A Prospective, Natural History Study to Assess the Occurrence of HPA-1a Alloimmunization in Women Identified at Higher Risk for Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)
Conditions: Fetal and Neonatal Alloimmune Thrombocytopenia
Sponsor: Rallybio

A prospective, natural history study to assess the occurrence of HPA-1a alloimmunization 
in women identified at higher risk for Fetal and Neonatal Alloimmune Thrombocytopenia 
(FNAIT) 
Unique Protocol ID: IPA2002 
NCT Number:  
NCT05345561 
EudraCT Number: 
Not Applicable 
Date of Protocol: 
20 May 2022 

Protocol Number: IPA2002 
 
Date: 20 May 2022 
Page 1 of 22 
 
TITLE PAGE 
Protocol Title 
A prospective, natural history study to assess the 
occurrence of HPA-1a alloimmunization in women 
identified at higher risk for Fetal and Neonatal 
Alloimmune Thrombocytopenia (FNAIT) 
Protocol Number 
IPA2002 
Sponsor 
Name 
Rallybio IPA, LLC 
Legal Registered 
Address 
 
 
New Haven, CT, USA 
06510 
Regulatory Agency Identifier 
Number 
NCT05345561 
Protocol Date 
Document Version 
Date 
Original (v1.0) 
13 April 2021 
Amendment 1 (v2.0) 
04 November 2021 
Amendment 2 (v3.0) 
20 May 2022 
 
This protocol was developed, reviewed, and approved in accordance with the Sponsor’s standard 
operating procedures. 
Confidentiality Notice 
This document contains confidential information of Rallybio IPA, LLC. This document must not 
be disclosed to anyone other than the site study staff and members of the Institutional Review 
Board/Independent Ethics Committee/Institutional Scientific Review Board or equivalent, as 
applicable. The information in this document cannot be used for any purpose other than the 
evaluation or conduct of the research without the prior written consent of Rallybio IPA, LLC. 

Protocol Number: IPA2002 
 
Date: 20 May 2022 
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SPONSOR SIGNATORY 
IPA2002: A prospective, natural history study to assess the occurrence of HPA-1a 
alloimmunization in women identified at higher risk for Fetal and Neonatal Alloimmune 
Thrombocytopenia (FNAIT) 
I, the undersigned, have approved version 3.0 of the clinical trial protocol with the date of 
20 May 2022. 
Name and Title 
Signature and Date 
 
Chief Medical Officer 
Rallybio IPA, LLC 
 

Protocol Number: IPA2002 
 
Date: 20 May 2022 
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INVESTIGATOR AGREEMENT 
I have read the attached protocol entitled “A prospective, natural history study to assess the 
occurrence of HPA-1a alloimmunization in women identified at higher risk for Fetal and 
Neonatal Alloimmune Thrombocytopenia (FNAIT)”, dated 20 May 2022, and agree to abide by 
all provisions set forth therein. 
I agree to ensure that Financial Disclosure Statements will be completed by: 
• me (including, if applicable, my spouse [or legal partner] and dependent children) 
• my sub-investigators (including, if applicable, their spouses [or legal partners] and dependent 
children) 
at the start of the study and for up to 1 year after the study is completed, if there are changes that 
affect my financial disclosure status. 
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the evaluation or conduct of the clinical investigation without the prior 
written consent of the Sponsor. 
 
 
 
 
 
______________________________ 
__________________________ 
Principal Investigator Name (printed) 
Signature 
______________________________ 
Date 

Protocol Number: IPA2002 
 
Date: 20 May 2022 
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TABLE OF CONTENTS 
TABLE OF CONTENTS .................................................................................................................4 
LIST OF TABLES ...........................................................................................................................5 
LIST OF ABBREVIATIONS ..........................................................................................................6 
1 
PROTOCOL SUMMARY ........................................................................................................7 
2 
RATIONALE AND BACKGROUND.....................................................................................9 
3 
RESEARCH OBJECTIVES AND OUTCOME VARIABLES .............................................11 
4 
RESEARCH METHODS .......................................................................................................11 
4.1 
Study Design ......................................................................................................................11 
4.1.1 
Study Sample Size .......................................................................................................12 
4.1.2 
Selection and Number of Sites .....................................................................................12 
4.1.3 
Participant Eligibility ...................................................................................................13 
4.2 
Assessments .......................................................................................................................13 
4.2.1 
Gestation Week 10 to 14 Pre-natal Visit Assessments ................................................13 
4.2.2 
Visit Assessments for Pregnancy Outcomes that are Live Births ................................14 
4.2.3 
Visit Assessments for Pregnancy Outcomes that are Not Live Births .........................14 
4.3 
Data Management ..............................................................................................................14 
4.4 
Data Analysis .....................................................................................................................15 
5 
PROTECTION OF HUMAN SUBJECTS .............................................................................15 
5.1 
Informed Consent...............................................................................................................15 
5.2 
Institutional Review Board/Independent Ethics Committee (IRB/IEC) ............................16 
5.3 
Participant Confidentiality .................................................................................................16 
5.4 
Subjects Decision to Withdraw ..........................................................................................16 
5.5 
Sample Storage and Destruction ........................................................................................17 
6 
SAFETY COLLECTION, RECORDING AND SUBMISSION REQUIREMENTS ...........17 
7 
ADMINISTRATIVE AND LEGAL OBLIGATIONS ..........................................................17 
7.1 
Protocol Amendments and Study Termination ..................................................................17 
7.2 
Source Documents .............................................................................................................18 
8 
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS ............18 
8.1 
Publication Policy ..............................................................................................................18 
9 
REFERENCES .......................................................................................................................19 
10 APPENDIX: SUB-STUDY TO SUPPORT VALIDATION OF THE FETAL HPA-1 
GENOTYPE ASSAY .............................................................................................................20 
10.1 
Rationale and Background .................................................................................................20 
10.2 
Sub-study Design ...............................................................................................................20 
11 SUMMARY OF CHANGES ..................................................................................................22 
 

