and 
the findings are reported). 
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs. 
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
follows: 
• Spontaneous abortion includes miscarriage and missed abortion; 
• Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the investigational product; 


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• Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, 
the investigator will provide the subject with the Pregnant Partner Release of 
Information Form to deliver to his partner. The investigator must document in the 
source documents that the subject was given the Pregnant Partner Release of 
Information Form to provide to his partner. 
8.4.3.2. Exposure During Breastfeeding 
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form. An exposure during breastfeeding report is not created when a Pfizer 
drug specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use. However, if the infant experiences an SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding. 
8.4.3.3. Occupational Exposure 
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE. 
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 
SAE. Since the information does not pertain to a subject enrolled in the study, the 
information is not recorded on a CRF; however, a copy of the completed CT SAE Report 
Form is maintained in the investigator site file. 
8.4.4. Medication Errors 
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors. 
 
Safety Event 
Recorded on the CRF 
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness 
Medication errors 
All (regardless of whether 
associated with an AE) 
Only if associated with an 
SAE 
8.4.4.1. Medication Errors 
Medication errors may result from the administration or consumption of the investigational 
product by the wrong subject, or at the wrong time, or at the wrong dosage strength. 
Medication errors include: 
• Medication errors involving subject exposure to the investigational product; 


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. 
• Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating subject. 
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page. 
In the event of a medication dosing error, the sponsor should be notified immediately. 
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and non-serious, are recorded on an AE page of the 
CRF. 
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE. 
9. DATA ANALYSIS/STATISTICAL METHODS 
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor. The SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment. 
 
 
 
 
 


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9.2. Efficacy Analysis 
Baseline for the primary endpoint is defined as the Week -1 UPCR measurement that is 
based on the 24-hour urine collection. The Week 13 value for the primary endpoint is also 
based on the 24-hour urine collection. 
Baseline for the secondary endpoints related to UPCR based on the 24-hour urine collection 
or estimated glomerular filtration rate (eGFR) will be based on the Week -1 measurement; 
otherwise, the Week 1 value will be used. 
9.2.1. Analysis of the Primary Endpoint 
The primary analysis will be based on the full analysis set (FAS), which will be defined to be 
all enrolled subjects who have received at least one dose of study treatment and have at least 
one post-baseline measurement of UPCR. A mixed effects model of repeated measures 
(MMRM) will be fitted to the post-dose 24-urine collection data on UPCR (ie, Weeks 5, 9 
and 13) using data through Week 13. The model will include treatment (if more than one 
dose), baseline, week (as a factor), baseline*week interaction and the week*treatment (if 
more than one dose) interaction, with week fitted as a repeated effect, and subject as a 
random effect. An unstructured correlation matrix will be used to estimate the variances and 
covariance within subject across time points. If convergence is not obtained or model fit is 
not adequate, then other covariance structures will be investigated as necessary. The 
Kenward-Roger approximation will be used for estimating degrees of freedom for the model 
parameters. The percentage change from baseline to Week 13 treatment effect(s) will be the 
primary comparison(s) of interest. 
The probabilities for the decision criteria for each of the doses (as required) will be 
calculated using the results of the MMRM. 
The back-transformed Least Squares Means (LSMeans) together with 90% confidence 
intervals will be obtained for each dose (if applicable) and week. 
Ratios in LSMeans (calculated by back-transforming modelled results), amongst the doses at 
the different weeks, together with 90% confidence intervals, will also be obtained if 
applicable. 
All values for UPCR (including baseline) will be loge-transformed prior to analyses, where 
analysis of changes from baseline will be performed. The percentage change from baseline 
will be derived by transforming the ratio using the following formula: 
Percentage change from baseline = 100*([back-transformed LSMean] – 1) 
Plots will be produced including: 
• The treatment back-transformed LSMeans (including confidence intervals) for each 
dose (as required) over time. 
Missing values will be imputed as part of the MMRM model assumptions. 


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As a sensitivity to the primary analysis, an analysis of covariance (ANCOVA) model 
including the Week 13 measurement as the dependent variable, with treatment included as a 
fixed effect and baseline as a covariate will be performed, using last observation carried 
forward (LOCF) for missing data. The same MMRM model to the primary analysis will also 
be fitted to the single morning void assessments of UPCR only as a further sensitivity 
 
A Per-Protocol (PP) analysis set will also be defined to be all subjects in the FAS with any 
post-baseline efficacy data who were not major protocol deviators. As a supportive analysis, 
the primary analyses may be repeated based on the PP analysis set. Full details of the primary 
analysis will be provided in the SAP. 
9.2.2. Analysis of Secondary Endpoints 
The secondary endpoints of percentage change from baseline in UPCR over time 
post-treatment will come from the same MMRM model used for the primary analysis using 
post-treatment data, including time points beyond Week 13 as applicable. Estimates of 
percentage changes from baseline to weeks post-treatment will be derived from a model 
similar to the primary MMRM model. 
Changes from baseline to Weeks 3, 5, 9, 13 and beyond as applicable, in eGFR over time 
post-treatment will be analyzed using an approach similar to that used for the primary 
endpoint. This will also be analyzed on the loge scale. 
Full details of these and all other secondary efficacy analyses will be included in the SAP. 
CCI 
 
 
9.3. Pharmacokinetic Analysis 
9.3.1. Analysis Population 
The PK concentration population is defined as all enrolled subjects who received at least one 
dose of PF-06730512 and have at least 1 measurable concentration. PK concentrations will 
be summarized and presented with summary statistics, and if appropriate, non-compartmental 
PK parameter estimates will be provided. A population PK model may be developed for the 
purpose of estimating PK parameters. Any population PK model developed to characterize 
the PK data will be reported separately. 
Data permitting, the relationship between exposure and clinical responses (efficacy and 
safety) may be explored using either observed or predicted exposures from the PK model. 
Any population analyses conducted will not be part of the clinical study report (CSR) and 
may be reported separately. 
analysis. CCI 


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CCI 
 
 
9.5. Safety Analysis 
Adverse events, ECGs, body weight, BP, PR, body temperature and safety laboratory data 
will be reviewed and summarized on an ongoing basis during the study to evaluate the safety 
of subjects. 
Any clinical laboratory, ECG, BP and PR abnormalities of potential clinical concern will be 
described. Safety data will be presented in tabular format and summarized descriptively, 
where appropriate. 
Medical history and physical and neurological examination information, as applicable, 
collected during the course of the study, will be considered source data and will not be 
required to be reported, unless otherwise noted. However, any untoward findings identified 
on physical and neurological examinations conducted after the administration of the first 
dose of investigational product will be captured as an adverse event, if those findings meet 
the definition of an adverse event. Data collected at Screening that is used for inclusion/ 
exclusion criteria, such as laboratory data, ECGs and vital signs will be considered source 
data, and will not be required to be reported, unless otherwise noted. Demographic data 
collected at Screening will be reported. 
Immunogenicity (ADA, NAb) results will be listed (including titers) and summarized by 
treatment group and time points. Effect of positive ADA and neutralizing immune response 
on safety, PD and PK may be assessed, if appropriate. Full details of analyses will be given 
in the SAP. 
9.5.1. Electrocardiogram (ECG) Analysis 
Changes from baseline for the ECG parameters QT interval, heart rate, QTcF interval, PR 
interval, and QRS interval will be summarized by treatment and time. 
The number (%) of subjects with maximum post-dose QTcF values and maximum increases 
from baseline in the following categories will be tabulated by treatment: 
Table 2. 
Safety QTcF Assessment 
 
Borderline (msec) 
Prolonged (msec) 
Absolute Value 
>450 - ≤480 
>480 
Absolute Change 
30 - ≤60 
>60 
In addition, the number of subjects with corrected and uncorrected QT values ≥500 msec will 
be summarized. 


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9.6. Interim Analysis 
Interim analyses will be performed to assess efficacy and safety after at intervals wherein 
half of the planned subjects for each cohort, ie, approximately 9 subjects, have completed the 
primary efficacy assessment. 
Up to five interim analyses are currently planned for this study, which are summarized 
below, but where more details (such as internal business decisions regarding future study 
planning based on interim results) will be documented and approved in a charter and an 
Interim Analysis SAP. Up to two such analyses per cohort may be performed. Interim 
analysis results may be used for internal business decisions regarding future study planning, 
stopping for futility, stopping for early success, advancing to a new cohort, or conducting a 
sample size re-estimation. Before any interim analysis is instigated, the details of the 
objectives, decision criteria, dissemination plan, and method of maintaining the study blind 
(if applicable) as per Pfizer’s SOPs will be documented and approved in a charter and an 
Interim Analysis SAP or final SAP (as applicable). These documents will be finalized before 
any interim analysis is instigated and may modify what is outlined below; however, any 
major modifications will also be reflected in a protocol amendment. The first interim 
analysis (IA1) will be conducted after at least 50% of the planned subjects from Cohort 1 
(ie, approximately 9 subjects) have completed the primary efficacy assessment. 
The second interim analysis (IA2) will be conducted after the remaining 50% of subjects 
from Cohort 1 (ie, approximately 18 subjects) have completed the primary efficacy 
assessment or discontinued from the study. Direct advancement to the optional Cohort 3 may 
also be determined at this IA2. 
A third interim analysis (IA3) will be conducted after at least 50% of the planned subjects 
from the next cohort (ie, approximately 9 subjects) have completed the primary efficacy 
assessment. Enrollment of the rest of the cohort or advancement to the next, optional cohort 
will be recommended based on the totality of the data from both doses, including observed 
efficacy and safety and a multitude of qualitative factors listed in the charter. 
Should it be considered necessary for the future development of the compound, further 
interim analyses may also be undertaken, as specified in the IA charter and/or SAP. The 
purpose of these interim analyses would be to give an early read out for the primary efficacy 
endpoint to enable efficient decision-making for this study, as well as for the entire project. 
9.7. Data Monitoring Committee 
This study will not use an external data monitoring committee (E-DMC). The study team 
and internal medical experts (eg, nephrologists) will review the accumulating safety data 
from this study on a regular basis. Decisions or outcomes which may impact the future 
conduct of the study will be forwarded to sites and regulatory authorities, as appropriate. 
Additional details of the reviewing process are provided in the safety review plan. 
Based on these reviews, there may be impact to the future conduct of the study. These may 
include amending safety monitoring procedures, modifying the protocol or consent, 
terminating the study, or continuing the study as designed. 