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LIST OF TABLES 
Table 1 
Pre-Natal FNAIT Laboratory Testing at Gestation Week 10 to 14 .......................12 
Table 2 
Maternal Samples for Cell-free Fetal DNA HPA-1 Genotyping ...........................21 
 

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LIST OF ABBREVIATIONS 
cffDNA 
cell-free fetal DNA 
CIOMS 
Council for International Organizations of Medical Sciences 
CRF 
case report form 
DNA 
deoxyribonucleic acid 
EDC 
electronic data capture 
FNAIT 
fetal and neonatal alloimmune thrombocytopenia 
GCP 
Good Clinical Practice  
HPA 
human platelet antigen 
ICF 
informed consent form  
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IQRs 
interquartile ranges 
IRB 
Institutional Review Board 
IVIG 
intravenous immune globulin 
 

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1 
PROTOCOL SUMMARY 
Title: A prospective, natural history study to assess the occurrence of HPA-1a alloimmunization 
in women identified at higher risk for Fetal and Neonatal Alloimmune Thrombocytopenia 
(FNAIT). 
Rationale: Data from this study will inform the frequency of women at higher FNAIT risk 
among pregnant women of different racial and ethnic characteristics obtaining pre-natal care at 
the involved institutions and consenting for the study and will assess the occurrence of human 
platelet antigen (HPA)-1a alloimmunization in these women. It is planned that data from this 
study be used as an external control for a future single arm registration study of an anti-HPA-1a 
antibody therapeutic for the prevention of FNAIT. 
Research Objectives and Outcome Variables 
Research Objectives 
Outcome Variables 
Primary 
To inform the frequency of women at 
higher FNAIT risk among pregnant women 
of different racial and ethnic characteristics 
who present for pre-natal care. 
The number of participants that are determined to be at 
higher FNAIT risk compared to the total number of 
pregnant women assessed for higher FNAIT risk, with 
attention to self-characterized race and ethnicity. 
Secondary 
To inform the frequency of HPA-1a 
alloimmunization among pregnant women 
identified at higher FNAIT risk. 
Occurrence of anti-HPA-1a maternal alloimmunization 
at Week 10 postpartuma 
To inform the frequency of pregnancy 
outcomes among pregnant women 
identified at higher FNAIT risk. 
• 
Rate of spontaneous abortion, defined as 
non-deliberate fetal death which occurs prior to 
19 weeks of gestation 
• 
Rate of elective abortion, defined as deliberate 
termination of pregnancy at any time in gestation 
• 
Rate of stillbirth, defined as non-deliberate fetal 
death anytime in gestation on or after 19 weeks of 
gestation 
• 
Rate of premature birth, defined as live birth prior to 
37 completed weeks of gestation 
• 
Rate of live births (≥ 37 completed weeks of 
gestation) 
To inform the frequency, where data are 
available, of neonatal thrombocytopenia in 
infants born to women who have 
alloimmunized, as determined by detectable 
anti-HPA-1a antibody at Week 10 
postpartum.a 
Neonatal thrombocytopenia and severe neonatal 
thrombocytopenia, as determined by a platelet count 
< 150 × 109/L and < 50 × 109/L respectively, within 
72 hours of birth, where data are available 
a For pregnancies that do not result in a live birth, the assessment of alloimmunization will be at 10 weeks from the 
date of the pregnancy-terminating event (ie, abortion [spontaneous/elective] or stillbirth). 

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Hypothesis/Estimation: No hypothesis will be tested in this study. 
Study Design: This is a prospective, non-interventional, natural history study. 
Study Population: Pregnant women (≥ 18 years of age) who have provided informed consent 
for the study. Women with a history of FNAIT will not be included in the study. 
Methodology: This study will be open to all pregnant women presenting at Gestation Week 10 
to 14 pre-natal visit at the involved institutions. 
At this pre-natal visit, the woman will be invited to provide informed consent for the study which 
includes collection of blood samples for the following tests: 
• Maternal HPA-1 genotype: to identify women who are HPA-1b/b genotype (ie, HPA-1a 
negative) 
• Maternal human leukocyte antigen (HLA)-DRB3*01:01 genotype: to identify women who 
are HLA-DRB3*01:01 positive 
• Maternal anti-HPA-1a antibodies: to identify women who have no detectable anti-HPA-1a 
antibodies 
• Fetal HPA-1 genotype: to inform on the presence of the antigenic stimulus (HPA-1a) for 
maternal alloimmunization 
It is preferred that all samples be collected at the Gestation Week 10 to 14-visit. If all blood 
samples cannot be collected during one visit, the collection can be split into 2 timepoints. The 
first timepoint should include blood samples for maternal HPA-1 genotype, maternal 
HLA-DRB3*01:01 genotype and the maternal anti-HPA-1a antibodies and must be collected at 
the Gestation Week 10 to 14-visit. The second timepoint should include blood samples for the 
fetal HPA-1 genotype and should be collected by 18 weeks of gestation.  
At the next pre-natal visit, for pregnant women who are HPA-1b/b genotype, HLA-DRB3*01:01 
positive, and anti-HPA-1a negative, a second maternal blood sample will be requested to 
determine the fetal HPA-1 genotype. 
At Week 10 postpartum, pregnant women who were assessed to be HPA-1b/b, positive for 
HLA-DRB3*01:01, negative for anti-HPA-1a antibodies, and positive fetal HPA-1a test result 
will be evaluated for the occurrence of HPA-1a alloimmunization, pregnancy outcome and, for 
those women who have alloimmunized, the occurrence of neonatal thrombocytopenia (where 
data are available). For pregnancies that do not result in a live birth, the assessment for 
alloimmunization will be performed at a visit scheduled 10 weeks from the date of the 
pregnancy-terminating event (ie, abortion [spontaneous/elective] or stillbirth). 
Study Sample Size: It is anticipated that approximately 20,000 to 30,000 participants will be 
enrolled with the goal of identifying approximately 30 to 50 pregnant women at higher FNAIT 
risk. Of the women identified at higher FNAIT risk, it is anticipated approximately 10 to 20 may 
alloimmunize. 

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Date: 20 May 2022 
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Data Analysis: This study is intended to be descriptive in nature. Demographic and baseline 
characteristics will be summarized. Discrete variables will be summarized using numbers and 
percentages; continuous variables will be summarized using means and SD or medians and 
interquartile ranges (IQRs), as appropriate. Administrative tabulated summaries of study 
variables will be generated periodically. 
Study Schema: 
 
a It is preferred that all samples be collected at the Gestation Week 10 to 14-visit. If all blood samples cannot be 
collected during one visit, the collection can be split into 2 timepoints. The first timepoint should include blood 
samples for maternal human platelet antigen (HPA)-1 genotype, maternal HLA-DRB3*01:01 genotype and the 
maternal anti-HPA-1a antibodies and must be collected at the Gestation Week 10 to 14-visit. The second 
timepoint should include blood samples for the fetal HPA-1 genotype and should be collected by 18 weeks of 
gestation. 
For pregnant women who are HPA-1b/b genotype (ie, HPA-1a negative), HLA-DRB3*01:01 positive, and 
anti-HPA-1a antibody negative, a second blood sample at the next pre-natal visit will be requested to determine 
the fetal HPA-1 genotype. 
b Neonatal thrombocytopenia to be sourced from the neonate’s medical records. 
c For pregnancies that do not result in a live birth, the assessment of alloimmunization will be at 10 weeks from the 
date of the pregnancy-terminating event (ie, abortion [spontaneous/elective] or stillbirth). 
2 
RATIONALE AND BACKGROUND 
Of the approximately 2% of Caucasian pregnant women who are HPA-1a negative 
(ie, HPA-1b/b), approximately 85% will be carrying an HPA-1a positive fetus. Overall, 
approximately 10% of these pregnant women will become alloimmunized and among the fetuses 
or neonates of alloimmunized women, about 10% will have severe thrombocytopenia 
(< 50 x 109/L; < 50,000 platelets/mL), many with bleeding sequelae; about 1% of the 
incompatible fetuses or neonates will suffer intracranial hemorrhage [1]. Among the women who 
become alloimmunized, 90% to 98% will come from among the approximately 27% who are 
HLA-DRB3*01:01 positive [2, 3], meaning that those women with this HLA allele face an 
alloimmunization risk of approximately 25% to 30% [4], vs 1% to 2% for those without the 
allele. 
Screening visit  
Final visit to assess: 
•
pregnancy outcome 
•
maternal 
alloimmunization 
•
occurrence of 
neonatal 
thrombocytopenia, 
where data are 
availableb 
Gestation 
Week 10-14a 
Postpartum 
Week 10c 
Gestation 
Week 18a 
Collection of blood samples 
(timepoint 2, optional) 
Collection of blood 
samples (timepoint 1) 

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Human platelet antigen genotype frequencies vary by race, and an alloimmune response to 
HPA-1a, the immunodominant platelet antigen in Caucasians (~75% to 80% of cases), is 
implicated in the majority of FNAIT cases (ie, in HPA-1b/b homozygous pregnant women 
exposed to fetal platelets expressing HPA-1a derived from a HPA-1a positive father) [5-9]. Data 
reporting on the frequency of the HPA-1b/b genotype in non-Caucasian populations is limited, 
with reports showing a lower frequency in African populations and in Asians [8, 10, 11]. Data 
reporting on the frequency of a population reporting Hispanic ethnicity are sparse. 
Data from this study will inform the frequency of women at higher FNAIT risk among pregnant 
women of different racial and ethnic characteristics obtaining pre-natal care at the involved 
institutions and consenting for the study and will assess the occurrence of HPA-1a 
alloimmunization in these women. It is planned that data from this study be used as an external 
control for a future single arm registration study of an anti-HPA-1a antibody therapeutic for the 
prevention of FNAIT. 
Pregnant women at FNAIT risk will be those who are confirmed to be HPA1b/b (HPA-1a 
negative). This cohort will be enriched for higher FNAIT risk by establishing those HPA-1b/b 
women who are also HLA-DRB3*01:01 positive. A baseline negative anti-HPA-1a antibody test 
will establish the absence of detectable antibody and allow assessment of the occurrence of new 
alloimmunization at Week 10 postpartum (or 10 weeks from the date of the 
pregnancy-terminating event [ie, abortion (spontaneous/elective) or stillbirth] for pregnancies 
that do not result in a live birth). Assessment of fetal HPA-1 status will inform on the presence of 
the antigenic stimulus for maternal alloimmunization (cell-free fetal DNA [cffDNA] HPA-1a 
positive). 