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10. QUALITY CONTROL AND QUALITY ASSURANCE 
Pfizer or its agent will conduct periodic monitoring visits during study conduct to ensure that 
the protocol and Good Clinical Practices (GCPs) are being followed. The monitors may 
review source documents to confirm that the data recorded on CRFs are accurate. The 
investigator and institution will allow Pfizer monitors/auditors or its agents and appropriate 
regulatory authorities direct access to source documents to perform this verification. This 
verification may also occur after study completion. 
During study conduct and/or after study completion, the investigator site may be subject to 
review by the IRB/EC, and/or to quality assurance audits performed by Pfizer, or companies 
working with or on behalf of Pfizer, and/or to inspection by appropriate regulatory 
authorities. 
The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with Pfizer 
or its agents to prepare the investigator site for the inspection and will allow Pfizer or its 
agent, whenever feasible, to be present during the inspection. The investigator site and 
investigator will promptly resolve any discrepancies that are identified between the study 
data and the subject's medical records. The investigator will promptly provide copies of the 
inspection findings to Pfizer or its agent. Before response submission to the regulatory 
authorities, the investigator will provide Pfizer or its agents with an opportunity to review 
and comment on responses to any such findings. 
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process. 
11. DATA HANDLING AND RECORD KEEPING 
11.1. Case Report Forms/Electronic Data Record 
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study. 
A CRF is required and should be completed for each included subject. The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer. 
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required. The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true. Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry. 


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In most cases, the source documents are the hospital or the physician subject chart. In these 
cases, data collected on the CRFs must match the data in those charts. 
In some cases, the CRF may also serve as the source document. In these cases, a document 
should be available at the investigator site and at Pfizer that clearly identifies those data that 
will be recorded on the CRF, and for which the CRF will stand as the source document. 
11.2. Record Retention 
To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the 
investigator agrees to keep records, including the identity of all participating subjects 
(sufficient information to link records, eg, CRFs and hospital records), all original signed 
informed consent documents, copies of all CRFs, safety reporting forms, source documents, 
and detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (eg, letters, meeting minutes, and telephone call reports). The records should 
be retained by the investigator according to the ICH guidelines, according to local 
regulations, or as specified in the clinical study agreement (CSA), whichever is longer. 
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified. The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or an independent third party arranged by Pfizer. 
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations. 
The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met. 
12. ETHICS 
12.1. Institutional Review Board/Ethics Committee 
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, 
eg, recruitment advertisements, if applicable, from the IRB/EC. All correspondence with the 
IRB/EC should be retained in the investigator file. Copies of IRB/EC approvals should be 
forwarded to Pfizer. 
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects. In 
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation. 
12.2. Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, legal and regulatory 
requirements, and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations of 


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Medical Sciences 2002), ICH Guideline for Good Clinical Practice, and the Declaration of 
Helsinki. 
12.3. Subject Information and Consent 
All parties will ensure protection of subject personal data and will not include subject names 
or other identifiable data in any reports, publications, or other disclosures, except where 
required by law. 
When study data are compiled for transfer to Pfizer and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by Pfizer in order to de-identify study subjects. The investigator 
site will maintain a confidential list of subjects who participated in the study, linking each 
subject’s numerical code to his or her actual identity. In case of data transfer, Pfizer will 
maintain high standards of confidentiality and protection of subjects’ personal data consistent 
with applicable privacy laws. 
The informed consent documents and any subject recruitment materials must be in 
compliance with ICH GCP, local regulatory requirements, and legal requirements, including 
applicable privacy laws. 
The informed consent documents used during the informed consent process, any subject 
recruitment materials, and any subject-facing materials must be reviewed and approved by 
Pfizer, approved by the IRB/EC before use, and available for inspection. 
The investigator must ensure that each study subject, or his or her legally acceptable 
representative, is fully informed about the nature and objectives of the study and possible 
risks associated with participation. 
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject before any study-specific activity is performed. The investigator 
will retain the original of each subject's signed consent document. 
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP 
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of. 


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13. DEFINITION OF END OF TRIAL 
13.1. End of Trial in a Member State 
End of trial in a Member State of the European Union is defined as the time at which it is 
deemed that a sufficient number of subjects have been recruited and completed the study as 
stated in the regulatory application (ie, clinical trial application [CTA]) and ethics application 
in the Member State. Thus end of trial in all concerned countries is the same: last subject last 
visit (LSLV). Poor recruitment (recruiting less than the anticipated number in the CTA) by a 
Member State is not a reason for premature termination but is considered a normal 
conclusion to the study in that Member State. 
13.2. End of Trial in All Other Participating Countries 
End of trial in all other participating countries is defined as last subject last visit (LSLV). 
14. SPONSOR DISCONTINUATION CRITERIA 
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or investigational product safety problems, or at the 
discretion of Pfizer. In addition, Pfizer retains the right to discontinue development of 
PF-06730512 at any time. 
If a study is prematurely terminated, Pfizer will promptly notify the investigator. After 
notification, the investigator must contact all participating subjects and the hospital pharmacy 
(if applicable) within 7 days. As directed by Pfizer, all study materials must be collected and 
all CRFs/data collection tools (DCTs) completed to the greatest extent possible. 
15. PUBLICATION OF STUDY RESULTS 
15.1. Communication of Results by Pfizer 
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations. 
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted. 
www.clinicaltrials.gov 
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
Pfizer product, regardless of the geographical location in which the study is conducted. US 
Basic Results are submitted for posting within 1 year of the primary completion date (PCD) 
for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations. 


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PCD is defined as the date that the final subject was examined or received an intervention for 
the purposes of final collection of data for the primary outcome, whether the clinical study 
concluded according to the prespecified protocol or was terminated. 
EudraCT 
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements. EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations. 
www.pfizer.com 
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov. 
15.2. Publications by Investigators 
Pfizer supports the exercise of academic freedom and has no objection to publication by the 
principal investigator (PI) of the results of the study based on information collected or 
generated by the PI, whether or not the results are favorable to the Pfizer product. However, 
to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “publication”) 
before it is submitted or otherwise disclosed. 
The investigator will provide any publication to Pfizer at least 30 days before it is submitted 
for publication or otherwise disclosed. If any patent action is required to protect intellectual 
property rights, the investigator agrees to delay the disclosure for a period not to exceed an 
additional 60 days. 
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results. 
If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all investigator sites, and that any subsequent publications 
by the PI will reference that primary publication. However, if a joint manuscript has not 
been submitted for publication within 12 months of completion or termination of the study at 
all participating sites, the investigator is free to publish separately, subject to the other 
requirements of this section. 


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For all publications relating to the study, the institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors. 
Publication of study results is also provided for in the CSA between Pfizer and the 
institution. In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA. 
If there is any conflict between the CSA and any attachments to it, the terms of the CSA 
control. If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study subjects, and the CSA will control as to all other 
issues. 


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16. REFERENCES 
1. 
Bose B, Cattran D. Glomerular diseases: FSGS. Clin J Am Soc Nephrol 2014; 
9(3):626-32. 
2. 
Sprangers B, Meijers B, Appel G. FSGS: Diagnosis and Diagnostic Work-Up. Biomed 
Res Int 2016; 2016:4632768. 
3. 
Blockus H, Chedotal A. Slit-Robo signaling. Development 2016; 143(17):3037-44. 
4. 
 
 
6. 
Heymann W, Hackel DB, Harwood S, et al. Production of nephrotic syndrome in rats 
by Freund’s adjuvant and rat kidney suspension. Proc Soc Exp Biol Med 1959; 100(4): 
660-64. 
7. 
Singhal R, Brimble KS. Thromboembolic complications in the nephrotic syndrome: 
Pathophysiology and clinical management. Thrombosis Research 2006; 118:397-407. 
8. 
 
 
 
10. 
 
 
 
 
 
CCI 
CCI 
CCI 


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17. APPENDICES 
17.1. Appendix 1: Abbreviations 
This following is a list of abbreviations that may be used in the protocol. 
 