Protocol Number: IPA2002 
 
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3 
RESEARCH OBJECTIVES AND OUTCOME VARIABLES 
Research Objectives 
Outcome Variables 
Primary 
To inform the frequency of women at 
higher FNAIT risk among pregnant women 
of different racial and ethnic characteristics 
who present for pre-natal care. 
The number of participants that are determined to be at 
higher FNAIT risk compared to the total number of 
pregnant women assessed for higher FNAIT risk, with 
attention to self-characterized race and ethnicity. 
Secondary 
To inform the frequency of HPA-1a 
alloimmunization among pregnant women 
identified at higher FNAIT risk. 
Occurrence of anti-HPA-1a maternal alloimmunization 
at Week 10 postpartuma 
To inform the frequency of pregnancy 
outcomes among pregnant women 
identified at higher FNAIT risk. 
• 
Rate of spontaneous abortion, defined as 
non-deliberate fetal death which occurs prior to 
19 weeks of gestation 
• 
Rate of elective abortion, defined as deliberate 
termination of pregnancy at any time in gestation 
• 
Rate of stillbirth, defined as non-deliberate fetal 
death anytime in gestation on or after 19 weeks of 
gestation 
• 
Rate of premature birth, defined as live birth prior to 
37 completed weeks of gestation 
• 
Rate of live births (≥ 37 completed weeks of 
gestation) 
To inform the frequency, where data are 
available, of neonatal thrombocytopenia in 
infants born to women who have 
alloimmunized, as determined by detectable 
anti-HPA-1a antibody at Week 10 
postpartum.a 
Neonatal thrombocytopenia and severe neonatal 
thrombocytopenia, as determined by a platelet count 
< 150 × 109/L and < 50 × 109/L respectively, within 
72 hours of birth, where data are available 
a For pregnancies that do not result in a live birth, the assessment of alloimmunization will be at 10 weeks from the 
date of the pregnancy-terminating event (ie, abortion [spontaneous/elective] or stillbirth). 
4 
RESEARCH METHODS 
4.1 
Study Design 
This is a prospective, non-interventional, natural history study that will be open to all pregnant 
women presenting at Gestation Week 10 to 14 pre-natal visit at the involved institutions. At this 
pre-natal visit, the woman will be invited to provide informed consent for blood samples to be 
collected. The blood samples will be tested to inform whether the woman is at higher FNAIT 
risk as described in Table 1. 

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Table 1 
Pre-Natal FNAIT Laboratory Testing at Gestation Week 10 to 14 
Test 
No. Test 
Description 
 
Result 
Protocol Specific Action 
1 Maternal HPA-1 
genotype 
Test will identify women who 
are HPA-1b/b, indicating risk 
for HPA-1a sensitization and 
occurrence of FNAIT 
1a HPA-1b/b  
(HPA-1a negative) 
Perform Test 2 
1b HPA-1a/b 
HPA-1a/a 
None – no further testing 
2 
Maternal 
HLA-DRB3*01:01 
genotype 
Test will identify women who 
are HLA-DRB3*01:01 
positive, indicating higher 
FNAIT risk 
2a HLA-DRB3*01:01 
positive 
Perform Test 3 
2b HLA-DRB3*01:01 
negative 
None – no further testing 
3 
Maternal 
anti-HPA-1a 
antibody 
Test will establish women who 
have no detectable 
anti-HPA-1a antibody 
3a Anti-HPA-1a antibody 
negative 
Perform Test 4 
3b Anti-HPA-1a antibody 
positive 
None – no further testing 
4 Fetal HPA-1 
genotype 
A cell-free fetal DNA 
(cffDNA) test to inform on the 
presence of the antigenic 
stimulus for maternal 
alloimmunization 
4a HPA-1a/b 
Will be followed for final 
assessments per Section 4.2.2 
or Section 4.2.3 
4b HPA-1b/b  
None – no further testing 
DNA = deoxynucleic acid; FNAIT = fetal and neonatal alloimmune thrombocytopenia; 
HLA = human leukocyte antigen; HPA = human platelet antigen 
If the pregnant woman meets the study-specific blood test results, ie, genotype HPA-1b/b, 
genotype HLA-DRB3*01:01 positive, anti-HPA-1a antibody negative, and carrying an HPA-1a 
positive fetus (Table 1, Test Results 1a, 2a, 3a, and 4a), a follow-up determination will be made 
at Week 10 postpartum on the occurrence of HPA-1a alloimmunization, pregnancy outcome and, 
for women who have alloimmunized, the occurrence of neonatal thrombocytopenia (where data 
are available). 
For women who meet the study specific tests results (ie, Test Results 1a, 2a, 3a, and 4a in 
Table 1) but the pregnancy does not result in a live birth, the assessment of alloimmunization 
will be at 10 weeks from the date of the pregnancy-terminating event (ie, abortion 
[spontaneous/elective] or stillbirth). 
4.1.1 
Study Sample Size 
It is anticipated that approximately 20,000 to 30,000 participants will be enrolled with the goal of 
identifying approximately 30 to 50 pregnant women at higher FNAIT risk. Of the women 
identified at higher FNAIT risk, it is anticipated approximately 10 to 20 may alloimmunize. 
4.1.2 
Selection and Number of Sites 
The study will be conducted across multiple sites in the United States (approximately 10 sites) 
and Europe (approximately 10 sites). 

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4.1.3 
Participant Eligibility 
All participants must sign and personally date the Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC) approved informed consent before any study-specific procedures are 
performed. 
4.1.3.1 
Inclusion Criteria  
Pregnant women (≥ 18 years of age) who have provided informed consent for the study. 
4.1.3.2 
Exclusion Criteria 
Prior history of FNAIT. 
4.2 
Assessments 
Data from the following sources (Section 4.2.1, Section 4.2.2, and Section 4.2.3) will be 
provided to the investigator for reviewing with the participant based on the assessment of the 
investigator and in accordance with local practices/guidelines. 
4.2.1 
Gestation Week 10 to 14 Pre-natal Visit Assessments 
• Maternal demographics: year of birth, weight, height, and self-characterized race and 
ethnicity 
• Gestational age in weeks as estimated by the principal investigator 
• Obstetric history: mode of delivery, gestational age of delivery, live birth, abortion  
• Blood samples will be collected (refer to the study Laboratory Manual for details): 
1. Maternal HPA-1 genotype 
2. Maternal HLA-DRB3*01:01 genotype 
3. Maternal anti-HPA-1a antibodies 
4. Fetal HPA-1 genotype 
It is preferred that all samples be collected at the Gestation Week 10 to 14-visit. If all blood 
samples cannot be collected during one visit, the collection can be split into 2 timepoints. The 
first timepoint should include blood samples for maternal HPA-1 genotype, maternal 
HLA-DRB3*01:01 genotype and the maternal anti-HPA-1a antibodies and must be collected at 
the Gestation Week 10 to 14-visit. The second timepoint should include blood samples for the 
fetal HPA-1 genotype and should be collected by 18 weeks of gestation. 
4.2.1.1 
Fetal HPA-1 Genotype Retest 
At the next pre-natal visit (ie, after the Gestation Week 10 to 14-visit), for pregnant women who 
are HPA-1b/b genotype, HLA-DRB3*01:01 positive, and anti-HPA-1a antibody negative, a 
second maternal blood sample will be requested to determine the fetal HPA-1 genotype. 

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4.2.2 
Visit Assessments for Pregnancy Outcomes that are Live Births 
For pregnancies that result in a live birth, the assessment of alloimmunization will be at 
10 weeks postpartum. 
• A blood sample will be collected for the assessment of maternal alloimmunization (refer to 
the study Laboratory Manual for details), as determined by the presence of detectable 
anti-HPA-1a antibodies. 
• Pregnancy outcome (Section 3): live births, premature birth, mode of delivery including the 
date (based on medical records). 
• Occurrence of neonatal thrombocytopenia and severe neonatal thrombocytopenia, as 
determined by a platelet count < 150 × 109/L and < 50 × 109/L, respectively, within 72 hours 
of birth where data are available (based on medical records). 
• Interventions used: eg, intravenous immune globulin (IVIG), steroids, fetal platelet 
transfusions, newborn platelet transfusions. 
4.2.3 
Visit Assessments for Pregnancy Outcomes that are Not Live Births 
For pregnancies that do not result in a live birth, the assessment of alloimmunization will be at 
10 weeks from the date of the pregnancy-terminating event (ie, abortion [spontaneous/elective] 
or stillbirth).  
• A blood sample will be collected for the assessment of maternal alloimmunization (refer to 
the study Laboratory Manual for details), as determined by the presence of detectable 
anti-HPA-1a antibodies. 
• Pregnancy outcome: spontaneous abortion, elective abortion, stillbirth, including the date 
(based on medical records) 
• Interventions used: eg, IVIG, steroids 
4.3 
Data Management 
The investigator is responsible for maintaining accurate, complete, and up-to-date records for 
each participant. The investigator is also responsible for maintaining any source documentation 
related to the study, including any films, tracings, computer discs, or tapes. 
Site personnel will abstract data from the participant medical record directly into the electronic 
data capture (EDC) system. 
The EDC system automatically generates queries resulting from computer checks embedded into 
the system to ensure accuracy, quality, consistency, and completeness of the database. Manual 
queries resulting from review by Data Management staff are also generated from within the EDC 
system, where they are tracked. Sites will resolve the queries and correct the entered data when 
necessary. Every change to data is captured in the EDC system audit trail. Upon completion of 
the study, or after reaching a pre-specified point in the study, Data Management will lock the 
database and the contract research organization will generate the SAS datasets necessary for data 
analysis and reporting. 