Abbreviation 
Term 
ADA 
anti-drug antibody 
ADCC 
antibody-dependent cell-mediated cytotoxicity 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
BBS 
biospecimen banking system 
BMI 
body mass index 
BP 
blood pressure 
bSAP 
biomarker statistical analysis plan 
BUMC 
Boston University Medical Center 
BUN 
blood urea nitrogen 
C1q 
complement protein 1q 
CDC 
complement-dependent cytotoxicity 
Ceff 
human efficacious concentration 
CK 
creatine kinase 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CL/F 
apparent clearance 
Cmax 
maximum plasma drug concentration 
CNI 
calcineurin inhibitor 
CCI 
CO2 
bicarbonate 
CRF 
case report form 
CRU 
clinical research unit 
CSA 
clinical study agreement 
CSR 
clinical study report 
CT 
clinical trial 
CTA 
clinical trial application 
%CV 
coefficient of variation 
DILI 
drug-induced liver injury 
DMC 
data monitoring committee 
DNA 
deoxyribonucleic acid 
DCT 
data collection tool 
DU 
dispensable unit 
EC 
ethics committee 
ECG 
electrocardiogram 
E-DMC 
external data monitoring committee 


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Abbreviation 
Term 
EDP 
exposure during pregnancy 
EU 
European Union 
eGFR 
estimated glomerular filtration rate 
ESoE 
early signal of efficacy 
ETS 
exploratory toxicity study 
EU 
European Union 
EudraCT 
European Clinical Trials Database 
FAS 
full analysis set 
Fc 
crystallized fragment 
FcγR 
fragment crystallizable gamma receptor 
FIH 
first in human 
FMV 
first morning void 
FPW 
foot process width 
FSGS 
focal segmental glomerulosclerosis 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
GLP 
Good Laboratory Practice 
GNA 
grounds for non-acceptance 
HBcAb 
hepatitis B core antibody 
HBsAg 
hepatitis B surface antigen 
HCG 
human chorionic gonadotropin hormone 
HCV Ab 
hepatitis C antibody 
HIV 
human immunodeficiency virus 
HRQL 
health-related quality of life 
HTRF 
homogenous time resolved fluorescence 
IA 
interim analysis 
IB 
Investigator Brochure 
ICD 
informed consent document 
ICH 
International Conference on Harmonisation 
ID 
identification 
IFN-y 
interferon gamma 
Ig 
immunoglobulin 
IgG1 Fc 
immunoglobulin G1 crystallized fragment IgG1 Fc 
IgGl 
immunoglobulin G1 
IL-6 
interleukin-6 
IMPDH 
inosine monophosphate dehydrogenase inhibitors 
IND 
investigational new drug application 
INR 
International Normalised Ratio 
INR 
international normalized ratio 
IP 
investigational product 
IRB 
institutional review board 
IRC 
internal review committee 


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Abbreviation 
Term 
IRT 
interactive response technology 
IUD 
intrauterine device 
IV 
intravenous 
IWR 
interactive web response 
K2EDTA 
dipotassium ethylenediaminetetraacetic acid 
Kg 
Kilogram 
LFT 
liver function test 
LOCF 
last observation carried forward 
LSLV 
last subject last visit 
LSMeans 
least squares mean 
MAD 
multiple ascending dose 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MMF 
mycophenolate mofetil 
MMRM 
mixed effects model of repeated measures 
CCI 
N/A 
not applicable 
NAb 
neutralizing antibody 
NOAEL 
no observed adverse effect level 
PACL 
Protocol Administrative Changes and Clarifications 
PCD 
primary completion date 
PD 
pharmacodynamics(s) 
PGIS 
Patient Global Impression of Severity 
PI 
principal investigator 
PK 
pharmacokinetic 
PMDA 
Pharmaceuticals and Medical Devices Agency 
PP 
per protocol 
PR 
pulse rate 
Prep B1 
K2EDTA plasma collection optimized for 
biomarker/proteomic/metabonomic analysis 
Prep D1 
dipotassium edetic acid 
PT 
prothrombin time 
q.o.d. 
every other day 
Q2W 
every 2 weeks 
QTc 
Corrected QT Interval 
QW 
every week 
RAAS 
renin–angiotensin–aldosterone system 
RBC 
red blood cell 
RNA 
ribonucleic acid 
ROBO2 
roundabout guidance receptor 2 
SAD 
single ascending dose 
SAE 
serious adverse event 


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Abbreviation 
Term 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SF-12 
12-Item Short Form Survey 
SIQ 
Symptom Impact Questionnaire 
SLIT 
slit guidance ligand 
SLIT2 
slit guidance ligand 2 
SLIT2-N 
slit guidance ligand 2, N-terminal fragment SLIT2-N 
SOP 
standard operating procedure 
SRSD 
single reference safety document 
SUSAR 
suspected unexpected serious adverse reaction 
Sym-D 
symptom diary 
TBili 
total bilirubin 
TEAE 
treatment-emergent adverse events 
TNF-α 
tumor necrosis factor-alpha 
CCI 
ULN 
upper limit of normal 
UPCR 
urine protein-to-creatinine ratio 
US 
United States 
VHP 
Voluntary Harmonization Procedure 
Vz/F 
apparent volume of distribution 
WBC 
white blood cell 
WFI 
water for injection 
WOCBP 
women of child-bearing potential 


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CCI 
 
 
 
 
CCI 
 
 
4. INCLUSION AND EXCLUSION CRITERIA 
 


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CCI 
CCI 
CCI 
 
 
CCI 
 
 
CCI 
 
 
 
 
 
 
CCI 
 
 
 
CCI 
 
 


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Signed By: 
Date(GMT) 
Signing Capacity 
 
Document Approval Record 
 
 
C0221002 Protocol Amendment 5 Clean 18 August 2021 
 
C0221002 Protocol Amendment 5 Clean 18 August 2021 
 
 
PPD 
  
PPD 
 
 
23- Aug-2021 17:23:59 
Final Approval 
 
24- Aug-2021 04:52:03 
Final Approval 
Document Name: 
Document Title: 

SAP_001.pdf: 
Protocol C0221002 (PF-06730512) Statistical Analysis Plan (v3 23-FEB-2023) 
PFIZER CONFIDENTIAL 
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Protocol C0221002 
 
 
 
 
 
 
 
 
A PHASE 2, 12-WEEK, ADAPTIVE, OPEN LABEL, SEQUENTIAL COHORT TRIAL TO 
EVALUATE THE EFFICACY, SAFETY, TOLERABILITY AND PHARMACOKINETICS OF 
PF-06730512 FOLLOWING MULTIPLE DOSES IN ADULT SUBJECTS WITH PRIMARY 
FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS) 
 
 
 
 
Statistical Analysis Plan 
(SAP) 
 
 
Version: 
3.0 
 
Author: 
PPD 
 (SAP Author – ECD Statistics) 
Date: 
23-FEB-2023 


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TABLE OF CONTENTS 
LIST OF TABLES ........................................................................................................................... 5 
LIST OF FIGURES .......................................................................................................................... 5 
1. VERSION HISTORY .................................................................................................................. 6 
2. INTRODUCTION ........................................................................................................................ 7 
2.1. STUDY OBJECTIVES ............................................................................................................. 8 
2.1.1. PRIMARY OBJECTIVE ....................................................................................................... 8 
2.2. STUDY DESIGN ...................................................................................................................... 8 
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS .................................................................................................................. 10 
3.1. PRIMARY ENDPOINT(S) ..................................................................................................... 10 
3.1.1.  PERCENTAGE CHANGE FROM BASELINE TO WEEK 13 IN URINARY 
PROTEIN TO CREATININE RATIO (UPCR) BASED ON 24-HOUR URINE 
COLLECTION ..................................................................................................................... 10 
3.2. SECONDARY ENDPOINT(S) ............................................................................................... 11 
3.2.1.  PERCENTAGE CHANGE FROM BASELINE TO WEEKS 2, 5, 9, AND 
BEYOND WEEK 13, AS APPLICABLE, IN URINARY PROTEIN TO 
CREATININE RATIO (UPCR) ........................................................................................... 11 
3.2.2.  PERCENTAGE CHANGE FROM BASELINE TO WEEKS 3, 5, 9, 13 AND 
BEYOND, AS APPLICABLE, IN ESTIMATED GLOMERULAR 
FILTRATION RATE (EGFR) ............................................................................................. 11 
3.2.3. SERUM CONCENTRATION OF PF-06730512 ................................................................ 12 
3.2.4. INCIDENCE OF THE DEVELOPMENT OF ANTIDRUG ANTIBODY (ADA) 
AND NEUTRALIZING ANTIBODY (NAB) ..................................................................... 13 
 