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4.4 
Data Analysis 
This study is intended to be descriptive in nature, no hypothesis will be tested in this study. 
Demographic and baseline characteristics will be summarized. Discrete variables will be 
summarized using numbers and percentages; continuous variables will be summarized using 
means and SD or medians and IQRs, as appropriate. Administrative tabulated summaries of 
study variables will be generated periodically. 
5 
PROTECTION OF HUMAN SUBJECTS 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the Declaration 
of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) 
International Ethical Guidelines 
• Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines 
• Applicable laws and regulations 
5.1 
Informed Consent 
Where an informed consent is required per local regulations, an initial sample informed consent 
form (ICF) is provided for the investigator or designee to prepare the informed consent document 
to be used at his or her site. Updates to the sample ICF are to be communicated formally in 
writing from the PPD Clinical Research Associate to the investigator or designee. The written 
ICF is to be prepared in the language(s) of the potential participant population and would be 
made available either electronically for subjects and investigator to sign or via paper. 
Before a participant’s participation in the study, the investigator or designee will explain to the 
subject the aims, methods, anticipated benefits, and potential hazards of the study, and answer all 
questions regarding the study. 
The acquisition of informed consent is to be documented in the participant’s medical records, 
and the ICF is to be signed and personally dated by the participant and by the person who 
conducted the informed consent discussion if a paper version is used, or electronically signed 
and dated through the electronic consenting system. For a paper process, the original signed ICF 
is to be retained in accordance with institutional policy and a copy of the ICF(s) must be 
provided to the participant. For an electronic process, the system would notify subject when a 
fully signed informed consent is received and would provide a copy of the informed consent for 
participant’s records. Site personnel would have access to the fully signed informed consent PDF 
version and would be able to print it from the system to be documented in the participant’s 
medical records.  
If local regulations do not require an informed consent to be signed but mandate that the 
participant is notified about the study, the investigator or designee should document the 
notification process in the participant’s medical record. 

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5.2 
Institutional Review Board/Independent Ethics Committee (IRB/IEC) 
The protocol, protocol amendments, ICF, and other relevant documents must be submitted to an 
IRB/IEC by the investigator and reviewed and approved by the IRB/IEC before the study is 
initiated. 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
• The investigator will be responsible for: 
o Providing written summaries of the status of the study to the IRB/IEC in accordance with 
the requirements, policies, and procedures established by the IRB/IEC 
o Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 for clinical 
studies (if applicable), European In Vitro Diagnostic Regulation 2017/746 for clinical 
device research (if applicable), and all other applicable local regulations 
5.3 
Participant Confidentiality 
The investigator must ensure that the participant’s confidentiality is maintained for documents 
submitted to the Sponsor. 
Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant names or 
any information which would make the participant identifiable will not be transferred. 
The participant must be informed that her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the informed consent. 
Documents that are not submitted to the Sponsor (eg, signed ICFs) are to be kept in confidence 
by the investigator, except as described below. 
In compliance with governmental regulations/ICH GCP Guidelines, it is required that the 
investigator and institution permit authorized representatives of the company and the IRB/IEC 
direct access to review the participant’s original medical records for verification of data. Direct 
access includes examining, analysing, verifying, and reproducing any records and reports that are 
important to the evaluation of the study. The investigator is obligated to inform and obtain the 
consent of the participant to permit such individuals to have access to her study-related records, 
including personal information. 
5.4 
Subjects Decision to Withdraw 
Participants have the right to withdraw from the study at any time and for any reason without 
prejudice to their future medical care by the physician or at the institution. 

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Withdrawal of consent for a study means that the participant does not wish to or is unable to 
continue further study participation. Participant data up to withdrawal of consent will be included 
in the analysis of the study and, where permitted, publicly available data can be included after 
withdrawal of consent. The investigator is to discuss with the subject appropriate steps for 
withdrawal of their consent from the study. 
5.5 
Sample Storage and Destruction 
Samples will be anonymized and tracked using a unique identifier that is assigned to the samples 
for the study. Results will be stored in a secure database to ensure confidentiality.  
If informed consent is provided by the subject, Rallybio may conduct additional testing on 
remaining samples to refine analytical methods to inform FNAIT risk. 
Since the evaluations of analytical methods are not expected to benefit the participant directly, 
the results of these analyses will not be placed in the participant’s medical record and will not be 
made available to the participant, members of the family, the personal physician, or other third 
parties, except as specified in the informed consent. Residual samples used for analytical method 
development can be retained for the duration of the study. 
Genotyping samples will be destroyed once all protocol-defined procedures are completed at the 
end of the study. Serum samples from enrolled subjects, who are assessed for the occurrence of 
alloimmunization for the pregnancy under study, will be retained for 5 years following the study 
for assay development and validation purposes. The participant retains the right to request that 
the sample material be destroyed prior to the end of the study by contacting the investigator. 
Following the request from the participant, the investigator is to provide the Sponsor with the 
required study and participant number so that any remaining samples can be located and 
destroyed. However, information collected from samples prior to the request for destruction, will 
be retained by Rallybio. 
6 
SAFETY COLLECTION, RECORDING AND SUBMISSION REQUIREMENTS 
This is a non-interventional natural history study in pregnant women at higher FNAIT risk. No 
investigational agent or treatment is being studied or supplied. Submission of reportable events 
to the study Sponsor is not required. Reportable events suspected to be related to any medicinal 
product a participant has received from their physician should be reported to the local authority 
in line with the local country requirements. 
7 
ADMINISTRATIVE AND LEGAL OBLIGATIONS 
7.1 
Protocol Amendments and Study Termination 
The Sponsor may amend the protocol at any time. If the Sponsor amends the protocol, written 
agreement from the Investigator must be obtained where applicable per local governing law 
and/or regulations. The IRB/IEC must be informed of all amendments and give approval. 
The investigator must send a copy of the approval letter from the IRB/IEC to the Sponsor. 