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3.3.7. BASELINE VARIABLES ................................................................................................... 14 
3.4. SAFETY ENDPOINTS ........................................................................................................... 15 
3.4.1. ADVERSE EVENTS (AES) ................................................................................................ 15 
3.4.2. LABORATORY DATA ...................................................................................................... 15 
3.4.3. VITAL SIGNS ..................................................................................................................... 15 
3.4.4. ELECTROCARDIOGRAM (ECG) ..................................................................................... 16 
3.4.5. BODY WEIGHT .................................................................................................................. 16 
4. ANALYSIS SETS ...................................................................................................................... 16 
4.1. FULL ANALYSIS SET .......................................................................................................... 16 
4.2. PER PROTOCOL ANALYSIS SET ....................................................................................... 16 
4.3. SAFETY ANALYSIS SET ..................................................................................................... 17 
4.4. OTHER ANALYSIS SETS .................................................................................................... 17 
4.4.1. PK CONCENTRATION ANALYSIS SET ......................................................................... 17 
4.4.2. PK PARAMETER ANALYSIS SET ................................................................................... 18 
4.4.3. IMMUNOGENICITY ANALYSIS SET ............................................................................. 18 
5. GENERAL METHODOLOGY AND CONVENTIONS .......................................................... 18 
5.1. GENERAL FORMAT ............................................................................................................ 18 
5.2. HYPOTHESES AND DECISION RULES ............................................................................. 18 
5.3. GENERAL METHODS .......................................................................................................... 19 
5.3.1. SUMMARY ANALYSES FOR CONTINUOUS DATA .................................................... 19 
5.3.2. SUMMARY ANALYSES FOR CATEGORICAL DATA ................................................. 19 
5.3.3. MIXED MODEL REPEATED MEASURES (MMRM) ..................................................... 19 
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5.4. METHODS TO MANAGE MISSING DATA ....................................................................... 20 
6. ANALYSES AND SUMMARIES ............................................................................................. 21 
6.1. PRIMARY ENDPOINT(S) ..................................................................................................... 21 
6.1.1.  PERCENTAGE CHANGE FROM BASELINE TO WEEK 13 IN URINARY 
PROTEIN TO CREATININE RATIO BASED ON 24-HOUR URINE 
COLLECTION (UPCR) ....................................................................................................... 21 
6.1.1.1. PRIMARY ANALYSIS .................................................................................................... 21 
6.1.1.2. SENSITIVITY/ROBUSTNESS ANALYSES .................................................................. 22 
6.1.1.3. STATISTICAL MODEL DIAGNOSIS ............................................................................ 22 


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6.2. SECONDARY ENDPOINT(S) ............................................................................................... 23 
6.2.1.  PERCENTAGE CHANGE FROM BASELINE TO WEEKS 2, 5, 9, AND 
BEYOND WEEK 13, AS APPLICABLE, IN URINARY PROTEIN TO 
CREATININE RATIO (UPCR) ........................................................................................... 23 
6.2.2.  PERCENTAGE CHANGE FROM BASELINE TO WEEKS 3, 5, 9, 13 AND 
BEYOND, AS APPLICABLE, IN ESTIMATED GLOMERULAR 
FILTRATION RATE (EGFR) ............................................................................................. 23 
6.2.3. PHARMACOKINETICS ANALYSIS ................................................................................ 23 
6.2.3.1. SERUM AND URINE PK CONCENTRATIONS ........................................................... 23 
6.2.3.2. SERUM PK PARAMETERS ............................................................................................ 24 
 
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6.5. BASELINE AND OTHER SUMMARIES AND ANALYSES ............................................ 26 
6.5.1. STUDY CONDUCT AND SUBJECT DISPOSITION ....................................................... 26 
6.5.2. DEMOGRAPHIC DATA .................................................................................................... 26 
6.5.3. CONCOMITANT AND PRIOR MEDICATIONS ............................................................. 26 
6.5.4. DISCONTINUATIONS ....................................................................................................... 26 
6.6. SAFETY SUMMARIES AND ANALYSES .......................................................................... 27 
6.6.1. ADVERSE EVENTS ........................................................................................................... 27 
6.6.2. LABORATORY DATA ...................................................................................................... 27 
6.6.3. VITAL SIGNS ..................................................................................................................... 27 
6.6.4. ELECTROCARDIOGRAM ................................................................................................. 27 
6.6.5. BODY WEIGHT .................................................................................................................. 27 
7. INTERIM ANALYSES ............................................................................................................. 27 
7.1. INTRODUCTION ................................................................................................................... 27 
7.2. INTERIM ANALYSES .......................................................................................................... 28 
7.3. ONGOING MONITORING OF SAFETY ............................................................................. 28 


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8. APPENDICES ............................................................................................................................ 29 
 
LIST OF TABLES 
Table 1. Summary of Changes ........................................................................................................ 6 
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Table 3 Potential reasons for exclusion of a subject from the PPAS .............................................17 
Table 4. Serum PK Parameters to be Summarized Descriptively by Dose Level ......................... 25 
Table 5 Timing of Interim Analyses ............................................................................................. 28 
 
 
LIST OF FIGURES 
Figure 1. 
Schematic of the Study Design .................................................................................... 9 
 
 
APPENDICES 
APPENDIX 1. SUMMARY OF EFFICACY ANALYSES ......................................................... 29 
Appendix 1.1. List of efficacy listings, figures and tables required .....................................29 
APPENDIX 2. STATISTICAL METHODOLOGY DETAILS ................................................... 31 
Appendix 2.1. Example SAS code for Statistical Analyses .................................................31 
Appendix 2.2. Code to be used for calculating the predictive probabilities .........................32 
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1. VERSION HISTORY 
This CSR Statistical Analysis Plan (SAP) for study C0221002 is based on Protocol 
Amendment 5 dated 18-Aug-2021. 
Table 1. Summary of Changes 
 
Version/ 
Date 
Associated 
Protocol 
Amendment 
Rationale 
Specific Changes 
2 
08 FEB 2023 
5 
18 Aug 2021 
Updates to minor 
components of 
analysis due to 
recent FDA 
• 
CCI 
• 
further clarification on analysis and 
presentation of multiple dose levels; 
• 
inclusion of robust standard error estimation 
included in SAS code due to updated FDA 
guidance on controlling for covariates in 
randomized controlled trials; 
• 
update sample SAS code due to incorrect 
coding in previous version; 
• 
update to language on missing values being 
imputed by MMRM; 
• 
CCI 
guidance, CCI 
2 
08 FEB 2023 
5 
18 Aug 2021 
Changes needed 
based on Protocol 
Amendment 5 
• 
Updated study objectives, study design and 
stiatistical methods to extend treatment 
duration from 12 weeks to 24 weeks, and to 
add an optional cohort (Cohort 3) to 
potentially explore a higher dose of PF- 
06730512 CCI 
 in 
subjects with FSGS, based on emerging data 
from the study. 
2 
08 FEB 2023 
4 
12 Jun 2020 
Changes needed 
based on emerging 
data to incorporate 
into IA1 and align 
with current IA 
Charter 
• 
Included PPAS analysis into IA readouts due 
to emerging discontinuations in the study 
(Section 4.2, 6.1.1.2 and Appendix 1.1). 
• 
Added predictive probability table related to 
first morning void sensitivity analysis as was 
required based on IA Charter (version 1.0) 
(Section 6.1.1.2 and Appendix 1.1). 
• 
Added safety summaries that may be 
required at IA2 and/or IA3 due to potential 
need for internal business decision making 
or external briefing documents (Section 6.5). 
• 
Clarified definition of baseline UPCR in 
case of scenario where Week -1 values were 
missing (Section 3.1.1). 


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• 
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• 
Updated study objectives and study design 
to align with current protocol (Section 2.1.3 
and 2.2) and removed any mention of “Part 
B”. 
• 
Clarified minor points for individual profile 
plots (Section 6.1.1.1). 
• 
Updated demographic tables as required for 
IA readouts (Sections 6.4.2 and 6.4.3). 
• 
Note: Minor formatting issues were 
identified during QC performed after 22 Dec 
2020 final draft version and were the only 
edits incorporated after database snapshot 
for IA1. 
• 
Included clinical output assessments, PK, 
ADA/Nab. 
 
NOTE: Italicized text within this document has been taken verbatim from the Protocol 
Amendment 5. 
2. INTRODUCTION 
This SAP provides the detailed methodology for summary and statistical analyses of the data 
collected in study C0221002. 


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2.1. Study Objectives 
2.1.1. Primary Objective 
 
Primary Objective(s): 
Primary Endpoint(s): 
 
• 
To evaluate the efficacy of PF-06730512 compared to 
baseline in the reduction of proteinuria following 
12 weeks of treatment in patients with FSGS. 
Secondary Objective(s): 
• 
To evaluate the safety and tolerability of PF-06730512 
following up to 24 weeks of treatment in subjects with 
FSGS. 
 
• 
To evaluate the effects of PF-06730512 on proteinuria 
time course. 
• 
To evaluate the effect of PF-06730512 on renal 
function. 
• 
To evaluate the serum exposure of PF-06730512 in 
FSGS patients. 
• 
To evaluate the immunogenicity profile of 
PF-06730512. 
 
CCI 
• 
Percentage change from baseline to Week 13 in 
Urinary Protein to Creatinine Ratio (UPCR), 
calculated from the 24-hour urine collection. 
Secondary Endpoint(s): 
• 
Adverse Events, Laboratory Safety Tests 
(Hematology, Clinical Chemistry, Urinalysis), Body 
Weight, Blood Pressure, Pulse Rate, Body 
temperature and Electrocardiogram (ECG). 
 
• 
Percentage change from baseline to Weeks 2, 5, 9, 
and beyond Week 13, as applicable, in UPCR. 
 
• 
Percentage change from baseline to Weeks 3, 5, 9, 
13 and beyond as applicable, in estimated 
glomerular filtration rate (eGFR). 
 
• 
Serum concentration of PF-06730512. 
• 
Incidence of the development of anti-drug antibody 
(ADA) and neutralizing antibody (NAb). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2.2. Study Design 
The adaptive study consists of a Screening Period of up to 43 days, an approximately 8-week 
Lead-in Period, an Investigational Treatment Period of up to 24 weeks during which subjects 
will receive PF-06730512 once every 2 weeks (Q2W), followed by an approximately 9-week 


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+ 
Follow-up 
Period 
(9 weeks) 
Treatment 
Period 
PF-06730512 
12 doses 
(24 weeks) 
Lead-in 
Period 
(8 weeks) 
CCI 
Cohort 2 (n=22, ~18 Completers) 
Follow-up 
Period 
(9 Weeks) 
Treatment 
Period 
PF-06730512 
12 doses 
(24 weeks) 
Lead-in 
Period 
(8 weeks) 
CCI 
Cohort 1 (n=22, ~18 Completers) 
 
 
Follow-up Period. Delays to the beginning of Lead-in or Investigational Treatment Period 
(up to 1 week from visit window specified) due to pending primary or repeat laboratory 
results that are submitted for analysis within the protocol specified window, will not be 
considered protocol deviations. 
Figure 1. Schematic of the Study Design 
 
 
+/- 
 
 
 
 
Upon commencement of active treatment with PF-06730512, subjects will be dosed 
intravenously Q2W for up to 24 weeks, but the primary endpoint result will be based on 
UPCR from a 24-hour urine collection at Week 13. There will be a maximum of 12 infusions 
of PF-06730512 within the 24-week Investigational Treatment Period. Subjects enrolled 
prior to Amendment 5 of the protocol will be dosed for 12 weeks with a maximum of 6 
infusions of PF-06730512 within a 12-week Investigational Treatment period. Telephone 
contact visits will be conducted the weeks in between dosing visits to check the subject’s 
overall status, including new or worsening adverse events, changes to concomitant 
medications, compliance with appropriate contraceptive use, and reminders about upcoming 
urine collections, when applicable. 
Follow-up 
Period 
(9 weeks) 
Treatment 
Period 
PF-06730512 
12 doses 
(24 weeks) 
Lead-in 
Period 
(8 weeks) 
CCI 
3
rd dose level 
Optional Cohort 3 (n= up to 22) 


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CCI 
CCI 
All cohorts will collect the same procedures at the same 
CCI 
 
 
 
timepoints, according to the Schedule of Activities. 
The duration of study participation will be up to approximately 11 months from Screening to 
the last post-treatment Follow-up Period visit. The durations of the study periods are listed 
below: 
• Screening Period up to 43 days; 
• Lead-in Period: approximately 8 weeks; 
• Investigational Treatment Period: up to 24 weeks (up to 12 weeks for subjects 
enrolled prior to Amendment 5); 
• Follow-up Period: approximately 9 weeks (after last dose given at visit Week 11 or 
23). 
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS 
3.1. Primary Endpoint(s) 
 
3.1.1. Percentage change from baseline to Week 13 in Urinary Protein to Creatinine 
Ratio (UPCR) based on 24-hour urine collection 
The primary efficacy endpoint is the percentage change from baseline to Week 13 in the 
Urinary Protein to Creatinine Ratio (UPCR) based on 24-hour urine collections. UPCR will 
be calculated as urinary protein divided by the urinary creatinine value at the same collection 
time point. If a value of protein or creatinine is missing, UPCR will be missing for that 
respective value. 
Baseline for the primary endpoint is defined as the Week -1 UPCR measurement that is 
based on the 24-hour urine collection. If the Week -1 24-hour UPCR value is not available, 
the nearest 24-hour UPCR measurement taken to the Week -1 visit will be used, provided it 
is pre-dose. 


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For sensitivity analyses utilizing first morning void UPCR assessments instead, the baseline 
is similarly defined as the Week -1 first morning void UPCR measurement. If the Week -1 
first morning void UPCR value is not available, the nearest first morning void UPCR 
measurement taken to the Week -1 visit will be used, provided it is pre-dose. 
Log-transformed change from baseline (i.e. the difference in loge-transformed values) will be 
the dependent variable in the analysis models. The results from the analysis models will be 
back-transformed to obtain the ratio to baseline. The percentage change from baseline will be 
derived by transforming the ratio using the following formula: 
Percentage change from baseline = 100*([back-transformed LSMean] – 1) 
For descriptive summaries, percentage change from baseline will be calculated as the Week 
13 measurement minus the baseline value divided by the baseline value multiplied by 100. 
3.2. Secondary Endpoint(s) 
3.2.1. Percentage change from baseline to Weeks 2, 5, 9, and beyond Week 13, as 
applicable, in Urinary Protein to Creatinine Ratio (UPCR) 
The secondary efficacy endpoints include percentage change from baseline to Weeks 2, 5 and 
9 in UPCR based on both the 24-hour urine collections and the first morning voids. All 
analyses and descriptive summaries will report first morning void assesments and 24-hour 
urine assessments of UPCR separately. Descriptive statistics will be used to summarize 
UPCR by dose and timepoint for all timepoints in the Lead-in Period and the Investigational 
Treatment Period, as well as Week 13 data for subjects enrolled prior to amendment 5 and 
Week 25 data for subjects enrolled after amendment 5. 
For descriptive summaries, percentage change from baseline will be calculated for each post- 
baseline measurement based on the respective urine collection, as that measurement minus 
the baseline value divided by the baseline value multiplied by 100. 
3.2.2. Percentage change from baseline to Weeks 3, 5, 9, 13 and beyond, as applicable, 
in estimated glomerular filtration rate (eGFR) 
The secondary efficacy endpoints of percentage change from baseline in estimated 
glomerular filtration rate (eGFR) include Weeks 3, 5, 9 and 13. Descriptive statistics will be 
used to summarize eGFR by dose and timepoint for all timepoints in the Lead-in Period and 
the Investigational Treatment Period, as well as Week 13 data for subjects enrolled prior to 
amendment 5 and Week 25 data for subjects enrolled after amendment 5. 
The eGFR will be calculated based on the Chronic Kidney Disease Epidemiology 
Collaboration (CKD-EPI) formula1 (see Appendix 4). 


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Baseline is defined as the Week -1 measurement. If the Week -1 eGFR measurement is not 
available, the nearest eGFR measurement taken to the Week -1 visit will be used, provided it 
is pre-dose. 
Log-transformed change from baseline will be the dependent variable in the analysis models. 
The percentage change from baseline will be calculated for each post-baseline measurement, 
as that measurement minus the baseline value divided by the baseline value multiplied by 
100. 
3.2.3. Serum concentration of PF-06730512 
Blood samples (approximately 3 mL whole blood) to provide a minimum of 1 mL of serum for 
pharmacokinetic (PK) analysis will be collected into appropriately labeled tubes at times 
specified in the Schedule of Activities section of the protocol. 
Serum PK parameters will be derived, if data permits, from the concentration-time data 
using standard noncompartmental methods of analysis as outlined in Table 1. Actual PK 
sampling times will be used in the derivation of PK parameters when available. In the case 
that actual PK sampling times are not available, nominal PK sampling time will be used in 
the derivation of PK parameters. 
Table 1. Serum PF-06730512 PK Parameters Definitions 
 
Parameter 
Definition 
Method of Determination 
AUCtau 
Area under the concentration- 
time profile from time zero to time 
tau (the dosing interval) 
Linear/Log trapezoidal method. 
AUCtau(dn) 
Dose normalized AUCtau 
AUCtau/Dose 
Cmax 
Maximum observed plasma 
concentration 
Observed directly from data 
Cmax(dn) 
Dose normalized maximum 
plasma concentration 
Cmax/Dose 
Tmax 
Time to reach Cmax 
Observed directly from data as time of 
first occurrence 
* 
t½ 
Terminal elimination half-life 
Loge(2)/kel, where kel is the terminal phase 
rate constant calculated by a linear 
regression of the loglinear concentration- 
time curve. Only those data points judged 
to describe the terminal loglinear decline 
will be used in the regression. 
CL/ 
Clearance 
Dose/AUCtau 
Volume of distribution at steady 
state 
Dose/(AUCtau • kel) 
• If data permits 