Protocol Number: IPA2002 
 
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The Sponsor reserves the right to terminate the study at any time. Both the Sponsor and the 
Investigator reserve the right to terminate the Investigator’s participation in the study according 
to the contractual agreement. The Investigator is to notify the IRB/IEC in writing of the study’s 
completion or early termination and send a copy of the notification to the Sponsor. 
7.2 
Source Documents 
• Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
• Data reported on the case report form (CRF) or entered in the electronic CRF that are 
transcribed from source documents must be consistent with the source documents or the 
discrepancies must be explained. The investigator may need to request previous medical 
records or transfer records, depending on the study. Also, current medical records must be 
available. 
• Definition of what constitutes source data can be found in the Source Data Agreement 
(eg, Site Trial Binder, other site communication, etc.). 
8 
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS 
The Sponsor will register and/or disclose the existence of, and the results of clinical studies as 
required by local laws and regulations. 
8.1 
Publication Policy 
• The results of this study may be published or presented at scientific meetings in accordance 
with agreed upon procedures. If this is foreseen under agreed upon procedures, the 
investigator will submit all manuscripts or abstracts to the Sponsor before submission. This 
allows the Sponsor to protect proprietary information and to provide comments under the 
outlined procedures. 
• In accordance with standard editorial and ethical practice, the Sponsor will generally support 
publication of multicenter studies only in their entirety and not as individual site data. 
A coordinating investigator may be designated. 
• Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors authorship requirements. 

Protocol Number: IPA2002 
 
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9 
REFERENCES 
1. 
Turner ML, Bessos H, Fagge T, Harkness M, Rentoul F, Seymour J, et al. Prospective 
epidemiologic study of the outcome and cost-effectiveness of antenatal screening to 
detect neonatal alloimmune thrombocytopenia due to anti-HPA-1a. Transfusion. 
2005;45(12):1945-56. 
2. 
Kjeldsen-Kragh J, Killie MK, Tomter G, Golebiowska E, Randen I, Hauge R, et al. 
A screening and intervention program aimed to reduce mortality and serious morbidity 
associated with severe neonatal alloimmune thrombocytopenia. Blood. 
2007;110(3):833-9. 
3. 
Williamson L, Hackett G, Rennie J, Palmer C, Maciver C, Hadfield R, et al. The natural 
history of fetomaternal alloimmunization to the platelet-specific antigen HPA-1a (PlA1, 
Zwa) as determined by antenatal screening. Blood. 1998;92(7):2280-7. 
4. 
Serrarens-Janssen VM, Semmekrot BA, Novotny VM, Porcelijn L, Lotgering FK, 
Delemarre FM, et al. Fetal/neonatal allo-immune thrombocytopenia (FNAIT): past, 
present, and future. Obstet Gynecol Surv. 2008;63(4):239-52. 
5. 
Ghevaert C, Campbell K, Walton J, Smith GA, Allen D, Williamson LM, et al. 
Management and outcome of 200 cases of fetomaternal alloimmune thrombocytopenia. 
Transfusion. 2007;47(5):901-10. 
6. 
Davoren A, Curtis BR, Aster RH, McFarland JG. Human platelet antigen-specific 
alloantibodies implicated in 1162 cases of neonatal alloimmune thrombocytopenia. 
Transfusion. 2004;44(8):1220-5. 
7. 
Spencer J, Burrows R. Feto-maternal alloimmune thrombocytopenia: a literature review 
and statistical analysis. Aust N Z J Obstet Gynaecol. 2001;41(1):45-55. 
8. 
Doughty HA, Murphy MF, Metcalfe P, Waters AH. Antenatal screening for fetal 
alloimmune thrombocytopenia: the results of a pilot study. Br J Haematol. 
1995;90(2):321-5. 
9. 
Mueller-Eckhardt C, Kiefel V, Grubert A, Kroll H, Weisheit M, Schmidt S, et al. 
348 cases of suspected neonatal alloimmune thrombocytopenia. Lancet. 
1989;1(8634):363-6. 
10. 
Tan J, Lian L, Nadarajan V. Genetic polymorphisms of human platelet antigens-1 to -6, 
and -15 in the Malaysian population. Blood Transfus. 2012;10(3):368-76. 
11. 
Kim H, Jin Y, Kickler T, Blakemore K, Kwon O, Bray P. Gene frequencies of the five 
major human platelet antigens in African American, white, and Korean populations. 
Transfusion. 1995;35(10):863-7. 
 