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3.2.4. Incidence of the development of antidrug antibody (ADA) and neutralizing 
antibody (NAb) 
Blood samples (approximately 5 mL) to provide at least 2 mL of serum to detect ADA and 
NAb against PF 06730512 (~1 mL each of ADA and Nab) will be collected from subjects 
enrolled at the times specified in the Schedule of Activities. 
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3.4. Safety Endpoints 
3.4.1. Adverse Events (AEs) 
An adverse event is considered treatment emergent relative to a given treatment if: 
• the event occurs for the first time during the Investigational Treatment Period and 
was not seen prior to the start of treatment (during the Lead-in Period), or 
• the event was seen prior to the start of treatment but increased in severity during 
treatment. 
Adverse events occurring during the Lead-in Period are considered non-treatment emergent. 
Events that occur during the Follow-Up Period will be counted as treatment emergent and 
attributed to the previous treatment taken. 
A 3-tier approach for summarizing AEs will not be used for this study as a placebo or active 
comparator arm is not included in the design and there is a low number of subjects planned to 
be enrolled. 
3.4.2. Laboratory Data 
Safety laboratory tests (hematological, clinical chemistry (serum), urinalysis and other safety 
tests) will be performed as described in the protocol. 
To determine if there are any clinically significant laboratory abnormalities, the 
hematological, clinical chemistry (serum) and urinalysis safety tests will be assessed against 
the criteria specified in the sponsor reporting standards. The assessment will take into 
account whether each subject’s baseline test result is within or outside the laboratory 
reference range for the particular laboratory parameter. 
Baseline for all laboratory measurements will be defined as the pre-dose Day 1 (Week 1) 
measurement. 
3.4.3. Vital Signs 
Vital sign measurements (sitting blood pressure, pulse rate, and oral body temperature) will 
be taken as detailed in the Schedule of Activities given in the protocol. 
Baseline is defined as the pre-dose Day 1 (Week 1) measurement. Changes from baseline for 
sitting systolic and diastolic blood pressure, pulse rate and body temperature will be 


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calculated for each post baseline measurement, as that measurement minus the baseline 
value. 
3.4.4. Electrocardiogram (ECG) 
A single standard 12-lead ECG (including QT, QTc, PR, QRS and heart rate) will be 
obtained at times detailed in the Schedule of Activities given in the protocol. 
Baseline will be defined as the pre-dose Day 1 (Week 1) measurement. Change from baseline 
will be calculated for each post baseline measurement, as that measurement minus the 
baseline value. 
3.4.5. Body Weight 
Body Weight will be measured at times detailed in the Schedule of Activities given in the 
protocol. 
Baseline will be defined as the pre-dose Day 1 (Week 1) measurement. Change from baseline 
will be calculated for each post baseline measurement, as that measurement minus the 
baseline value. 
4. ANALYSIS SETS 
4.1. Full Analysis Set 
The Full Analysis Set (FAS) is defined as all enrolled subjects who have received at least one 
dose of study treatment and have at least one post-baseline measurement of UPCR based on 
24-hour urine collection. 
4.2. Per Protocol Analysis Set 
The Per Protocol Analysis Set (PPAS) will be a subset of the FAS dataset. The primary 
analysis of the efficacy endpoints will be based on the FAS, with a sensitivity analysis 
conducted on the PPAS, which will include all subjects who were not major protocol 
deviators. Each deviation will be reviewed on a case by case basis to determine whether the 
subject should be excluded from the PPAS (based on Table 3). 


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Table 3 Potential reasons for exclusion of a subject from the PPAS 
 
Exclusion of a subject 
Responsibility 
Action/Source 
Required 
Listings 
from Programming 
No valid primary 
efficacy measurement 
post-baseline (i.e. no 
readings in 24h UPCR 
at Weeks 5, 9 or 13) 
Programmer/ 
Clinical/ Statistician 
Programming check to highlight 
any subject with incomplete 
data, and those subjects with no 
primary efficacy readings at the 
scheduled time point. 
Listing will be reviewed by the 
clinician and statistician to 
determine if there is insufficient 
data. 
Listing of whether 
primary efficacy 
reading was 
completed (including 
date/times of 
measurements). 
Change in background 
treatment for FSGS (e.g. 
starting new 
immunosuppressant or 
increasing the dose of 
background steroids) 
Programmer/ 
Clinical/ Statistician 
Listing will be reviewed by the 
clinician and statistician to 
determine if subjects’ change in 
background immunosuppressant 
medication (i.e. change of 
dosage or frequency) could have 
impact on efficacy 
Listing of 
immunosuppressant 
medication (including 
dosage and frequency 
throughout study) 
Falsely enrolled into 
study despite violating 
inclusion/exclusion 
criteria 
Programmer/ 
Clinical/ Statistician 
Review of all screening and 
baseline data listings. 
Screening/Baseline 
data listings 
Outside the visit 
window (±3 days) for 
the final primary 
endpoint time point 
(Week 13) 
Programmer/ 
Clinical/ Statistician 
Review of actual study day 
(collection date – first dosing 
date +1) for Week 13 visit. The 
window is 80~87. 
Listing of actual 
study day for all 
subjects at Week 13. 
Did not receive all 
specified doses of PF- 
06730512 as per 
protocol (i.e. missed 
dose not due to 
withdrawal from study) 
Programmer/ 
Clinical/ Statistician 
Programming check to highlight 
any subject who missed 1 or 
more dose of PF-06730512 
Listing of study 
medication. 
 
4.3. Safety Analysis Set 
The Safety Analysis Set (SAS) is defined as all enrolled subjects who have received at least 
one dose of study treatment. 
4.4. Other Analysis Sets 
4.4.1. PK Concentration Analysis Set 
The PK Concentration Analysis Set is defined as all enrolled subjects treated who received at 
least one dose of PF-06730512 and have at least 1 measureable concentration. 


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Subjects who experience events that may affect their PK profile (e.g. dosing error) may be 
excluded from the PK analysis. At the discretion of the pharmacokineticist a concentration 
value may also be excluded from PK summaries if the deviation in sampling time is of 
sufficient concern or if the concentration is anomalous for any other reason. 
4.4.2. PK Parameter Analysis Set 
The PK parameter analysis population is defined as all enrolled subjects treated who have at 
least 1 of the PK parameters. 
 
4.4.3. Immunogenicity Analysis Set 
The immunogenicity analysis population includes all treated subjects with at least 1 ADA 
sample (pre-dose or post-treatment) analyzed. If a subject only has pre-dose baseline data 
and no post-treatment immunogenicity data, this subject is not evaluable for subject-level 
ADA and NAb status and should not be included in subject-level data analysis (eg. overall 
ADA/NAb incidence, duration of ADA/NAb response). 
 
 
5. GENERAL METHODOLOGY AND CONVENTIONS 
The planned statistical methods and analyses for the primary and secondary endpoints are 
described in detail in Sections 6.1 and 6.2 below 
 
 
5.1. General Format 
All tables, figures and listings for the final analyses will include titles/footnotes indicating the 
file in which the item is located and the date on which the item was produced as per Pfizer 
standards. All tables, figures and listings will also have a subtitle that will indicate the 
population on which the presentation is based. 
5.2. Hypotheses and Decision Rules 
No classical hypothesis testing will be done, as decisions will be based on Bayesian 
(posterior) probabilities. This Bayesian interpretation is based on the assumption that the 
model provides an adequate approximation to a Bayesian analysis with “vague” priors for all 
parameters in the model. 
For final analysis, the decision criteria are given below and apply to each dose of PF- 
06730512 separately: 
• C1: At least 95% confident that the PF-06730512 reduction > 0%; 


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• C2: At least 50% confident that the PF-06730512 reduction > 35%. 
Interim Bayesian decisions, that is, the posterior predictive probability that at an interim 
analysis where less than the entirety of the cohort has been enrolled, that decisions C1 and 
C2 would be achieved once full enrollment has completed were performed at IA1 and IA3 
for cohorts 1 and 3, respectively. Those probabilities will not be reproduced here. For the 
CSR, Table 14.2.1.1.7 and Table 14.2.1.1.6, Summary of Predictive Probabilities based on 
24-Hour Urine Collection, at IA1 and IA3 using IA1 FAS and IA3 FAS may be used to 
present interim findings in the CSR. 
5.3. General Methods 
5.3.1. Summary Analyses for Continuous Data 
Continuous variables will be presented using summary statistics: number of observations, 
arithmetic mean, standard deviation, median, minimum and maximum values. For endpoints 
to be analysed on the natural log scale, the geometric mean and geometric coefficient of 
variation will additionally be calculated. 
5.3.2. Summary Analyses for Categorical Data 
Categorical variables will be presented using summary statistics: number of observations, 
counts and percentages in each category. 
5.3.3. Mixed Model Repeated Measures (MMRM) 
The efficacy analyses over time will be based on the FAS and will use a mixed model 
repeated measures (MMRM) approach. The mixed effect repeated measures model will 
include baseline, week (as a factor), baseline*week interaction, and will use an unstructured 
covariance matrix for within-subject time-dependent correlation. 
If convergence is not obtained or model fit is not adequate then other covariance structures 
will be investigated as necessary. The Kenward-Roger approximation will be used for 
estimating degrees of freedom for the model parameters. 
The probabilities for the decision criteria (listed in Section 5.2) for each of the doses (as 
required) will be calculated using the results of the MMRM (e.g. back-transformed LSmean 
estimate, standard error and degrees of freedom for Week 13). 
The Least Squares Means (LSMeans) (back-transformed if loge transformation is performed) 
together with 90% confidence intervals and standard errors will be obtained for each dose 
individually (if applicable) and week, and will be summarized in a table and a profile plot 
with a separate plot for each dose (if applicable). 


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Ratios in LSMeans (calculated by back-transforming modelled results if loge transformation 
is performed), between doses at the different weeks, together with 90% confidence intervals 
and standard errrors, will also be obtained if applicable. 
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5.4. Methods to Manage Missing Data 
Missing values will not be imputed in the analysis. However, in the event of extensive 
missing data, alternative imputation methods may be explored. 


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6. ANALYSES AND SUMMARIES 
6.1. Primary Endpoint(s) 
6.1.1. Percentage change from baseline to Week 13 in Urinary Protein to Creatinine 
Ratio based on 24-hour urine collection (UPCR) 
6.1.1.1. Primary Analysis 
The primary analysis will be based on the FAS. A MMRM approach as specified in Section 
5.3.3 will be fit to the post-dose 24-hour urine collection data on UPCR (i.e. Weeks 5, 9 and 
13). All UPCR values (including baseline) will be loge-transformed prior to analyses. The 
primary analysis will include the change from baseline values of UPCR (on the loge-scale) as 
the dependent variable. 
Absolute values and percentage changes from baseline in UPCR (based on 24-hour urine 
collection) will be summarized descriptively by dose (if applicable) and timepoint as 
described in Section 5.3.3. Tables will present all Lead-in Period, baseline and post-baseline 
time points where applicable. All 24-hour urine collection data will be included in the data 
listings. 
The probabilities for the decision criteria for each of the doses (as required) will be 
calculated directly from the results of the MMRM. These are the probabilities that the 
reduction from baseline due to PF-06730512 (each dose level) is greater than (i) 0% and (ii) 
35%. The LSMeans at Week 13 will be used to derive the posterior probabilities associated 
with the decision criteria. 
A table showing the estimate of the mean of the posterior distribution for the percentage 
change from baseline for each dose of PF-06730512 (if applicable), the 90% credible interval 
and the posterior probabilities of passing the decision criteria will be produced (Appendix 3). 
The following results from the above primary analysis will be plotted: 
• Individual profile plots of the raw values (including all time points from Week -8, to 
Week 33) against time. Two plots per dose will be generated of absolute values and 
percentage changes from baseline. To distinguish between subjects enrolled before 
and after amendment 5, assessments from each individual’s Follow-up Period will be 
interpolated with a different line style (e.g., a dashed line) than assessments from the 
Investigational Treatment Period. 
• Profile plots of the back-transformed LSMeans (including 90% confidence intervals) 
over time, with a separate line included for each dose (if applicable). 
No imputation of missing values will be conducted and all available data through Week 13 
will be used in the MMRM models. 


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6.1.1.2. Sensitivity/Robustness Analyses 
The following sensitivity analyses to the primary endpoint will be carried out: 
• 
 
• The primary efficacy endpoint will be analyzed for individual dose levels separately, 
and will follow the format described in section 5.3.3 and 5.3.4.. 
• The primary efficacy endpoint of % change from baseline in UPCR at week 13, and 
for all study weeks will be performed including the following potentially relevant 
covariates: GFR; disease duration (quantized into four categories);; and FSGS type, 
as measured by Columbia Classification consisteing of the following categories: 
PERIHILAR, CELLULAR, COLLAPSING, NOT OTHERWISE SPECIFIED. In the 
event the model does not converge due to sparseness in FSGS type, for example, a 
modified model excluding sparse covariates that impact model performance will be 
performed. 
• 
 
 
 
 
 
 
 
• 
 
 
 
 
• The primary analysis MMRM model described in Section 6.1.1.1 will be repeated 
using the associated PPAS. 
6.1.1.3. Statistical Model Diagnosis 
The presence of outliers will be investigated for the primary analysis. An outlier will be 
defined as any response data value with a studentized (conditional) residual greater than 3, or 
less than -3. A listing will be generated of any subjects meeting these criteria for diagnostic 
purposes. The assumptions of normality will be verified graphically using residual plots. 
If there are outliers or major deviations from normality then the effect of these on the 
conclusions will be investigated through alternative transformations and/or analyses 
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excluding outliers. Justification for any alternative to the planned analysis will be given in 
the report of the study. 
6.2. Secondary Endpoint(s) 
6.2.1. Percentage change from baseline to Weeks 2, 5, 9, and beyond Week 13, as 
applicable, in Urinary Protein to Creatinine Ratio (UPCR) 
The analysis methodology for this secondary endpoint is summarized in Section 3.2.1. 
For the CSR, an additional summary statistic table will be provided that is based on the 
respective SAS population. 
6.2.2. Percentage change from baseline to Weeks 3, 5, 9, 13 and beyond, as applicable, 
in estimated glomerular filtration rate (eGFR) 
The analysis for this eGFR endpoint will follow the same type of MMRM model and 
descriptive summary statistics as the primary analysis model (Section 6.1.1). Additional 
details regarding the handling of the eGFR endpoint can be found in Section 3.2.2. 
6.2.3. Pharmacokinetics Analysis 
The PK concentration population is defined as all enrolled subjects who received at least one 
dose of PF-06730512 and have at least 1 measurable concentration. 
6.2.3.1. Serum and urine PK concentrations 
Presentations for PF-06730512 concentrations for subjects in the Concentration Analysis Set 
(as defined in Section 4.4.1) will include: 
• A listing of all concentrations sorted by dose level, subject ID, day, nominal time 
post-dose, actual times, and whether a subject was enrolled prior to or after protocol 
amendment 5. Deviations from the nominal time will be given in a separate listing. 
• A summary of concentrations by dose level and cohort, day, nominal time postdose, 
and enrollment prior to or after protocol amendment 5, where the set of statistics will 
include n, mean, median, standard deviation, coefficient of variation (cv%), 
minimum, maximum and the number of concentrations above the lower limit of 
quantification; 
• Median concentrations time plots for timepoints 
o up to Week 13 predose (on both linear and semi-log scales) against nominal 
time post-dose by dose (all dose levels on the same plot per scale) 
o up to Week 13 predose (on both linear and semi-log scales) against nominal 
time post-dose by dose and ‘Baseline Nephrotic Range Proteinuria’ (see 


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Section 6.4; all dose levels and subgroups on the same plot per scale, using 
different line types to distinguish ‘non-nephrotic’ and ‘nephrotic’ range 
proteinuria at baseline) 
o from Week 13 predose to last follow-up visit (on both linear and semi-log 
scales) against nominal time post-dose by dose and enrollment prior to or after 
protocol amendment 5 (all dose levels on the same plot per scale). Enrollment 
prior to, and after protocol amendment 5 will be distinguished with different 
line styles and/or symbols (e.g., solid vs dashed line) 
• Mean concentrations time plots for timepoints 
o up to Week 13 predose (on both linear and semi-log scales) against nominal 
time post-dose by dose (all dose levels on the same plot per scale) 
o up to Week 13 predose (on both linear and semi-log scales) against nominal 
time post-dose by dose and ‘Baseline Nephrotic Range Proteinuria’ (see 
Section 6.4; all dose levels and subgroups on the same plot per scale, using 
different line types to distinguish ‘non-nephrotic’ and ‘nephrotic’ range 
proteinuria at baseline) 
o from Week 13 predose to last follow-up visit (on both linear and semi-log 
scales) against nominal time post-dose by dose and enrollment prior to or after 
protocol amendment 5 (all dose levels on the same plot per scale). Enrollment 
prior to, and after protocol amendment 5 will be distinguished with different 
line styles and/or symbols (e.g., solid vs dashed line) 
• Individual concentration time plots by dose level and cohort (on both linear and 
semilog scales) against actual time post-dose (there will be separate spaghetti plots 
for each dose per scale). To distinguish between subjects enrolled before and after 
amendment 5, assessments from each individual’s Follow-up Period will be 
interpolated with a different line style (e.g., a dashed line) than assessments from the 
Investigational Treatment Period. 
The length of time used for the x-axes of these plots will be decided on review of the data, 
and will depend on how long PF-06730512 concentration is quantifiable above the limit of 
quantification in the matrix. 
For summary statistics, median and mean plots by sampling time, the nominal PK sampling 
time will be used, for individual subject plots by time, the actual PK sampling time will be 
used. 
6.2.3.2. Serum PK parameters 
The serum PK parameters detailed in Section 3.2.3 will be listed and summarized 
descriptively by dose level, as data permit. Missing values will be handled as detailed in 


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Section 5.4.1. Each PK parameter will be summarized by dose level and will include the set 
of summary statistics as specified in Table 4. 
Table 4. Serum PK Parameters to be Summarized Descriptively by Dose Level 
 
Parameter 
Summary Statistics 
Day 1 and Day 71 AUCtau, 
AUCtau(dn), Cmax, Cmax(dn) 
CL, Vss 
N, arithmetic mean, median, SD, %CV, minimum, maximum, 
geometric mean and geometric %CV 
Day 1 and Day 71 Tmax 
N, median, minimum, maximum 
t½ 
N, arithmetic mean, median, SD, %CV, minimum, maximum 
 
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6.5. Baseline and Other Summaries and Analyses 
6.5.1. Study Conduct and Subject Disposition 
Subject evaluation groups will show subject disposition and will show which subjects were 
analysed for efficacy (FAS) and safety (SAS). Frequency counts and percentages will be 
supplied for subject discontinuation(s) by dose. 
6.5.2. Demographic Data 
A summary of demographic data will be based on the respective SAS and provided for age, 
race, weight, body mass index and height. Baseline disease characteristics (duration of FSGS 
diagnosis, type of FSGS subtype and disease recurrence type) will be summarized in a 
further separate table. 
Each will be summarized by sex at birth and ‘All Subjects’ for each dose separately. 
6.5.3. Concomitant and Prior Medications 
All prior and concomitant medication(s) will be reported and will be generated from the 
SAS. Three tables will be reported, one listing all concomitant medication(s), 1 restricted to 
treatments for FSGS and 1 restricted to antihypertensives and diuretics only. 
6.5.4. Discontinuations 
Subject discontinuations, temporary discontinuations or dose reductions due to adverse 
events will be detailed and summarised by dose (if applicable) and will be based on the 
respective SAS. 
 