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10 APPENDIX: SUB-STUDY TO SUPPORT VALIDATION OF THE FETAL HPA-1 
GENOTYPE ASSAY 
10.1 Rationale and Background 
IPA2002 is a prospective, natural history study to assess the occurrence of human platelet 
antigen (HPA)-1a alloimmunization in women identified at higher risk for Fetal and Neonatal 
Alloimmune Thrombocytopenia (FNAIT). It is planned that data from this study be used to 
contextualize results from a future single arm registration study of an anti-HPA-1a antibody 
therapeutic for the prevention of FNAIT.  
In the IPA2002 study, assessment of fetal HPA-1 genotype is needed to confirm the presence of 
the antigenic stimulus (ie, fetal HPA-1a antigen) that may result in maternal alloimmunization. 
At the time of starting this natural history study, a validated assay to confirm fetal HPA-1 
genotype using cell-free fetal DNA (cffDNA) is not available at the same central laboratory 
where all other FNAIT screen tests will be analyzed. The purpose of this sub-study is to collect 
an additional blood sample in a subset of women who provided their consent to participate in the 
IPA2002 study, to support validation of the fetal HPA-1 genotype/cffDNA test.  
10.2 Sub-study Design 
A total of 140 women who are HPA-1b/b is required for this sub-study. Two blood samples will 
be collected from each participant that can be used in the development and validation of a fetal 
HPA-1 genotype assay using cffDNA. The first of the 2 samples will be sourced from the blood 
sample collected at the Gestation Week 10 to 14 visit (Section 4.2.1). The second sample will be 
obtained as follows: 
• Participants who are HPA-1b/b and human leukocyte antigen (HLA)-DRB3*01:01 negative 
at Gestation Week 10 to 14 will be asked to provide one additional blood sample at a 
subsequent pre-natal visit. 
• Participants who are HPA-1b/b, HLA-DRB3*01:01 positive and anit-HPA-1a antibody 
negative at Gestation Week 10 to 14 will not be requested to provide an additional blood 
sample, since a second sample is already scheduled in the main study (Section 4.2.1.1). 
A summary on how the 2 blood samples will be collected for all participants in the sub-study is 
described in the Table 2. 
Written informed consent for the sub-study will be obtained from all participating women. 

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Table 2 
Maternal Samples for Cell-free Fetal DNA HPA-1 Genotyping  
Study/Visit 
Population 
Blood Sample Collected for cffDNA 
Main study 
Sub-study 
Gestation Week 10-14/ 
pre-natal visit 
All participants who are HPA-1b/b  
X 
 
Fetal HPA-1 genotype 
re-test at a subsequent 
pre-natal visit/post 
Gestation Week 10-14 
All participants who are HPA-1b/b and 
HLA-DRB3*01:01 negative genotype 
 
X 
All participants who are HPA-1b/b, 
HLA-DRB3*01:01 positive, and 
anit-HPA-1a antibody negative 
X 
 
cffDNA = cell-free fetal DNA; HLA = human leukocyte antigen; HPA = human platelet antigen 

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11 SUMMARY OF CHANGES 
Version 3.0 (20 May 2022) superseding Version 2.0 (04 November 2021). 
Rationale for Protocol Amendment 2: 
• To provide clarification on blood sample collection for Gestation Week 10 to 14 
Pre-natal Visit Assessments with the preferred approach to collect all samples at the 
Gestation Week 10 to 14-visit and an alternate approach to split blood collection into 
2 timepoint along with the details of the timing and laboratory test(s) at each timepoint. 
o Targeted changes have been made in the protocol to reflect this clarification.  
• Language under Section 4.2 regarding provision of data to the investigator has been updated 
for reviewing the laboratory test results with the participant.  
• To establish a sub-study (Section 10) designed to collect an additional blood sample in a 
subset of women who provided their consent to participate in the IPA2002 study, to support 
validation of the fetal HPA-1 genotype/cffDNA test.  
o Targeted changes have been made in the protocol to reflect the addition of this sub-study.  
Version 2.0 (04 November 2021) superseding Version 1.0 (13 April 2021). 
Rationale for Protocol Amendment 1: 
• The Week 10 Postpartum Visit has been clarified for where the pregnancy did not result in a 
live birth, a Week 10 visit should occur after the pregnancy event (ie, abortion, stillbirth). 
• The repeat sample collection to determine HPA-1 status of the fetus has been clarified to 
apply only to the subset of pregnant woman who are determined to be HPA-1b/b genotype, 
HLA-DRB3*01:01 positive, and anti-HPA-1a antibody negative at Gestation Week 10 to 14. 
• Rationale and Background (Section 2) has been updated to explain that data generated from 
this study is planned to be used as an external control for a future single-arm registration 
study of an anti-HPA-1a antibody therapeutic for the prevention of FNAIT. Additionally, this 
section has been updated for consistency with contemporary FNAIT literature. 
• Inclusion Criteria (Section 4.1.3) have been clarified to accurately reflect the population who 
will be invited to consent and participate in screening for FNAIT risk. 
• Details on the FNAIT blood tests to be performed have been moved to the Methodology 
section of the Protocol Summary and the Study Design (Section 4.1). A summary table which 
describes the Pre-Natal FNAIT Laboratory Testing (Table 1) has been added to Section 4.1 
for the testing of blood samples for FNAIT risk. 
• Section 5.5 (Sample Storage and Destruction) has been updated to permit remaining serum 
samples to be used for future assay development and validation. 
• Administrative and editorial changes have been made throughout the protocol for consistent 
terminology use, to reduce redundant text, and for typographical, grammatical, and 
formatting changes.