 
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6.6. Safety Summaries and Analyses 
Safety summaries will be based on the SAS. 
6.6.1. Adverse Events 
Listings and summary tables of adverse events will be based on the SAS. 
6.6.2. Laboratory Data 
Laboratory data will be listed and summarized by dose. Baseline is as defined in Section 
3.5.2. 
6.6.3. Vital Signs 
Absolute values and changes from baseline in sitting systolic and diastolic blood pressure, 
pulse rate and body temperature will be summarized by dose. Tables will be paged by 
parameter. Baseline is as defined in Section 3.5.3. 
6.6.4. Electrocardiogram 
Absolute values and changes from baseline for the ECG parameters QT interval, heart rate, 
QTcF interval, PR interval, and QRS interval will be summarized by dose and time. Baseline 
is as defined in Section 3.5.4. 
The number (%) of subjects with maximum postdose QTcF values and maximum increases 
from baseline in the categories specified in Appendix 5 will be tabulated by dose. In addition, 
the number of subjects with corrected and uncorrected QT values > 500 msec will be 
summarized and listed. 
6.6.5. Body Weight 
Absolute values and changes from baseline for body weight will be summarized by dose and 
time. Baseline is as defined in Section 3.5.5. 
7. INTERIM ANALYSES 
7.1. Introduction 
The first interim analysis (IA1) and first committee meeting to review study data were 
scheduled after at approximately 50% of the planned subjects from the high dose cohort have 
completed the primary efficacy assessment. The second interim analysis (IA2) was 
conducted after all subjects from the high dose cohort completed the Week 13 visit or 
discontinued from the study. The third interim analysis (IA3) occurred after approximately 
50% of the planned subjects from the low dose cohort completed the primary efficacy 
assessment. These details for IA1, IA2 and IA3 are summarised in Table 5. 


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Table 5 Timing of Interim Analyses 
 
Name 
Details of timing 
IA1 
After approximately 50% of the planned subjects from the high dose cohort have 
completed the primary efficacy assessment (expect ~9 completers) 
IA2 
After all subjects from the high dose cohort have completed the Week 13 visit or 
discontinued from the study 
IA3 
After approximately 50% of the planned subjects from the low dose cohort have 
completed the primary efficacy assessment (expect ~9 completers) 
 
 
7.2. Interim Analyses 
As this study is an open-label, Phase 2 non-pivotal study, a subset of the study team 
(hereafter referred to as “the committee”) had continued access to the primary efficacy data 
throughout the conduct of the study oversaw the interim analyses, organized governance 
meetings, and ensured appropriate communications were conducted. 
 
 
7.3. Ongoing monitoring of safety 
This study will not use an external data monitoring committee (E-DMC). The study team and 
internal medical experts (eg, nephrologists) will review the accumulating safety data from 
this study on a regular basis. Additional details of the reviewing process are provided in the 
Charter for the safety review group. 
Based on these reviews, there may be impact on the future conduct of the study. These may 
include amending safety monitoring procedures, modifying the protocol or consent, 
terminating the study, or continuing the study as designed. 


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8. APPENDICES 
Appendix 1. SUMMARY OF EFFICACY ANALYSES 
Appendix 1.1. List of efficacy listings, figures and tables required 
All plots produced may be used as in-text plots in the CSR and therefore need to be 
optimized for inclusion, i.e., legends, axis labels and titles should be clearly legible when 
inserted into one half of a page within the CSR. 
Primary Analysis Output 
Note for Table Type: L=listing, S=summary, SS=statistical summary, SA=statistical analysis (SAS 
Output is not needed form IA2), P=plot. 
 
Table 
Type 
Data 
Type 
Analysis 
Set(s) 
Title 
Ref 
Table Shell 
L 
UPCR 
FAS 
Listing of Urinary Protein to Creatinine Ratio 
(UPCR) based on 24-hour urine collection –FAS 
1 
16.2.6.1.1 in IA1 
16.2.6.1.1.1 in IA2 
& IA3 
S 
UPCR 
FAS 
Summary of Urinary Protein to Creatinine Ratio 
(UPCR) based on 24-hour urine collection –FAS 
2 
14.2.1.1.1 in IA1 
14.2.1.1.1.1 in IA2 
& IA3 
SS 
UPCR 
FAS 
Statistical Summary of MMRM analysis of Urinary 
Protein to Creatinine Ratio (UPCR) based on 24-hour 
urine collection –FAS 
3 
14.2.1.1.2 in IA1 
14.2.1.1.2.1 in IA2 
& IA3 
SA 
UPCR 
FAS 
Statistical Analysis: Supporting Output for 
MMRM analysis of Urinary Protein to Creatinine 
Ratio (UPCR) based on 24-hour urine collection – 
FAS 
4 
16.1.9.2.1 
P 
UPCR 
FAS 
Individual Subject Data Plot of Urinary Protein to 
Creatinine Ratio (UPCR) based on 24-hour urine 
collection –FAS 
5 
Figure 14.2.1.1.3, 
14.2.1.1.4 in IA1, 
IA2 & IA3 
P 
UPCR 
FAS 
LS Mean profile (including 90% CI) plot for Urinary 
Protein to Creatinine Ratio (UPCR) based on 24-hour 
urine collection –FAS 
6 
Figure 14.2.1.1.5 in 
IA1 
Figure 14.2.1.1.5.1 
in IA2 & IA3 
SS 
UPCR 
FAS 
Summary of decision criteria –FAS 
7 
Shell 1 


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14.2.1.1.6 in IA1 
14.2.1.1.7 in IA2 & 
IA3 
 
Sensitivity Analysis to Primary Endpoint 
• Outputs 1-6 & 8 to be repeated on MMRM analysis of first morning void UPCR. 
• CCI 
 
• Outputs 3, 4 & 6 to be repeated on MMRM analysis of the PPAS. 
Secondary Endpoints 
Table 
Type 
Data 
Type 
Analysis 
Set 
Title 
Ref 
Table Shell 
I 
 
S 
UPCR 
FAS 
Summary of Urinary Protein to Creatinine Ratio 
(UPCR) based on 24-hour urine collection by 
nephrotic-range proteinuria group –FAS 
10 
Shell 3 
14.2.1.5.2 in IA1 
14.2.1.1.1.3 in 
IA2 & IA3 
L 
eGFR 
FAS 
Listing of estimated Glomerular Filtration Rate 
(eGFR) - FAS 
11 
16.2.6.2.1 in IA2 
& IA3 
S 
eGFR 
FAS 
Summary of estimated Glomerular Filtration Rate 
(eGFR) - FAS 
12 
14.2.2.1.1 in IA2 
& IA3 
SS 
eGFR 
FAS 
Statistical Summary of MMRM Analysis of 
estimated Glomerular Filtration Rate (eGFR) - FAS 
13 
14.2.2.1.2 in IA2 
& IA3 
P 
eGFR 
FAS 
Individual Subject Data Plot of estimated 
Glomerular Filtration Rate (eGFR) - FAS 
14 
Figure 14.2.2.1.3, 
Figure 14.2.2.1.4 
in IA2 & IA3 
P 
eGFR 
FAS 
LS Mean profile (including 90% CI) plot for 
estimated Glomerular Filtration Rate (eGFR) - FAS 
15 
Figure 14.2.2.1.5 
in IA2 & IA3 


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Appendix 2. STATISTICAL METHODOLOGY DETAILS 
Appendix 2.1. Example SAS code for Statistical Analyses 
Primary Analysis [Mixed Model Repeated Measures (MMRM)]: 
Note: Loge_endpoint = log(UPCR at week x) – log(baseline) 
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CATEGORICAL CLASSES FOR ECG AND VITAL SIGNS OF POTENTIAL 
CLINICAL CONCERN 
Categories for QTcF 
 
QTcF (ms) 
450< max. ≤ 480 
480< max. ≤500 
max. >500 
QTcF (ms) 
increase from 
baseline 
30< max. ≤60 
max. >60 
 
Categories for PR and QRS 
 
PR (ms) 
max. ≥300 
PR (ms) increase 
Baseline >200 
Baseline ≤200 and 
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from baseline 
and max. 
≥25% increase 
max. ≥50% 
increase 
QRS (ms) 
max. ≥140 
QRS (ms) 
increase from 
baseline 
≥50% increase 
 
Categories for Vital Signs 
 
Systolic BP (mm Hg) 
min. <90 
Systolic BP (mm Hg) 
change from baseline 
max. decrease ≥30 
max. increase ≥30 
Diastolic BP (mm Hg) 
min. <50 
Diastolic BP (mm Hg) 
change from baseline 
max. decrease ≥20 
max. increase ≥20 
Supine pulse rate (bpm) 
min. <40 
max. >120 
 
Measurements that fulfill these criteria are to be listed in the report.